Toronto Notes 2023 [39 ed.] 9781998874019

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TORONTO NOTES 2 23

COMPREHENSIVE MEDICAL REFERENCE AND A REVIEW FOR MCCQE Editors-in-Chief • Anders Erickson & Jennifer Parker Associate Editors, Primary • Dorrin Zarrin Khat & Ming Li Associate Editors, Medicine • Karolina Gaebe & Alyssa Li Associate Editors, Surgery • Vrati Mehra & Chunyi Christie Tan

Title Page

TORONTO NOTES 2023 Comprehensive Medical Reference and a Review for the Medical Council of Canada Qualifying Exam (MCCQE)

39th Edition Editors-in-Chief: Anders W. Erickson & Jennifer Parker

Toronto Notes for Medical Students, Inc. Toronto, Ontario, Canada

Copyright 2 Editorial

Toronto Notes 2023

Thirty-ninth Edition Copyright © 2023 – Toronto Notes for Medical Students, Inc. Toronto, Ontario, Canada Typeset and production by Type & Graphics Inc. ISBN 978-1-998874-01-9 (39th ed.) All rights reserved. Printed in Toronto, Ontario, Canada. Toronto Notes 2023 is provided for the sole use of the purchaser. It is made available on the condition that the information contained herein will not be sold or photocopied. No part of this publication may be used or reproduced in any form or by any means without prior written permission from the publisher. Every eort has been made to obtain permission for all copyrighted material contained herein. Previous editions copyright © 1985 to 2023. Cover illustration: Jennifer Xin Ran Shao and Aimy Meng Yu Wang Illustrations: Biomedical Communications, University of Toronto

Notice: THIS PUBLICATION HAS NOT BEEN AUTHORED, REVIEWED, OR OTHERWISE SUPPORTED BY THE MEDICAL COUNCIL OF CANADA NOR DOES IT RECEIVE ENDORSEMENT BY THE MEDICAL COUNCIL AS REVIEW MATERIAL FOR THE MCCQE PART I. THIS PUBLICATION HAS NOT BEEN AUTHORED, REVIEWED, OR OTHERWISE SUPPORTED BY THE NATIONAL BOARD OF MEDICAL EXAMINERS U.S.A. NOR DOES IT RECEIVE ENDORSEMENT BY THE NATIONAL BOARD AS REVIEW MATERIAL FOR THE USMLE. e editors of this edition have taken every eort to ensure that the information contained herein is accurate and conforms to the standards accepted at the time of publication. However, due to the constantly changing nature of the medical sciences and the possibility of human error, the reader is encouraged to exercise individual clinical judgement and consult with other sources of information that may become available with continuing research. e authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this textbook, atlas, or soware and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. In particular, the reader is advised to check the manufacturer’s insert of all pharmacologic products before administration.

FEEDBACK AND ERRATA We are constantly trying to improve the Toronto Notes and welcome your feedback. If you have found an error in this edition please do not hesitate to contact us. As well, we look forward to receiving any comments regarding any component of the Toronto Notes package and website. Please send your feedback to: [email protected] Alternatively, send mail to:

e Toronto Notes for Medical Students Inc. Editors-in-Chief, c/o e Medical Society 1 King’s College Circle, Room 2260 Toronto, Ontario M5S 1A8, Canada email: [email protected]

Library of Congress Cataloging-in-Publication Data is available upon request

Dedication 3 Editorial

Toronto Notes 2023

Dedicated to all the many contributors and supporters of Toronto Notes, both past and present, who have shaped the 2023 edition!

e Toronto Notes for Medical Students is dedicated to helping fund many charitable endeavours and medical student initiatives at the University of Toronto’s Faculty of Medicine and beyond. Programs that have received Toronto Notes for Medical Students funding include: Community Aairs Programs Adventures in Science (AIS) Adventures in Science (AIS) MAM Allies Live Here Altitude Mentoring Altitude Mentoring MAM Blood Drive Exercise is Medicine Growing Up Healthy Growing Up Healthy MAM Healing Tonics Imagine Immigrant and Refugee Equitable Access to Health Care (iREACH) Kids2Hear Kids2See Kindler Arts Noteworthy Music Program Parkdale/Central Toronto Academy Mentorship Program Saturday Program Saturday Program MAM Scadding Court Mentorship Program Seniors Outreach

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N: Many of you have wondered about the Toronto Notes logo, which is based on the rod of Asclepius, the Greek god of medicine. e rod of Asclepius consists of a single serpent entwined around a sta. is icon symbolizes both rebirth, by way of a snake shedding its skin, and also authority, by way of the sta. In ancient Greek mythology, Asclepius was the son of Apollo and a skilled practitioner of medicine who learned the medical arts from the centaur Chiron. Asclepius’ healing abilities were so great that he was said to be able to bring back people from the dead. ese powers displeased the gods, who punished Asclepius by placing him in the sky as the constellation Orphiuchus. e rod of Asclepius is at times confused with the caduceus, or wand, of Hermes, a sta entwined with two serpents and oen depicted with wings. e caduceus is oen used as a symbol of medicine or medical professionals, but there is little historical basis for this symbolism. As you may have guessed, our logo uses the rod of Asclepius that is modied to also resemble the CN Tower – our way of recognizing the university and community in which we have been privileged to learn the art and science of medicine. omas O’Brien, MD Class of 2009, M.D. Program, University of Toronto

Preface 4 Editorial

Toronto Notes 2023

Preface – From the Editors Dear reader, We are grateful to present Toronto Notes 2023 to you. is edition is the product of an exceptional eort from the hundreds of editors and contributors who worked tirelessly with us as we navigated through the year. Together, we have created the thirty-ninth edition of Toronto Notes, thus continuing our organization’s rich tradition of providing an up-to-date, comprehensive, and concisely written medical resource to our readers. irty-nine years ago, Toronto Notes began as a humble initiative, with medical students from the University of Toronto collecting and circulating their notes. Nearly four decades later – with annual editions and an ever-expanding vision – Toronto Notes has become one of the most trusted medical review texts; it is a resource that is cherished by trainees and physicians throughout Canada and around the world. e Toronto Notes for Medical Students Inc. is a nonprot corporation whose mission is to provide a trusted medical resource in order to give back to our community. Keeping in line with our values and community needs, all proceeds from Toronto Notes sales are directly donated to support both global and local initiatives. Among other initiatives, we have supported U of T Medicine class activities, student scholarships and bursaries (such as the Mohammad and Zeynab Asadi-Lari award), our Day annual musical fundraiser for the Canadian Cancer Society, and the entirety of our (over twenty-ve) student-led outreach programs that seek to enrich lives in the community. is is why we, and all the members of our U of T team, gladly dedicated so many hours toward this immensely involved project. As our valued reader, we thank you for your honest and vital nancial contribution through your purchase of our textbook. Each book sold makes an important dierence. e 2023 edition features substantial content revisions to the text, gures, and graphics of all 32 chapters, following a comprehensive review by our student and faculty editorial team. Up-to-date, evidence-based medicine studies are also summarized in highlighted boxes throughout the text. In particular, the Ethical, Legal, and Organizational Medicine chapter has been thoroughly revised and expanded, and all chapters reect the most-updated COVID-19 guidelines. e new MCCQE objectives on Clinical Informatics and Health

and the Climate Crisis are also fully addressed. In addition to content updates, the Toronto Notes 2023 Clinical Handbook has been restructured to prioritize high-yield content to guide your learning during clerkship rotations. Toronto Notes prioritizes cultural sensitivity, health equity, and strives for accurate representation of our vibrant and diverse communities. To enhance our team’s editorial lens on these concepts while editing the chapters, training was provided by the Anti-Racism and Cultural Diversity Oce and Oce of Inclusion & Diversity at the University of Toronto. We sincerely thank each of our 170 student editors and 103 faculty editors, whose meticulous revisions and shared dedication to the bettering of this text has helped make Toronto Notes 2023 possible. We have learned so much from leading this team, and are especially grateful to everyone for contributions to Toronto Notes with challenging time commitments and demands. We thank our incredible Associate Editors – Ming Li, Dorrin Zarrin Khat, Christie Tan, Vrati Mehra, Alyssa Li, and Karolina Gaebe – for their tireless leadership, exceptional organization, and wonderful teamwork. We, and the success of this edition, lean on their shoulders. We also thank our Clinical Handbook Editors – Justin Lu, Janice Chan, and Rayoun Ramendra – for their exceptional editorial leadership and spearheading the work on this resource. We owe a great deal of gratitude to the Editors-in-Chief of the 2022 edition – Yuliya Lytvyn and Maleeha Qazi – for their continued guidance over the past two years. We would also like to thank the wonderful BMC illustration team for their work and especially the cover designs, with inspiration from the medical illustrations of Barry T. O’Neil. Lastly, we thank our longtime partners at Type & Graphics Inc – especially our backbone, Enrica Aguilera and Maria Garcia — for their years of support and excellent work producing Toronto Notes 2023. Finally, we thank you for supporting our initiative by purchasing and reading our product. We hope that you will nd Toronto Notes 2023 to be a useful companion on your medical journey, both now and for years to come.

Sincerely, Anders W. Erickson, MD/PhD student Jennifer Parker, MD/PhD student Editors-in-Chief, Toronto Notes 2023

Acknowledgements 5 Editorial

Toronto Notes 2023

Acknowledgements We would like to acknowledge the exceptional work of all previous Toronto Notes (formerly MCCQE Notes) Editors-in-Chief and their editorial teams. e 39th edition of this text was made possible with their contributions. 2022 (38th ed.): Yuliya Lytvyn and Maleeha A. Qazi 2021 (37th ed.): Megan Drupals and Matthaeus Ware 2020 (36th ed.): Sara Mirali and Ayesh Seneviratne 2019 (35th ed.): Taraneh (Tara) Toghi and Mark Shafarenko 2018 (34th ed.): Tina Binesh Marvasti and Sydney McQueen 2017 (33rd ed.): Jieun Kim and Ilya Mukovozov 2016 (32nd ed.): Zamir Merali and Justin D. Woodne 2015 (31th ed.): Justin Hall and Azra Premji 2014 (30th ed.): Miliana Vojvodic and Ann Young 2013 (29th ed.): Curtis Woodford and Christopher Yao 2012 (28th ed.): Jesse M. Klostranec and David L. Kolin 2011 (27th ed.): Yingming Amy Chen and Christopher Tran 2010 (26th ed.): Simon Baxter and Gordon McSherey 2009 (25th ed.): Sagar Dugani and Danica Lam 2008 (24th ed.): Rebecca Colman and Ron Somogyi 2007 (23rd ed.): Marilyn Heng and Joseph Ari Greenwald 2006 (22nd ed.): Carolyn Jane Shiau and Andrew Jonathan Toren 2005 (21st ed.): Blair John Normand Leonard and Jonathan Chi-Wai Yeung 2004 (20th ed.): Andrea Molckovsky and Kashif S. Pirzada 2003 (19th ed.): Prateek Lala and Andrea Waddell 2002 (18th ed.): Neety Panu and Sunny Wong 2001 (17th ed.): Jason Yue and Gagan Ahuja 2000 (16th ed.): Marcus Law and Brian Rotenberg 1999 (15th ed.): Soa Ahmed and Matthew Cheung 1998 (14th ed.): Marilyn Abraham and M Appleby 1997 (13th ed.): William Harris and Paul Kurdyak 1996 (12th ed.): Michael B. Chang and Laura J. Macnow 1995 (11th ed.): Ann L. Mai and Brian J. Murray 1994 (10th ed.): Kenneth Pace and Peter Ferguson 1993 (9th ed.): Joan Cheng and Russell Goldman 1992 (8th ed.): Gideon Cohen-Nehemia and Shanthi Vasudevan All former Chief Editors from 1991 (7th ed.) to 1985 (1st ed.)

Student Contributors 6 Editorial

Toronto Notes 2023

Student Contributors Editors-in-Chief Anders Erickson Jennifer Parker

Clinical Handbook Editors Justin Lu Rayoun Ramendra

BMC Production Editors Jennifer Xin Ran Shao Aimy Meng Yu Wang

Online Content Managers Jerey Lam Shin Cheung Sandra Lee Amanda Mac Muhammad Shahid

Copyright Managers Mercy Danquah Marta Karpinski

BMC ILLUSTRATORS Viktoriya Khymych

Viola Yu

Amy Ke Er Zhang

PRIMARY Associate Editors Ming Li Dorrin Zarrin Khat

EBM Editor Vijithan Sugumar

CHAPTER EDITORS Ethical, Legal, and Organizational Medicine Kenya Costa-Dookhan Zuhal Mohmand

Dermatology Natalie Kozlowski Yuliya Lytvyn Sara Mirali

Family Medicine Neda Pirouzmand Bree Sharma Maryam raya

Anesthesia Evan Tang Kathak Vachhani

Emergency Medicine Vinyas Harish Danny Ma Kwasi Nkansah Tsz Ying So

Medical Genetics Andrew Mazzanti

Dermatology Chidalu Edechi Jaycie Dalson

Family Medicine Jaskaran Gill Shiyu Sunny Zheng

Emergency Medicine Graham Colby Sanch Gupta Lara Murphy Daniel Shane

Medical Genetics Ryan Karimi

Clinical Pharmacology Max Solish

Medical Imaging Grace Graam Jerey Lam Shin Cheung

Paediatrics Onyinyechukwu Esenwa Anna Jiang Rahna Rasouli Mary Xie Tinting Yang Palliative Medicine Manu Sharma Christine Wu

Psychiatry Tania Da Silva Rawaan Elsawi Rachel Goud Public Health and Preventive Medicine Jenny Cho Muhammad Maaz

COPY EDITORS Ethical, Legal, and Organizational Medicine Noroh Dakim Alex German Anesthesia Max Solish Janet Tang Clinical Pharmacology Fatimah Roble

Medical Imaging Victoria Anthes Hayley McKee

Paediatrics Tania Da Silva Priscilla Kim Ajantha Nadarajah Yasmeen Razvi Palliative Medicine Samuel Wier

Psychiatry David Kim Public Health and Preventive Medicine Caitlin Monaghan Hunster Yang

7 Editorial

Toronto Notes 2023

Student Contributors MEDICINE Associate Editors Karolina Gaebe Alyssa Li

EBM Editors Wei Fang Dai Camilla Giovino

CHAPTER EDITORS Cardiology and Cardiac Surgery Hardil Bhatt Akachukwu Nwakoby Jeremy Rosh Emily Tam Endocrinology Maria Samy Claire Sethuram

Gastroenterology Sahibjot Grewal Anna Lee Andrew Rogalsky

Hematology Reid Gallant Syed Shahan Haider Nathan Kuehne

Geriatric Medicine Imaan Kherani Saba Manzoor

Infectious Diseases Christopher Knox Erika Nakajima Rachel Tran

Endocrinology Winston Li Kathryn Wiens

Hematology Pedro Boasquevisque Daniel Lindsay Brandon Tse

Nephrology David Buchan Huaqi Li Neurology omas Milazzo Maleeha Qazi

Respirology Brian Bursic Emma Price Rajiv Tanwani Rheumatology Rachel Goldfarb Eden Meisels

COPY EDITORS Cardiology and Cardiac Surgery Shamara Nadarajah Julianah Oguntala Calum Slapnicar Vivian Tam

Gastroenterology Oliver Chow Parker McNabb

Infectious Diseases Nicholas Chiang Tedi Hoxha

Nephrology Anders Erickson Jennifer Parker

Respirology Andrew Rogalsky Raza Syed

Neurology Lauren Kanee Kristiana Xhima

Rheumatology Serena Dienes Tsz Ying So

Urology Adree Khondker Shamir Malik

Geriatric Medicine Pooja Sankar

SURGERY Associate Editors Vrati Mehra Chunyi Christie Tan

EBM Editor Arjan Dhoot

CHAPTER EDITORS General and oracic Surgery Ryan Daniel Jacqueline Lim Smruthi Ramesh Gynaecology Eliot Winkler Sarah Zachariah Rehona Zamani

Neurosurgery Dan Budiansky Jack Su Raza Syed

Ophthalmology Michael Balas Josh Herman Michelle Lim

Otolaryngology Alyssa Li Jessica Trac Sheila Yu

Obstetrics Harsukh Benipal Emma Sparks Jane Zhu

Orthopaedic Surgery John-Peter Bonello Kalter Hali Robert Koucheki Marc Manzo

Plastic Surgery Shaishav Datta Tiany Ni

Neurosurgery Bhadra Pandya Jacob Peller

Ophthalmology Kevin Chen Matthew Veitch

Otolaryngology Ryan Daniel Siddhartha Sood

Urology Kellie Kim Gabriela Leon

Obstetrics Julia Avolio Hayley Good Erin Puersten

Orthopaedic Surgery Hannah Drkulec Anders Erickson

Plastic Surgery omas Milazzo Jenn Parker

Vascular Surgery Serena Hope

Vascular Surgery George Elzawy Raumil Patel

COPY EDITORS General and oracic Surgery Tasnim Abdalla Audrey Jong Lisa Vi Gynaecology Laura Diamond Katherine Kim Hafsa Zia

Faculty Contributors 8 Editorial

Toronto Notes 2023

Faculty Contributors, University of Toronto All of the following contributors have been appointed at the University of Toronto.

PRIMARY ETHICAL, LEGAL, AND ORGANIZATIONAL MEDICINE Andria Bianchi, PhD Bioethicist, University Health Network Assistant Professor, Dalla Lana School of Public Health, University of Toronto Aliate Scientist, KITE Research Institute, Toronto Rehab Education Investigator 2, TIER (e Institute for Education Research) Nadia Incardona, MD, MHSc, BSc, CCFP (EM) Assistant Professor Department of Family and Community Medicine Michael Garron Hospital Chase Everett McMurren, BA, BEd, MD, CCFP Department of Family and Community Medicine University of Toronto ANESTHESIA Ahtsham Niazi, MBBS, FCARCSI, FRCPC Department of Anesthesia and Pain Management, University Health Network

Kaif Pardhan, BSc MD MMEd FRCPC Emergency Physician Sunnybrook Health Sciences Centre & McMaster Children’s Hospital FAMILY MEDICINE Ruby Alvi, MD, CCFP, MHSc FCFP Department of Family and Community Medicine University of Toronto Chung Kit (Jacky) Lai, MD, CCFP Department of Family and Community Medicine Royal Victoria Regional Health Centre University of Toronto Chase Everett McMurren, BA, BEd, MD, CCFP Department of Family and Community Medicine University of Toronto Rachel Walsh, MD, MSc, CCFP Department of Family and Community Medicine Sunnybrook Health Sciences Centre University of Toronto

CLINICAL PHARMACOLOGY David Juurlink, BPhm, MD, PhD, FRCPC Division of Clinical Pharmacology and Toxicology, Departments of Medicine and Paediatrics, Sunnybrook Health Sciences Centre

MEDICAL GENETICS Vanda McNiven, MD, MSc, FRCPC Division of Clinical Genetics and Metabolics & Division of Hematology and Oncology Departments of Paediatrics and Medicine e Hospital for Sick Children, e University Health Network, and Mount Sinai Hospital

Cindy Woodland, PhD Associate Professor, Teaching Stream Director, Collaborative Specialization in Biomedical Toxicology Director, Applied Clinical Pharmacology Program

Graeme AM Nimmo, MBBS, MSc, FRCPC, FCCMG e Fred A Litwin Family Centre in Genetic Medicine, Department of Medicine Mount Sinai Hospital and University Health Network

DERMATOLOGY Patrick Fleming, Sc (Nutrition), MSc (Community Health), MD, FRCPC, FCDA Assistant Professor of Medicine, Department of Medicine, University of Toronto Dermatologist, York Dermatology & Research Centre Consultant Dermatologist, University Health Network Marissa Joseph, MD, MScCH, FRCPC, FRCPC Division of Dermatology, Department of Medicine Women’s College Hospital and e Hospital for Sick Children Jensen Yeung, MD, FRCPC Division of Dermatology, Department of Medicine Women’s College Hospital EMERGENCY MEDICINE Mark Freedman, BSc, MD, FRCPC Department of Emergency Medicine Sunnybrook Health Sciences Centre Laura Hans, MD, CCFP (EM) Department of Emergency Medicine St. Michael’s Hospital Adam Kaufman, MD CCFP(EM) Emergency Physician, Michael Garron Hospital, Toronto East Health Network Assistant Professor, Department of Family and Community Medicine, University of Toronto Jo Jo Leung, MD, CCFP(EM), MScCH(HPTE) Emergency Physician, University Health Network and Trillium Health Partners Assistant Professor, Department of Family and Community Medicine, University of Toronto

MEDICAL IMAGING Andrew Brown, MD, MBA, FRCPC Assistant Professor Vascular and Interventional Radiology Department of Medical Imaging Unity Health Toronto - St. Michael’s Hospital Benjamin Fine, SM, MD, FRCPC Clinician Scientist, Medical Imaging Trillium Health Partners, University of Toronto Kieran Murphy, MB, FRCPC, FSIR Interventional Neuroradiology, Professor of Medical Imaging Ciara O’Brien, MB BCh BAO (MD), FFR RCSI Sta Radiologist, Abdominal Division Joint Department of Medical Imaging University Health Network, Mt. Sinai Hospital, Women’s College Hospital Assistant Professor, Department of Medical Imaging, University of Toronto Anastasia Oikonomou, MD, PhD, FRCPC Associate Professor, University of Toronto Division of Cardiothoracic Imaging, Department of Medical Imaging, Sunnybrook Health Sciences Centre PAEDIATRICS Tanvi Agarwal, MD, FRCPC, MScCH (c) Division of Paediatric Medicine Department of Paediatrics e Hospital for Sick Children Jillian Baker, MD, MSc, FRCPC Assistant Professor of Pediatrics, University of Toronto Divisions of Pediatrics and Hematology/Oncology Department of Pediatrics, Unity Health Toronto (St. Michael’s Hospital) & e Hospital for Sick Children

Tyler Groves, MSc, MBBS, FRCPC Department of Paediatrics, Michael Garron Hospital Giuseppe (Joey) Latino, MD, FRCPC Department of Paediatrics Division of Genetics, Department of Medicine North York General Hospital Laila Premji, MD, FRCPC Division of Paediatric Medicine, Department of Paediatrics e Hospital for Sick Children Shazeen Suleman, MSc, MD, MPH (FRCPC) Women and Children’s Health St. Michael’s Hospital, Unity Health Toronto Janaki Vallipuram, MD, FRCPC Division of Paediatric Medicine, Department of Paediatrics e Hospital for Sick Children, Markham Stouville Hospital PALLIATIVE MEDICINE Risa Bordman, MD, CCFP(PC), FCFP Associate Professor Faculty Development Program Lead, Oce of Education Scholarship Department of Family & Community Medicine Adam Rapoport, MD, FRCPC, MHSc Departments of Paediatrics and Family & Community Medicine, University of Toronto Paediatric Advanced Care Team, SickKids Emily’s House Children’s Hospice Donna Spaner, MD, CCFP(PC), FCFP, MScCH Division of Palliative Care, Department of Family and Community Medicine Toronto Grace Health Centre PSYCHIATRY Saulo Castel, MD, PhD, FRCPC Director, Inpatient Services Sunnybrook Health Sciences Centre Assistant Professor, Department of Psychiatry Tamara Milovic, MD, MBA, FRCPC Psychiatrist, Centre for Addiction and Mental Health Lecturer, Department of Psychiatry, University of Toronto Jerome Perera, MD, FRCPC Psychiatrist, North York General Hospital Clinician Teacher, Department of Psychiatry, University of Toronto Ilana Shawn, MD FRCPC Department of Psychiatry, St. Michael’s Hospital Assistant Professor, Department of Psychiatry PUBLIC HEALTH AND PREVENTIVE MEDICINE Jason J Pennington, MD, MSc, FRCSC Division of General Surgery, Department of Surgery, Scarborough Health Network Assistant Professor, Department of Surgery, University of Toronto Andrew Pinto, BSc, MD, CCFP, FRCPC, MSc Department of Family and Community Medicine, St. Michael’s Hospital Department of Family and Community Medicine, University of Toronto Dalla Lana School of Public Health, University of Toronto

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Toronto Notes 2023

Faculty Contributors, University of Toronto MEDICINE CARDIOLOGY AND CARDIAC SURGERY Paul Dorian, MD, MSc, FRCPC Division of Cardiology St. Michael’s Hospital Douglas J. Ing, MD, FRCPC, FACC Division of Cardiology Toronto General Hospital Bobby Yanagawa, MD, PhD, FRCSC Division of Cardiac Surgery St Michael’s Hospital ENDOCRINOLOGY Angela Assal, MD, MHSc, FRCPC Division of Endocrinology and Metabolism, Department of Medicine Sunnybrook Health Sciences Centre University of Toronto Jeremy Gilbert, MD, FRCPC Division of Endocrinology and Metabolism Sunnybrook Health Sciences Centre Adrian Lau, MD, MScCH, FRCPC Division of Endocrinology and Metabolism Department of Medicine Women’s College Hospital University of Toronto Maria Wolfs, MD MHSc FRCPC Division of Endocrinology and Metabolism St. Michael’s Hospital GASTROENTEROLOGY Maria Cino, BSc(Hon), Hon BSc, MSc, MD, FRCPC, CAGF Division of Gastroenterology, Department of Medicine University Health Network - Toronto Western Site Associate Professor, University of Toronto Flavio Habal, MD,PhD,FRCP,FAGA Division of Gastroenterology University Health Network, Toronto Western Division Associate Professor, University of Toronto Piero Tartaro, MD, MScCH, FRCPC Division of Gastroenterology, Department of Medicine Sunnybrook Health Sciences Centre GERIATRIC MEDICINE Jillian Alston, MD, FRCPC, MScCH Division of Geriatrics Department of Medicine St. Michael’s Hospital Vicky Chau, MD, MScCH, FRCPC Division of Geriatric Medicine, Department of Medicine Sinai Health System & University Health Network

iru Yogaparan, MD, FRCP Division of Geriatric Medicine, Department of Medicine, Baycrest Health Sciences

Alireza Zahirieh, MD, FRCPC Division of Nephrology, Department of Medicine Sunnybrook Health Sciences Centre

HEMATOLOGY Matthew Cheung, MD, FRCPC Division of Medical Oncology and Hematology, Department of Medicine Sunnybrook Health Sciences Centre

NEUROLOGY Charles D. Kassardjian, MD, MSc, FRCPC Division of Neurology, Department of Medicine St. Michael’s Hospital

Lisa Chodirker, MD, FRCPC Division of Medical Oncology and Hematology, Department of Medicine Sunnybrook Health Sciences Centre Helena Dhamko, MD, FRCPC, MScCH Division of Hematology, Department of Medicine University Health Network Zachary Liederman, MD, FRCPC, MScCH Division of Hematology, Department of Medicine University Health Network Michael Scott, MD, FRCPC Clinical Hematologist; Adjunct Lecturer, Division of Medical Oncology and Hematology Department of Medicine, Unity Health Toronto, St. Michael’s Hospital Martina Trinkaus, MD, FRCPC Division of Hematology, Department of Medicine St. Michael’s Hospital INFECTIOUS DISEASES Andrea K. Boggild, BSc, MSc, MD, DTMH, FRCPC Tropical Disease Unit, Toronto General Hospital Division of Infectious Diseases, University Health Network Department of Medicine, University of Toronto Institute of Medical Science, University of Toronto Paul E. Bunce, BSc, MA, MD, FRCPC Division of Infectious Diseases Department of Medicine University Health Network Susan M. Poutanen, MD, MPH, FRCPC Department of Microbiology, University Health Network & Sinai Health Division of Infectious Diseases, Department of Medicine University Health Network & Mount Sinai Hospital NEPHROLOGY Damien Noone, MB BCh BAO, MSc Division of Paediatric Nephrology, Department of Paediatrics e Hospital for Sick Children Gemini Tanna, MD, FRCPC Division of Nephrology, Department of Medicine Sunnybrook Health Sciences Centre

Alexandra Muccilli, MD, MEd, FRCPC Division of Neurology, Department of Medicine St. Michael’s Hospital Liza Pulcine, MD, MSc, FRCPC Assistant Professor, Fellowship Director Children’s Stroke Program Division of Neurology, Department of Paediatrics, e Hospital for Sick Children RESPIROLOGY Samir Gupta, MD, FRCPC Division of Respirology, Department of Medicine Unity Health Toronto Ambrose Lau, MD, MEd, FRCPC Division of Respirology, Department of Medicine University Health Network and Unity Health Toronto Assistant Professor, University of Toronto Christopher Li, MD, FRCPC, DABSM Division of Respirology, Department of Medicine Unity Health Toronto - St. Michael’s RHEUMATOLOGY Ahmed Omar, MBBCh, MRCP, MSc Assistant Professor, University of Toronto Division of Rheumatology, Department of Medicine Mount Sinai Hospital, University Health Network Arthur Bookman, MD, FRCPC Division of Rheumatology, Department of Medicine University Health Network Sahil Koppikar, MD FRCPC Assistant Professor, Division of Rheumatology Department of Medicine, Women’s College Hospital Dharini Mahendira, MD, FRCPC, MScCH Assistant Professor, Division of Rheumatology Department of Medicine, St. Michael’s Hospital Medha L. Soowamber, MD, MSc, FRCPC Division of Rheumatology, Department of Medicine Mount Sinai Hospital

10 Editorial

Toronto Notes 2023

Faculty Contributors, University of Toronto SURGERY GENERAL AND THORACIC SURGERY Abdollah Behzadi, MD, MBA, FRCSC, FACS Division of oracic Surgery, Department of Surgery Trillium Health Partners, University of Toronto Sayf Gazala, MD, MSc, FRCSC Assistant Professor, oracic Surgery Department of Surgery, Michael Garron Hospital Jesse Pasternak, MD, MPH, FRCSC Section of Endocrine Surgery Division of General Surgery, Department of Surgery University Health Network Fayez Quereshy, MD, MBA, FRCSC Department of General Surgery University Health Network, Toronto Western Hospital GYNAECOLOGY Michael Chaikof, MD, FRCSC, MS-HPEd Division of Urogynecology Department of OB/GYN Sunnybrook Health Sciences Centre Sari Kives, MD, FRCSC Associate Professor Division of Obstetrics and Gynecology Department of Obstetrics and Gynecology St Michaels hospital NEUROSURGERY Sunit Das, MD, PhD Division of Neurosurgery St. Michael’s Hospital Michael G. Fehlings, MD, PhD, FRCSC, FACS Professor of Neurosurgery, Department of Surgery, University of Toronto Vice Chair Research, Department of Surgery, University of Toronto Senior Scientist, Krembil Brain Institute, University Health Network Sta Neurosurgeon, University Health Network Co-Director, University of Toronto Spine Program Eric M. Massicotte MD, MSc, MBA, FRCSC Associate Professor University of Toronto Sta Neurosurgeon, University Health Network Medical Director, Back & Neck Program Altum Health OBSTETRICS Richard Pittini, MD, MEd, FRCSC, FACOG Department of Obstetrics and Gynecology, University of Toronto Sunnybrook Health Sciences Centre Mara Sobel, MD, MSc, FRCSC Department of Obstetrics and Gynecology, University of Toronto Mount Sinai Hospital, University Health Network, Toronto General Hospital, Women’s College Hospital

Melissa Walker, MD, MSc, FRCSC Sta Obstetrician Gynecologist, Department of Obstetrics & Gynecology, Mount Sinai Hospital Assistant Professor, Department of Obstetrics & Gynecology, University of Toronto

PLASTIC SURGERY Joel Fish, MD, MSC, FRCS Professor, Plastic and Reconstructive Surgery Department of Surgery e Hospital for Sick Children

OPHTHALMOLOGY Asim Ali, MD, FRCSC Professor of Ophthalmology, University of Toronto Ophthalmologist-in-Chief, e Hospital for Sick Children

Siba Haykal, MD, PhD, FRCSC, FACS Division of Plastic and Reconstructive Surgery, Department of Surgery University Health Network

Wai-Ching Lam, MD, FRCSC Department of Ophthalmology and Vision Science University Health Network, Toronto Western Hospital e Hospital for Sick Children Jonathan Micieli, MD, FRCSC Department of Ophthalmology and Vision Sciences; Division of Neurology, Department of Medicine; Kensington Vision and Research Centre, St. Michael’s Hospital, University of Toronto ORTHOPAEDIC SURGERY Jeremy Hall, MD, FRCSC Division of Orthopaedic Surgery, Department of Surgery, St. Michael’s Hospital Paul Kuzyk, MD, MASc, FRCSC Assistant Professor Lower Extremity Reconstruction Surgery Division of Orthopaedic Surgery Jesse Wolfstadt, MD, MSc, FRCSC Granovsky Gluskin Division of Orthopaedic Surgery, Department of Surgery, Sinai Health System OTOLARYNGOLOGY Yvonne Chan, MD, MSc, FRCSC Otolaryngologist-in-chief, St. Michael’s Hospital, Unity Health Associate Professor and Continuing Professional Development Director Department of Otolaryngology Head & Neck Surgery Antoine Eskander, MD, ScM, FRCSC Assistant Professor Department of Otolaryngology Head & Neck Surgery Sunnybrook Health Sciences Centre, Odette Cancer Centre Michael Garron Hospital Jonathan Irish, MD, MSc, FRCSC Department of Otolaryngology, Head and Neck Surgery, University Health Network

UROLOGY Monica Farcas, BEng, MEng, MD, FRCSC Assistant Professor, Division of Urology Department of Surgery, Unity Health Toronto Yonah Krakowsky, MD, FRCSC Division of Urology Women’s College & Mount Sinai Hospital Jason Lee, MD, MHPE, FRCSC Division of Urology, Department of Surgery University Health Network, Toronto General Hospital Michael Ordon, MD, MSc, FRCSC Division of Urology, Department of Surgery St. Michael’s Hospital VASCULAR SURGERY Elisa Greco, BSc, MEd, MD, RPVI, FRCSC Vascular Surgeon, St Michael’s Hospital George Oreopoulos, MD, MSc, FRCSC Division of Vascular Surgery, Department of Surgery University Health Network

Table of Contents 11 Editorial

Toronto Notes 2023

Table of Contents Index Abbreviations Common Acronyms and Abbreviations Used in Medicine Common Unit Conversions Commonly Measured Laboratory Values Ethical, Legal, and Organizational Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ELOM Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A Cardiology and Cardiac Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C Clinical Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CP Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . D Emergency Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ER Endocrinology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E Family Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . FM Gastroenterology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . G General and Thoracic Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GS Geriatric Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GM Gynaecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GY Hematology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . H Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ID Medical Genetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MG Medical Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . MI Nephrology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NP Neurology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . N Neurosurgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NS Obstetrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OB Ophthalmology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OP Orthopaedic Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OR Otolaryngology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OT Paediatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . P Palliative Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PM Plastic Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PL Psychiatry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PS Public Health and Preventive Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PH Respirology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . R Rheumatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RH Urology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . U Vascular Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VS

How to Use Book 12 Editorial

Toronto Notes 2023

How To Use This Book is book has been designed to remain as one book or to be taken apart into smaller booklets. Identify the beginning and end of a particular section, then carefully bend the pages along the perforated line next to the spine of the book. en tear the pages out along the perforation. e layout of Toronto Notes allows easy identication of important information. ese items are indicated by icons interspersed throughout the text: Icon

Icon Name

Significance

Key Objectives

is icon is found next to headings in the text. It identies key objectives and conditions as determined by the Medical Council of Canada or the National Board of Medical Examiners in the USA. If it appears beside a dark title bar, all subsequent subheadings should be considered key topics.

Clinical Pearl

is icon is found in sidebars of the text. It identies concise, important information which will aid in the diagnosis or management of conditions discussed in the accompanying text.

Memory Aid

is icon is found in sidebars of the text. It identies helpful mnemonic devices and other memory aids.

Clinical Flag

is icon is found in sidebars of the text. It indicates information or ndings that require urgent management or specialist referral.

Evidence Based Medicine

is icon is found in sidebars of the text. It identies key research studies for evidencebased clinical decision making related to topics discussed in the accompanying text.

Colour Photo Atlas

is icon is found next to headings in the text. It indicates topics that correspond with images found in the Colour Photo Atlas available online (www.torontonotes.ca).

Radiology Atlas

is icon is found next to headings in the text. It indicates topics that correspond to images found in the Radiology Atlas available online (www.torontonotes.ca).

Online Resources

is icon is found next to headings in the text. It indicates topics that correspond with electronic resources such as Functional Neuroanatomy or ECGs Made Simple, available online (www.torontonotes.ca).

Chapter Divisions To aid in studying and nding relevant material quickly, many chapters incorporate the following general framework:

Basic Anatomy/Physiology Review • features the high-yield, salient background information students are oen assumed to have remembered from their early medical school education

Common Dierential Diagnoses • aims to outline a clinically useful framework to tackle the common presentations and problems faced in the area of expertise

Diagnoses • the bulk of the book • etiology, epidemiology, pathophysiology, clinical features, investigations, management, complications, and prognosis

Common Medications • a quick reference section for review of medications commonly prescribed

Acronyms and Abbreviations 13 Editorial

Toronto Notes 2023

Common Acronyms and Abbreviations Used in Medicine The following are common medical acronyms/abbreviations that may be used without definition throughout the Toronto Notes text. These are typically not included in the acronym list at the beginning of each chapter. Please refer back to this list for definitions.

[] β-hCG

concentration beta human chorionic gonadotropin

ABx ACE ACTH AIDS ALP ALT AR ASA AST aSx AXR

antibiotics angiotensin-converting enzyme Adrenocorticotropic hormone acquired immune deciency syndrome alkaline phosphatase alanine aminotransferase absolute risk acetylsalicylic acid aspartate transaminase asymptomatic abdominal x-ray

BID BMI BP BPM/bpm

twice a day (bis in die) body mass index blood pressure beats per minute

C/I C&S CAD CBC CC CHF COPD CPR Cr CRH CSF CT CXR

contraindication culture and sensitivity coronary artery disease complete blood count chief complaint congestive heart failure chronic obstructive pulmonary disease cardiopulmonary resuscitation creatinine corticotropin-releasing hormone cerebrospinal uid computed tomography chest x-ray

D&C dBP DDx DM DNR Dx

dilatation and curettage diastolic blood pressure dierential diagnosis diabetes mellitus do not resuscitate diagnosis

ECG ED EEG EMG ENT ESR EtOH

electrocardiogram emergency department electroencephalography electromyography ears, nose, and throat erythrocyte sedimentation rate ethanol/alcohol

FMHx FSH

family medical history follicle stimulating hormone

G6PD GGT GH GHB GI GU

glucose-6-phosphate dehydrogenase gamma-glutamyl transferase growth hormone gamma hydroxybutyrate gastrointestinal genitourinary

Hb HIV HR HTN Hx

hemoglobin human immunodeciency disease heart rate hypertension history

I&D ICP ICU IM IV

incision and drainage intracranial pressure intensive care unit intramuscular intravenous

JVP

jugular venous pressure

LDH LFT LH LR

lactate dehydrogenase liver function test luteinizing hormone likelihood ratio

14 Editorial

Toronto Notes 2023

MAO MAOI MDI MI MRI MSK

monoamine oxidase monoamine oxidase inhibitor metered-dose inhaler myocardial infarction magnetic resonance imaging musculoskeletal

N/V NG NMDA NPO NSAID

nausea/vomiting nasogastric N-Methyl-D-aspartate nothing by mouth (nil per os) non-steroidal anti-inammatory drug

OR OTC

operating room over-the-counter

PCR PE PMHx PO POCUS PPI PRN

polymerase chain reaction pulmonary embolism past medical history oral administration (per os) point-of-care ultrasound proton pump inhibitor as needed (pro re nata)

QID RBC RCT ROS Rx

sBP SC SL SLE SOB STAT STI Sx

systolic blood pressure subcutaneous sublingual systemic lupus erythematosus shortness of breath urgent or immediately (statum) sexually transmitted infection symptom(s)

T1DM T2DM TB TID TNM TRH TSH Tx

type 1 diabetes mellitus type 2 diabetes mellitus tuberculosis three times a day (ter in die) tumour, nodes, and metastases thyroid releasing hormone thyroid stimulating hormone treatment

U/A U/S UTI UTox

urinalysis ultrasound urinary tract infection urine toxicology screen

VDRL

Venereal Disease Research Laboratory test

WBC wt

white blood cell weight

four times a day (quater in die) red blood cell randomized controlled trial review of symptoms medical prescription

Unit Conversions 15 Editorial

Toronto Notes 2023

Common Unit Conversions To convert from the conventional unit to the SI unit, multiply by conversion factor To convert from the SI unit to the conventional unit, divide by conversion factor Conventional Unit

Conversion Factor

SI Unit

ACTH

pg/mL

0.22

pmol/L

Albumin

g/dL

10

g/L

Bilirubin

mg/dL

17.1

µmol/L

Calcium

mg/dL

0.25

mmol/L

Cholesterol

mg/dL

0.0259

mmol/L

Cortisol

µg/dL

27.59

nmol/L

Creatinine

mg/dL

88.4

µmol/L

Creatinine clearance

mL/min

0.0167

mL/s

Ethanol

mg/dL

0.217

mmol/L

Ferritin

ng/mL

2.247

pmol/L

Glucose

mg/dL

0.0555

mmol/L

HbA1c

%

0.01

proportion of 1.0

Hemaglobin

g/dL

10

g/L

HDL cholesterol

mg/dL

0.0259

mmol/L

Iron, total

µg/dL

0.179

µmol/L

Lactate (lactic acid)

mg/dL

0.111

mmol/L

LDL cholesterol

mg/dL

0.0259

mmol/L

Leukocytes

x 10 3cells/mm 3

1

x 109cells/L

Magnesium

mg/dL

0.411

mmol/L

MCV

µm3

1

fL

Platelets

x 10 3cells/mm 3

1

x 109cells/L

Reticulocytes

% of RBCs

0.01

proportion of 1.0

Salicylate

mg/L

0.00724

mmol/L

Testosterone

ng/dL

0.0347

nmol/L

Thyroxine (T4)

ng/dL

12.87

pmol/L

Total Iron Binding Capacity

µg/dL

0.179

µmol/L

Triiodothyronine (T3)

pg/dL

0.0154

pmol/L

Triglycerides

mg/dL

0.0113

mmol/L

Urea nitrogen

mg/dL

0.357

mmol/L

Uric acid

mg/dL

59.48

µmol/L

Celsius → Fahrenheit

F = (C x 1.8) + 32

Fahrenheit → Celsius

C = (F – 32) x 0.5555

Kilograms → Pounds

1 kg = 2.2 lbs

Pounds → Ounces

1 lb = 16 oz

Ounces → Grams

1 oz = 28.3 g

Inches → Centimetres

1 in = 2.54 cm

Measured Laboratory Values 16 Editorial

Toronto Notes 2023

Commonly Measured Laboratory Values Test

Conventional Units

SI Units

Arterial Blood Gases pH PCO2 PO2

7.35-7.45 35-45 mmHg 80-105 mmHg

7.35-7.45 4.7-6.0 kPa 10.6-14 kPa

Serum Electrolytes Bicarbonate Calcium Chloride Magnesium Phosphate Potassium Sodium

22-28 mEq/L 8.4-10.2 mg/dL 95-106 mEq/L 1.3-2.1 mEq/L 2.7-4.5 mg/dL 3.5-5.0 mEq/L 136-145 mEq/L

22-28 mmol/L 2.1-2.5 mmol/L 95-106 mmol/L 0.65-1.05 mmol/L 0.87-1.45 mmol/L 3.5-5.0 mmol/L 136-145 mmol/L

Serum Nonelectrolytes Albumin ALP ALT Amylase AST Bilirubin (direct) Bilirubin (total) BUN Cholesterol Creatinine (female) Creatinine (male) Creatine Kinase – MB fraction Ferritin (female) Ferritin (male) Glucose (fasting) HbA1c LDH Osmolality

3.5-5.0 g/dL 35-100 U/L 8-20 U/L 25-125 U/L 8-20 U/L 0-0.3 mg/dL 0.1-1.0 mg/dL 7-18 mg/dL 60%) (Normal) • Grade II (EF = 40-59%) • Grade III (EF = 21-39%) • Grade IV (EF ≤20%)

C41 Cardiology and Cardiac Surgery

Toronto Notes 2023

Table 15. Signs and Symptoms of Left vs. Right HF Low CO (Forward)

Venous Congestion (Backward)

Left Failure

Right Failure

Fatigue Syncope Systemic hypotension Cool extremities Slow capillary refill Peripheral cyanosis Pulsus alternans MR S3

Left failure symptoms if decreased RV output leads to LV underfilling TR S3 (right-sided)

Dyspnea, orthopnea, PND Cough Crackles

Peripheral edema Elevated JVP with abdominojugular reflux, and ± Kussmaul’s sign Hepatomegaly Pulsatile liver

Pathophysiology • most common causes are ischemic heart disease, risk factors for CAD, LVH (HTN), valvular heart disease, and tachyarrhythmia • myocardial insult causes pump dysfunction/impaired lling leading to myocardial remodeling and the following maladaptive changes: ■ pressure overload (e.g. AS or HTN) leads to compensatory hypertrophy (i.e. concentric remodeling) and eventually interstitial brosis ■ volume overload (e.g. aortic insuciency) leads to dilatation (i.e. eccentric remodeling) • remodeling results in decreased forward CO resulting in activation of the SNS and RAAS • SNS causes tachycardia • RAAS causes Na+ and water retention to increase preload and aerload • net result is increased cardiac demand leading to eventual decompensation Heart Failure with Reduced Ejection Fraction (HFrEF: LVEF ≤40%) • impaired myocardial contractile function → decreased LVEF and SV → decreased CO • volume overload is the typical phenotype • ndings: apex beat displaced, S3, cardiothoracic ratio >0.5, decreased LVEF, LV dilatation • causes ■ ischemic (e.g. extensive CAD, previous MI) ■ non-ischemic ◆ HTN ◆ DM ◆ EtOH (and other toxins) ◆ myocarditis ◆ DCM (multiple causes see Dilated Cardiomyopathy, C47) ◆ tachycardia-induced Heart Failure with Mid-Range Ejection Fraction (HF-mrEF: LVEF 41-49%) • includes patients who are recovering from HFrEF, declining from HFpEF, and transitioning to HFpEF • characterization of HFmEF ongoing; guideline management does not currently exist Heart Failure with Preserved Ejection Fraction (HFpEF: LVEF ≥50%) • previously known as “diastolic HF” • concentric remodelling with a “sti” LV is the typical phenotype • 50% of patients with HF have preserved EF; confers similar prognosis to HFrEF; more common in the elderly and females • reduced LV compliance causes increased LV lling pressures, increased LA pressure/volume, and pulmonary congestion • ndings: HTN, apex beat sustained, S4, normal-sized heart on CXR, LVH on ECG/echo, normal EF • causes ■ transient: ischemia (e.g. CAD, MI) ■ permanent: severe hypertrophy (HTN, AS, HCM), RCM (e.g. amyloid), MI High-Output Heart Failure • caused by demand for increased CO • oen exacerbates existing HF or decompensates a patient with other cardiac pathology • DDx: anemia, thiamine deciency (beriberi), hyperthyroidism, arteriovenous (A-V) stula or le to right (L-R) shunting, Paget’s disease, renal disease, hepatic disease Precipitants of Symptomatic Exacerbations • consider natural progression of disease vs. new precipitant • always search for reversible cause

See Landmark Cardiac Trials for more information on DAPA-HF which details the ecacy of SGLT2 inhibition in patients with HFrEF and without T2DM.

See Landmark Cardiac Trials for more information on PARADIGM-HF which details the survival outcomes of HFrEF patients treated with an ACEI or an angiotensinneprilysin inhibitor.

A Validated Clinical and Biochemical Score for the Diagnosis of Acute Heart Failure: t he ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Acute Heart Failure Score Am Heart J 2006;151:48-54

Predictor

Possible Score

Age >75 yr

1

Orthopnea present

2

Lack of cough

1

Current loop diuretic use (before presentation)

1

Rales on lung exam

1

Lack of fever

2

Elevated NT-proBNP (>450 pg/mL if 900 pg/mL if >50 yr)

4

Interstitial edema on CXR

2

Total

/14

Likelihood of HF Low = 0-5 Intermediate = 6-8 High = 9-14

BNP is secreted by Vs due to LV stretch and wall tension. Cardiomyocytes secrete BNP precursor that is cleaved into proBNP. After secretion into Vs, proBNP is cleaved into the active C-terminal portion and the inactive NT-proBNP. The above scoring algorithm developed by Baggish et al. is commonly used. A score of 300 pg/ml), uric acid • urinalysis • ECG: look for chamber enlargement, arrhythmia, ischemia/infarction • CXR: cardiomegaly, pleural eusion, redistribution, Kerley B lines, bronchiolar-alveolar cung • echo: systolic function (LVEF), diastolic function (E/A ratio, E/e’), cardiac dimensions, wall motion abnormalities, RV systolic pressure (from TR jet), valvular disease, pericardial eusion • radionuclide angiography: LVEF • myocardial perfusion scintigraphy (thallium or sestamibi SPECT) Additional Diagnostic Investigations • cardiac catheterization • cardiopulmonary exercise testing • other tests (CMR, MPI, MUGA, CT scan) Acute Treatment of Pulmonary Edema • treat acute precipitating factors (e.g. ischemia, arrhythmias) ■ L Lasix® (furosemide) 40-500 mg IV ■ M morphine 2-4 mg IV: decreases anxiety and preload (venodilation) ■ N nitroglycerin: topical/IV/SL - use with caution in preload-dependent patients (e.g. right HF or RV infarction) as it may precipitate CV collapse ■ O oxygen: in hypoxemic patients ■ P positive airway pressure (continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BiPAP)): decreases preload and need for ventilation when appropriate ■ P position: sit patient up with legs hanging down unless patient is hypotensive • in ICU setting or failure of LMNOPP: other interventions may be necessary ■ nitroprusside IV ■ hydralazine PO ■ sympathomimetics ◆ dopamine – low dose: selective renal vasodilation (high potency D1 agonist) – medium dose: inotropic support (medium potency β1 agonist) – high dose: increases SVR (low potency β1 agonist), which is undesirable ◆ dobutamine – β1-selective agonist causing inotropy, tachycardia, hypotension (low dose) or HTN (high dose); most serious side eect is arrhythmia, especially AFib phosphodiesterase inhibitors (milrinone) – inotropic eect and vascular smooth muscle relaxation (decreased SVR), similar to dobutamine • consider pulmonary artery catheter to monitor PCWP if patient is unstable or a cardiac etiology is uncertain (PCWP >18 indicates likely cardiac etiology) • mechanical ventilation as needed • rarely used, but potentially life-saving measures: ■ IABP - reduces aerload via systolic unloading and improves coronary perfusion via diastolic augmentation ■ LVAD/RVAD ■ cardiac transplant Long-Term Management • overwhelming majority of evidence-based management applies to HFrEF • currently no proven pharmacologic therapies shown to reduce mortality in HFpEF; control risk factors for HFpEF (e.g. HTN) • prevent uid overload with appropriate diuretic strategies Conservative Measures • symptomatic measures: oxygen in hospital, bedrest, elevate the head of bed • lifestyle measures: diet, exercise, DM control, smoking cessation, decrease EtOH consumption, patient education, sodium, and uid restriction • multidisciplinary HF clinics: for management of individuals at higher risk, or with recent hospitalization

Toronto Notes 2023

Five Most Common Causes of CHF • CAD (60-70%) • HTN • Idiopathic (often DCM) • Valvular (e.g. AS, AR, and MR) • EtOH (DCM)

Precipitants of HF HEART FAILED HTN (common) Endocarditis/environment (e.g. heat wave) Anemia Rheumatic heart disease and other valvular disease Thyrotoxicosis Failure to take medications (very common) Arrhythmia (common) Infection/Ischemia/Infarction (common) Lung problems (PE, pneumonia, COPD) Endocrine (pheochromocytoma, hyperaldosteronism) Dietary indiscretions (common)

The most common cause of right HF is left HF

Measuring NT-proBNP BNP is secreted by Vs due to LV stretch and wall tension Cardiomyocytes secrete BNP precursor that is cleaved into proBNP After secretion into Vs, proBNP is cleaved into the active C-terminal portion and the inactive NT-proBNP portion NT-proBNP levels (pg/mL) Age

HF very likely

450

50-75

>900

>75

>1800

Limitations: Age, body habitus, renal function, PE

Features of HF on CXR HERB-B Heart enlargement (cardiothoracic ratio >0.50) Pleural Eusion Re-distribution (alveolar edema) Kerley B lines Bronchiolar-alveolar cung

Patients on β-blocker therapy who have acute decompensated HF should continue β-blockers where possible (provided they are not in cardiogenic shock or in severe pulmonary edema)

C43 Cardiology and Cardiac Surgery

Non-Pharmacological Management • from 2021 CCS guidelines • restrict salt intake to 2-3 g/d • monitor daily weight for patients with HF, uid retention, or congestion that is dicult to control with diuretics or renal dysfunction • restrict daily uid intake to approximately 2 L/d for patients with uid retention or congestion that is dicult to control with diuretics • cardiac rehabilitation: participation in a structured exercise program for NYHA class I-III aer clinical status assessment to improve quality of life (HF-ACTION trial) Pharmacological Therapy • ACEI/ARB: RAAS blockade ■ ACEI: slows progression of LV dysfunction and improves survival ◆ all symptomatic patients functional class II-IV ◆ all asymptomatic patients with LVEF 5.2 mmol/L

Toronto Notes 2023

CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure with Reduced Ejection Fraction Can J Cardiol 2021;37:531-46 Management of HFrEF: It is recommended that, in the absence of contraindications, HFrEF patients be treated with combination therapy including 1 drug from each of the following categories: ARNI (or ACEI/ARB), β-blocker, mineralocorticoid receptor antagonist (MRA) and SGLT2 inhibitor. It is recommended that patients admitted with acute decompensated HFrEF should be switched to an ARNI, from an ACEI/ARB when stabilized. It is recommended that β-blockers be initiated as soon as possible after HF diagnosis, not waiting until hospital discharge to initiate treatment in stabilized patients. MRA treatment is recommended for patients with acute MI and LVEF 1 of these major risk factors: family history of HCM SCD, NSVT on ambulatory monitor, massive LVH, and unexplained syncope † In patients >16 yr of age, 5-yr risk estimates can be considered to fully inform patients during shared decision-making discussions ‡ It would seem most appropriate to place greater weight on frequent, longer, and faster runs of NSVT CMR = cardiovascular magnetic resonance; EF = ejection fraction; HCM = hypertrophic cardiomyopathy; ICD = implantable cardioverter-defibrillator; LGE = late gadolinium enhancement; LVH = left ventricular hypertrophy; NSVT = nonsustained ventricular tachycardia; SCD = sudden cardiac death

Figure 44. ICD implantation in HCM

Restrictive Cardiomyopathy C49 Cardiology and Cardiac Surgery

Toronto Notes 2023

Management • avoid factors which increase obstruction (e.g. volume depletion) ■ avoidance of high-intensity competitive sports unless exceptional circumstances ■ mild-to-moderate-intensity exercise is safe • treatment of HOCM ■ medical agents: β-blockers, verapamil or diltiazem (started only in monitored settings), disopyramide, phenylephrine (in setting of cardiogenic shock) ■ avoid digoxin and vasodilators (e.g. nitrates, dihydropyridine calcium channel blockers, and ACEi/ARB) as they are inotropic and aerload reducing, respectively • patients with HOCM and drug-refractory symptoms require septal reduction therapy at experienced centres ■ surgical myectomy ■ alcohol septal ablation - percutaneous intervention that ablates the hypertrophic septum with 100% ethanol via the septal artery ■ dual chamber pacing (rarely done) • treatment of non-obstructive HCM ■ symptomatic: β-blockers or non-dihydropyridine calcium channel blockers and diuretics if refractory symptoms • comorbid atrial brillation: direct oral anticoagulant or warfarin regardless of CHA2DS2-VASc score • consequent systolic dysfunction: consider candidacy for transplant • treatment of patients at high-risk of sudden death: ICD (see Figure 44, ICD implantation in HCM, C48) ■ history of survived cardiac arrest/sustained VT ■ FMHx of premature sudden death ■ other factors associated with increased risk of SCD ◆ syncope (presumed to be arrhythmic in origin) ◆ LVEF 50mmHg, NYHA II-III) from 68 clinical centers in 13 countries were randomized to mavacamten or placebo for 30 wk. The primary endpoint was a >1.5mL/kg/min increase in peak O consumption and at least one NYHA class reduction, or >3.0mL/kg/min increase in peak O consumption with no NYHA class reduction. Results: 45 (37%) of 123 patients on mavacamten vs. 22 (17%) of 128 on placebo met the primary endpoint. Patients on mavacamten had greater reductions in post-exercise LVOT gradient and greater increase in peak O consumption.34% more patients in the mavacamten group improved by at least 1 NYHA class. Safety and tolerability were comparable to placebo. Conclusion: Mavacamten improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with HOCM.

RCM vs. Constrictive Pericarditis Present similarly but constrictive pericarditis is treatable with surgery RCM

Constrictive Pericarditis

• • • • •

• prior surgical history in some cases • pulsus paradoxus may be present • pericardial rub • no LVH • pericardial calcification and pericardial thickening • pericardial late gadolinium enhancement (LGE) • reduced BNP

family history no pulsus paradoxus systolic murmurs LVH normal pericardium (intracardiac pathology) • myo- and endocardial later gadolinium enhancement (LGE) • elevated BNP

Left Ventricular Noncompaction Cardiomyopathy C50 Cardiology and Cardiac Surgery

Management • exclude constrictive pericarditis • control HR, anticoagulate if AFib • treat underlying disease: (e.g. cardiac amyloidosis, cardiac sarcoidosis, hemochromatosis) • supportive care and treatment for CHF, arrhythmias, and prevention of SCD when indicated ■ judicious use of diuretics (excess volume reduction reduces lling pressures versus pathologic requirements triggering hypoperfusion) • cardiac transplant: might be considered for CHF refractory to medical therapy Prognosis • depends on etiology

Left Ventricular Noncompaction Cardiomyopathy Definition • failure of LV compaction leading to endomyocardial trabeculations that increase in number and prominence • characterized by abnormal trabeculations in the LV, most frequently at the apex Etiology • genetics are incompletely understood • mutations have been mainly observed in genes coding sarcomeric, cytoskeletal and mitochondrial proteins • can occur in healthy individuals (e.g. athletes and pregnancy) as well as concomitantly with congenital heart diseases and other cardiomyopathies (i.e. HCM, RCM, DCM, ARVC) • can be reversible Clinical Manifestations • if occurring in absence of concomitant cardiomyopathy and congenital heart disease, LV noncompaction can be benign • symptoms range from SOBOE to rest symptoms ■ many patients are asymptomatic • ventricular arrhythmias or complete AV block (presents as syncope and sudden death) • thromboembolic events ■ more likely when systolic dysfunction and LV dilatation are present Investigations • directed by primary pathology when LV non-compaction is comorbid with congenital disease or other cardiomyopathies • TTE and cardiac MRI ■ most common diagnostic method is the ratio of the thickness of the non-compacted layer to that of the compacted layer (greater than 2:1 at the end of diastole) • role of routine genetic screening remains in question ■ typically performed in the setting of LV non-compaction with comorbid cardiomyopathy Management • at-risk rst-degree relatives are recommended to undergo screening • therapy is largely driven by concomitant myocardial dysfunction, arrhythmias, and congenital heart disease • ICD is an option if patients have syncope or documented VT • antiplatelets or systemic anticoagulation should be considered in adults, especially when the LV or atria are dilated Prognosis • dependent on LV function and presence of comorbid conditions (e.g. congenital heart disease and cardiomyopathy)

Cardiac Transplantation • treatment for end-stage heart failure • median survival is 12 yr • matching is according to blood type, body size and weight (should be within 25%), HLA tissue matching, and geographical considerations (to minimize ischemic time) Indications for Surgery • severe cardiac disability despite maximal medical therapy (e.g. recurrent hospitalizations for CHF, NYHA III or IV, peak metabolic oxygen consumption 10 mmHg during quiet breathing) • JVP “x” descent only, blunted “y” descent • hepatic congestion/peripheral edema • severity of signs/symptoms depend on rate of accumulation, volume of pericardial contents, pericardial distensibility, cardiac lling pressures, and chamber compliance Investigations • ECG: electrical alternans (pathognomonic variation in R wave amplitude), low voltage • CXR: enlarged cardiac silhouette; slow-accumulating eusions • CT/CMR: less available; usually only necessary if Doppler echo is infeasible • echo (diagnostic modality of choice): pericardial eusion (size, location, hemodynamic impact), swinging of the heart, compression of cardiac chambers (RA and RV) in diastole, etc. → echo also used for the purpose of guiding pericardiocentesis • cardiac catheterization (rare) Treatment • urgent drainage: needle pericardiocentesis recommended (with echo or uoroscopic guidance); surgery (i.e. pericardiotomy) is an alternative drainage approach (e.g. with purulent pericarditis or in an urgent situation involving bleeding into the pericardium) • avoid diuretics and vasodilators (these decrease venous return to already under-lled RV → decrease LV preload → decrease CO) as well as mechanical ventilation • IV uid may increase CO • treat underlying cause

Constrictive Pericarditis C66 Cardiology and Cardiac Surgery

Toronto Notes 2023

A. No pathology

B. Cardiac tamponade (inspiration)

Ventricular wall collapse on inspiration Pericardial effusion

Interventricular septum Pericardium (pericardial sac with pericardial fluid)

C. Cardiac tamponade (expiration)

Pericardial fluid pressure on cardiac chambers

D. Pericardiocentesis

Improvement in cardiac output on expiration

Resolution of ventricular wall collapse

Pericardial effusion Pericardial fluid pressure on cardiac chambers

Removal of excess pericardial fluid

©Jennifer Lee 2021

Figure 53. Cardiac tamponade pathophysiology

Constrictive Pericarditis Definition • loss of pericardial elasticity caused by granulation tissue formation; leads to restricted ventricular lling Etiology • chronic pericarditis resulting in brosed, thickened, adherent, and/or calcied pericardium • any cause of acute pericarditis may result in chronic pericarditis • major causes are idiopathic, post-infectious (viral, bacterial pericarditis/purulent pericarditis, TB), radiation, post-cardiac surgery, uremia, MI, collagen vascular disease • any pericardial disease process can cause constrictive pericarditis; risk of progression to constrictive pericarditis is based on the etiology of the pericardial disease Pathophysiology • rigid, brous pericardium impairs ventricular lling during diastole → decreased venous return to the heart → rise in systemic venous pressure → signs and symptoms of right-sided HF (classically with preserved ventricular function and otherwise no myocardial disease) ■ in advanced cases, there can be systolic dysfunction if myocardial brosis or atrophy present

C67 Cardiology and Cardiac Surgery

Toronto Notes 2023

Signs and Symptoms • dyspnea, fatigue, palpitations • abdominal pain • may mimic CHF (especially right-sided HF) ■ venous congestion, ascites, hepatosplenomegaly, edema, pleural eusions • increased JVP, Kussmaul’s sign (paradoxical increase in JVP with inspiration), Friedreich’s sign (prominent “y” descent) • BP usually normal (and usually no pulsus paradoxus) • precordial examination: ± pericardial knock (early diastolic sound) • see Table 19 for dierentiation from cardiac tamponade Investigations • ECG: non-specic ndings low voltage, at T wave, ± AFib • CXR: pericardial calcication, eusions • echo/CT/CMR: pericardial thickening, calcication ± characteristic echo-Doppler ndings (Note: CMR is discouraged if patient is hemodynamically impaired) • cardiac catheterization: indicated if other, non-invasive imaging modalities are insucient to make diagnosis; assess for equalization of end-diastolic chamber pressures • diagnosis: right HF symptoms + diastolic lling impairment caused by constriction (documented on ≥1 imaging modality including echo, CT, CMR, and/or catheterization) • note: in up to 20% of patients, constriction can occur even with normal thickness of the pericardium (pericardiectomy equally ecacious in these patients) Treatment • surgery (pericardiectomy): mainstay treatment for chronic, permanent constrictive pericarditis • medical therapy: can be used in 3 situations 1. for specic pathologies/etiologies (e.g. TB) 2. for transient constriction that is temporarily caused by pericarditis, or new constriction diagnosis with evidence of inammation of the pericardium (use anti-inammatories) 3. supportive when high/prohibitive surgical risk (goal is to relieve congestive symptoms with diuretics, salt restriction) • prognosis best with idiopathic or infectious cause and worst in post-radiation • death may result from HF Table 19. Dierentiation of Constrictive Pericarditis vs. Cardiac Tamponade Characteristic

Constrictive Pericarditis

Cardiac Tamponade

JVP

“y” > “x”

“x” > “y”

Kussmaul’s sign

Present

Absent

Pulsus paradoxus

Uncommon

Always

Pericardial knock

Present

Absent

Hypotension

Variable

Severe

DDx Pulsus Paradoxus • Most etiologies of RV failure except restrictive cardiomyopathy (e.g. acute RV MI) • Constrictive pericarditis (rarely) • Severe obstructive pulmonary disease (e.g. asthma) • Pneumothorax • PE • Cardiogenic shock • Cardiac tamponade • Eusive-Constrictive pericarditis

Extracorporeal Circulation C68 Cardiology and Cardiac Surgery

Toronto Notes 2023

Extracorporeal Circulation Aortic cross-clamp Systemic flow line

Pressure P T Temperature

Cardioplegia delivery line Aortic root suction

Cardioplegic solution

Cardiotomy suction Left ventricular vent One-way valve Venous clamp

Cardiotomy reservoir Filter

Vent Arterial filter and bubble trap

Suction

Suction

Venous reservoir

Level sensor Gas filter

Blood cardioplegia pump

Flowmeter

Oxygenator

Systemic blood pump Cooler heater water source

Air O2 Anaesthetic vaporiser

Gas flow meter

Blender

Figure 54. Cardiopulmonary bypass schematic Modified from Cardiac Surgery in the Adult, second edition, Robert A.E Dion, p. 729, Copyright (2020), with permission from Elsevier

© Roxanne Ziman 2021

Cardiopulmonary Bypass C69 Cardiology and Cardiac Surgery

Toronto Notes 2023

Cardiopulmonary Bypass Overview • CPB is commonly used in cardiac and thoracic aortic surgeries to obtain a still, bloodless surgical eld by circumventing the heart and lungs while supplying blood to the systemic circulation • essential functions of CPB: oxygenation, ventilation, circulation, temperature control Components • the standard components of a CPB circuit: ■ arterial cannula (aortic, femoral, or axillary) and line (3/8” heparin-coated tubing) ■ oxygenator (membrane oxygenator, defoamer, and heat exchanger) ■ pump (peristaltic/roller or centrifugal) ■ venous cannula (RA, SVC and IVC, or femoral) and line (1/2” heparin-coated tubing) ■ venous reservoir (rigid high capacitance reservoir or closed so reservoir) Mechanics • venous blood is drained into venous reservoir. e blood is oxygenated, and CO 2 is eliminated, heated, or cooled (if applicable) and returned to the systemic circulation via the arterial cannula ■ heparin is rst administered so that pump suckers can be turned on when the patient’s ACT is >400 s and CPB initiated when ACT is >480 s ◆ ACT is measured every 30 min while on CPB and additional heparin boluses are administered to maintain ACT >480 s ◆ anticoagulation is reversed following separation of CPB by administering protamine which neutralizes heparin ■ the rate of blood draining into the venous reservoir is determined by the: CVP, height dierential between venous cannula and venous reservoir, luminal radius of venous cannula and tubing, presence of air within the tubing ■ arterial cannulation is typically performed at the distal ascending aorta, distal to the aortic cross clamp, with alternative sites for cannulation including the aortic arch, innominate artery, subclavian artery, axillary artery, femoral artery, and LV apex ■ optimal ow rate is calculated to achieve a cardiac index of 2.4 L/min/m 2 ■ patient parameters measured during CPB: ECG, BP, CVP, SaO 2, ETCO2, peripheral and core temperature, urine output, ABG ■ CPB pump parameters measured during CPB: blood ow rate, roller pump/centrifugal speed, gas ow, pump blood temperature, heat exchanger water temperature, arterial line pressure, arterial and venous line O2 saturations, delivered O 2 concentration Complications • reaction to non-endothelialized foreign surfaces: systemic inammatory response, hemolysis, coagulopathy • vessel injury from cannulation: aortic dissection and embolization of aortic debris (e.g. porcelain aorta) • heparin-related: heparin-associated thrombocytopenia, heparin-induced thrombocytopenia (HIT) • systemic embolization: cerebrovascular accident, renal and splanchnic hypoperfusion ■ includes biologic and nonbiologic microemboli as well as air/gas/bubble emboli ■ cardiotomy reservoir must be ltered to reduce risk of microemboli

Cardiac and Neurological Protection during Cardiopulmonary Bypass Myocardial Protection Techniques • myocardial protection reduces myocardial ischemia during CPB by reducing myocardial oxygen consumption and maintaining oxygenated myocardial perfusion • methods of myocardial protection to reduce oxygen demands include: unloading the heart (CPB), stopping the heart (cardioplegic diastolic arrest), cooling the heart (core hypothermia, cold saline external washing, hypothermic cardioplegia solutions) • cardioplegia (given continuously or intermittently) induces diastolic arrest by altering myocytes’ resting potential and ionic gradients via concentrated K+ solutions ■ crystalloid cardioplegia ◆ extracellular solutions (high sodium) (e.g. St. omas’ solution, del Nido solution) increase extracellular K+ concentration to prevent cardiomyocyte repolarization ◆ intracellular solutions (low sodium) lower extracellular Na+ concentration thereby blocking depolarization ■ blood cardioplegia: autologous cold blood combined with tailored crystalloid solutions in various ratios ◆ blood typically comprises majority of overall solution (e.g. 8:1, 4:1, 2:1)

Special Consideration of Blood Conservation for Jehovah’s Witness Patients • Preoperatively: • Administer erythropoietin • Stop all anticoagulant and antiplatelet medications for 7 d, if possible • Intraoperatively: • Continuous cell salvage circuit • Meticulous hemostasis • OPCAB • Pharmacological adjuncts (tranexamic acid or aprotinin) • Postoperatively: • Low threshold for resternotomy due to bleeding

Common Medications C70 Cardiology and Cardiac Surgery

Toronto Notes 2023

Cerebral Protection • cerebral protection techniques are required when CPB cannot supply the head vessels, such as during surgery on the aortic arch • methods of cerebral protection to reduce oxygen demands include: hypothermia (most important) and anterograde/retrograde cerebral perfusion Deep Hypothermic Circulatory Arrest • deep hypothermic circulatory arrest reduces cerebral metabolism and oxygen consumption to the point that CPB can be discontinued ■ (30-40 min safe circulatory arrest at 20°C; 45-60 min safe circulatory arrest at 16°C) ◆ concurrent ACP enables circulatory arrest at higher temperatures than DHCA alone ■ EEG monitoring occurs throughout to conrm adequate cerebral protection ■ mannitol (reduces cerebral edema) and steroids (decrease cerebral inammation) are used adjunctively ■ complications related to deep hypothermic circulatory arrest include: coagulopathy and platelet dysfunction, systemic inammatory response, neurological injury secondary to ischemia in watershed areas (neurologic dysfunction may be persistent or transient depending on etiology)

Common Medications Table 20. Commonly Used Cardiac Therapeutics Drug Class

Examples

Mechanism of Action

Indications

Contraindications

Side Eects

Inhibit ACE-mediated conversion of angiotensin I to angiotensin II (AT II), causing peripheral vasodilation and decreased aldosterone synthesis

HTN, CAD, CHF, post-MI, DM

Bilateral renal artery stenosis, Dry cough (10%), hypotension, pregnancy, caution in fatigue, hyperkalemia, renal decreased GFR insuciency, angioedema

Block AT II receptors, causing similar eects as ACEI

Same as ACEI, although evidence is generally less for ARBs; often used when ACEI are not tolerated

Same as ACEI

Similar to ACEI, but do not cause dry cough

Sacubitril inhibits neprilysin which leads to vasodilation and natriuresis Valsartan (ARB) - see above

HFrEF

Angioedema, pregnancy

Angioedema, hyperkalemia, hypotension, renal insuciency

aliskiren

Directly blocks renin thus inhibiting the conversion of angiotensinogen to angiotensin I; this also causes a decrease in AT II

HTN (exact role of this drug remains unclear) Not recommended as initial therapy

Pregnancy, severe renal impairment

Diarrhea, hyperkalemia (higher risk if used with an ACEI), rash, cough, angioedema, reflux, hypotension, rhabdomyolysis, seizure

atenolol, metoprolol, bisoprolol, propranolol, labetalol, carvedilol, acebutolol

Block β-adrenergic receptors, decreasing HR, BP, contractility, and myocardial oxygen demand; also slow conduction through the AV node

HTN, CAD, acute MI, post-MI, CHF (start low and go slow), AFib, SVT

Sinus bradycardia, 2nd or 3rd degree heart block, hypotension Caution in asthma, claudication, Raynaud’s phenomenon, and decompensated CHF

Hypotension, fatigue, light-headedness, depression, bradycardia, hyperkalemia, bronchospasm, impotence, depression of counterregulatory response to hypoglycemia, exacerbation of Raynaud’s phenomenon, and claudication

Benzothiazepines Phenylalkylamines (non-dihydropyridines)

diltiazem verapamil

Block smooth muscle and myocardial calcium channels causing eects similar to β-blockers Also vasodilate

HTN, CAD, SVT, AFib, diastolic dysfunction

Sinus bradycardia, 2nd or 3rd degree heart block, hypotension, CHF

Hypotension, bradycardia, edema

Dihydropyridines

amlodipine (Norvasc®), nifedipine (Adalat®), felodipine (Plendil®)

Block smooth muscle calcium channels causing peripheral vasodilation

HTN, CAD

Severe AS and liver failure

Hypotension, edema, flushing, headache, light-headedness

ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEI) enalapril (Vasotec®), perindopril (Coversyl®), ramipril (Altace®), lisinopril (Zestril®)

ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs) candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan ANGIOTENSIN RECEPTOR-NEPRILYSIN INHIBITOR (ARNI) sacubitril/valsartan (Entresto®)

DIRECT RENIN INHIBITORS (DRIs)

β-BLOCKERS β1 antagonists β1/β2 antagonists α1/β1/β2 antagonists β1 antagonists with intrinsic sympathomimetic activity

CALCIUM CHANNEL BLOCKERS

C71 Cardiology and Cardiac Surgery

Toronto Notes 2023

Table 20. Commonly Used Cardiac Therapeutics Drug Class

Examples

Mechanism of Action

Indications

Contraindications

Side Eects

canagliflozin dapagliflozin empagliflozin ertugliflozin

Proposed mechanisms include: osmotic diuresis and natriuresis reducing preload; vasodilation leading to reduced afterload; myocardial metabolic stabilization

Dapagliflozin trial (DAPA-HF) indicates potential use in HFrEF with DM/non-DM, with multiple other SGLT2 inhibitors trials underway. Although dapagliflozin has received guideline recommendations in Canada, US and EU for use in HFrEF, no SGLT2 inhibitors have formal approval for HFrEF without DM by Health Canada HFpEF (see EMPEROR-Preserved trial)

Severe CKD (dapagliflozin contraindicated in patients with eGFR 2 yr; discontinue earlier if possible May consider rotating therapy with other drugs to minimize adverse eects of each drug

Dapsone

50-100-150 mg PO once daily tapering to 25-50 mg PO once daily to as low as 50 mg 2x/wk

Dermatitis herpetiformis, neutrophilic dermatoses

Monitoring G6PD before treatment starts; CBC qwk x 4, qmo x 6, then q6 mo thereafter; LFTs at baseline, then periodically Side eects Neuropathy Hemolysis (Vitamin C and E supplementation can help prevent this) Drug interactions Substrate of CYP2C8/9 (minor), 2C19 (minor), 2E1 (minor), 3A4 (major) Often a dramatic response within hours

D54 Dermatology

Toronto Notes 2023

Table 29. Common Oral Therapies Drug Name

Dosing Schedule

Indications

Comments

Doxycycline

100 mg PO BID

Acne vulgaris Rosacea Bullous pemphigoid

Contraindications Pregnancy, hepatic impairment, drug hypersensitivity Taking acitretin, isotretinoin, or penicillin antibiotic Oral typhoid vaccine

Isotretinoin (Accutane®, Clarus®, Epuris®)

0.5-1 mg/kg/d given once daily to achieve a total dose of 120 mg/kg (20-24 wk)

Severe nodular and/or inflammatory acne Acne conglobata Recalcitrant acne Widespread comedonal acne

Monitoring Fasting lipid panel at baseline, then q1-2 wk until lipid response to isotretinoin is established or if risk factors more frequently; LFTs at baseline, then q1-2 wk until stable; pregnancy test x 2 at baseline; glucose frequently if risk factors Contraindications Teratogenic – in sexually active females, 2 forms of reliable contraception necessary Generally regarded as unsafe in lactation Side eects Decreased night vision, decreased tolerance to contact lenses, dry mucous membranes May transiently exacerbate acne, dry skin Depression, myalgia Drug interactions Caution if used at the same time as tetracycline family antibiotics – both may cause pseudotumour cerebri Discontinue vitamin A supplements Drug may be discontinued at 16-20 wk when nodule count has dropped by >70%; a second course may be initiated after 2 mo prn Refractory cases may require >3 courses

Itraconazole (Sporanox®)

100-400 mg PO once daily, Onychomycosis depending on infection Tinea corporis, cruris, pedis, Tinea corporis/cruris/versicolor: versicolor, capitis 200 mg PO once daily x 7 d Tinea pedis: 200 mg PO BID x 3 d Toenails: 200 mg PO BID x 3 d once per mo, repeated 3x Fingernail involvement only: 200 mg BID PO x 3 d once per mo

Contraindications CHF Side eects Serious hepatotoxicity Drug Interactions Inhibits CYP3A4 Increases concentration of some drugs metabolized by this enzyme (i.e. statins, diabetic drugs) Give capsules with food, capsules must be swallowed whole

Ivermectin (Mectizan®, Stromectol®)

200-250 µg/kg PO weekly x 2 Take once as directed; repeat one wk later

Onchocerciasis (USA only) Not licensed for use in Canada Also eective for: scabies

No significant serious side eects Ecacious

Methotrexate

10-25 mg qwk, PO, IM, or IV Max: 30 mg/wk To minimize side eects, administer with folic acid supplementation: 1-5 mg once daily

Psoriasis AD Lymphomatoid papulosis May also be eective in: cutaneous sarcoidosis

Monitoring Pregnancy test at baseline; CBC at baseline, then q6 mo or more frequently if initial treatment, dose change, elevated serum level risk, or chemotherapy use; BUN/Cr, LFTs at baseline, then q4-8 wk or more frequently if initial Tx, dose change, elevated serum level risk, or chemotherapy use; serum albumin at baseline if psoriasis, then continue periodically; CXR at baseline; liver biopsy at baseline if psoriasis or if RA with history of alcoholism, persistently abnormal baseline LFTs, or chronic HBV or HCV infection, then if psoriasis repeat after total cumulative dose 1.5 g and each additional 1-1.5 g; serum drug levels if renal impairment, or high dose chemotherapy use Contraindications Pregnancy, lactation, alcohol abuse, liver dysfunction, immunodeficiency syndrome, blood dyscrasias, hypersensitivity to drug Restricted to severe, recalcitrant or disabling psoriasis not adequately responsive to other forms of therapy May be combined with cyclosporine to allow lower doses of both drugs

OCPs (TriCyclen®, Diane 35®, Alesse®)

1 pill PO once daily

Hormonal acne (chin, jawline) Acne associated with polycystic ovarian syndrome or other endocrine abnormalities

All combined OCPs are helpful in acne but those listed on the left have undergone RCTs Contraindications Smoking, HTN, migraines with aura, pregnancy Routine gynaecological health maintenance should be up to date

Spironolactone

50-100 mg PO once daily alone or with OCPs

Hormonal acne (chin, jawline) Acne with endocrine abnormality

Contraindications Pregnancy Side eects Menstrual irregularities at higher doses if not on OCPs Breast tenderness, mild diuresis common Risk of hyperkalemia – counsel patients to reduce intake of potassium rich foods such as bananas

Terbinafine (Lamisil®)

250 mg PO once daily x 2 wk Fingernails x 6 wk Toenails x 12 wk Confirm diagnosis prior to treatment

Onychomycosis Tinea corporis, cruris, pedis, capitis

Contraindications Pregnancy, chronic or active liver disease Drug interactions Potent inhibitor of CYP2D6; use with caution when also taking β-blockers, certain anti-arrhythmic agents, MAOI type B, and/or antipsychotics Drug concentrates rapidly in skin, hair, and nails at levels associated with fungicidal activity

Tetracycline

250-500 mg PO BID to TID Acne vulgaris Taken 1 h before or 2 h after a meal Rosacea Bullous pemphigoid

Contraindications Severe renal or hepatic dysfunction

Traumatic and Mechanical Disorders D55 Dermatology

Traumatic and Mechanical Disorders PERNIOSIS Definition • abnormal inammatory response to cold, damp, non-freezing conditions Epidemiology • common in the United Kingdom and northwestern Europe; common for those whose homes lack central heating • women, the elderly, and children are most aected Clinical Features • single or multiple erythematous to blue-violet macules, nodules, or papules • blistering or ulceration seen in severe cases • lesions present on the distal toes and ngers, and less oen on the heels, ears, and nose • symptoms of burning, itching, or pain, lasting 1-3 wk Pathophysiology • unknown but may be associated with cryoglobulins or cold agglutinins Dierential Diagnosis • chilblain lupus erythematosus, lupus pernio Treatment • warming clothing, avoidance of cold, damp conditions, keeping feet dry, smoking cessation • nifedipine, nicotinamide, phenoxybenzamine, sympathectomy, and erythemogenic UVB phototherapy TRAUMATIC AURICULAR HEMATOMA (CAULIFLOWER EAR) • see Plastic Surgery, PL34 ANIMAL BITES • see Cellulitis, D30 BITES • see Plastic Surgery, PL11 BURN INJURIES • see Plastic Surgery, PL18 FROSTBITE • see Emergency Medicine, ER46 KELOIDS • see Keloids, D10 THERMAL INJURY • see Plastic Surgery, PL18 UV LIGHT INJURIES • see Sunscreens and Preventative erapy, D52

Toronto Notes 2023

Landmark Dermatology Trials D56 Dermatology

Toronto Notes 2023

Landmark Dermatology Trials Trial Name

Reference

Clinical Trial Details

Hodi et al. 2010

NEJM 2016; 375:311322

Title: Improved Survival with Ipilimumab in Patients with Metastatic Melanoma Purpose: To compare ipilimumab administered with or without a glycoprotein 100 (gp100) peptide vaccine to gp100 alone in patients with previously treated metastatic melanoma. Methods: 676 HLA-A*0201–positive patients with unresectable stage III or IV melanoma, were randomized in a 3:1:1 ratio to receive ipilimumab+gp100 (n=403), ipilimumab alone (n=137), or gp100 alone (n=136). Results: Median survival was 10 mo among patients receiving ipilimumab plus gp100, as compared with 6.4 mo among patients receiving gp100 alone and 10.1 mo median survival with ipilimumab alone. No significant dierence in survival between ipilimumab groups was noted. Grade 3 or 4 immune-related adverse events occurred in 10-15% of patients treated with ipilimumab and 3% treated with gp100 alone. Conclusions: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.

BRIM-3

NEJM 2011; 364:25072516

Title: Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation Purpose: To compare the ecacy of BRAF kinase inhibitor vemurafenib (PLX4032) vs. dacarbazine in patients with metastatic melanoma. Methods: Phase 3 RCT comparing vemurafenib with dacarbazine in 675 patients with untreated, metastatic melanoma with BRAF V600E mutation. Patients were randomized to receive vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m 2 of body-surface area intravenously every 3 weeks). Coprimary endpoints: overall and progression-free survival. Results: At 6 mo, overall survival was 84% in the vemurafenib group and 64% in the dacarbazine group. Vemurafenib was associated with a relative reduction of death risk by 63% and a reduction of 74% in the risk of either death or disease progression vs. dacarbazine. Response rates were reported to be 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib: arthralgia, rash, fatigue, alopecia, keratoacanthoma, photosensitivity, nausea, and diarrhea. Conclusions: Vemurafenib improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation.

BE VIVID

Lancet 2021, 397: 475-486

Title: Bimekizumab versus Ustekinumab for the Treatment of Moderate to Severe Plaque Psoriasis (BE VIVID): Ecacy and Safety from a 52 wk, Multicentre, Double-blind, Active Comparator and Placebo Controlled Phase 3 Trial Purpose: To compare the ecacy and safety of a 52 wk treatment with bimekizumab vs. placebo vs. ustekinumab in patients with moderate to severe plaque psoriasis. Methods: Multicentre RCT involving adults 18 yr of age or older with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥12, ≥10% body surface area aected by psoriasis, and Investigator’s Global Assessment [IGA] score ≥3 on a five point scale). Patients were randomly assigned (4:2:1) to bimekizumab 320 mg every 4 wk, ustekinumab 45 mg or 90 mg at wk 0 and 4, then every 12 wk, or placebo every 4 wk. At 16 wk, patients in the placebo group were switched to bimekizumab. Results: The study enrolled 567 patients. At wk 16, 85% of patients in bimekizumab group had PASI90 vs. 50% in ustekinumab group and 5% in placebo group. Approximately 84% patients in bimekizumab group had an IGA response vs. 53% in ustekinumab group and 5% in placebo groups. Major cardiac adverse events occurred in 5 patients with pre-existing CV risk factors in the bimekizumab group whereas none occurred in the ustekinumab group. Additionally, oral candidiasis rates were higher than placebo and ustekinumab, and one case of IBD was recorded. Conclusion: Bimekizumab was more ecacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. Additional studies may be needed to assess safety.

ADVANCE

J Am Acad Dermatol 2022;86(1):77

Title: Ecacy and Safety of Apremilast (Phosphodiesterase Inhibitor) in Patients with Mild-to-moderate Plaque Psoriasis Purpose: To evaluate the eectiveness of apremilast in treating mild-to-moderate plaque psoriasis. Methods: A phase 3, double-blind, placebo-controlled study was conducted in 595 adults with mild-to-moderate psoriasis. Patients were randomized to either 30 mg twice daily oral apremilast or placebo (oral tablets of no pharmacological significance) for the first 16 wk. The outcome of interest was the achievement of a static Physician Global Assessment score of 0 (clear) or 1 (almost clear). Results: A significantly larger proportion of the apremilast group met the desired static Physician Global Assessment response rate when compared with the placebo group (21.6% vs. 4.1%). Conclusions: Apremilast proved eective as a treatment for mild-to-moderate plaque psoriasis.

MELANOMA

PSORIASIS

ATOPIC DERMATITIS ECZTRA

Br J Dermatol 2021;184(3):450

Title: Tralokinumab (Monoclonal Antibody) Plus Topical Corticosteroids (TCS) for the Treatment of Moderate-to-severe Atopic Dermatitis Purpose: To evaluate the safety and eectiveness of tralokinumab in treating moderate to severe atopic dermatitis Methods: A double-blind placebo study was conducted using 380 patients, 253 of which were randomized to the treatment group (subcutaneous tralokinumab 300 mg every 2 wk with TCS as needed over 16 wk) and the remainder to the placebo group (placebo every 2 wk with TCS as needed over 16 wk). The outcome of interest was a 75% improvement in the Eczema Area and Severity Index (EASI). Results: After 16 wk of treatment there was a significantly larger proportion of patients treated with tralokinumab (56%) that achieved the EASI benchmark when compared to the placebo group (35.7%). Conclusions: Tralokinumab in combination with the current standard of care was proven to be eective and well tolerated in treatment for atopic dermatitis.

References D57 Dermatology

Toronto Notes 2023

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Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol 2008;9:713. Brougham ND, Dennett ER, Cameron R, et al. The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. J Surg Oncol 2012;106:811. Camacho-Martínez, FM. Hair loss in women. Semin Cutan Med Surg 2009;28:19-32. Cribier B, Caille A, Heid E. Erythema nodosum and associated diseases. Int J Dermatol 1998;37:667-672. Cummings SR, Tripp MK, Herrmann NB. Approaches to the prevention and control of skin cancer. Cancer Metast Rev 1997;16:309-327. deShazo RD, Kemp SF. Allergic reactions to drugs and biologic agents. JAMA 1997;278:1895-1906. Dreno B, Amici JM, Basset-Seguin N, et al. Management of actinic keratosis: a practical report and treatment algorithm from AKTeam™ expert clinicians. JEADV 2014;28:1141-1149. Dyall-Smith D. Herpangina [Internet]. DermNet NZ; [updated 2010; cited 2020 Apr 28]. 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Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med 2021;23(8):1506-1513. Leung A, Balaji S, Keswani SG. Biology and function of fetal and pediatric skin. Facial plast surg clin of North Am. 2013 Feb;21(1):1. Mastrolorenzo A, Urbano FG, Salimbeni L, et al. Atypical molluscum contagiosum in an HIV-infected patient. Int J Dermatol 1998;37:378-380. Manual of Medicine. Dermatology skin lesion atlas [Internet]. GrepMed; [updated 2018; cited 2020 Apr 28]. Available from: https://www.grepmed.com/images/3926. Mason AR, Mason J, Cork M, et. al. Skin treatments for chronic plaque psoriasis. Cochrane DB Syst Rev 2013:CD005028. National Institutes of Health, U.S. National Library of Medicine. Xeroderma pigmentosum [Internet]. National Institutes Health; [updated 2010 May; cited 2020 Apr 28]. Available from: https://ghr.nlm.nih.gov/ condition/xeroderma-pigmentosum#synonyms. 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Biologic therapies in the treatment of psoriasis: a comprehensive evidence-based basic science and clinical review and a practical guide to tuberculosis monitoring. Clin Rev Allerg Immu 2013;44:121-140. Sterry W, Paus W, Burgdorf W (editors). Thieme clinical companions: dermatology, 5th ed. New York: Thieme, 2005. Stojkovic-Filipovic J, Kittler H. Dermatoscopy of amelanotic and hypomelanotic melanoma. JDDG 2014;12(6):467-472. Ting PT, Banankin B. Can you identify this condition? Melasma. Can Fam Physician 2005;51:353-355. UCB Canada Inc. Product monograph Cimzia [Internet]. UCB Canada Inc. [updated 2019 Feb 8; cited 2021 Sept 6]. Available from: https://pdf.hres.ca/dpd_pm/00049574.PDF Van Zuuren EJ, Fedorowicz Z, Christensen R, et. al. Emollients and moisturisers for eczema. Cochrane DB Syst Rev 2017:CD012119. Walsh SRA, Shear NH. Psoriasis and the new biologic agents: interrupting a T-AP dance. CMAJ 2004;170:1933-1941. Wanat K, Noe MH. Cutaneous xanthomas [Internet]. Wolters Kluwer; [updated 2019 Oct 21; cited 2020 Apr 28]. Available from: https://www.uptodate.com/contents/cutaneous-xanthomas. Watson S. What causes petechiae? [Internet]. Healthline; [updated 2017 Sept 13; cited 2020 Apr 28]. Available from: https://www.healthline.com/health/petechiae#pictures. WebMD. Slideshow: acne visual dictionary [Internet]. WebMD; [updated 2018 Jun 24; cited 2020 Apr 28]. Available from: https://www.webmd.com/skin-problems-and-treatments/acne/ss/slideshow-acnedictionary. Whited JD, Grichnik JM. The rational clinical examination. Does this patient have a mole or a melanoma? JAMA 1998;279:696-701. Wikipedia. Purpura [Internet]. Wikipedia; [updated 2020 Apr 28; cited 2020 Apr 28]. Available from: https://en.wikipedia.org/wiki/Purpura. Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol 2002;46:584-587. Wol K, Johnson RA. Fitzpatrick’s colour atlas and synopsis of clinical dermatology, 6th ed and 7th ed. New York: McGraw Hill, 2009. Yun MH. Changes in regenerative capacity through lifespan. Int J Mol 2015;16(10):25392-25432. Zak A, Zeman M, Slaby A, et al. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014;158(2):181-188. Zheng JF, Mo HY, Wang ZZ. Clinicopathological characteristics of xeroderma pigmentosum associated with keratoacanthoma: a case report and literature review. Int J Clin Exp Med 2014;7(10):3410-3414. Zang Y, Mosler EL, Jing HU, et. al. Topical benzoyl peroxide for acne. Cochrane DB Syst Rev 2020:CD011154.

Emergency Medicine

ER

Emergency Medicine Vinyas Harish, Danny Ma, Kwasi Nkansah, and Tsz Ying So, chapter editors Ming Li and Dorrin Zarrin Khat, associate editors Vijithan Sugumar, EBM editor Dr. Mark Freedman, Dr. Laura Hans, Dr. Adam Kaufman, Dr. Jo Jo Leung, and Dr. Kaif Pardhan, sta editors Acronyms.............................................................................ER2 Patient Assessment/Management.......................................ER2 1. Rapid Primary Survey 2. Resuscitation 3. Secondary Survey Ethical Considerations Traumatology...................................................................... ER7 Considerations for Traumatic Injury Head Trauma Mild Traumatic Brain Injury Spine and Spinal Cord Trauma Chest Trauma Abdominal Trauma Genitourinary Tract Injuries Orthopaedic Injuries Wound Management Approach to Common ED Presentations............................ ER18 Abdominal Pain Acute Pelvic Pain Altered Level of Consciousness Chest Pain Headache Joint and Back Pain Seizures Shortness of Breath Syncope Sexual Assault

Toxicology..........................................................................ER49 Approach to the Overdose Patient “ABCD3EFG” of Toxicology D1 – Universal Antidotes D2 – Draw Bloods D3 – Decontamination and Enhanced Elimination E – Expose and Examine the Patient F – Full Vitals, ECG Monitor, Foley, X-Rays G – Give Specific Antidotes and Treatments Alcohol Related Emergencies Disposition from the Emergency Department Psychiatric Emergencies....................................................ER56 Approach to Common Psychiatric Presentations Acute Psychosis Suicidal Patient Common Paediatric ED Presentations............................... ER57 Modified Glasgow Coma Score Respiratory Distress Febrile Infant and Febrile Seizures Abdominal Pain Common Infections Child Abuse and Neglect Common Medications........................................................ER60 Landmark Emergency Medicine Trials................................ER61 References.........................................................................ER62

Medical Emergencies.........................................................ER29 Anaphylaxis and Allergic Reactions Asthma Cardiac Dysrhythmias Acute Exacerbation of COPD Heart Failure Venous Thromboembolism Diabetic Emergencies Electrolyte Disturbances Hypertensive Emergencies Acute Coronary Syndrome Sepsis Stroke and Transient Ischaemic Attack Otolaryngological Presentations and Emergencies...........ER39 Epistaxis Gynaecologic/Urologic Emergencies.................................ER40 Vaginal Bleeding Pregnant Patient in the ED Nephrolithiasis (Renal Colic) Ophthalmologic Emergencies............................................ER42 Dermatologic Emergencies................................................ER43 Environmental Injuries.......................................................ER45 Heat Exhaustion and Heat Stroke Hypothermia and Cold Injuries Inhalation Injury Bites Near Drowning

ER1 Emergency Medicine

Toronto Notes 2023

Acronyms ER2 Emergency Medicine

Toronto Notes 2023

Acronyms AAA ABG ACEI ACLS ACS AED AFib AG ARDS AVN AVPU AXR Bi-PAP BSA BUN CAS CIWA CNS CPAP CPP CRP CVA CVS D5W

abdominal aortic aneurysm arterial blood gas angiotensin-converting enzyme inhibitor Advanced Cardiac Life Support acute coronary syndrome automatic external defibrillator atrial fibrillation anion gap acute respiratory distress syndrome avascular necrosis alert, voice, pain, unresponsive abdominal x-ray bilevel positive airway pressure body surface area blood urea nitrogen Children’s Aid Society Clinical Institute Withdrawal Assessment for Alcohol central nervous system continuous positive airway pressure cerebral perfusion pressure c-reactive protein costovertebral angle cardiovascular system dextrose 5% in water

D10W D50W D25W DGI DIC DKA DRE DT DVT ED EM ESR ETT FAST FEV1 FFP GERD GCS HEENT HI H&N IBD IBS ICS

dextrose 10% in water dextrose 50% in water dextrose 25% in water disseminated gonococcal infection disseminated intravascular coagulation diabetic ketoacidosis digital rectal exam delirium tremens deep vein thrombosis emergency department erythema multiforme erythrocyte sedimentation rate endotracheal tube focused assessment with sonography for trauma forced expiratory volume in 1 second fresh frozen plasma gastroesophageal reflux disease glasgow coma scale head eyes ears nose throat head injury head and neck inflammatory bowel disease irritable bowel syndrome intercostal space

INR IVC LBBB LOC LP LSD LVH MAP MDI MDMA

international normalized ratio inferior vena cava left bundle branch block level of consciousness lumbar puncture lysergic acid diethylamide left ventricular hypertrophy mean arterial pressure metered dose inhaler methylenedioxymethamphetamine MMSE mini-mental state examination MVC motor vehicle collision NS normal saline NSTEMI non-ST elevation myocardial infarction PID pelvic inflammatory disease PNS parasympathetic nervous system POG plasma osmolar gap pRBC packed red blood cells PT prothrombin time PTT partial thromboplastin time RAPD relative aerent pupillary defect RBBB right bundle branch block ROM range of motion RPS rapid primary survey RSI rapid sequence induction

rt-PA SAH SBP SCI SJS SNS SOB SSRI SSSS STEMI TBI TCA Tdap TEN TIA TSS VBG VFib VTach VTE

recombinant tissue plasminogen activator subarachnoid hemorrhage spontaneous bacterial peritonitis spinal cord injury Stevens-Johnson syndrome sympathetic nervous system shortness of breath selective serotonin reuptake inhibitor staphylococcal scalded skin syndrome ST elevation myocardial infarction traumatic brain injury tricyclic antidepressant tetanus, diphtheria, acellular pertussis toxic epidermal necrolysis transient ischaemic attack toxic shock syndrome venous blood gas ventricular fibrillation ventricular tachycardia venous thromboembolism

Patient Assessment/Management 1. Rapid Primary Survey • • • • •

Airway maintenance with C-spine control Breathing and ventilation Circulation (pulses, hemorrhage control) Disability (neurological status) Exposure (complete) and Environment (temperature control) ■ continually reassessed during secondary survey ■ changes in hemodynamic and/or neurological status necessitates a return to the primary survey beginning with airway assessment • IMPORTANT: always watch for signs of shock while doing primary survey • addressing the “ABCs” is the hallmark of the emergency department ■ in the setting of cardiac arrest, the approach changes to the “CABs”: chest compressions, airway, and breathing ■ CAB can also be applied in massive trauma situations in the setting of massive blood loss to treat hypovolemic shock A. AIRWAY • rst priority is to secure airway • assume a cervical injury in every trauma patient and immobilize with collar • assess ability to breathe and speak • listen for evidence of airway obstruction (e.g. stridor) • can change rapidly, therefore reassess frequently • assess for facial fractures/edema/burns (impending airway collapse) Airway Management • anatomic optimization to allow for oxygenation and ventilation 1. Basic Airway Management • protect the C-spine • chin li (if C-spine injury not suspected) or jaw thrust to open the airway • sweep and suction to clear mouth of foreign material 2. Temporizing Measures • nasopharyngeal airway (if gag reex present, i.e. conscious) • oropharyngeal airway (if gag reex absent, i.e. unconscious) • “rescue” airway devices (e.g. laryngeal mask airway, Combitube®) • especially for children 140

Blood Pressure

Normal

Normal

Decreased

Decreased

Respiratory Rate

20

30

35

>45

Capillary Refill

Normal

Decreased

Decreased

Decreased

Urinary Output

30 cc/h

20 cc/h

10 cc/h

None

Fluid Replacement

Crystalloid

Crystalloid

Crystalloid + blood

Crystalloid + blood

Management of Hemorrhagic Shock • clear airway and assess breathing either rst or simultaneously • apply direct pressure on external wounds while elevating extremities. Do not remove impaled objects in the emergency room setting as they may tamponade bleeds • start two large bore (14-16 G) IVs in the brachial/cephalic vein of each arm • permissive hypotension with pRBC transfusion, ideally crossmatched. If crossmatched blood is unavailable in a timely manner, consider O- for women of childbearing age and O+ for men. Use FFP, platelets or tranexamic acid in early bleeding. If available, activate ‘massive transfusion protocol’ • consider common sites of internal bleeding (abdomen, chest, pelvis, long bones, GI tract) where surgical intervention may be necessary D. DISABILITY • assess LOC using GCS • pupils ■ assess equality, size, symmetry, reactivity to light • unequal or sluggish suggests local eye problem or lateralizing CNS lesion • non-reactive pupils + decreased LOC: structural cause (especially if asymmetric) • lateralizing motor decits

Table 3. Glasgow Coma Scale Best Verbal Response

Best Motor Response

Spontaneously

4

Answers questions appropriately

5

Obeys commands

6

To voice

3

Confused, disoriented

4

Localizes to pain

5

To pain

2

Inappropriate words

3

Withdraws from pain

4

No response

1

Incomprehensible sounds

2

Decorticate (flexion)

3

No verbal response

1

Decerebrate (extension)

2

No response

1

13-15 = mild injury, 9-12 = moderate injury, ≤8 = severe injury See

Common Sites of Bleeding • External (e.g. scalp) • Chest • Abdomen (peritoneum, retroperitoneum) • Pelvis • Long bones • GI

Fluid Resuscitation Give bolus until HR decreases, urine output increases, and patient stabilizes • Maintenance: 4:2:1 rule • 0-10 kg: 4 cc/kg/h • 10-20 kg: 2 cc/kg/h • Remaining weight: 1 cc/kg/h • Replace ongoing losses and deficits (assume 10% of body weight) Shortcut for calculating maintenance fluids for any patient ≥20kg: Fluid rate (in cc/hr) = 40 + patient’s weight in kg

Glasgow Coma Scale • GCS is for use in trauma patients with decreased LOC; good indicator of severity of injury and neurosurgical prognosis • most useful if repeated; change in GCS with time is more relevant than the absolute number • less meaningful for metabolic coma • patient with deteriorating GCS needs immediate attention • prognosis based on best post-resuscitation GCS • reported as a 3-part score: Eyes + Verbal + Motor = Total • if patient intubated, GCS score reported out of 10 + T (T = tubed, i.e. no verbal component)

Eyes Open

SHOCKED Septic, spinal/neurogenic Hemorrhagic Obstructive (e.g. tension pneumothorax, cardiac tamponade, PE) Cardiogenic (e.g. blunt myocardial injury, dysrhythmia, MI) anaphylactiK Endocrine (e.g. Addison’s, myxedema, coma) Drugs

Unilateral, Dilated, Non-Reactive Pupil • Focal mass lesion • Epidural hematoma • Subdural hematoma

Table 36, ER57 for Modified GCS for infants and children

E. EXPOSURE/ENVIRONMENT • expose patient completely and assess entire body for injury; log roll to examine back • DRE for trauma patients • keep patient warm with a blanket ± radiant heaters; avoid hypothermia • warm IV uids/blood • keep providers safe (contamination, combative patient)

2. Resuscitation • • • • • • •

done concurrently with primary survey attend to ABCs manage life-threatening problems as they are identied vital signs q5-15 min ECG, BP, and O2 monitors Foley catheter and NG tube if indicated tests and investigations: CBC, electrolytes, BUN, Cr, glucose, amylase, INR/PTT, β-hCG, toxicology screen, cross and type

Contraindications to Foley Insertion • Blood at urethral meatus • Scrotal hematoma • High-riding prostate on DRE

NG Tube Contraindications • Significant mid-face trauma • Basal skull fracture

3. Secondary Survey ER5 Emergency Medicine

Toronto Notes 2023

Table 4. 2010 AHA CPR Guidelines with 2020 Updates Step/Action

Adult: >8 yr

Child: 1-8 yr

Infant: 24 h, little or no signs of brainstem dysfunction ◆ severe: coma >24 h, frequent signs of brainstem dysfunction B. focal injuries ■ contusions ■ intracranial hemorrhage (epidural, subdural, intracerebral) ASSESSMENT OF BRAIN INJURY History • prehospital status • mechanism of injury Physical Exam • assume C-spine injury until ruled out • vital signs ■ shock (not likely due to isolated brain injury, except in infants) ■ Cushing’s response to increasing ICP (bradycardia, HTN, irregular respirations) • severity of injury determined by 1. LOC ◆ GCS ≤8 intubate, any change in score of 3 or more = serious injury ◆ GCS of mild TBI = 13-15, moderate = 9-12, severe = 3-8 2. pupils: size, anisocoria >1 mm (in patient with altered LOC), response to light 3. lateralizing signs (motor/sensory) ◆ may become subtler with increasing severity of injury ◆ reassess frequently Investigations • labs: CBC, electrolytes, INR/PTT, glucose, toxicology screen • CT head (non-contrast) to exclude intracranial hemorrhage/hematoma • C-spine imaging Management • goal in ED: reduce secondary injury by avoiding hypoxia, ischaemia, decreased CPP, seizure • general ■ ABCs ■ ensure oxygen delivery to brain through intubation and prevent hypercarbia ■ maintain BP (sBP >90) ■ treat other injuries • early neurosurgical consultation for acute and subsequent patient management aer imaging • seizure treatment/prophylaxis ■ benzodiazepines, phenytoin, phenobarbital • treat suspected raised ICP: ■ intubate (neuroprotective RSI where possible) ■ calm (sedate) if risk for high airway pressures or agitation ■ paralyze if agitated ■ hyperventilate (100% O2) to a pCO2 of 30-35 mmHg ■ elevate head of bed to 20° ■ adequate BP to ensure good cerebral perfusion ■ give mannitol 1g/kg infused rapidly (contraindicated in shock/renal failure) or 3 mL/kg of hypertonic (3%) saline Disposition • neurosurgical ICU admission for severe HI • in a hemodynamically unstable patient with other injuries, prioritize most life-threatening injuries and maintain cerebral perfusion • for minor HI not requiring admission, provide 24 h HI protocol (regular assessment of the patient for signs of loss of consciousness, confusion or amnesia) to competent caregiver, follow up with concussion and/or sports clinic as even seemingly minor HI may cause lasting decits

Warning Signs of Severe Head Injury • GCS 3 ft or five stairs) Minor HI is defined as witnessed loss of consciousness, definite amnesia, or witnessed disorientation in a patient with a GCS score of 13-15. NB: Canadian CT Head Rule does not apply for nontrauma cases, for GCS 100 mmHg) • insert NG (for decompression of paralytic ileus) and Foley catheter (only if no concerns about urethral injury) • complete imaging of spine and consult spine service • continually reassess high cord injuries as edema can travel up cord • if cervical cord lesion, watch for respiratory insuciency ■ low cervical transection (C5-T1) produces abdominal breathing (phrenic innervation of diaphragm still intact but loss of innervation of intercostals and other accessory muscles of breathing) ■ high cervical cord injury (above C4) may require intubation and ventilation • if patient is in shock, treat with: warm blanket, Trendelenburg position (occasionally), volume infusion, consider vasopressors

2. Any low-risk factor that allows safe Yes assessment of ROM? Simple rear-end MVC† or No Sitting position in ED or Radiography Ambulatory at any time or Delayed (not immediate) onset of neck pain or Absence of midline C-spine tenderness

Approach to C-Spine Imaging • CT of the spine is the screening modality of choice • C-Spine CT can detect 97-100% of injuries • compared to radiography, CT scans allows for more rapid clearance of the C-Spine • MRI of C-Spine is the preferred technique for so tissue injuries (spinal cord lesions, intervertebral discs, and spinal ligaments) • CT of C-Spine is the preferred modality. If only C-Spine x-rays are available, radiography can be assessed as follows Table 6. Interpretation of Lateral View: The ABCS A

Adequacy and Alignment Follow the anterior and posterior contour lines Translation of the vertebra >3.5 mm and angulation of >11 degrees is considered significant for spinal instability Next, follow the spinolaminar line; the diameter between the posterior cortex and the spinolaminar line should be >18 mm Fanning of spinous processes suggests posterior ligamentous disruption Widening of facet joints Check atlanto-occipital joint Line extending inferiorly from clivus should transect odontoid Atlanto-axial articulation, widening of predental space (normal: 2 rib fractures, each Palpable crepitus of ribs at 2 sites Decreased air entry on aected side Underlying lung contusion (cause of morbidity and mortality) Cardiac Tamponade Clinical diagnosis Pericardial fluid accumulation impairing ventricular function

Penetrating wound (usually) Beck’s triad: hypotension, distended neck veins, mued heart sounds Tachycardia, tachypnea Kussmaul’s sign (increased JVP with inspiration)

Echocardiogram FAST

IV fluids Open thoracotomy

Supine Oblique Views • Rarely used • Better visualization of posterior element fractures (lamina, pedicle, facet joint) • Good to assess patency of neural foramina • Can be used to visualize the C7-T1 junction

20% of C-spine fractures are accompanied by other spinal fractures, so ensure thoracic and lumbar spine CT is normal before proceeding to OR

Trauma to the chest accounts for 50% of trauma deaths

80% of all chest injuries can be managed non-surgically with simple measures such as intubation, chest tubes, and pain control

3-way Seal for Open Pneumothorax (i.e. sucking chest wound) Allows air to escape during the expiratory phase (so that you do not get a tension pneumothorax) but seals itself to allow adequate breaths during the inspiratory phase

Pulsus Paradoxus: a drop in BP of >10 mmHg with inspiration. Recall that BP normally drops with inspiration, but what’s “paradoxical” about this is that it drops more than it should

Abdominal Trauma ER12 Emergency Medicine

Toronto Notes 2023

Table 8. Potentially Life-Threatening Chest Injuries Found in Secondary Survey Physical Exam

Investigations

Management

Pulmonary Contusion

Blunt trauma to chest Interstitial edema impairs compliance and gas exchange

CT: areas of opacification of lung within 6 h of trauma

Maintain adequate ventilation Monitor with ABG, pulse oximeter, and ECG Chest physiotherapy Positive pressure ventilation if severe

Ruptured Diaphragm

Blunt trauma to chest or abdomen (e.g. high lap belt in MVC)

CXR: abnormality of diaphragm/ lower lung fields/NG tube placement CT scan and endoscopy: sometimes helpful for diagnosis

Laparotomy for diaphragm repair and associated intra-abdominal injuries

Esophageal Injury

Usually penetrating trauma (pain out of proportion to degree of injury)

CXR: mediastinal air (not always) Esophagram (Gastrogran®) Flexible esophagoscopy

Early repair (within 24 h) improves outcome)

Aortic Tear 90% tear at subclavian (near ligamentum arteriosum), most die at scene Salvageable if diagnosis made rapidly

Sudden high speed deceleration CXR, CT scan, transesophageal (e.g. MVC, fall, airplane crash), echocardiogram, aortography complaints of chest pain, dyspnea, (gold standard) hoarseness (frequently absent) Decreased femoral pulses, dierential arm BP (arch tear)

Blunt Myocardial Injury (rare)

Blunt trauma to chest (usually in setting of multi-system trauma and therefore dicult to diagnose) Physical exam: overlying injury (e.g. fractures, chest wall contusion)

Thoracotomy (may treat other severe injuries first)

O2 ECG: dysrhythmias, ST changes Cardiac blood work (e.g. troponin) Antidysrhythmic agents Analgesia 2-D Echo: Can assess for tamponade, wall motion, valve function, or thrombi. Patients with a normal ECG, normal troponin, and normal hemodynamics rarely get dysrhythmias

Other Potentially Life-Threatening Injuries Related to the Chest Penetrating Neck Trauma • includes all penetrating trauma to the three zones of the neck • management: injuries deep to platysma require further evaluation by angiography, contrast CT, or surgery • do not explore penetrating neck wounds except in the OR Airway Injuries • always maintain a high index of suspicion • larynx ■ history: strangulation, direct blow, blunt trauma, any penetrating injury involving platysma, inhalational injury (e.g. burns) ■ triad: hoarseness, subcutaneous emphysema, palpable fracture ■ other symptoms: hemoptysis, dyspnea, dysphonia ■ investigations: CXR, CT scan, arteriography (if penetrating) ■ management ◆ airway: manage early because of edema ◆ C-spine may also be injured, consider mechanism of injury ◆ surgical: tracheotomy vs. repair • trachea/bronchus ■ frequently missed ■ history: deceleration, penetration, increased intrathoracic pressure, complaints of dyspnea, hemoptysis ■ examination: subcutaneous emphysema, Hamman’s sign (crunching sound synchronous with heartbeat) ■ CXR: mediastinal air, persistent pneumothorax, or persistent air leak aer chest tube inserted for pneumothorax ■ management ◆ surgical repair if >1/3 circumference

Abdominal Trauma • two mechanisms ■ blunt: usually causes solid organ injury (spleen = most common, liver = second most common) ■ penetrating: usually causes hollow organ injury or liver injury (most common) BLUNT TRAUMA • results in two types of hemorrhage: intraperitoneal and retroperitoneal • adopt high clinical suspicion of bleeding in multi-system trauma

Ruptured diaphragm is more often diagnosed on the left side, as the liver conceals right side defects

Aortic Tear ABC WHITE X-ray features of Aortic tear Depressed left mainstem Bronchus pleural Cap Wide mediastinum (most consistent) Hemothorax Indistinct aortic knuckle Tracheal deviation to right side Esophagus (NG tube) deviated to right (Note: these features are present in 85% of cases, but cannot rule out if absent)

If Penetrating Neck Trauma Present, DON’T: • Clamp structures (can damage nerves) • Probe • Insert NG tube (leads to bleeding) • Remove weapon/impaled object

Zone III Zone II Zone I

Zone III: Superior aspect of neck Zone II: Midportion of neck (cricoid to the angle of mandible) Zone I: Base of neck (thoracic inlet to cricoid cartilage)

Figure 5. Zones of the neck in trauma

ER13 Emergency Medicine

Toronto Notes 2023

History • mechanism of injury, SAMPLE history Physical Exam • oen unreliable in multi-system trauma, wide spectrum of presentations ■ slow blood loss not immediately apparent ■ tachycardia, tachypnea, oliguria, febrile, hypotension ■ other injuries may mask symptoms ■ serial examinations are required • abdomen ■ inspect: contusions, abrasions, seat-belt sign, distention ■ auscultate: bruits, bowel sounds ■ palpate: tenderness, rebound tenderness, rigidity, guarding ■ DRE: rectal tone, blood, bone fragments, prostate location ■ placement of NG and Foley catheter should be considered part of the abdominal exam • other systems to assess: cardiovascular, respiratory (possibility of diaphragm rupture), genitourinary, pelvis, back/neurological Investigations • labs: CBC, electrolytes, coagulation, cross and type, glucose, Cr, CK, lipase, amylase, liver enzymes, VBG, blood EtOH, β-hCG, U/A, toxicology screen Table 9. Imaging in Abdominal Trauma Imaging

Strengths

Limitations

Ultrasound: FAST

Identifies presence/absence of free fluid in peritoneal cavity RAPID exam: less than 5 min Can also examine pericardium and pleural cavities Can do serial examinations quickly

NOT used to identify specific organ injuries If patient has ascites, FAST will be falsely positive False negatives with small amounts of blood, retroperitoneal blood, delayed presentations, prior abdominal surgery, or incorrect positioning Technically dicult if patient is obese

X-Ray

Chest (looking for free air under diaphragm, Soft tissue not well visualized diaphragmatic hernia, air-fluid levels), pelvis, cervical, thoracic, lumbar spines

CT Scan

Most specific test

Diagnostic Peritoneal Most sensitive test Lavage (rarely used) Tests for intraperitoneal bleed

Radiation exposure 20x more than x-ray Use with caution if hemodynamic instability Cannot test for retroperitoneal bleed or diaphragmatic rupture Cannot distinguish lethal from trivial bleed Results can take up to 1 h

• imaging must be done if: ■ equivocal abdominal examination, altered sensorium, or distracting injuries (e.g. head trauma, spinal cord injury resulting in abdominal anesthesia) ■ unexplained shock/hypotension ■ patients have multiple traumas and must undergo general anesthesia for orthopaedic, neurosurgical, or other injuries ■ fractures of lower ribs, pelvis, spine ■ positive FAST Management • general: ABCs, early blood products, and stabilization • surgical: watchful waiting vs. laparotomy • solid organ injuries: decision based on hemodynamic stability, not the specic injuries • hemodynamically unstable or persistently high transfusion requirements: laparotomy • hollow organ injuries: laparotomy • even if low suspicion of injury: admit and observe for 24 h PENETRATING TRAUMA • high-risk of gastrointestinal perforation and sepsis • history: size of blade, calibre/distance from gun, route of entry • local wound exploration under direct vision may determine lack of peritoneal penetration (not reliable in inexperienced hands) with the following exceptions: ■ thoracoabdominal region (may cause pneumothorax) ■ back or anks (muscles too thick) Management • general: ABCs, uid resuscitation, and stabilization • gunshot wounds always require laparotomy

Seatbelt Injuries May Cause • Retroperitoneal duodenal trauma • Intraperitoneal bowel transection • Mesenteric injury • L-spine injury

Indications for Foley and NG Tube in Abdominal Trauma Foley catheter: unconscious or patient with multiple injuries who cannot void spontaneously NG tube: used to decompress the stomach and proximal small bowel. Contraindicated if suspected facial or basal skull fractures

Point-of-Care Ultrasonography for Diagnosing Thoracoabdominal Injuries in Patients with Blunt Trauma Cochrane DB Syst Rev 2018:CD012669 Purpose: Determine the diagnostic accuracy of POCUS for detecting and excluding free fluid, organ injuries, vascular lesions, and other injuries compared to diagnostic reference standards in patients with blunt trauma. Methods: Systematic review of prospective or retrospective diagnostic cohort studies of patients with any type of blunt trauma. Results: 34 studies, 8635 participants. For abdominal trauma, POCUS had a sensitivity of 0.68 (95% CI 0.59-0.75) and a specificity of 0.95 (95% CI 0.92-0.97). In children, pooled sensitivity of POCUS was 0.63 (95% CI 0.46-0.77), as compared to 0.78 (95% CI 0.69-0.84) in an adult/mixed population. For chest injuries, POCUS had a sensitivity of 0.96 (95% CI 0.88-0.99) and a specificity of 0.95 (95% CI 0.97-1.00). Conclusions: In patients with blunt thoracoabdominal trauma, positive POCUS findings are helpful for guiding treatment decisions. However, with regard to abdominal trauma, a negative POCUS does not rule out injuries and must be verified. This is of particular importance in paediatric trauma, where the sensitivity of POCUS is poor. Based on a small number of studies in a mixed population, POCUS may have a higher sensitivity in chest injuries.

Laparotomy is Mandatory if Penetrating Trauma and: • Shock • Peritonitis • Evisceration • Free air in abdomen • Blood in NG tube, Foley catheter, or on DRE

“Rule of Thirds” for Stab Wounds • 1/3 do not penetrate peritoneal cavity • 1/3 penetrate but are harmless • 1/3 cause injury requiring surgery

Genitourinary Tract Injuries ER14 Emergency Medicine

Toronto Notes 2023

Genitourinary Tract Injuries • see Urology, U35 Etiology • blunt trauma: oen associated with pelvic fractures ■ upper tract ◆ renal – contusions (minor injury – parenchymal ecchymoses with intact renal capsule) – parenchymal tears/laceration: non-communicating (hematoma) vs. communicating (urine extravasation, hematuria) ◆ ureter: rare, at uretero-pelvic junction ■ lower tract ◆ bladder – extraperitoneal rupture of bladder from pelvic fracture fragments – intraperitoneal rupture of bladder from trauma and full bladder ◆ urethra – posterior urethral injuries: MVCs, falls, pelvic fractures – anterior urethral injuries: blunt trauma to perineum, straddle injuries/direct strikes ■ external genitalia • penetrating trauma ■ damage to: kidney, bladder, ureter (rare), external genitalia • acceleration/deceleration injury ■ renal pedicle injury: high mortality rate (laceration and thrombosis of renal artery, renal vein, and their branches) • iatrogenic ■ ureter and urethra (from instrumentation) History • mechanism of injury • hematuria (microscopic or gross), blood on underwear • dysuria, urinary retention • history of hypotension Physical Exam • abdominal pain, ank pain, CVA tenderness, upper quadrant mass, perineal lacerations • DRE: sphincter tone, position of prostate, presence of blood • scrotum: ecchymoses, lacerations, testicular disruption, hematomas • bimanual exam, speculum exam • extraperitoneal bladder rupture: pelvic instability, suprapubic tenderness from mass of urine or extravasated blood • intraperitoneal bladder rupture: acute abdomen • urethral injury: perineal ecchymosis, blood at penile meatus, high riding prostate, pelvic fractures Investigations • urethra: retrograde urethrography • bladder: U/A, CT scan, urethrogram ± retrograde cystoscopy ± cystogram (distended bladder + postvoid) • ureter: retrograde ureterogram • renal: CT scan (best, if hemodynamically stable), intravenous pyelogram Management • urology consult • renal ■ minor injuries: conservative management ◆ bed rest, hydration, analgesia, antibiotics ■ major injuries: admit ◆ conservative management with frequent reassessments, serial U/A ± re-imaging ◆ surgical repair (exploration, nephrectomy): hemodynamically unstable or continuing to bleed >48 h, major urine extravasation, renal pedicle injury, all penetrating wounds and major lacerations, infections, renal artery thrombosis • ureter ■ ureteroureterostomy • bladder ■ extraperitoneal ◆ minor rupture: Foley drainage x 10-14 d ◆ major rupture: surgical repair ■ intraperitoneal • urethra ■ anterior: conservative, if cannot void, Foley or suprapubic cystostomy and antibiotics ■ posterior: suprapubic cystostomy (avoid catheterization) ± surgical repair

Gross hematuria suggests bladder injury

In the case of gross hematuria, the genitourinary system is investigated from distal to proximal (i.e. urethrogram, cystogram, etc.)

Orthopaedic Injuries ER15 Emergency Medicine

Toronto Notes 2023

Orthopaedic Injuries • see Orthopaedic Surgery (see Shoulder OR2, Knee OR34, Wrist OR23, Ankle OR41) Goals of ED Treatment • diagnose potentially life/limb-threatening injuries • reduce and immobilize fractures (cast/splint) as appropriate • provide adequate pain relief • arrange proper follow-up if necessary History • use SAMPLE, mechanism of injury may be very important Physical Exam • look (inspection): “SEADS” = swelling, erythema, atrophy, deformity, and skin changes (e.g. bruises) • feel (palpation): all joints/bones for local tenderness, swelling, warmth, crepitus, joint eusions, and subtle deformity • move: joints aected plus those above and below injury – active ROM preferred to passive • neurovascular status: distal to injury (before and aer reduction) LIFE- AND LIMB-THREATENING INJURIES Table 10. Life- and Limb-Threatening Orthopaedic Injuries Life-Threatening Injuries (usually blood loss)

Limb-Threatening Injuries (usually interruption of blood supply)

Major pelvic fractures Traumatic amputations Massive long bone injuries and associated fat emboli syndrome Vascular injury proximal to knee/elbow

Fracture/dislocation of ankle (talar AVN) Crush injuries Compartment syndrome Open fractures Dislocations of knee/hip Fractures above knee/elbow

Open Fractures • communication between fracture site and external surface of skin – increased risk of osteomyelitis • remove gross debris, irrigate, cover with sterile dressing – formal irrigation and debridement oen done in the OR • control bleeding with pressure (no clamping) • splint • antibiotics (1st generation cephalosporin and aminoglycoside) and tetanus prophylaxis • standard of care is to secure denitive surgical management within 6 h, time to surgery may vary from case-to-case Vascular Injuries • realign limb/apply longitudinal traction and reassess pulses (e.g. Doppler probe) • surgical consult • direct pressure if external bleeding Compartment Syndrome • when the intracompartmental pressure within an anatomical area (e.g. forearm or lower leg) exceeds the capillary perfusion pressure, eventually leading to muscle/nerve necrosis • clinical diagnosis: maintain a high index of suspicion ■ pain out of proportion to the injury ■ pain worse with passive stretch ■ tense compartment ■ look for “e 6 Ps” (note: radial pulse pressure is 120/80 mmHg while capillary perfusion pressure is 30 mmHg, seeing any of the 6 Ps indicates advanced compartment syndrome, therefore do not wait for these signs to diagnose and treat) ■ in the unconscious patient, a Stryker compartment pressure monitor can be used • requires prompt decompression: remove constrictive casts, dressings; emergent fasciotomy may be needed

Description of Fractures SOLARTAT Site Open vs. closed Length Articular Rotation Translation Alignment/Angulation Type e.g. Salter-Harris, etc.

Eect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain i n the ED JAMA 2017;318:1661-1667 Purpose: To compare the ecacy of 4 analgesics on acute extremity pain. Methods: RCT including 416 patients with moderate to severe acute extremity pain. Participants received ibuprofen 400 mg and acetaminophen 1000 mg; oxycodone 5 mg and acetaminophen 325 mg; hydrocodone 5 mg and acetaminophen 300 mg; or codeine 30 mg and acetaminophen 300 mg. The primary outcome was the dierence in decline in pain 2 h after ingestion. Pain was assessed using an 11-point numerical rating scale (NRS). Results: At 2 h, the mean NRS pain score decreased by 4.3 in the ibuprofen and acetaminophen group; by 4.4 in the oxycodone and acetaminophen group; by 3.5 in the hydrocodone and acetaminophen group; and by 3.9 in the codeine and acetaminophen group (P=0.053). Conclusions: For patients presenting to the ED with acute extremity pain, there were no statistically significant or clinically important dierences in pain reduction at 2 h among single-dose treatment with ibuprofen and acetaminophen or with 3 dierent opioid and acetaminophen combination analgesics.

When Dealing with an Open Fracture, Remember “STAND” Sp lint Tetanus prophylaxis Antibiotics Neurovascular status (before and after) Dressings (to cover wound)

Vascular injury/compartment syndrome is suggested by “The 6 Ps” Injury Compartment Syndrome 6 Ps Pulse discrepancies Pallor Paresthesia/hypoesthesia Paralysis Pain (especially when refractory to usual analgesics) Polar (cold)

ER16 Emergency Medicine

Toronto Notes 2023

LOWER EXTREMITY INJURIES • knee injuries ■ see Ottawa Knee Rules • ankle and foot fractures ■ see Ottawa Ankle and Foot Rules • avulsion of the base of 5th metatarsal ■ occurs with inversion injury ■ supportive tensor or below knee walking cast for 3 wk • calcaneal fracture ■ associated with fall from height ■ associated with axial loading (other injuries may involve ankles, knees, hips, pelvis, lumbar spine)

1

2 Lateral view 3 4

5 6 A-P view

© Willa Bradshaw 2005

UPPER EXTREMITY INJURIES • anterior shoulder dislocation ■ axillary nerve (lateral aspect of shoulder) and musculocutaneous nerve (extensor aspect of forearm) at risk ■ seen on lateral view: humeral head anterior to glenoid ■ many techniques for reduction (e.g. traction, scapular manipulation), immobilize in internal rotation, repeat x-ray, out-patient follow-up with orthopaedics ■ with forceful injury, look for fracture • Colles’ fracture ■ distal radius fracture with dorsal displacement from “Fall on Outstretched Hand” (FOOSH) ■ anteroposterior lm: radial shortening, radial deviation, radial displacement ■ lateral lm: dorsal displacement, volar angulation ■ reduce, immobilize with splint, out-patient follow-up with orthopaedics or immediate orthopaedic referral if complicated fracture ■ if involvement of articular surface, consider outpatient fracture clinic or orthopaedic referral if unsatisfactory reduction in ED • scaphoid fracture ■ tenderness in anatomical snu box, pain on scaphoid tubercle, pain on axial loading of thumb ■ negative x-ray: thumb spica splint, repeat x-ray in 1 wk ± CT scan/bone scan ■ positive x-ray: thumb spica splint x 6-8 wk, repeat x-ray in 2 wk ■ treat based on clinical suspicion even in absence of radiological scaphoid fracture ■ risk of AVN of scaphoid if not immobilized ■ outpatient orthopaedic follow-up

1. Dorsal tilt 2. Dorsal displacement 3. Ulnar styloid fracture 4. Radial displacement 5. Radial tilt 6. Shortening

Figure 6. Colles’ fracture

Ulna

Radius Scaphoid

Lunate

Trapezium Triquetrum Pisiform Hamate

1

Trapezoid Capitate

54 3 2 Metacarpal bones (1-5) © Elisheva Marcus

A knee x-ray examination is required only for acute injury patients with one or more of: • • • • •

Age 55 yr or older Tenderness at head of fibula Isolated tenderness of patella Inability to flex to 90º Inability to bear weight both immediately and in the ED (four steps)

Figure 8. Ottawa knee rules Adapted from: Stiell IG, Wells GA, Hoag RH, et al. JAMA 1997;278:2075-2079.

LATERAL VIEW A. Posterior edge or tip of lateral malleolus

An ankle radiographic series is required only if there is any pain in malleolar zone and any of these findings:

Malleolar Zone 6 cm

Midfoot Zone

C. Base of 5th metatarsal

MEDIAL VIEW Malleolar Zone 6 cm

Midfoot Zone

B. Posterior edge or tip of medial malleolus

D. Navicular

1. Bony tenderness at A or 2. Bony tenderness at B or 3. Inability to bear weight both immediately and in ED A radiographic series is required only if there is any pain in midfoot zone and any of these findings: 1. Bony tenderness at C or 2. Bony tenderness at D or 3. Inability to bear weight both immediately and in ED

©Natalie Cormier 2016

Figure 9. Ottawa ankle and foot rules Adapted from: Stiell IG, McKnight RD, Greenberg GH, et al. JAMA 1994;271:827-832.

Figure 7. Carpal bones

Wound Management ER17 Emergency Medicine

Toronto Notes 2023

Wound Management Goals of ED Treatment • identify injuries and stop any active bleeding – direct pressure • manage pain • wound examination and exploration • cleansing ± antibiotic and tetanus prophylaxis • closure and dressing

Acute Treatment of Contusions RICE Res t Ice Compression Elevation

Tetanus Prophylaxis • both tetanus toxoid (Td) and immunoglobulin (TIG) are safe in pregnancy Table 11. Guidelines for Tetanus Prophylaxis for Wounds Clean, Minor Wounds

All Other Wounds*

Vaccination History

Tdap or Td†

TIG

Tdap or Td†

TIG

Unknown or fewer than 3 doses

Yes

No

Yes

Yes

3 or more doses

No§

No

No¶

No

*Such as, but not limited to, wounds contaminated with dirt, feces, soil, and saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns, and frostbite †Tdap is preferred to Td for adults who have never received Tdap. Single antigen tetanus toxoid (TT) is no longer available in the United States §Yes, if more than ten years since the last tetanus toxoid-containing vaccine dose ¶Yes, if more than five years since the last tetanus toxoid-containing vaccine dose Source: MMWR 1991;40(No. RR-10):1-28

Bruises • non-palpable = ecchymosis • palpable collection (not swelling) = hematoma following blunt trauma • assess for coagulopathy (e.g. liver disease), anticoagulant use Abrasions • partial to full thickness break in skin • management ■ clean thoroughly with brush to prevent foreign body impregnation ± local anesthetic antiseptic ointment (Polysporin® or Vaseline®) for 7 d ± tetanus prophylaxis Lacerations • see Plastic Surgery, PL8, sidebar PL24 • consider every structure deep to a laceration injured until proven otherwise • in hand injury patients, include the following in history: handedness, occupation, mechanism of injury, previous history of injury • physical exam ■ think about underlying anatomy ■ examine tendon function actively against resistance and neurovascular status distally ■ clean and explore under local anesthetic; look for partial tendon injuries ■ x-ray or U/S wounds if a foreign body is suspected (e.g. shattered glass) and not found when exploring wound (remember: not all foreign bodies are radiopaque), or if suspect intra-articular involvement • management ■ disinfect skin/use sterile techniques ■ irrigate copiously with normal saline or tap water ■ analgesia ± anesthesia ■ maximum dose of lidocaine ◆ 7 mg/kg with epinephrine ◆ 5 mg/kg without epinephrine • in children, topical anesthetics such as LET (lidocaine, epinephrine, and tetracaine), distraction provided by Child Life Specialist or parent; and in selected cases a short-acting benzodiazepine (midazolam or other agents) for sedation and amnesia are useful • secure hemostasis • evacuate hematomas, debride non-viable tissue, remove hair and foreign bodies • ± prophylactic antibiotics (consider for animal/human bites, intra-oral lesion, or puncture wounds to the foot) • suture unless: delayed presentation (>24 h), puncture wound, mammalian bite, crush injury, or retained foreign body • take into account patient and wound factors when considering suturing • advise patient when to have sutures removed • cellulitis and necrotizing fasciitis (see Plastic Surgery, PL16)

High-Risk Factors for Infection Wound Factors • Puncture wounds • Crush injuries • Wounds >12 h old • Hand or foot wounds Patient Factors • Age >50 yr • Prosthetic joints or valves (risk of endocarditis) • Immunocompromised

Suture Use and Duration Suture to:

Close with Nylon or Other Nonabsorbable Suture

Approx. Duration (d)

Face

6-O or 5-O

5

Not Joint

4-O

7

Joint

3-O

10

Scalp

4-O

7

Mucous Membrane

Absorbable (vicryl)

N/A

N.B. Patients on steroid therapy may need sutures for longer periods of time

Early wound irrigation and debridement are the most important factors in decreasing infection risk

Alternatives to Sutures • Tissue glue • Steristrips® • Staples

Approach to Common ED Presentations ER18 Emergency Medicine

Toronto Notes 2023

Approach to Common ED Presentations Abdominal Pain Table 12. Selected Dierential Diagnosis of Abdominal Pain GI

Emergent

Usually Less Emergent

Perforated viscus, bowel obstruction, ischaemic bowel, appendicitis, strangulated hernia, IBD flare, esophageal rupture, peptic ulcer disease

Diverticulitis, gastroenteritis, GERD, esophagitis, gastritis, IBS

Hepatobiliary Hepatic/splenic injury, pancreatitis, cholangitis, spontaneous bacterial peritonitis

Biliary colic, cholecystitis, hepatitis

Genital

Female: Ovarian torsion, ectopic pregnancy, tubo-ovarian abscess Male: Testicular torsion

Female: PID, ovarian cyst, salpingitis, endometriosis Male: epididymitis, prostatitis, orchitis

Urinary

Pyelonephritis

Renal colic, cystitis

CVS

MI, aortic dissection, AAA

Pericarditis

Respirology

PE, empyema

Pneumonia

Metabolic

DKA, sickle cell crisis, toxin, Addisonian crisis

Toxic ingestions (e.g. acetaminophen, Iron, NSAIDs, etc.), lead poisoning, porphyria

Other

Significant trauma, acute angle closure glaucoma

Abdominal wall injury, herpes zoster, psychiatric, abscess, hernia, mesenteric adenitis

• dierential can be focused anatomically by location of pain: right upper quadrant, le upper quadrant, right lower quadrant, le lower quadrant, epigastric, periumbilical, diuse History • pain: OPQRST • review symptoms from genitourinary, gynecological, gastrointestinal, respiratory, and cardiovascular systems • abdominal trauma/surgeries, most recent colonoscopy, most recent endoscopy, last FOBT/FIT test Physical Exam • vitals, abdominal (including DRE, CVA tenderness), pelvic/genital, respiratory, and cardiac exams as indicated by history Investigations • ABCs, do not delay management and consultation if patient unstable • labs: CBC, electrolytes, glucose, BUN/Cr, U/A ± liver enzymes, LFTs, lipase, β-hCG, ECG, troponins, ± VBG/lactate • AXR: if suspicious of foreign body or SBO (small bowel obstruction) in low resource setting. Can also use if frequent SBOs and usual conservative management • CXR upright: look for pneumoperitoneum (free air under diaphragm), lung disease • U/S: all gynaecologic structure, testicles, biliary tract, ectopic pregnancy, appendicitis in children and young adults, nephro-urolithiasis in young patients, AAA, free uid; in select cases, can proceed to CT if U/S if non-diagnostic but there is high clinical suspicion • CT: SBO, trauma, AAA, pancreatitis, nephro-/urolithiasis, appendicitis, and diverticulitis Management • NPO, IV, NG tube (if SBO), analgesics, consider antibiotics and anti-emetics • growing evidence that small amounts of opioid analgesics improve diagnostic accuracy of physical exam of surgical abdomen • consult as necessary: internal medicine, general surgery, vascular surgery, gynecology, etc. Disposition • admission: surgical abdomen, workup of signicant abnormal ndings, need for IV antibiotics or pain control • discharge: patients with a negative lab and imaging workup who improve clinically during their stay; instruct the patient to return if severe pain, fever, or persistent vomiting develops

Acute Pelvic Pain ER19 Emergency Medicine

Toronto Notes 2023

Acute Pelvic Pain Etiology • gynecological ■ ovaries: ruptured ovarian cysts (most common cause of pelvic pain), ovarian abscess, ovarian torsion (rare, 50% will have ovarian mass) ■ fallopian tubes: salpingitis, tubal abscess, hydrosalpinx ■ uterus: leiomyomas (uterine broids) – especially with torsion of a pedunculated broid or in a pregnant patient (degeneration), PID ■ other: ectopic pregnancy (ruptured/expanding/leaking), spontaneous abortion (threatened or incomplete), endometriosis and dysmenorrhea, sexual or physical abuse • non-gynecological (see causes of lower abdominal pain above) History and Physical Exam • pain: OPQRST • associated symptoms: vaginal bleeding, discharge, dyspareunia, bowel and/or bladder symptoms • pregnancy and sexual history, including oligo/amenorrhea, menorrhagia, and broids • vitals • gynecological exam: assess for cervical motion tenderness/“chandelier sign” (suggests PID) • abdominal exam Investigations • β-hCG for all women of childbearing age • CBC and dierential, electrolytes, glucose, creatinine, BUN, culture and sensitivity, PTT/INR • U/A to rule out urologic causes • vaginal and cervical swabs for culture and sensitivity if performing a pelvic exam or urine NAAT for STI testing if no pelvic exam is performed • pelvic and abdominal U/S: evaluate adnexa, thickness of endometrium, pregnancy, free uid or masses in the pelvis • Doppler ow studies for ovarian torsion Management • general: analgesia, determine if admission and consults are needed • specic: ■ ovarian cysts ◆ unruptured or ruptured, and hemodynamically stable: analgesia and follow-up ◆ ruptured with signicant hemoperitoneum: may require surgery ■ ovarian torsion: surgical detorsion or removal of ovary ■ uncomplicated leiomyomas, endometriosis, and secondary dysmenorrhea can usually be treated on an outpatient basis, discharge with gynecology follow-up ■ PID: broad spectrum antibiotics, recommend low threshold to treat empirically Disposition • referral: gynecological or obstetrical causes requiring surgical intervention, requiring admission, or oncological in nature • admission: patients requiring surgery, IV antibiotics/pain management • discharge: negative workup and resolving symptoms; give clear instructions for appropriate follow-up

Altered Level of Consciousness Definitions • altered mental status: collective, non-specic term referring to change in cognitive function, behaviour, or attentiveness, including: ■ delirium (see Psychiatry, PS23) ■ dementia (see Psychiatry, PS24) ■ lethargy: state of decreased awareness and alertness (patient may appear wakeful) ■ stupor: unresponsiveness but rousable ■ coma: a sleep-like state, not rousable to consciousness

Gynaecological Causes of Pelvic Pain • Ovarian cyst • Dysmenorrhea • Mittelschmerz • Endometriosis • Ovarian torsion • Uterine fibroids/neoplasm • Adnexal neoplasm • PID + cervicitis

U/S is the preferred imaging modality in the assessment of acute pelvic pain

Possible Causes of Coma AEIOU TIPS Acidosis/Alcohol Epilepsy Infection Oxygen (hypoxia)/Opiates Uremia Temperature/Trauma (especially head) Insulin (too little or too much) Psychogenic/Poisoning Structural or space-occupying lesion

ER20 Emergency Medicine

Toronto Notes 2023

Coma (GCS 40 yr, women >60 yr

HEART Score H (History) Highly suspicious history Moderately suspicious history Slightly or non-suspicious history

2 pts 1 pt 0 pst

E (ECG) Acute ischemia LBBB, RBBB, LVH, PM No signs of acute ischemia

2 pts 1 pt 0 pts

A (Age) >65 yr age 45 – 65 yr 42 ng/L troponin 15-42 ng/L troponin 14 ng/L

2 pts 1 pt 0 pts 2 pts 1 pt 0 pts

* Risk factors: Diabetes mellitus, current or recent (20 mmHg or pulse deficit between arms; aortic regurgitant murmur

CT angiogram; CXR - wide mediastinum, left pleural eusion, indistinct aortic knob, >4 mm separation of intimal calcification from aortic shadow, 20% normal

ABCs, reduce BP and HR; classify type A (ascending aorta, urgent surgery) vs. B (not ascending aorta, medical) on CT angiogram and urgent consult

Cardiac Tamponade

Dyspnea, cold extremities, ± chest pain; often a recent cardiac intervention or symptoms of malignancy, connective tissue disease

Beck’s triad - hypotension, elevated JVP, mued heart sounds; tachycardia, pulsus paradoxus >10 mmHg

Clinical diagnosis CXR: may show cardiomegaly, evidence of trauma, ECG may show electrical alternans

ABCs, cardiac surgery or cardiology consult, pericardiocentesis if unstable, treat underlying cause

Esophageal Rupture

Sudden onset severe pain Subcutaneous after endoscopy, forceful emphysema, findings consistent with sepsis vomiting, labour, or convulsion, or in context of corrosive injury or cancer

CXR: pleural eusion (75%), pneumomediastinum; CT or water soluble contrast esophagogram

ABCs, early antibiotics, resuscitation, thoracics consult, NPO, consider chest tube

Esophagitis or GERD

Frequent heartburn, acid reflux, dysphagia, relief with antacids

Oral thrush or ulcers (rare)

None acutely

ABCs, PPI medication, avoid EtOH, tobacco, trigger foods

Herpes Zoster

Abnormal skin sensation – itching/tingling/pain – preceding rash by 1-5 d

None if early; maculopapular rash developing into vesicles and pustules that crust

Clinical diagnosis; direct ABCs, anti-virals (if < 80 yr. Anginal equivalents include dyspnea, diaphoresis, fatigue, non-retrosternal pain

It is important to look for reciprocal changes in STEMI in order to dierentiate from pericarditis (diuse elevations)

Tracheal deviation is away from tension or towards non-tension pneumothorax

Does this Patient with Chest Pain have Acute Coronary Syndrome?: The Rational Clinical E xamination Systematic Review JAMA 2015;314:1955-1965 Purpose: To review accuracy of the initial history, physical examination, ECG, and risk scores incorporating these elements with the first cardiacspecific troponin. Methods: Systematic review of prospective studies among patients admitted to the ED with symptoms suggesting ACS. Results: Prior abnormal stress test (specificity 96%; LR 3.1, 95% CI 2.0-4.7), peripheral artery disease (specificity 97%; LR 2.7, 95% CI 1.5-4.8), and pain radiating to both arms (specificity 96%; LR 2.6, 95% CI 1.8-3.7) were most suggestive of ACS. The most suggestive ECG findings were ST-segment depression and any evidence of ischaemia. The History, ECG, Age, Risk Factors, Troponin (HEART) (LR 13, 95% CI 7-24) and the Thrombolysis in MI (TIMI) risk scores (LR 6.8, 95% CI, 5.2-8.9) were both predictive of ACS in the high-risk scores. Conclusions: Among patients with suspected ACS presenting to the ED, the initial history, physical examination, and ECG alone did not confirm or exclude the diagnosis of ACS. Instead, the HEART or TIMI risk scores, which incorporate the first cardiac troponin, provided more diagnostic information.

Conservative vs. Interventional Treatment for Spontaneous Pneumothorax N EJM 2020;382:405-415 Purpose: Determine whether conservative management is an acceptable alternative to interventional management for uncomplicated, moderate-to-large primary spontaneous pneumothorax. Methods: Open-label, multicenter, noninferiority trial. Patients 14-50 yr were recruited with a first-known, unilateral, moderate-to-large primary spontaneous pneumothorax. Patients (n=316) were randomly assigned to immediate interventional management of the pneumothorax or a conservative observational approach and were followed for 12 mo. The primary outcome was lung re-expansion within 8 wk. Results: Re-expansion within 8 wk occurred in 129 of 131 patients with interventional management and in 118 of 125 with conservative management (P=0.02, for noninferiority). Conservative management resulted in a lower risk of serious adverse events or pneumothorax recurrence than interventional management. Conclusions: The trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events.

Headache ER23 Emergency Medicine

Toronto Notes 2023

Table 16. Common Life-Threatening ECG Changes Pathology

ECG Findings

Dysrhythmia Torsades de pointes

Ventricular complexes in upward-pointing and downward-pointing continuum (160-250 bpm)

Ventricular tachycardia

3 or more consecutive premature ventricular beats (>100 bpm, QRS >120 ms)

Ventricular flutter

Smooth sine wave pattern of similar amplitude (>200 bpm)

Ventricular fibrillation

Erratic ECG tracing, no identifiable waves

Conduction 2nd degree heart block (Mobitz Type II)

PR interval stable, some QRSs dropped

3rd degree heart block

Prolonged QRS complex (>0.12 s) RSR’ in V5 or V6 Total AV dissociation, but stable P-P and R-R intervals

Left bundle branch block

Monophasic I and V6 May see ST elevation Dicult to interpret, new LBBB is considered STEMI equivalent

Ischaemia STEMI

ST elevation in leads associated with injured area of heart and reciprocal lead changes (depression)

Metabolic Hyperkalemia

Initially, tall T-waves Followed by PR prolongation, QRS widening, loss of P waves Finally, sinusoidal pattern and pulse electrical activity (PEA)/Vfib/Asystole

Hypokalemia

P wave flattening QRS complex widening and flattening U waves appear Flattened T waves

Digitalis Toxicity

Supraventricular tachycardia Slow ventricular response Frequent premature ventricular contractions At risk for AV blocks and ventricular irritability

Syndromes Brugada

RBBB with ST elevation in V1, V2, and V3 Susceptible to deadly dysrhythmias, including VFib

Wellens

Marked T wave inversion in V2 and V3 Left anterior descending coronary stenosis

Long QT syndrome

QT interval longer than ½ of cardiac cycle Predisposed to ventricular dysrhythmias

Headache • see Neurology, N46 Etiology • common and less serious ■ common migraine (without aura)/classic migraine (with aura) ◆ common: unilateral, throbbing, aggravated by activity, moderate/severe intensity, N/V, photo-/phonophobia ◆ classic: fully reversible aura symptoms that precede headache, e.g. ashing lights, pins and needles (paresthesia), loss of vision, dysarthria ◆ treatment: simple analgesics (NSAIDs, acetaminophen, Aspirin®), antiemetics, triptans ◆ family physician to consider prophylactic treatment ■ tension headache ◆ bilateral, non-throbbing, not aggravated by routine physical activity, mild-moderate intensity. ◆ can last between 30 min to 7 d ◆ triggered with stress, sleep deprivation ◆ treatment: modify stressor(s), simple analgesics (NSAIDs, acetaminophen, Aspirin®) • less common but potentially fatal ■ subarachnoid hemorrhage (SAH) (see Neurosurgery, NS22) ◆ sudden onset, “worst headache of life,” maximum intensity within minutes, “thunderclap headache” ◆ increased pain with exertion, N/V, meningeal signs ◆ diagnosis – new generation CT 100% sensitive within 6 h of onset (hyperattenuating signal around Circle of Willis) – LP to look for xanthochromia if suspected SAH and normal CT aer 6 h ◆ management: urgent neurosurgery consult ■ increased ICP ◆ worse in morning, when supine or bending down, with cough or Valsalva ◆ physical exam: neurological decits, cranial nerve palsies, papilledema

Diagnosis of Pulmonary Embolism with D-Dimer Adjusted to Clinical Probability NE JM 2019;381:2125-2134 Purpose: Retrospective analyses suggest that PE is ruled out by a D-dimer level of legs), contralateral homonymous hemianopsia, ipsilateral gaze

Atrophy

Absent/ minimal

Present

Posterior Cerebral Artery

Contralateral homonymous hemianopsia, cortical blindness, impaired memory

Downgoing

Wide variety of cranial nerve, cerebellar, and brainstem deficits: vertigo, nystagmus, diplopia, visual field deficits, dysphagia, dysarthria, facial hypoesthesia, syncope, ataxia Loss of pain and temperature sensation in ipsilateral face and contralateral body

Plantar Response

Upgoing

Vertebrobasilar Artery

Otolaryngological Presentations and Emergencies ER39 Emergency Medicine

Toronto Notes 2023

Investigations • CBC, electrolytes, blood glucose, coagulation studies ± cardiac biomarkers ± toxicology screen • CT angiography and perfusion of the head and neck • ECG: rule out AFib, acute MI as source of emboli • other imaging: if you are suspicious of a TIA a plain CT followed by carotid Doppler, outpatient CT angiography neck and/or head, magnetic resonance angiography (MRA) can be arranged based on local resources Management • ABCs; intubation with RSI if GCS ≤8, rapidly decreasing GCS, or inadequate airway protective reexes • thrombolysis (rt-PA, e.g. alteplase): immediate assessment for eligibility; need acute onset, 200 mmHg, dBP >120 mmHg, MAP >140 mmHg) or HTN associated with hemorrhagic stroke transformation, cardiac ischaemia, aortic dissection, or renal damage; use IV nitroprusside or labetalol • glycemic control serum glucose of 7.8 - 10 mmol/L • cerebral edema control: hyperventilation, mannitol to decrease ICP if necessary • consult neurosurgery, neurology, medicine as indicated • following acute event: ■ antiplatelet agents to: prevent recurrent stroke or stroke aer TIAs, e.g. Aspirin® (1st line); clopidogrel, Aggrenox® (2nd line) ■ consider anticoagulation: if Ab present or if immobile for DVT prophylaxis ■ follow-up for consideration of carotid endarterectomy, cardiovascular risk optimization

Otolaryngological Presentations and Emergencies • ear symptoms: otalgia, aural fullness, otorrhea, hearing loss, tinnitus, vertigo, pruritus, fever • risk factors for hearing loss: Q-tip use, hearing aids, headphones, occupational noise exposure Dizziness and Vertigo • distinguish four types of dizziness: vertigo (“room spinning”), lightheadedness (“disconnected from environment”), presyncope (“almost blacking out”), dysequilibrium (“unstable,” “o-balance”) • broad dierential and diverse management (see Family Medicine, FM28 and Otolaryngology, OT6) • rule out stroke • consider adverse drug events Otalgia (see Otolaryngology, OT6) • dierential diagnosis ■ infections: acute otitis externa, acute otitis media, otitis media with eusion, mastoiditis, myringitis, malignant otitis externa in patients with diabetes, herpes simplex/zoster, auricular cellulitis, external canal abscess, dental disease ■ others: trauma, temporomandibular joint dysfunction, neoplasm, foreign body, cerumen impactions, trigeminal neuralgia, granulomatosis with polyangiitis • inspect for otorrhea, palpate outer ear/mastoid, otoscopic examination to look for bulging erythematous tympanic membrane, perforation, membrane retraction, inltration, vesicles, ulcers, masses, lesions • C&S of ear canal discharge, if present • CT head if suspicion of mastoiditis, malignant otitis externa • antibiotics/antifungals/antivirals for respective infections Hearing Loss (see Otolaryngology, OT9) • dierentiate conductive vs. sensorineural hearing loss • rule out sudden sensorineural hearing loss (SSNHL), a medical emergency requiring high dose steroids and urgent referral • an elderly patient presenting with unilateral tinnitus or SSNHL must be presumed to have an acoustic neuroma (vestibular schwannoma) until proven otherwise • consider audiogram and referral to or follow-up with family physician

If a patient presents within 4.5 h of onset of disabling neurological deficits >60 min with no signs of resolution, they may be a candidate for thrombolysis. Do brief assessment and order CT head S TAT Absolute Exclusion Criteria for Tissue Plasminogen Activator (tPA) • Suspected subarachnoid hemorrhage • Previous intracranial hemorrhage • Cerebral infarct or severe HI within the past 3 mo • sBP >185 mmHg, or dBP >110 mmHg • Bleeding diathesis • Prolonged PT >15 s or INR >1.7 • Platelet count 40 mmHg) Shallow anterior chamber ± cells

Ophthalmology consult for laser iridotomy Medications: AABCDE/EAT PAL α-agonist: epinephrine α2-agonist: apraclonidine β-blocker: timolol Cholinomimetic: pilocarpine Diuretic: acetazolamide, mannitol Eicosanoid: latanoprost

Corneal Abrasion

Pain, redness, tearing, photophobia, foreign body sensation De-epithelialized area stains with fluorescein dye

Most clear spontaneously within 24-48 h If due to foreign body, remove under magnification using local anesthetic and sterile needle, or consult ophthalmology for removal under magnification Topical antibiotic (drops or ointment)

Chemical Burn

Known exposure to acids or alkali (worse) Pain, decreased visual acuity Vascularization or defects of cornea Iris and lens damage

Irrigate site of accident with NS with eyelid retracted until neutral pH achieved Sweep fornices Cycloplegic drops and topical antibiotics

Orbital Cellulitis

Red, painful eye, decreased visual acuity Headache, fever Lid erythema, edema, and diculty opening eye Conjunctival injection and chemosis Proptosis, opthalmoplegia ± RAPD

Admission, ophthalmology consult Blood cultures, orbital CT IV antibiotics (ceftriaxone + vancomycin) Drainage of abscess

Retinal Artery Occlusion

Sudden, painless, monocular vision loss RAPD Cherry red spot and retinal pallor on fundoscopy if central retinal artery occlusion

Restore blood flow 50%) ■ Toxic Shock Syndrome (TSS) ◆ see Infectious Diseases, ID22 ◆ caused by superantigen from S. aureus or Group A Streptococcus (GAS) activating T-cells and cytokines ◆ patient oen presents with onset of shock and multi-organ failure, fever ◆ diuse erythematous macular rash ◆ at least 3 organ systems involved: CNS, respiratory, GI, muscular, mucous membranes, rena l, liver, hematologic, and skin (necrotizing fasciitis, gangrene) ◆ vesiculobullous lesions ■ Erythema Multiforme (EM) ◆ immunologic reaction to herpes simplex ◆ viral prodrome 1-14 d before rash ◆ target lesion: central grey bulla or wheal surrounded by concentric rings of erythema and normal skin ◆ Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome B. Discrete Lesions ■ Pyoderma Gangrenosum ◆ oen associated with IBD, rheumatoid conditions, leukemia, and monoclonal gammopathies ◆ oen occurs in arms, hands, feet, or perineal region ◆ usually begins as painless macule/vesicle/pustule/bulla on red/blue base sloughing, leavinga gangrenous ulcer ■ Disseminated Gonococcal Infection (DGI) ◆ see Dermatology, D38 ◆ fever, skin lesions (pustules/vesicles on erythematous base ~5 mm in diameter), arthritis (joint swelling and tenderness), and septic arthritis (in larger joints, such as knees, ankles, and elbows) ◆ most commonly in gonococcus-positive women during menstruation or pregnancy ◆ skin lesions usually appear in extremities and resolve quickly (5 yr or incomplete primary series (see Table 11, ER17) Prophylactic Antibiotics • types of infections resulting from bites: cellulitis, lymphangitis, abscesses, tenosynovitis, osteomyelitis, septic arthritis, sepsis, endocarditis, meningitis • a 3-5 d course of antibiotics is recommended for all bite wounds to the hand and should be considered in other bites if any high-risk factors present • dog and cat bites (pathogens: Pasteurella multocida, S. aureus, S. viridans) ■ 10-50% of cat bites, and 5% of dog bites become infected ■ 1st line: amoxicillin + clavulanic acid (not cefalexin as it does not cover Pasteurella spp. or Eikenella corrodens) • human bites (pathogens: Eikenella corrodens, S. aureus, S. viridans, oral anaerobes) ■ 1st line: amoxicillin + clavulanic acid • rabies (see Infectious Diseases, ID19) ■ reservoirs: warm-blooded animals except rodents (primarily bats and raccoons in Canada), lagomorphs (e.g. rabbits) ■ post-exposure vaccine is eective; treatment depends on local prevalence

Near Drowning • most common in children 50 mmHg, or pO2 24 h Toxic dose >200 mg/kg (>7.5 g adult) Monitor drug level 4 h post-ingestion; also liver enzymes, INR, PTT, BUN, Cr Hypoglycemia, metabolic acidosis, encephalopathy poor prognosis Dialysis may be required to manage in very high overdoses

Acute Dystonic Reaction

Benztropine: 1-2 mg IM/IV then 2 mg PO 3 d OR Diphenhydramine 1-2 mg/kg IV, then 25 mg PO QID x3 d

Benztropine (Cogentin®) has euphoric eect and the potential for misuse

Anticholinergics

Consider decontamination (activated charcoal) Supportive care

Special antidotes available; consult Poison Information Centre

ASA

Consider decontamination (activated charcoal) Alkalinize urine; want urine pH >7.5

Monitor serum pH and drug levels closely Monitor K+level; may require supplement for urine alkalinization Hemodialysis may be needed if intractable metabolic acidosis, very high levels, or end-organ damage (i.e. unable to diurese)

Benzodiazepines

Consider decontamination (activated charcoal) Flumazenil (only use in iatrogenic overdose (operative oversedation) due to extensive contraindications (mixed overdose, Hx of EtOH, seizures)) Supportive care

β-blockers

Consider decontamination (activated charcoal, consider whole bowel irrigation for extended-release ingestion) IV glucagon, IV calcium chloride, IV high-dose insulin (with dextrose), IV lipid emulsification

Calcium Channel Blockers

Consider decontamination (activated charcoal, consider Order ECG, electrolytes (especially Ca2+, Mg 2+, Na+, K +) whole bowel irrigation for extended-release ingestion) IV glucagon, IV calcium chloride, IV high-dose insulin (with dextrose), IV intralipid

Cocaine

Decontaminate (activated charcoal) if oral Aggressive supportive care

β-blockers are contraindicated in acute cocaine toxicity Intralipid for life-threatening symptoms Consider benzodiazepines for any major side eect of cocaine overdose (agitation, hypertension, tachycardia, etc.)

CO Poisoning

See Inhalation Injury, ER47 Supportive care 100% O 2 ; may require hyperbaric O2

Order ECG, VBG. Consider lactate and troponin depending on specific presentation

Cyanide

Hydroxocobalamin 5 g IV (Cyanokit™)

Consider in all patients found in a fire

Digoxin

Consider decontamination (activated charcoal) Digoxin-specific antibody fragments 10-20 vials IV if acute; 3-6 if chronic 1 vial (40 mg) neutralizes 0.5 mg of toxin

Use for life-threatening dysrhythmias unresponsive to conventional therapy, 6 h serum digoxin >12 nmol/L, initial K+ >5 mmol/L, ingestion >10 mg (adult)/>4 mg (child) Common dysrhythmias include VFib, VTach, and conduction blocks

Ethanol

Thiamine 100 mg IM/IV Manage airway and circulatory support

Mouthwash = 70% EtOH; perfumes and colognes = 40-60% EtOH Order serum EtOH level and glucose level; treat glucose level appropriately

Ethylene Glycol/ Methanol

Fomepizole (4-methylpyrazole) 15 mg/kg IV load over 30 min, then 10 mg/kg q12 h OR Ethanol (10%) 10 mL/kg over 30 min, then 1.5 mL/h

CBC, electrolytes, glucose, ethanol level Consider hemodialysis

Heparin

Protamine sulfate 25-50 mg IV

For unfractionated heparin overdose only

Insulin IM/SC/ Oral Hypoglycemic

Glucose IV/PO/NG tube Glucagon: 1-2 mg IM (if no access to glucose)

Glyburide carries highest risk of hypoglycemia among oral agents Consider octreotide for oral hypoglycemics (50-100 g SC q6 h) in these cases; consult local Poison Information Centre

MDMA

Consider decontamination (activated charcoal) Supportive care

Monitor CK; treat rhabdomyolysis with high flow fluids: aggressive external cooling for hyperthermia Review medical history if possible for serotonergic use

Opioids

See Universal Antidotes, ER49

TCAs

Consider decontamination (activated charcoal) Aggressive supportive care NaHCO 3 bolus for wide QRS/seizures

Organophosphate 100% O 2 + endotracheal intubation Atropine Pralidoxime (2-PAM)

Flumazenil antidote contraindicated in combined TCA and benzodiazepine overdose Also consider cardiac and hypotension support, seizure control Intralipid therapy Succinylcholine

* Call local Poison Information Centre for reporting of cases, specific doses, and treatment recommendations. Most toxicology cases should involve communication with your local Poison Information Centre

Alcohol Related Emergencies ER54 Emergency Medicine

Toronto Notes 2023

Alcohol Related Emergencies • see Psychiatry, PS29 Acute Intoxication • slurred speech, CNS depression, disinhibition, lack of coordination • nystagmus, diplopia, dysarthria, ataxia, may progress to coma • hypotension (peripheral vasodilation) • if obtunded, rule out ■ head trauma/intracranial hemorrhage ■ associated depressants, toxic alcohols • may also contribute to respiratory/cardiac depression ■ hypoglycemia (screen with bedside glucometer) ■ hepatic encephalopathy: confusion, altered LOC, coma • precipitating factors: GI bleed, infection, sedation, electrolyte abnormalities, protein meal ■ Wernicke’s encephalopathy (ataxia, ophthalmoplegia, delirium) ■ post-ictal state, basilar stroke Withdrawal • beware of withdrawal signs • treatment ■ diazepam 10-20 mg IV/PO or lorazepam 2-4 mg IV/PO q1 h (if known liver dysfunction) until two negative CIWA scores • frequency of dosing may have to be increased depending on clinical response ■ may use CIWA protocol and give benzodiazepines as above until CIWA 2 suggests alcohol as the cause • peritonitis/spontaneous bacterial peritonitis ■ leukocytosis, fever, generalized abdominal pain/tenderness ■ occasionally accompanies cirrhosis ■ paracentesis for diagnosis (common pathogens: E. coli, Klebsiella, Streptococcus) ■ albumin shown to improve outcomes in sBP patients • GI bleeds ■ most commonly gastritis or ulcers, even if patient known to have varices ■ consider Mallory-Weiss tear secondary to retching ■ oen complicated by underlying coagulopathies ■ minor: treat with antacids ■ severe or recurrent: endoscopy ■ variceal bleeds: octreotide

Disposition from the Emergency Department • alcohol ■ before patient leaves ED ensure stable vital signs, can walk unassisted, and fully oriented ■ oer social services to nd shelter or detox program ■ ensure patient can obtain any medications prescribed and can complete any necessary follow-up • methanol, ethylene glycol ■ delayed onset, admit, and watch clinical and biochemical markers • TCAs ■ prolonged/delayed cardiotoxicity warrants admission to monitored ICU bed ■ if asymptomatic and no clinical signs of intoxication: 6 h ED observation adequate with proper decontamination and no ECG abnormalities ■ sinus tachycardia alone (most common nding) with history of overdose warrants observation in ED • hydrocarbons/smoke inhalation ■ pneumonitis may lag 6-8 h ■ consider observation for repeated clinical and radiographic examination • ASA, acetaminophen ■ if borderline level, get second level 2-4 h aer rst ■ for ASA, must have at least 2 measurements showing decreasing toxin serum concentration before discharge (3 levels minimum) • oral hypoglycemics ■ admit all patients for minimum 24 h if hypoglycemic and 12 h aer last octreotide dose ■ observe asymptomatic patient for at least 8 h • opioids ■ administer naloxone, a short-acting opioid antagonist, preferably IV in incremental doses (0.2-1 mg) ■ patients in cardiorespiratory arrest following possible opioid overdose should be given 2 mg of naloxone minimum ■ admit and observe for 24h ■ referral to rapid access clinic and oer a naloxone kit Psychiatric Consultation • once patient medically cleared, arrange psychiatric intervention if required • beware – suicidal ideation may not be expressed

Toronto Notes 2023

Psychiatric Emergencies ER56 Emergency Medicine

Toronto Notes 2023

Psychiatric Emergencies Approach to Common Psychiatric Presentations • see Psychiatry, PS2 • before seeing patient, ensure your own safety; have security/police available if necessary History • safety ■ assess suicidality: suicidal ideation (SI; passive/active), intent, plan, lethal means, past attempts, protective factors ■ assess homicidality: homicidal ideation (HI), access to weapons, intended victim, and history of violence ■ driving and children ■ command hallucinations • identify current stressors and coping strategies • mood symptoms: manic, depressive • anxiety: panic attacks, generalized anxiety, phobias, obsessive-compulsive disorder, post-traumatic stress disorder • psychotic symptoms: delusions, hallucinations, disorganized speech, disorganized or catatonic behaviour, negative symptoms (aective attening, alogia, avolition) • substance use history: most recent use, amount, previous withdrawal reactions • past psychiatric history, medications, adherence with medications, admissions • medical history: obtain collateral if available Physical Exam • complete physical exam focusing on: vitals, neurological exam, signs of head trauma, signs of drug toxicity, signs of metabolic disorder; which could be contributing or causing psychiatric presentation • mental status exam: general appearance, behaviour, cooperation, speech, mood and aect, thought content and form, perceptual disturbances, cognition (including MMSE if indicated), judgment, insight, reliability

Key Functions of Emergency Psychiatric Assessment • Is the patient medically stable? • Rule out medical cause • Is psychiatric consult needed? • Are there safety issues (SI, HI)? • Is patient certifiable? (must demonstrate risk (present/past test) and apparent mental illness (future test))

Psychiatric Review of Systems MOAPS Mood Organic Anxiety Psychosis Safety

Investigations • investigations vary with age, established psychiatric diagnosis vs. rst presentation, history and physical suggestive of organic cause • as indicated: blood glucose, urine and serum toxicology screen, pregnancy test, electrolytes, TSH, AST/ALT, bilirubin, serum Cr, BUN, and osmolality • blood levels of psychiatric medications • CT head if suspect neurological etiology • LP if indicated (anti-NMDA receptor encephalitis)

Acute Psychosis Dierential Diagnosis • primary psychotic disorder (e.g. schizophrenia) • secondary to medical condition (e.g. delirium) • drugs: substance intoxication or withdrawal, medications (e.g. steroids, anticholinergics) • infectious (CNS) • metabolic (hypoglycemic, hepatic, renal, thyroid) • structural (hemorrhage, neoplasm) ■ autoimmune (anti-NMDA receptor encephalitis) Management • violence prevention ■ remain calm, empathic, and reassuring ■ ensure safety of sta and patients, have extra sta and/or security on hand ■ patients demonstrating escalating agitation or overt violent behaviour may require physical restraint and/or chemical restraint • treat agitation: whenever possible, oer medication to patients as opposed to administering with force (helps calm and engage patient) ■ benzodiazepines: lorazepam 2 mg PO/IM/SL ■ antipsychotics: olanzapine 5-10 mg PO/IM, haloperidol 5 mg PO/IM • treat underlying medical condition • psychiatry or Crisis Intervention Team consult

Suicidal Patient Epidemiology • attempted suicide F>M, completed suicide M>F • second leading cause of death in people 45 yr Depression Previous attempts Ethanol use Rational thinking loss Suicide in family Organized plan No spouse, no support system Serious illness

Modified Glasgow Coma Score Table 36. Modified GCS Modified GCS for Infants Motor Response 6 – normal, spontaneous movement 5 – withdraws to touch 4 – withdraws to pain 3 – decorticate flexion 2 – decerebrate extension 1 – no response

Verbal Response 5 – coos, babbles 4 – irritable cry 3 – cries to pain 2 – moans to pain 1 – no response

Eye Opening 4 – spontaneously 3 – to speech 2 – to pain 1 – no response

Modified GCS for Infant (60 (>40 if preschool age, >30 if school age), retractions, tracheal tug ■ see Paediatrics, P3 for age specic vital signs • pulsus paradoxus (rarely used clinically) • wheezing, grunting, vomiting Table 37. Stridorous Upper Airway Diseases: Dierential Diagnosis Feature

Croup

Bacterial Tracheitis

Epiglottitis1 2-8

Age Range (yr)

0.5-4

5-10

Prodrome

Mild for days then acutely severe

Hours to days

Minutes to hours

Temperature

Low grade

High

High

Radiography

Steeple sign

Exudates in trachea2

Thumb sign

Etiology

Parainfluenza

S. aureus/GAS

H. influenzae type b

Barky Cough

Yes

Yes

No

Drooling

Occasionally

No

Yes

Appear Toxic

No

Yes

Yes

Intubation/ICU

No but yes if severe (rare)

Yes

Yes

Antibiotics

No

Yes

Yes

NOTE

Oral exam

Oral exam

No oral exam, consult ENT

1Now rare with Hib vaccine in common use 2Found

as diuse haziness and irregularity of the anterior wall of trachea; consider imaging only after ruling out epiglottitis

Any trauma or suspected trauma patient 38°C without obvious focus ■ 90 d ◆ toxic: admit, treat, full septic workup ◆ non-toxic and no focus: investigate as indicated by history and physical ◆ antibiotics (Ceriaxone or cefotaxime (if available), add acyclovir or vancomycin when indicated) FEBRILE SEIZURES • see Paediatrics, P88 Etiology • children ages 6 mo-6 yr with fever or history of recent fever • typical vs. atypical febrile seizures • normal neurological exam aerward • no evidence of intracranial infection or history of previous non-febrile seizures • oen positive family history of febrile seizures • relatively well-looking aer seizure Investigations and Management • if conrmed febrile seizure: treat fever and look for source of fever • if not a febrile seizure: treat seizure and look for source of seizure ■ note: may also have fever but may not meet criteria for febrile seizure • ± EEG (especially if rst seizure), head U/S (if fontanelle open) Table 38. Typical vs. Atypical Febrile Seizures Characteristic

Typical

Atypical

Duration

5 min

Type of Seizure

Generalized

Focal features

Frequency

1 in 24 h

>1 in 24 h

Rochester Criteria for Febrile Infants Ages 28-90 Days Old • Helps identify SBI (serious bacterial infection) and guide testing/work-up for well-looking febrile neonates • Non-toxic looking • Previously well (>37 wk gestational age, home with mother, no hyperbilirubinemia, no prior antibiotics or hospitalizations, no chronic/underlying illness) • No skin, soft tissue, bone, joint, or ear infection on physical exam • WBC 5000-15000, bands 35 kg: 50 mg PO TID

STREP PHARYNGITIS Group A β-hemolytic Streptococcus

penicillin/amoxicillin, cefalexin, or erythromycin (can cause GI upset)

E. coli, Proteus, H. influenzae, Pseudomonas, S. saprophyticus, Enterococcus, GBS

Oral: cefalexin IV: aminoglycoside (gentamycin) ± ampicillin

1-3 mo

Viral, S. pneumoniae, C. trachomatis, B. pertussis, S. aureus, H. influenzae

cefuroxime ± macrolide (erythromycin) OR ampicillin ± macrolide

3 mo-5 yr

Viral, S. pneumoniae, S. aureus, H. influenzae, Mycoplasma pneumoniae

ampicillin/amoxicillin or cefuroxime

>5 yr

As above

ampicillin/amoxicillin + macrolide OR cefuroxime + macrolide

UTI

PNEUMONIA

Red Flags for Abdominal Pain • Significant weight loss or growth retardation (need growth chart) • Fever • Joint pain with objective physical findings • Rash • Rectal bleeding • Rebound tenderness and radiation of pain to back, shoulders, or legs • Pain wakes from sleep • Severe diarrhea and encopresis

Child Abuse and Neglect ER60 Emergency Medicine

Toronto Notes 2023

Child Abuse and Neglect • see Paediatrics, P18 • obligation to report any suspected/known case of child abuse or neglect to CAS yourself (do not delegate) • document injuries • consider skeletal survey x-rays (especially in non-ambulatory child), ophthalmology consult, CT head • injury patterns associated with child abuse ■ HI: torn frenulum, dental injuries, bilateral black eyes, traumatic hair loss, diuse severe CNS injury, retinal hemorrhage ■ Shaken baby syndrome: diuse brain injury, subdural/SAH, retinal hemorrhage, minimal/no evidence of external trauma, associated bony fractures ■ skin injuries: bites, bruises/burns in shape of an object, glove/stocking distribution of burns, bruises of various ages, bruises in protected areas ■ bone injuries: rib fractures without major trauma, femur fractures 50 and women > 60 with one additional risk factor: low HDL-C, IFG, high WC, smoker, HTN or with presence of other risk modifiers: hsCRP > 2.0 mg/L, CAC >0 AU, family history of premature CAD, Lp(a) > 50 mg/dL (100 nmol/L)

FRS >20%

Discuss health behavioural modifications

Statin therapy not recommended for most low risk individuals; exceptions include: a. LDL-C >5.0 mmol/L (or ApoB >1.45 g/L or non-HDL-C >4.2 mmol/L) or b. FRS is 5-9.9% with LDL-C >3.5 mmol/L (or non-HDL-C > 4.2 mmol/L or ApoB >1.05 g/L), particularly with other CV risk modifiers (e.g. FHx, Lp(a) >50 mg/dL [or 100 nmol/L] or CAC >0 AU) as the proportional benefit from statin therapy may be similar to other treated groups

Initiate Statin Treatment

NO Health Behaviour Modifications: • Smoking cessation • Diet: it is recommended all individuals adopt a healthy dietary pattern • Exercise: it is recommended adults accumulate at least 150 min/wk of moderate-vigorous intensit y aerobic physical activity

Monitor • Response to statin Rx • Response to add-on lipid-lowering Rx • Health behaviour changes

If LDL-C>2.0 mmol/L or ApoB >0.8 g/L or non-HDL-C>2.6 mmol/L on maximally tolerated statin dose

YES

YES

Discuss add-on therapy with patient: Evaluate reduction in CVD risk vs. cost/access and side effects

NO ADD-ON YES

Ezetimibe as 1st line (BAS as alternative)

Figure 3a. Treatment approach for primary prevention patients (without a statin indicated condition‡) Adapted from 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Canadian Cardiovascular Society.

For Statin Follow-Up • Liver enzymes and lipid profile: liver enzymes measured at the beginning of treatment, then once after therapy initiated. Lipids (once stabilized) measured annually. Order both if patient complains of jaundice, right upper quadrant pain, dark urine • CK at baseline and if patient complains of myalgia • Discontinue statin if CK >10x upper limit of normal or patient has persistent myalgia

2021 Canadian Cardiovascular Society Guidelines on the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the A dult Can J Cardiol 2021; S0828-282X(21)00165-3 • Patients with clinical atherosclerosis, AAA, LDL-C ≥5.0 mmol/L, and most with diabetes or CKD should be started on statin therapy • Lipid/lipoprotein screening is recommended in patients >40 yr or at any age for those at increased risk • Non-HDL cholesterol or ApoB are preferred to LDL-C as lipid parameters for screening in patients with TG >1.5 mmol/L • LP(a) should be measured once in a person’s lifetime as part of initial lipid screening to assess cardiovascular risk • Lipid-lowering therapy should be intensified with ezetimibe and/or PCSK9 inhibitors in patients with LDL-C remaining ≥1.8 mmol/L (or nonHDL cholesterol ≥2.4 mmol/L or ApoB ≥0.7 g/L) on a maximally tolerated statin dose

See Landmark Endocrinology Trials for more information on the JUPITER trial. It details the eects of statin treatment on cardiovascular events in patients with elevated high-sensitivity CRP levels.

E6 Endocrinology

Toronto Notes 2023

Statin Indicated Conditions LDL > 5.0 mmol/L • or ApoB >1.45 g/L or non-HDL-C >5.8 mmol/L • Familial hypercholesterolemia or genetic dyslipidemia

Most patients with diabetes: • Age >40 • Age >30 & DM x >15 yr duration • Microvascular disease Most patients with diabetes: • Age >50 and eGFR 3 mg/mmol

Atherosclerotic Cardiovascular Disease: • Myocardial infarction, acute coronary syndromes • Stable angina, documented coronary artery disease by angiography • Stroke, TIA, document carotid disease • Peripheral arterial disease, claudication and/or ABI 3.0 cm or previous aneurysm surgery

Review/Discuss health behavioural modifications

Initiate Statin Treatment

NO

If LDL-C >2.5 mmol/L (or 0.85 g/L or non-HDL-C >3.2 mmol/L

If LDL-C >2.0 mmol/L or ApoB >0.80 g/L or non-HDL-C >2.6 mmol/L on maximally tolerated statin dose

YES

YES

Discuss add-on therapy with patient Evaluate reduction in CVD risk vs. cost/access and side effects ADD-ON Ezetimibe or PCSK9 inhibitor

NO

If LDL-C > 1.8 mmol/L or ApoB >0.70 g/L or non-HDL-C >2.4 mmol/L on maximally tolerated statin dose YES Discuss intensification of therapy with patient

ADD-ON Ezetimibe as 1st line (BAS as alternative - add-on to other drugs)

NO

INTENSIFICATION Refer to Figure Treatment Intensification Approach for Patients with ASCVD

Monitor • Response to statin Rx • Response to add-on lipid-lowering Rx • Health behaviour modifications

NO

Figure 3b. Treatment approach for patients with a statin indicated condition Adapted from 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Canadian Cardiovascular Society.

Patients with Atherosclerotic Cardiovascular Disease

If LDL-C >1.8 mmol/L or ApoB >0.70 g/L or if non-HDL-C >2.4 mmol/L

LDL-C 1.8-2.2 mmol/L or ApoB 0.70-0.80 g/L or non-HDL-C 2.4-2.9 mmol/L

LDL-C >2.2 mmol/L or ApoB >0.80 g/L or non-HDL-C >2.9 mmol/L or high PCSK9i benefit patient

Consider Ezetimibe +PCSK9 inhibitor

Consider PCSK9 inhibitor +ezetimibe

If TG >1.5 to 5.6 mmol/L

Consider Icosapent ethyl 2000 mg BID

Figure 3c. Treatment intensification approach for patients with atherosclerotic cardiovascular disease (ASCVD) Adapted from 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Canadian Cardiovascular Society.

Disorders of Glucose Metabolism E7 Endocrinology

Toronto Notes 2023

Disorders of Glucose Metabolism

cells of the pancreas stimulated to release insulin into the blood stream

© Susan Le 2016

Overview of Glucose Regulation Insulin

Body cells take up more glucose

Liver takes up excess glucose and stores it as glycogen

Increase in blood glucose levels

Blood Glucose Level Liver breaks down glycogen stores and releases glucose into the blood

Glucagon

Decrease in blood glucose levels

cells of the pancreas stimulated to release glucagon into the blood

Figure 4. Blood glucose regulation

Pre-Diabetes (Impaired Glucose Tolerance/Impaired Fasting Glucose) • • • • •

Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial - REDUCE-IT NEJM 2019;380:11-22 Study: Multicenter, randomized, double-blind, placebo-controlled trial with 5 yr of follow-up. Population: 8179 patients with established CVD or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting TG level of 135-499 mg/dL and a LDL level of 41-100 mg/dL. Intervention: Randomly assigned to receive 2 g of icosapent ethyl BID or placebo. Primary Outcome: Composite of cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization or unstable angina. Results: A primary endpoint event occurred in 17.2% of the patients in the icosapent ethyl group compared to 22% of the patients in the placebo group (HR=0.75, 95% CI: 0.68-0.83, P10 mU/L and young and middle-aged patients with symptoms of mild hypothyroidism.

Signs and Symptoms of HYPOthyroidism HIS FIRM CAP Hypoventilation Intolerance to cold Slow HR Fatigue Impotence Renal impairment Menorrhagia/amenorrhea Constipation Anemia Paresthesia

Non-Thyroidal Illness (Sick Euthyroid Syndrome) E32 Endocrinology

Clinical Features • decreased mental status and hypothermia are hallmark symptoms • hyponatremia, hypotension, hypoglycemia, bradycardia, hypoventilation, and generalized non-pitting edema oen present Investigations • decreased T4, increased TSH, decreased glucose • check ACTH and cortisol for evidence of adrenal insuciency Treatment • aggressive and immediate treatment required • ABCs: ICU admission • corticosteroids (for risk of concomitant adrenal insuciency): hydrocortisone 100 mg q8 h • L-thyroxine 0.2-0.5 mg IV loading dose, then 0.1 mg IV once daily until oral therapy tolerated; also consider T3 therapy • supportive measures: mechanical ventilation, vasopressors, passive rewarming, IV dextrose, uids if necessary (risk of overload) • monitor for arrhythmia

Non-Thyroidal Illness (Sick Euthyroid Syndrome) Definition • changes in the regulation of the hypothalamic-pituitary-thyroid axis, and thyroid hormone metabolism and transport among patients with severe illness, trauma, surgery, or starvation • not due to intrinsic thyroid, pituitary, or hypothalamic disease • initially low free T3 may be followed by low TSH and, if severe illness, low free T4 • with recovery of illness, TSH may become transiently high Pathophysiology • abnormalities include alterations in: ■ peripheral transport and metabolism of thyroid hormone ■ regulation of TSH secretion • may be protective during illness by reducing tissue catabolism Labs • initially decreased free T3 followed by decreased TSH and nally decreased free T4 • with recovery of illness, TSH may become elevated Treatment • treat the underlying disease; thyroid hormone replacement has not shown to be benecial • thyroid function tests normalize once patient is well (initially with a transient increase in TSH) Non-Toxic Goitre Definition • generalized enlargement of the thyroid gland in a euthyroid individual that does not result from inammatory or neoplastic processes Pathophysiology • the appearance of a goitre is more likely to present during adolescence, pregnancy, and lactation due to increased thyroid hormone requirements • early stages: goitre is usually diuse • later stages: multinodular non-toxic goitre with nodule, cyst formation, and areas of ischemia, hemorrhage, and brosis Etiology • iodine deciency or excess • goitrogens: brassica vegetables (e.g. turnip, cassava) • drugs: iodine, lithium, para-aminosalicylic acid • any disorder of hormone synthesis with compensatory growth • peripheral resistance to thyroid hormone Treatment • remove goitrogens • radioiodine therapy (very high doses required given low iodine uptake, used as last resort in very highly selected cases where the goiter is causing symptoms and surgery is not feasible) • suppression with L-thyroxine (rarely done) • surgery may be necessary if severe compressive symptoms develop (rare); patients are oen asymptomatic Complications • compression of neck structures causing stridor, dysphagia, pain, and hoarseness of voice • multinodular goitre may become autonomous leading to toxic multinodular goitre and hyperthyroidism

Toronto Notes 2023

Thyroid Nodules E33 Endocrinology

Toronto Notes 2023

Thyroid Nodules Definition • discrete lesion that can be distinguished sonographically from the rest of the thyroid parenchyma • 19-67% prevalence based on incidentally found nodules on U/S Etiology • benign tumours (e.g. follicular adenoma) • thyroid malignancy • hyperplastic area in a multinodular goitre • cyst: true thyroid cyst, area of cystic degeneration in a multinodular goitre Investigations • approach to thyroid biopsy depending on U/S characteristics of the nodule • benign or very small nodules suspicious for thyroid cancer do not require ongoing surveillance • small nodules suspicious for thyroid cancer require up to ve years of surveillance • larger nodules suspicious for thyroid cancer require biopsy Thyroid nodule on U/S

Third generation TSH Low TSH Thyroid scan Hot nodule No biopsy Treat hyperthyroidism

Cold nodule

Normal/elevated TSH U/S-guided biopsy if indicated based on U/S characteristics

U/S-guided biopsy if indicated based on U/S characteristics Treat hyperthyroidism

Figure 13. Approach to the evaluation of a thyroid nodule Adapted from Dr. J Goguen, University of Toronto, MMMD 2013

Thyroid Malignancies • see Otolaryngology, OT37

Adrenal Cortex Adrenocorticotropic Hormone • a polypeptide (cleaved from prohormone POMC), secreted in a pulsatile fashion from the anterior pituitary with diurnal variability (peak: 0200-0400 h; trough: 1800-2400 h) • secretion regulated by CRH and AVP • stimulates growth of adrenal cortex and release of glucocorticoids, adrenal androgens and, to a very limited extent, mineralocorticoids • ACTH can directly bind to MSH receptors on melanocytes, enhancing melanogenesis

Adrenocortical Hormones Aldosterone • a mineralocorticoid which regulates ECFV through Na +(and Cl–) retention and K +(and H +) excretion (stimulates distal tubule Na +/K+ ATPase) • regulated by the RAAS and hyperkalemia • negative feedback to juxtaglomerular apparatus (JGA) by long loop (aldosterone ↑ volume expansion) and short loop (angiotensin II ↑ peripheral vasoconstriction)

 blood glucose, trauma, infection,

emotion, circadian rhythm CNS Hypothalamus

CRH

AVP

Pituitary ACTH

Cortisol

Adrenal gland

Figure 14. Regulation of CRH-ACTHadrenal gland axis

E34 Endocrinology

Toronto Notes 2023

Cholesterol 2

1 17-hydroxylase 2 3- -dehydrogenase

Pregnenolone

*3 21-hydroxylase

1

4 11-hydroxylase

1

Progesterone

17-OH-pregnenolone

*3

DHEAS

2

2

17-OH-progesterone

11-deoxycorticosterone 4

5 17- -dehydrogenase 7 5- -reductase

11-deoxycortisol

8 18-hydroxycorticosterone

9 18-oxidase

Testosterone

4

6

Cortisol

Estradiol

*Most common enzyme defect

Dihydrotestosterone

9 Aldosterone Glucocorticoids (zona fasciculata)

Mineralocorticoids (zona glomerulosa)

Sex Steroids (zona reticularis)

Figure 15. Pathways of major steroid synthesis in the adrenal gland and their enzymes volume arterial pressure Na +delivery to macula densa

 volume  arterial pressure

Dopamine Renal Na + retention

Prostaglandins Sympathetic stimulation

Inhibition of JGA

Stimulation of JGA Renin (kidney) Angiotensinogen

ACE (lung and kidney)

Angiotensin I

ACE = angiotensin converting enzyme JGA = juxtaglomerular apparatus

Zona Glomerulosa produces mineralocorticoids (aldosterone) Zona Fasciculata produces glucocorticoids (cortisol)

8 18-hydroxylase

5 7

Corticosterone

OUTSIDE

6 Aromatase

Androstenedione

*3

Layers of the Adrenal Cortex

Angiotensin II (with negative feedback to inhibit JGA)

Aldosterone release Arteriolar vasoconstriction Promotion of ADH release

Renal Na+ retention, K +excretion

Figure 16. Renin-angiotensin-aldosterone axis (see Nephrology, NP4)

Cortisol • a glucocorticoid regulated by the HPA axis • involved in metabolism regulation • supports blood pressure and vasomotor tone • also involved in behavioural regulation and immunosuppression Table 21. Physiological Eects of Glucocorticoids Stimulatory Eects

Inhibitory Eects

Stimulate hepatic glucose production (gluconeogenesis)

Inhibit bone formation; stimulate bone resorption

Increase insulin resistance in peripheral tissues

Inhibit fibroblasts, causing collagen and connective tissue loss

Increase protein catabolism

Suppress inflammation; impair cell-mediated immunity

Stimulate leukocytosis and lymphopenia

Inhibit growth hormone axis*

Increase cardiac output, vascular tone, Na +retention

Inhibit reproductive axis*

Increase PTH release, urine calcium excretion

Inhibit vitamin D3and inhibit calcium uptake

*Typically only occurs with cortisol excess

Androgens • sex steroids regulated by ACTH; primarily responsible for adrenarche (growth of axillary and pubic hair) • principal adrenal androgens are: DHEA, androstenedione, and 11-hydroxyandrostenedione • proportion of total androgens (adrenal to gonadal) increases with age

Zona Reticularis produces androgens (DHEA, androstenedione)

INSIDE

Adrenocortical Functional Workup E35 Endocrinology

Adrenocortical Functional Workup STIMULATION TEST • purpose: diagnose hormone deciencies • method: measure target hormone aer stimulation with tropic (pituitary) hormone Tests of Glucocorticoid Reserve • Cosyntropin (ACTH analogue) Stimulation Test ■ administer 250 µg cosyntropin IV/IM, and measure plasma cortisol levels before and 30 and 60 min aer administration ■ physiologic response: stimulated plasma cortisol of >500 nmol/L (>18 µg/dL) at 30 or 60 min ◆ physiologic response rate threshold may be lower with newer assays and should be conrmed with local lab ■ inappropriate response: inability to stimulate increased plasma cortisol; peak cortisol levels below 500 nmol/L (18 µg/dL) at 30 or 60 min SUPPRESSION TESTS • purpose: diagnose of hormone hypersecretion • method: measure target hormone aer suppression of its tropic (pituitary) hormone 1. Tests of Pituitary-Adrenal Suppressibility • DXM suppression test • principle: DXM suppresses pituitary ACTH, plasma cortisol should be lowered if HPA axis is normal • screening test: low-dose overnight DXM suppression test ◆ oral administration of 1 mg DXM between 11 pm and midnight, then measure plasma cortisol levels the following day between 8 am and 9 am ◆ physiologic response: plasma cortisol 277 pmol/L is consistent with PA, 20 ng/dL:ng/mL/h and PAC >15 ng/dL ( >416 pmol/L)

Investigate for causes of secondary hyperaldosteronism

Investigate for Primary aldosteronism

Renovascular HTN Diuretic use Renin-secreting tumour Malignant HTN Coarctation of the aorta

Investigate for: Congenital adrenal hyperplasia Exogenous mineralcorticoid DOC-producing tumour Cushing’s syndrome 11- -HSD deficiency Altered aldosterone metabolism Liddle’s syndrome Glucocorticoid resistance

Figure 17. Approach to mineralocorticoid excess syndromes

Clinical Features • HTN • hypokalemia (± mild hypernatremia), metabolic alkalosis • normal K +,hyponatremia in secondary hyperaldosteronism (low eective circulating volume leads to ADH release) • increased cardiovascular risk: LV hypertrophy, atrial brillation, stroke, and MI • elevated risk of metabolic syndrome and T2DM • fatigue, weakness, paresthesia, headache; severe cases present with tetany, intermittent paralysis (only if K+, 277 pmol/L (140-277 indeterminant range)

Not performed

Treatment • inhibit action of aldosterone: spironolactone, eplerenone, triamterene, amiloride (act on sodium channels) • surgical excision of adrenal adenoma • secondary hyperaldosteronism: treat underlying cause

Cushing’s Syndrome E37 Endocrinology

Toronto Notes 2023

Cushing’s Syndrome Definition • metabolic disorder caused by chronic glucocorticoid excess

Clinical Features • symptoms: weakness, insomnia, mood disorders, impaired cognition, easy bruising, oligo-/ amenorrhea, hirsutism, and acne (ACTH dependent) • signs: central obesity, round face (“moon face”), supraclavicular and dorsal fat pads, facial plethora, proximal muscle wasting, purple abdominal striae, skin atrophy, acanthosis nigricans, HTN, hyperglycemia, osteoporosis, pathologic fractures, hyperpigmentation, hyperandrogenism (if ACTHdependent) Diagnosis • rule out excessive glucocorticoid exposure leading to iatrogenic Cushing’s syndrome by conducting a thorough drug history before conducting biochemical testing • perform one of: 1) 24 h urine free cortisol (≥2 tests), 2) low dose DXM suppression test, or 3) late night salivary cortisol (≥2 tests) • consider reasons for a false positive (e.g. pregnancy, depression, alcoholism, morbid obesity, poorly controlled DM, glucocorticoid resistance, physical stress, malnutrition, anorexia nervosa, intense chronic exercise, hypothalamic amenorrhea) • conrm with one of the remaining tests Treatment • adrenal ■ adenoma: unilateral adrenalectomy (curative) with glucocorticoid supplementation postoperatively, tapering slowly until HPA axis has recovered ■ carcinoma: adrenalectomy in patients with disease localized to the adrenal, adjunctive mitotane for individuals with high-risk for current disease Mitotane ± chemotherapy for patients with metastatic disease ■ medical treatment: ketoconazole to reduce cortisol, mitotane can be used – typically reserved for patients with malignant disease • pituitary ■ transsphenoidal resection, with glucocorticoid supplementation postoperatively ■ if surgery delayed, contraindicated, or unsuccessful, consider medical management e.g. ketoconazole, mitotane, pasireotide, or cabergoline • ectopic ACTH tumour (paraneoplastic syndrome): usually bronchogenic cancer (poor prognosis) surgical resection, if possible; chemotherapy/radiation for primary tumour ■ medical treatment with mitotane or ketoconazole to reduce cortisol synthesis. Oen required when surgery is delayed, contraindicated, or unsuccessful • treat comorbidities associated with hypercortisolism

Congenital Adrenal Hyperplasia • see Paediatrics, P35

O

P

Figure 18. Clinical features of Cushing’s syndrome

© Min Jee Kim

Etiology • ACTH-dependent (85%) – bilateral adrenal hyperplasia and cortisol hypersecretion due to: ■ ACTH-secreting pituitary adenoma (Cushing’s disease; 80% of ACTH-dependent) ■ ectopic ACTH-secreting tumour (e.g. small cell lung carcinoma, bronchial, pancreatic islet cell, pheochromocytoma, or medullary thyroid tumour) • ACTH-independent (15%) ■ primary adrenocortical tumours: adenoma and carcinoma (uncommon) ■ bilateral adrenal nodular hyperplasia • iatrogenic Cushing’s syndrome is likely more common than endogenous cortisol excess but is infrequently reported; it is ACTH-independent

ks,

Hyperandrogenism E38 Endocrinology

Toronto Notes 2023

Hyperandrogenism Definition • state of having excessive secretion of androgens (DHEA, DHEA-sulfate, testosterone) Etiology and Pathophysiology Table 23. Etiology of Hyperandrogenism Medications Androgen-Mediated

Anabolic steroids, ACTH, androgens, progestational agents

Ovarian

PCOS Ovarian hyperthecosis Theca cell tumours Pregnancy: placental sulfatase/aromatase deficiency

Adrenal

Congenital adrenal hyperplasia (CAH, late-onset CAH) Tumours (adenoma, carcinoma)

Pituitary

Cushing’s disease – high ACTH Hyperprolactinemia

Clinical Features Females • hirsutism ■ male pattern growth of androgen-dependent terminal body hair in women: back, chest, upper abdomen, face, linea alba ■ Ferriman-Gallwey scoring system is used to quantify severity of hirsutism (score of >8 is abnormal for white/black women, ≥9 abnormal for Mediterranean/Hispanic/Middle-Eastern women, ≥2 for Asian women) ◆ scores should be interpreted in the context of the specic patient and acknowledge limitations such as the use of cosmetic hair removal ■ scores between 8-15 are mild, 16-25 moderate, and >25 severe hirsutism • virilization ■ frontal balding, clitoromegaly, increased muscle mass, deepening of the voice • amenorrhea, ↓ breast size, infertility, anabolic appearance, acne Males • minimal eects on hair, muscle mass, etc. • inhibition of gonadotropin secretion may cause reduction in testicular size, testicular testosterone production, and spermatogenesis Investigations • testosterone, DHEA-S as a measure of adrenal androgen production • LH/FSH (commonly in PCOS >2.5) • 17-OH progesterone, elevated in CAH due to 21-OH deciency; check on day 3 of menstrual cycle with a progesterone level • for virilization: CT/MRI of adrenals and ovaries (identify tumours) • if PCOS, check blood glucose and lipids Treatment • discontinue causative medications (e.g. oral DHEA, valproate, danazol) • antiandrogens, e.g. spironolactone • oral contraceptives (increase sex hormone binding globulin, which binds androgens>estrogens; reduces ovarian production of androgens) • surgical resection of tumour • glucocorticoid ± mineralocorticoid if CAH conrmed • treat specic causative disorders, e.g. tumours, Cushing’s, etc. • cosmetic therapy (laser, electrolysis)

Conditions that do Not Represent True Hirsutism • Androgen-independent hair (e.g. lanugo hair) • Drug-induced hypertrichosis (e.g. phenytoin, diazoxide, cyclosporine, minoxidil) • Topical steroid use

Adrenocortical Insufficiency E39 Endocrinology

Toronto Notes 2023

Adrenocortical Insuciency Definition • state of inadequate cortisol and/or aldosterone production by the adrenal glands Etiology PRIMARY ADRENOCORTICAL INSUFFICIENCY Table 24. Etiology of Primary Adrenocortical Insuciency Autoimmune (70-90%)

Isolated adrenal insuciency (Addison’s Disease) Polyglandular autoimmune syndromes types I and II Antibodies often directed against adrenal enzymes and 3 cortical zones

Infections

Tuberculosis (7-20%) (most common in developing world) Fungal: histoplasmosis, paracoccidioidomycosis HIV, CMV Syphilis African trypanosomiasis

Infiltrative

Metastatic cancer (lung>stomach>esophagus>colon>breast); lymphoma Sarcoidosis, amyloidosis, hemochromatosis

Vascular

Bilateral adrenal hemorrhage (risk increased by heparin and warfarin) Sepsis (meningococcal, Pseudomonas) Coagulopathy in adults or Waterhouse-Friderichsen syndrome in children Thrombosis, embolism, adrenal infarction

Drugs

Inhibit cortisol: ketoconazole, etomidate, megestrol acetate Increase cortisol metabolism: rifampin, phenytoin, barbiturates

Others

Adrenoleukodystrophy and adrenomyeloneuropathy Congenital adrenal hypoplasia (impaired steroidogenesis) Familial glucocorticoid deficiency or resistance Defective cholesterol metabolism

SECONDARY ADRENOCORTICAL INSUFFICIENCY • inadequate pituitary ACTH secretion • multiple etiologies (see Hypopituitarism, E23), including withdrawal of exogenous steroids Clinical Features Table 25. Clinical Features of Primary and Secondary Adrenal Insuciency (AI) Primary AI (Addison’s or Acute AI)

Secondary AI

Skin and Mucosa

Dark (palmar crease, extensor surface)

Pale

Potassium

High

Normal

Sodium

Normal or low

Normal or Low

Metabolic Acidosis

Present

Absent

Associated Diseases

Primary hypothyroidism, T1DM, vitiligo

Central hypogonadism or hypothyroidism, growth hormone deficiency, DI

Associated Symptoms

Weakness, fatigue, weight loss, hypotension, salt craving, postural dizziness, myalgia, arthralgia GI: N/V, abdominal pain, diarrhea

Weakness, fatigue, weight loss, hypotension, postural dizziness, myalgia, arthralgia, headaches, visual abnormalities

Diagnostic Test

Cosyntropin Stimulation Test High morning plasma ACTH High renin

Insulin tolerance test Cosyntropin Stimulation Test Low or inappropriately normal morning plasma ACTH

Adapted from: Salvatori R. JAMA 2005;294:2481-2488

Treatment • acute adrenal crisis – can be life-threatening ■ IV NS 1 L within the rst hour followed by continuous IV NS guided by patient requirements; add D5W if hypoglycemic ■ hydrocortisone 100 mg IV stat followed by 50 mg IV q6 h ■ identify and correct precipitating factors • maintenance ■ hydrocortisone 15-25 mg PO or cortisone acetate 20-35 mg PO total daily dose in 2-3 divided doses, highest dose in the morning ■ prednisolone 3-5 mg once daily or 3-5 mg BID can be used as an alternative to hydrocortisone, especially in patients with reduced compliance ■ Florinef™ (udrocortisone, synthetic mineralocorticoid) 0.05-0.2 mg PO once daily if mineralocorticoid decient ■ stress dosing ◆ increase dose of steroids 2-3 fold for a few days during moderate-severe illness (e.g. with vomiting, fever) ◆ major stress (e.g. surgery, trauma) requires 150-300 mg hydrocortisone IV daily divided into 3 doses ■ medical alert bracelet and instructions for emergency hydrocortisone/dexamethasone IM/SC injection

Adrenal Medulla E40 Endocrinology

Toronto Notes 2023

Adrenal Medulla Catecholamine Metabolism • catecholamines are synthesized from tyrosine in postganglionic sympathetic nerves (norepinephrine) and chroman cells of adrenal medulla (epinephrine) • broken down into metanephrines and other metabolites (VMA, HVA) and excreted in urine

Pheochromocytoma/Paraganglioma Definition • paragangliomas are rare neuroendocrine tumours that arise from the extra-adrenal autonomic paraganglia (small organs comprised of neuroendocrine cells that secrete catecholamines) • pheochromocytomas are catecholamine-secreting tumours derived from chroman cells of the adrenal gland Epidemiology • most commonly a single tumour of adrenal medulla • rare cause of HTN (90%) Medullary thyroid cancer (MTC)

Physical signs are variable and often subtle

Adrenal medulla (40-50%) Pheochromocytoma (40-50%)

Neck mass or thyroid nodule; non-tender, anterior lymph nodes HTN, palpitations, headache, sweating

Parathyroid (20-30%) 1° parathyroid hyperplasia

Symptoms of hypercalcemia

Skin Cutaneous lichen amyloidosis

Scaly skin rash

2. Familial MTC (a variant of MEN 2A)

Thyroid MTC (100%)

MTC without other clinical manifestations of MEN 2A or MEN 2B

3. MEN 2B (also known as MEN3)

Thyroid MTC (>90%)

MTC: most common component, more aggressive and earlier onset than MEN 2A

Adrenal medulla Pheochromocytoma (≥50%)

HTN, palpitations, headache, sweating

Neurons Mucosal neuroma, intestinal ganglioneuromas (100%) MSK Marfanoid

Chronic constipation; megacolon Marfanoid habitus (no aortic abnormalities)

Investigations • MEN 1 ■ laboratory ◆ oer genetic testing to all patients with a clinical diagnosis of MEN1 and their rst-degree relatives ◆ gastrinoma: signicantly elevated serum gastrin level with a low gastric pH; when gastrin is 0.25 mmol/L (1.0 mg/dL) above the upper limit of normal • Creatinine clearance 3 mmol/L (12 mg/dL) Increased alertness Anxiety Depression Cognitive dysfunction Organic brain syndromes >4 mmol/L (16 mg/dL) Psychosis (moans)

Hypotonia Hyporeflexia Myopathy Paresis

Constipation Anorexia Nausea Vomiting (groans) PUD Pancreatitis

Weakness Bone pain (bones)

** Hypercalcemic crisis (usually >4 mmol/L or 16 mg/dL): primary symptoms include oliguria/anuria and mental status changes including somnolence and eventually coma → this is a medical emergency and should be treated immediately!

Treatment • 3.5 mmol/L: severe hypercalcemia requiring urgent correction due to risk of dysrhythmia and coma • aggressive treatment of acute symptomatic hypercalcemia • next treat the underlying cause • mild asymptomatic hypercalcemia: monitor and avoid thiazide, volume depletion, high Ca 2+diet, lithium, and bed rest Table 29. Treatment of Acute Hypercalcemia/Hypercalcemic Crisis Increase Urinary Ca 2+Excretion

FLUIDS, FLUIDS, FLUIDS! Isotonic saline (4-6 L) over 24 h ± loop diuretic (e.g. furosemide) but only if hypervolemic (urine output >200 mL/h) Calcitonin: 4 IU/kg IM/SC q12 h 8 IU/kg IM/SC q6 h Only works for 48 h, can develop tachyphylaxis Rapid onset within 4-6 h Before prescribing calcitonin, remember to ask about fish allergies

Diminish Bone Resorption

Bisphosphonates (treatment of choice) Suggest zoledronic acid 4 mg IV over 15 min or pamidronate 60-90 mg IV over 2 h Inhibits osteoclastic bone resorption, preventing calcium release from bone Eects on calcium levels are typically seen at 24-48 h after administration Calcitonin often given in conjunction with bisphosphonate, given rapid onset of eect Indicated in malignancy-related hypercalcemia (IV pamidronate or zoledronic acid used) If bisphosphonates are contraindicated (i.e. severe renal impairment), denosumab can be administered concurrently with calcitonin

Decrease GI Ca 2+ Absorption

Corticosteroids can be used in hypercalcemia mediated by 1,25 vitamin D. Corticosteroids are potent inhibitors of 1a-hydroxylase and therefore, decrease calcitriol production by activated mononuclear cells (e.g. in lymphoma, granuloma) Eects will be seen in 2-5 d

Dialysis

Treatment of last resort Indication: severe malignancy-associated hypercalcemia and renal insuciency or heart failure

Hypocalcemia Definition • total corrected serum Ca 2+65 yr, in men with T2DM with low testosterone concentrations, or in men planning fertility in the near term ■ testosterone therapy only to treat symptoms of hypogonadism, oen results in decreased spermatogenesis (and reduced sperm counts) by further suppression of hypothalamic-pituitarygonadal axis and suppression of endogenous testosterone production • goal: fertility ■ treat underlying cause ■ GnRH agonist if hypothalamic dysfunction with intact pituitary, administered SC in pulsatile fashion using an external pump ■ hCG ± recombinant follicle stimulating hormone (rFSH) in cases of either hypothalamic or pituitary lesions ■ dopamine agonist (e.g. bromocriptine, cabergoline) if prolactinoma ■ testicular sperm extraction (TESE) or microscopic sperm extraction (MICROTESE) – only if testicular tissues are not functioning Other Causes of Male Infertility • hereditary disorders: Kartagener syndrome (primary ciliary dyskinesia), cystic brosis (absence of the vas deferens) • anatomy: hypospadias, retrograde ejaculation • obstruction: vasal occlusion, vasal aplasia, vasectomy, seminal vesicle disease • sexual dysfunction: erectile dysfunction, premature ejaculation, infrequent coitus • surgery: transurethral resection of the prostate (TURP), radical prostatectomy, orchiectomy DEFECTS IN ANDROGEN ACTION Etiology • complete androgen insensitivity (CAIS) • partial androgen insensitivity (PAIS) • 5-α-reductase deciency • mixed gonadal dysgenesis • defects in testosterone synthesis • infertile male syndrome • undervirilized fertile male syndrome Clinical Features • depends on age of onset Table 39. Eects of Testosterone Deficiency First Trimester in utero

Incomplete virilization of external genitalia (ambiguous genitalia) Incomplete development of Wolan ducts to form male internal genitalia (male pseudohermaphrodism)

Third Trimester in utero

Micropenis Cryptorchidism (failure of normal testicular descent)

Prepuberty

Incomplete pubertal maturation (high pitch voice, sparse pubic + axillary hair, absence of facial hair) Eunuchoidal body habitus (greater growth of extremity long bones relative to axial bones) Poor muscle development, reduced peak bone mass

Postpuberty

Decrease in energy, mood, and libido Fine wrinkles in corners of mouth and eyes Decrease in pubic/axillary hair, hematocrit, muscle mass, strength, and BMD

Adapted from: UpToDate, 2010; Cecil’s Essentials of Medicine

Treatment • hormone replacement or supplementation • psychological support • gonadectomy for cryptorchidism (due to increased risk for testicular cancer)

Erectile Dysfunction E54 Endocrinology

Toronto Notes 2023

Erectile Dysfunction • see Urology, U33

Gynecomastia Definition • true gynecomastia refers to benign proliferation of the glandular component of the male breast, resulting in the formation of a concentric, rubbery, rm mass extending from the nipple(s) • pseudogynecomastia or lipomastia refers to enlargement of so adipose tissue, especially seen in obese individuals

Pubertal Gynecomastia • This benign condition peaks between ages 13-14 and spontaneously regresses in 90% of cases within 2 yr • Waiting is often the best approach

Etiology Physiologic • neonatal (maternal hormone) • puberty • elderly Pathologic • physiologic gynecomastia – trimodal distribution in neonatal, pubertal, and older males • drugs – spironolactone, cimetidine, ketoconazole, recombinant human GH, hCG, estrogens, antiandrogens, GnRH agonists, 5-α-reductase inhibitors, androgen deprivation therapy (ADT) • surgical ADT (orchiectomy) for prostate cancer • starvation and refeeding • male hypogonadism • cirrhosis • treatment of HIV infection – due to fat tissue as part of lipodystrophy • herbal products – plant-derived oils such as lavender and tea tree oil • idiopathic • testicular neoplasms • CKD • other rare causes: feminizing adrenal tumours, disorders of sex development, ectopic hCG, familial prepubertal gynecomastia • hyperthyroidism

Causes of Gynecomastia DOC TECH Drugs (especially antiandrogens, i.e. spironolactone) Other Congenital (Klinefelter syndrome) Tumour (especially germ cell tumours) Endocrine (hyperthyroidism) CHronic disease (cirrhosis, CKD)

Drugs Causing Gynecomastia DISCKO Digoxin Isoniazid Spironolactone Cimetidine Ketoconazole Oestrogen/anti-testosterone

Pathophysiology • hormonal imbalance due to: ■ increased estrogen activity ◆ increased production, or increased availability of estrogen precursors for peripheral conversion to estrogen ■ decreased androgen activity ◆ decreased androgen production, binding of androgen to sex hormone binding globulin (SHBG), or androgen receptor blockage History • recent change in breast characteristics • pain • trauma to testicles • mumps • alcohol and/or drug use • FHx • sexual dysfunction Physical Exam • signs of feminization • breast ■ rule out red ags suggesting breast cancer: unilateral, eccentric, hard or xed mass, skin dimpling or retraction, and nipple discharge (especially bloody) or crusting ■ gynecomastia occurs concentrically around nipple, is not xed to underlying tissue • genito-urinary exam • stigmata of liver or thyroid disease Investigations • laboratory: serum TSH, PRL, LH, FSH, testosterone, estradiol, LFTs, creatinine, hCG (if hCG is elevated, need to locate the primary tumour); however not all investigations are required for every case of gynecomastia • CXR and CT of chest/abdomen/pelvis (to locate neoplasm) • testicular U/S (if primary hypogonadism suspected or mass on physical examination) • MRI of hypothalamic-pituitary region if secondary hypogonadism or pituitary adenoma suspected

Occurrence of Gynecomastia 3 Peaks

% Aected

Infancy

60-90

Puberty

4-69

Ages 50-80

24-65

Female Reproductive Endocrinology E55 Endocrinology

Toronto Notes 2023

Measure serum hCG, luteinizing hormone, testosterone, and estradiol

Increased hGC

Increased luteinizing hormone, decreased testosterone

Normal or decreased luteinizing hormone, decreased testosterone

Increased luteinizing hormone, increased testosterone

Normal or decreased luteinizing hormone, increased estradiol

Normal

Testicular U/S

Primary hypogonadism

Measure serum prolactin

Measure thyroxine, TSH

Testicular U/S

Idiopathic gynecomastia

Mass

Testicular germ-cell tumour

Normal

Elevated

Extragonadal germ-cell tumour

hCG- secreting nontrophoblastic neoplasm

Normal

Increased thyroxine, decreased TSH

Normal

Normal

Adrenal CT or MRI Probable prolactinsecreting pituitary tumour

Secondary hypogonadism

Hyperthyroidism

Androgen resistance

Chest x-ray Abdominal CT

Figure 25. Approach to investigating gynecomastia

Treatment • initial observation for most men with gynecomastia (aer stopping oending medications and treating underlying cause) • medical ■ correct the underlying disorder, discontinue responsible drug ■ androgens for hypogonadism ■ anti-estrogens: tamoxifen has most evidence for benet • surgical ■ longstanding (>12 mo, brotic), discomfort, or causing psychological distress

Female Reproductive Endocrinology • see Gynaecology, GY23

Mass

Leydig- or Sertolli-cell tumour

Mass

Normal

Adrenal neoplasm

Increased extraglandular aromatase activity

Paraneoplastic Syndrome E56 Endocrinology

Toronto Notes 2023

Paraneoplastic Syndrome • clinical syndromes involving non-metastatic systemic eects that accompany malignant disease • triggered by antibodies against neoplasm cross-reacting with normal tissue or by production of a physiologically active substance by the neoplasm • commonly present with cancers of lung, breast, ovaries, or lymphatic system Table 40. Clinical Features Syndrome Class

Symptoms/Syndrome

Associated Malignancies

Mechanism

Endocrine

Cushing’s syndrome

Small-cell lung cancer Pancreatic carcinoma Neural tumours Thymoma

Ectopic ACTH and ACTH-mimicking substance secretion

Syndrome of inappropriate ADH secretion (SIADH)

Small-cell lung cancer CNS malignancies

Antidiuretic hormone secretion

Hypercalcemia

Lung cancer Breast carcinoma Renal cell carcinoma Multiple myeloma Ovarian carcinoma

PTH-related protein, transforming growth factor alpha (TGF-α), tumour necrosis factor (TNF) secretion

Hypoglycemia

Hepatocellular carcinoma Fibrosarcoma insulinoma

Insulin or insulin-like substance secretion

Carcinoid

Gastrointestinal neuroendocrine tumours

Serotonin, bradykinin secretion

Lambert-Eaton myasthenic syndrome (LEMS) Muscle weakness in limbs

Small-cell lung cancer

Ab interferes with acetylcholine (ACh) release

Myasthenia gravis Fluctuating muscle weakness and fatigability

Thymoma

Ab interferes with ACh release

Paraneoplastic limbic encephalitis Depression, seizures, short-term memory loss

Small-cell lung cancer

Unknown

Hypokalemic nephropathy

Small-cell lung cancer

Ectopic ACTH and ACTH-like substance secretion

Nephrotic syndrome

Lymphoma Melanomas

Immunocomplex sedimentation in nephrons

GI

Watery diarrhea

MTC VIPoma

Calcitonin, prostaglandin secretion VIP secretion

Hematologic

Erythrocytosis

Renal cell carcinoma Hepatocellular carcinoma

Erythropoietin (EPO) production

Rheumatologic

SLE

Lymphomas Lung cancer Breast carcinoma Gonadal carcinoma

Anti-nuclear Ab production

Scleroderma

Breast carcinoma Lung cancer Uterine cancer

Anti-nuclear Ab production

Neurologic

Renal

Investigations • CBC, electrolytes, creatinine, LFTs, ALP, erythrocyte sedimentation rate (ESR), CRP, serum/urine electrophoresis • serum autoantibodies, lumbar puncture • imaging: skeletal survey, CT, MRI, positron emission tomography (PET) scan • ± endoscopy Treatment • treat underlying tumour: surgery, radiation, chemotherapy • treat immune-mediated disorder: intravenous immunoglobulin (IVIG), steroids, immunosuppressive drugs, plasmapheresis (reserved for patients with identiable antibodies in serum)

Common Medications E57 Endocrinology

Toronto Notes 2023

Common Medications Diabetes Medications Drug Class

Mechanism of Action

Generic Drug Name

Canada Name

Biguanide

Sensitizes peripheral tissues to insulin → increases glucose uptake Decreases hepatic glucose production by simulation of hepatic AMPactivated protein kinase (AMPK)

metformin

Glucophage® Glumetza®

Insulin Secretagogue

Stimulates insulin release from β cells by causing K + channel closure → depolarization → Ca 2+mediated insulin release Use in nonobese T2DM

sulfonylureas: glyburide

gliclazide glimepiride

Diabeta® Euglucon®

US Name (if dierent)

Micronase® Glynase PreTab®

Diamicron® Diamicron® MR

Dosing

Indications

Contraindications

Side Eects

Comments

500 mg once daily titrated to 2000 mg/d maximum (split BID unless extended release)

T2DM Improves both fasting and postprandial hyperglycemia Also → TG

ABSOLUTE: Moderate to severe liver dysfunction Moderate renal dysfunction GFR 5 mg BID Max: 20 mg/d

T2DM, taken with meals

40-160 mg BID 30-120 mg once daily

Amaryl®

1-8 mg once daily

Meglitinides

Stimulates insulin release from β cells by causing K + channel closure → depolarization → Ca 2+mediated insulin release

Insulin Sensitizers Sensitizes (thiazolidinedione) peripheral tissues to insulin → increases glucose uptake Decreases FFA release from adipose Binds to nuclear receptor peroxisome proliferatoractivated receptor gamma (PPAR-γ) α-Glucosidase Inhibitor

↓ carbohydrate GI absorption by inhibiting brush border α-glucosidase

Inhibits Dipeptidyl Peptidase-IV (DPP- degradation of IV) Inhibitor endogenous antihyperglycemic incretin hormones Incretin hormones stimulate insulin secretion, inhibit glucagon release, and delay gastric emptying

↓ A1c 0.8% Gliclazide lowest incidence of hypoglycemia

Hypoglycemia (less than sulfonylurea) Weight gain

60-120 mg TID

ABSOLUTE: Severe liver dysfunction Short t1/2 of 1 INTERACTIONS: h causes brief Do not combine with but rapid ↑ in insulin, therefore a sulfonylurea or preprandial insulin eective for postprandial control

↓ A1c 0.7% for repaglinide and 0.5-1.0% for nateglinide Costly Must be dosed with meals

Avandia®

2-8 mg once daily

T2DM – not as initial therapy

15-45 mg once daily

Peripheral edema CHF Anemia Fluid retention and CHF Increased risk of cardiac events with rosiglitazone (requires written informed consent when prescribing) Increased risk of bladder cancer with pioglitazone Fractures Mild increase in LDL

↓ A1c 0.8% Delayed maximum ecacy (6-12 wk)

Actos®

ABSOLUTE: New York Heart Association (NYHA) > class II CHF, bladder cancer INTERACTIONS: Do not combine with insulin

ABSOLUTE: Inflammatory bowel disease Severe liver dysfunction

Flatulence Abdominal cramps Diarrhea

↓ A1c 0.6% Not recommended as initial therapy in patients with HbA1c >8.5%

ABSOLUTE (sitagliptin): T1DM DKA

Nasopharyngitis Upper respiratory tract infection (URTI) Headache Pancreatitis Stevens Johnson syndrome Bullous pemphigoid

↓ A1c 0.7% Weight neutral Expensive Negligible risk of hypoglycemia as monotherapy

nonsulfonylureas: repaglinide

GlucoNorm®

nateglinide

Starlix®

rosiglitazone pioglitazone

Prandin®

Glucobay®

sitagliptin

Januvia®

100 mg once daily

saxagliptin

Onglyza™

2.5-5 mg once daily

Trajenta®

Precose®

0.5-4 mg TID

acarbose

linagliptin

Hypoglycemia ABSOLUTE: Weight gain Moderate to severe liver dysfunction RELATIVE (glyburide and glimepiride): Adjust dose in mild to moderate kidney dysfunction and avoid in severe kidney dysfunction Avoid glyburide in the elderly INTERACTIONS: Do not combine with a non-sulfonylurea insulin secretagogue or preprandial insulin

25 mg once daily titrated to 100 mg TID

5 mg once daily

↓ postprandial hyperglycemia

RELATIVE (sitagliptin and saxagliptin): Use with dose reduction in kidney dysfunction

NOTE: This class of medication is rarely used anymore due to side eects and concerns about potential increased cardiovascular (CV) mortality

E58 Endocrinology

Toronto Notes 2023

Diabetes Medications Drug Class

Mechanism of Action

Generic Drug Name

Canada Name

Glucagon-Like Peptide (GLP)-1 Analogue

Binds to GLP-1 receptor to promote insulin release Insulinotropic eect suppressed as plasma glucose 3.5 mmol/L

colestipol

Colestid®

5-30 g/d

Constipation, nausea Flatulence Bloating Rise in TG Binds other medications

Inhibits cholesterol absorption at the small intestine brush border

ezetimibe

Ezetrol®

Used for ↑ LDL

Hypersensitivity Hepatic dysfunction (when used with statin) Do not combine with fibrates or bile acid resins

Fatigue Pharyngitis Sinusitis Abdominal pain Diarrhea Arthralgia

Cholesterol Absorption Inhibitors

Zetia®

10 mg/d

Thyroid Medications E59 Endocrinology

Toronto Notes 2023

Dyslipidemia Medications Drug Class

Mechanism of Action

Generic Drug Name

Canada Name

Anti-PCSK9

Inhibits degradation of the LDL receptor by PCSK9 enzyme LDL clearance

evolocumab

Repatha®

alirocumab

Praluent®

US Name (if dierent)

Dosing

Indications

Contraindications

Side Eects

140 mg q2 wk or 420 mg once monthly 75 mg q2 wk or 300 mg once monthly

Add-on to maximally tolerated statin therapy in heterozygous familial hypercholesterolemia (FH) (evolocumab, alirocumab) and homozygous FH (evolocumab) Consider in patients with atherosclerotic CVD and LDL-C not at target despite maximally tolerated statin ± ezetimibe

Hypersensitivity No studies regarding use in severe hepatic or renal impairment

Nasopharyngitis, URTI, influenza Sinusitis Back pain Myalgia Arthralgia Nausea

Indications

Thyroid Medications Drug Class

Mechanism of Action

Generic Drug Canada Name US Name (if Dosing Name dierent)

Antithyroid Agent (thionamides)

Decreases thyroid hormone production by inhibiting iodine and peroxidase from interacting with thyroglobulin to form T and T PTU also interferes with conversion of T to T

propylthiouracil (PTU)

Propyl-Thyracil®

Start 100 mg Hyperthyroidism, Hypersensitivity PO TID, thyroid storm PTU recommended in 1st then adjust trimester, MMI during 2nd accordingly and 3rd trimester Thyroid storm: Lactation: safe with PTU start 135/85 mmHg NO White Coat Hypertension

Figure 12. Diagnostic algorithm for hypertension in adults

YES

FM39 Family Medicine

Toronto Notes 2023

Treatment • hypertension means high pressure/strain. Without increasing a patient’s potential distress, consider what may be causing their high pressure or strain. It may be important to support a patient in reducing sources of stress and worry • treat to target BP: 2.0 mg/mmol renal disease, CVD or additional CV risk factors)

ACEI or ARB

Addition of a dihydropyridine CCB is A loop diuretic could be preferred over a thiazide/ thiazide- considered in hypertensive like diuretic chronic kidney disease patients with extracellular fluid volume overload

DM without Albuminuria (criteria ACEI, ARB, DHP CCB, or thiazide/ listed above) thiazide-like diuretics

Combination of first-line drugs If combination with ACEI is being considered, a dihydropyridine CCB is preferable to a thiazide/thiazide like diuretic

Normal urine microalbumin to creatinine ratio 500 mg/24 h or Diuretics as additive therapy ACR >30 mg/mmol)

Combinations of additional agents

Patients on an ACEI or ARB should have careful monitoring of renal function and potassium. ACEI and ARB combinations are not recommended in patients without proteinuria

Does not aect initial treatment Combinations of additional agents recommendations Atherosclerotic renal artery stenosis should be primarily managed medically, while revascularization should be considered for renal fibromuscular dysplasia

Caution in using ACEI or ARB if bilateral renal artery stenosis or unilateral disease with solitary kidney Renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled HTN

Renovascular Disease

2020 Hypertension Highlights, Hypertension Canada. https://hypertension.ca/wp-content/uploads/2018/07/Hypertension-Guidelines-English2018-Web.pdf

Table 21. Common Antihypertensive Medications in Pregnancy and Lactation Pregnancy

Lactation

First line oral drugs

Second line oral drugs

Medications to avoid

Oral drugs

Labetalol Methyldopa Long-acting oral nifedipine Other β-blockers (acebutolol, metoprolol, pindolol, and propranolol)

Clonidine Hydralazine Thiazide diuretics

ACEIs* ARBs*

Labetalol Methyldopa Long-acting oral nifedipine Enalapril Captopril

* Fetotoxicity of renal system

Follow-Up • assess and encourage adherence to pharmacological and non-pharmacological therapy at every visit • lifestyle modication q3-6 mo • pharmacological ■ follow-up q1-2 mo until BP under target for 2 consecutive visits, q3-6 mo once at target BP ■ follow-up frequently for patients with symptomatic/severe HTN, antihypertensive drug intolerance, target organ damage • referral is indicated for cases of refractory HTN, suspected secondary causes, or worsening renal failure • hospitalization is indicated for malignant HTN

Systematic Review for 2017 ACC/AHA Guidelines for Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults Hypertension 2018;71:e116-135 Purpose: Determine evidence for self-measured BP without other augmentation for clinical outcomes and BP control. Determine optimal target for BP lowering during antihypertensive therapy in adults. Determine benefits and harms of dierent classes of antihypertensive drugs. Methods: Systematic review and meta-analysis using PubMed and EMBASE. Results: There is a modest but significant improvement in sBP in RCTs of self-measured BP vs. usual care at 6 but not 12 mo; may be a helpful adjunct to routine oce care. sBP lowering to a target of 30 min) Soft tissue swelling, erythema

Physical Exam • vitals • specic joint exams to aected areas • systemic features (skin, nails, eyes, hands) Investigations (Guided by the History and Physical Exam) • general: CBC and dierential, electrolytes, creatinine • acute phase reactants: ESR, CRP • complement (C3, C4) • urinalysis to detect disease complications (proteinuria, active sediment) • serology (tailored to clinical suspicion, see Rheumatology, RH4) ■ antinuclear antibody (ANA), negative ANA helps to exclude SLE, positive ANA in subset of RA ■ anti-double stranded DNA (anti-dsDNA), perform anti-dsDNA and anti-smith (anti-Sm) for SLE if positive ANA ■ human leukocyte antigen B27 (HLA-B27), more consistent with reactive arthritis than RA ■ anti-histidyl tRNA synthetase autoantibodies (anti-Jo1), positive in dermatomyositis and polymyositis ■ anti-Sm ■ anti-La antibodies (anti-La), positive in Sjögren’s disease ■ anti-Sjögren’s-syndrome-related antigen A (anti-SSA/Ro), positive in Sjögren’s disease ■ rheumatoid factor (RhF), positive in RA and other conditions including Sjögren’s disease ■ anti-cyclic citrullinated peptide (anti-CCP), positive in RA • synovial uid analysis (cell count and dierential, culture, Gram stain, microscopy) • radiology (plain lm, CT, MRI, U/S, bone densitometry, bone scan) Treatment • tailor therapy depending on the specic cause; consider referral to rheumatologist • non-pharmacological: patient education, lifestyle modication, assisted devices, physiotherapy, occupational therapy • pharmacological: analgesia (acetaminophen, NSAIDs), anti-inammatory (disease-modifying antirheumatic drugs (DMARDs), steroids, antibiotics ■ if osteoarthritis, consider steroid injections, hyaluronic acid injections

Low Back Pain • see Orthopaedic Surgery, OR28 • Clinically Organized Relevant Exam (CORE) Back Tool: https://cep.health/clinical-products/low-backpain/ Definition • acute: 12 wk Epidemiology • 5th most common reason for visiting a physician • lifetime prevalence: 90%, peak prevalence: ages 45-60 • largest WSIB category and most common cause of chronic disability for individuals 2 cm or historical loss >6 cm) and weight (weight loss >10% since age 25) ■ rib-to-pelvis distance ≤2 ngers’ breadth

How Much Calcium Do We Need? Age

Amount/day

4-8

1000 mg

9-18

1300 mg

19-50

1000 mg

>50

1200 mg

Calcium Content of Common Foods 1 cup milk = 300 mg ¾ cup yogurt = 332 mg ½ can salmon with bones = 240 mg ½ cup cooked broccoli = 33 mg 1 medium orange = 50 mg

Vitamin D Content in Food • Milk fortified with vitamin D3 contains 100 IU per 250 mL glass • Foods such as margarine, eggs, chicken livers, salmon, sardines, herring, mackerel, swordfish, and fish oils (halibut and cod liver oils) all contain small amounts; supplementation is necessary to obtain adequate levels as dietary intake has minimal impact • Most multivitamins provide 400 IU of vitamin D3 • Recommended daily intake of vitamin D: • adults 19-50 years old, including women who are pregnant or breastfeeding: 400-1000 IU daily • individuals over 50 years, or younger people who have risk factors (osteoporosis, multiple fractures, or conditions aecting the absorption of vitamin D): 8002000 IU daily

Rash FM46 Family Medicine

Toronto Notes 2023

■ occiput-to-wall distance >5 cm ■ assess fall risk by ability to get up from chair without support with arms, and walking several steps and return Investigations • CBC, Cr, corrected Ca 2+, ALP, TSH, 25-hydroxyvitamin D (aer 3-4 mo of adequate supplementation), and serum protein electrophoresis if there are vertebral fractures Indications for Bone Mineral Density Testing and Management • see Endocrinology, E47

Rash • see Dermatology, D16

When an STI is detected in a child, evaluation for sexual abuse is mandatory

Sexually Transmitted Infections • see Gynaecology, GY28 Definition • diverse group of infections caused by multiple microbial pathogens • transmitted by either secretions or uids from mucosal surfaces Epidemiology • high incidence rates worldwide • Canadian prevalence in clinical practice ■ common: chlamydia (most common), gonorrhea (2nd most common), HPV, genital herpes ■ less common: hepatitis B, HIV, syphilis, trichomoniasis ■ rare: chancroid, granuloma inguinale, lymphogranuloma venereum • non-sexually transmitted genital tract infections: vulvovaginal candidiasis (VVC), bacterial vaginosis (BV) • three most common infections associated with vaginal discharge in adult women are BV, VVC, and trichomoniasis History • sexual history ■ age of rst intercourse, gender of sexual partners (past and present), sexual activity (oral, anal, vaginal intercourse, use of sex toys), contraception use, sexual activity during travel ■ total number of partners in the past year/month/week and duration of involvement with each • STI history ■ STI awareness, previous STIs and testing (including Pap tests), partner communication/history regarding STIs ■ local symptoms such as burning, itching, discharge, sores, vesicles, testicular pain, dysuria, abdominal pain ■ systemic symptoms such as fever, lymphadenopathy, arthralgia Investigations/Screening • individuals at increased risk should be screened for hepatitis B, HIV, and syphilis • Pap test q3 yr for anyone with a cervix aged 25 to 69 who has ever been sexually active • annual screening for all sexually active people under 30 for gonorrhea and chlamydia Management • primary prevention is vastly more eective than treating STIs and their sequelae • oer hepatitis B vaccine if not immune • oer Gardasil® to females and males aged 9-14 yr • discuss STI risk factors (e.g. decreasing the number of sexual partners) • direct advice to ALWAYS use barrier contraception or to abstain from intercourse • condoms are not 100% eective against HPV or HSV • a person with an STI is not considered treated until the management of his/her partner(s) is ensured (contact tracing by Public Health) • patients diagnosed with bacterial STI or trichomonas infection should abstain from sexual activity until treatment completion and for 7 d aer treatment for both partners, or until test of cure completed • mandatory reporting: chlamydia, gonorrhea, hepatitis B, HIV, syphilis, chancroid

STI Risk Factors • Sexually active males and females 2 sexual partners in the past 12 mo • Street involved, homeless, and/or substance misuse

Sexual History 5 P’s Partners (numbers, gender) Practices (vaginal, oral, anal insertive/ receptive) Protection Past history of STIs Pregnancy prevention

Ecacy of Human Papillomavirus Vaccines – A Systematic Quantitative Review Int J Gynecol Cancer 2009;19:1166-1176 Purpose: To evaluate two vaccines for human papillomavirus (HPV) in terms of ecacy, safety and immunogenicity. Methods: Systematic review of RCTs involving women between the ages of 9 and 26 yr, randomly assigned to receive vaccination with HPV L1 virus-like particle in either quadrivalent (HPV 6, 11, 16, 18), bivalent (HPV 16, 18), or univalent (HPV 16) form or placebo. Main outcomes were prevention of cytologically and/ or histologically proven lesions (including LSIL, HSIL, VIN, VAIN, AIN, adenocarcinoma in situ of the cervix, or cancer of the cervix associated with HPV infection). Results: Six studies involving 47236 women were included. Bivalent and quadrivalent vaccines reduced the rate of lesions in the cervix, vulva, vagina, and anogenital region with ecacy of 93% (95% CI 87-96%) and 62% (95% CI 27-70), respectively. More symptoms were found in the bivalent vaccine group (35%, 5-73%) compared to control groups. Conclusion: Prophylactic vaccination can prevent HPV infection in women ages 9-26 not previously infected with HPV subtypes covered by the vaccines.

Sinusitis FM47 Family Medicine

Toronto Notes 2023

Table 23. Diagnosis and Treatment of Common STIs Gonococcal Urethritis/ Cervicitis (Neisseria gonorrhoeae)

Signs and Symptoms

Investigations

Treatment

Complications

M: urethral discharge, unexplained pyuria, dysuria, irritation, testicular swelling, symptoms of epididymitis

M: first-void urine NAAT, urethral swab for Gram stain and culture

Ceftriaxone 250 mg IM single dose* Test of cure: cultures 3-7 d posttreatment for pharyngeal infections, ongoing signs or symptoms, treatment failure, or pregnancy Repeat screening in all patients 6 mo post-treatment

M: urethral strictures, epididymitis, infertility

F: mucopurulent endocervical discharge, vaginal bleeding, dysuria, pelvic pain, dyspareunia

F: vaginal swab or urine NAAT, endocervical swab for Gram stain and culture, vaginal swab for wet mount (to rule out trichomonas)

F: PID, infertility, ectopic pregnancy, perinatal infection, chronic pelvic pain M and F: arthritis, increased risk of acquiring and transmitting HIV

M and F: often asymptomatic, can involve M and F: urine NAAT, rectal/pharyngeal rectal symptoms in cases of unprotected swabs if indicated anal sex Non-Gonococcal Urethritis/Cervicitis (Usually Chlamydia trachomatis**)

~70% asymptomatic If symptoms appear (usually 2-6 wk after infection) then similar to gonococcal symptoms (see above)

Same as above

Azithromycin 1 g PO single dose + gonococcal urethritis/cervicitis prescription* Same follow-up as above

Same as above

Human Papillomavirus (genital warts, cervical dysplasia)

Most are asymptomatic M: cauliflower lesions (condylomata acuminata) on skin/mucosa of penile or anal area

None needed if simple condylomata Potential biopsy of suspicious lesions

For condylomata: cryotherapy, electrocautery, laser excision, topical therapy (patient-applied or oce-based) For cervical dysplasia: colposcopy and possible excision, dependent on grade of lesion

M and F: anal cancer MSM and F who have receptive anal sex: rectal cancer

1° episode: painful vesiculoulcerative Swab of vesicular content for culture genital lesions ± fever, tender or NAAT lymphadenopathy, protracted course Recurrent episodes: less extensive lesions, shorter course may have “trigger factors”

1° Episode Acyclovir 200 mg PO 5x/d x 5-10 d or Famciclovir 250 mg PO TID x5 d or Valacyclovir 1000 mg PO BID x 10 d

Genital pain, urethritis, cervicitis, aseptic meningitis, increased risk of acquiring and transmitting HIV

1°: chancre (painless sore), regional lymphadenopathy 2°: rash and flu-like symptoms, meningitis, headache, uveitis, retinitis, condyloma lata, mucous lesions, alopecia Latent Phase: asymptomatic 3°: neurologic, cardiovascular, and tissue complications

Benzathine penicillin G 2.4 million units Chronic neurologic and cardiovascular IM single dose sequelae, increased risk of acquiring Notify partners (last 3-12 mo) and transmitting HIV Continuous follow-up and testing until patients are seronegative

F: cauliflower lesions and/or pre-neoplastic/neoplastic lesions on cervix/vagina/vulva Genital Herpes (HSV-1 and -2)

Infectious Syphilis (Treponema pallidum)

F: screening for cervical dysplasia through regular Pap smears

Specimen collection from 1° and 2° lesions, screen high-risk individuals with serologic syphilis testing (VDRL), universal screening of pregnant women

F: cervical/vaginal/vulvar cancer

Recurrent Episode Acyclovir 200 mg PO 5x/d x5 d or 800 mg PO TID x2 d or Famciclovir 125 mg PO BID x5 d or Valacyclovir 500 mg PO BID x3 d or 1000 mg PO once daily x3 d

F = females; M = males *N.B. if urethritis/cervicitis is suspected, always treat for both gonococcal and non-gonococcal types (i.e. ceftriaxone AND azithromycin) **Most common reportable STI in Canada

Sinusitis • see Otolaryngology, OT25 Definition • acute or chronic inammation of the sinuses, oen also involving the nasal cavities Etiology • viral etiology is more common • viral: rhinovirus, inuenza, parainuenza • bacterial: S. pneumoniae, H. inuenzae, M. catarrhalis Clinical Presentation • oen presents with PODS symptoms (see Figure 16, FM48) Management of Acute Sinusitis • for symptom relief: oral analgesics (acetaminophen, NSAIDs), nasal saline rinse, short-term use of topical or oral decongestants • antihistamines are ineective • mild to moderate acute bacterial sinusitis: intranasal corticosteroids • severe acute bacterial sinusitis: antibiotics and intranasal corticosteroids ■ rst-line antibiotic is amoxicillin, and second line may include amoxicillin-clavulanic acid or a uoroquinolone ■ ENT referral if: anatomic defect (e.g. deviated septum, polyp, adenoid hypertrophy), failure of second-line therapy, or ≥4 episodes/yr, refer urgently for the red ags listed in the side box

Red Flags for Urgent Referral • Altered mental status • Headache • Systemic toxicity • Swelling of the orbit or change in visual acuity or extraocular muscles • Hard neurological findings • Signs of meningeal irritation • Suspected intracranial complications (meningitis, intracranial abscess, cavernous sinus thrombosis) • Involvement of associated structures (periorbital cellulitis, Pott’s puy tumour)

Sleep Disorders FM48 Family Medicine

Toronto Notes 2023

Symptoms of Sinusitis Recurrent/ABRS

>7 d

7 d

Continue course

Use second-line agent or change antibiotic class Clinical response in 72 h? Yes

No

For symptoms lasting more than 4 wk, consider chronic rhinosinusitis (CRS) Persistent severe symptoms require prompt urgent referral

Figure 16. Diagnosis and management of sinusitis ABRS = acute bacterial rhinosinusitis. Adapted from: Desrosiers M, et al. Allergy Asthma Clin Immunol 2011;7:doi:10.1186/1710-1492-7-2

Sleep Disorders • see Respirology, R29 and Neurology, N48 Definition and Clinical Presentation • most oen characterized by one of three complaints: insomnia, parasomnias, excessive daytime sleepiness • insomnia: diculty falling asleep, diculty maintaining sleep, early morning wakening, nonrefreshing sleep • parasomnias: night terrors, nightmares, restless leg syndrome, somnambulism (performing complex behaviour during sleep with eyes open but without memory of event) • excessive daytime sleepiness: abnormal fatigue or tiredness extending into waking hours Epidemiology • 1/3 of patients in primary care setting have occasional sleep problems, 10% have chronic sleep problems

FM49 Family Medicine

Toronto Notes 2023

Etiology • primary sleep disorders ■ primary insomnia, narcolepsy, OSA, restless leg syndrome, periodic limb movements of sleep • secondary causes ■ medical: COPD, asthma, CHF, hyperthyroidism, chronic pain, BPH, menopause, GERD, PUD, pregnancy, neurological disorders ■ drugs: alcohol, caeine, nicotine, nicotine replacement therapy, β-agonists, antidepressants, steroids, decongestants, amphetamine, cocaine, modanil, acetylcholinesterase inhibitors, dopamine agonists, and others ■ psychiatric: mood and anxiety disorders ■ lifestyle factors: shi work, jet lag Investigations • complete sleep diary every morning for 1-2 wk, see https://app.consensussleepdiary.com/#/ ■ record bedtime, sleep latency, total sleep time, awakenings, quality of sleep • rule out specic medical problems (e.g. CBC and dierential, TSH) • refer for sleep study, nocturnal polysomnogram, or daytime multiple sleep latency test if suspicion of sleep apnea or periodic leg movements of sleep Management of Specific Problems • primary insomnia ■ person reacts to insomnia with fear or anxiety around bedtime or with a change in sleep hygiene, which can progress to a chronic disorder (psychophysiological insomnia) ■ consider asking the patient if they have questions or fears about sleep that you might be able to address ■ treat any suspected medical or psychiatric cause ■ exercise regularly, avoid heavy exercise within 3 h of bedtime ■ rst-line treatment (CBT) ◆ sleep hygiene: avoid alcohol, caeine, nicotine; comfortable sleep environment; regular sleep schedule; no napping ◆ relaxation therapy: deep breathing, meditation, biofeedback ◆ stimulus control therapy: re-association of bed/bedroom with sleep, re-establishment of a consistent sleep-wake schedule, reduce activities that cue staying awake ◆ sleep restriction therapy: total time in bed should closely match the total sleep time of the patient ◆ address inappropriate beliefs and attitudes that perpetuate dysfunctional sleep ■ pharmacologic treatment (used to supplement CBT; short-term prescription of 15 apneic/hypopneic episodes/h of sleep ■ consequences ◆ daytime somnolence, non-restorative sleep ◆ poor social and work performance ◆ mood changes: anxiety, irritability, depression ◆ sexual dysfunction: poor libido, impotence ◆ morning headache (due to hypercapnia) ◆ HTN (2x increased risk), CAD (3x increased risk), stroke (4x increased risk), arrhythmias ◆ OSA is an independent risk factor for CAD

Risk Factors for Obstructive Sleep Apnea • 2% of women, 4% of men between ages 30-60 • Obesity (due to upper airway narrowing). BMI >28 kg/m2present in 60-90% of cases • Children (commonly due to large tonsils and adenoids) • Aging (due to decreased muscle tone) • Persistent URTIs, allergies, nasal tumours, hypothyroidism (due to macroglossia), neuromuscular disease • Family history

Sore Throat (Pharyngitis) FM50 Family Medicine

Toronto Notes 2023

◆ pulmonary HTN, right ventricular dysfunction, cor pulmonale (due to chronic hypoxemia) ◆ memory loss, decreased concentration, confusion ■ investigations ◆ evaluate BP, inspect nose, and oropharynx (enlarged adenoids or tonsils) ◆ blood gas not helpful, TSH if clinically indicated ◆ nocturnal polysomnography ■ treatment ◆ modiable factors: avoid sleeping supine; weight loss; avoid alcohol, sedatives, opioids; inhaled steroids if nasal swelling present; dental appliances to modify mandibular position ◆ primary treatment of OSA is CPAP: maintains patent airway in 95% of OSA cases ◆ surgery: somnoplasty, uvulopalatopharyngoplasty (UPPP), tonsillectomy, and adenoidectomy (in children) ◆ report patient to Ministry of Transportation if OSA is not controlled by CPAP

Sore Throat (Pharyngitis) Definition • inammation of the oropharynx • may be caused by a wide range of infectious organisms, most of which produce a self-limited infection with no signicant sequelae Etiology • viral: adenovirus, rhinovirus, inuenza virus, RSV, Epstein-Barr virus (EBV), coxsackie virus, herpes simplex virus, cytomegalovirus (CMV), HIV • bacterial: β-hemolytic Streptococcus, Neisseria gonorrhoeae, Chlamydia pneumoniae, Mycoplasma pneumoniae, Corynebacterium diphtheriae, Fusobacterium necrophorum Epidemiology • viral ■ most common cause (90% in adults is viral), occurs year round • bacterial ■ Group A β-hemolytic Streptococcus (GABHS) ◆ most common bacterial cause ◆ occurs most oen in winter months ◆ 5-15% of adult cases and up to 50% of all paediatric cases of acute pharyngitis ◆ most prevalent between 5-17 y/o Clinical Presentation • viral ■ pharyngitis, conjunctivitis, rhinorrhea, hoarseness, cough ■ nonspecic u-like symptoms such as fever, malaise, and myalgia ■ oen mimics bacterial infection ■ common viral infections ◆ EBV (infectious mononucleosis) – pharyngitis, tonsillar exudate, fever, lymphadenopathy, fatigue, rash ◆ coxsackie virus (hand, foot, and mouth disease) – primarily late summer, early fall – sudden onset of fever, pharyngitis, headache, abdominal pain, and vomiting – appearance of small vesicles that rupture and ulcerate on so palate, tonsils, pharynx – ulcers are pale grey and several mm in diameter, have surrounding erythema, and may appear on hands and feet ◆ herpes simplex virus – like coxsackie virus, but ulcers are fewer and larger – pharyngitis, tonsillar exudate, fever, lymphadenopathy, fatigue, rash • bacterial ■ symptoms: pharyngitis, fever, malaise, headache, abdominal pain, absence of cough ■ signs: fever, tonsillar or pharyngeal erythema/exudate, swollen/tender anterior cervical nodes, halitosis ■ complications: ◆ suppurative: abscess, sinusitis, otitis media, cervical adenitis, pneumonia ◆ non-suppurative: acute rheumatic fever, acute glomerulonephritis

Red Flags in Patients with “Sore Throat” • Persistence of symptoms longer than 1 wk without improvement • Respiratory diculty (particularly stridor, croup, etc.) • Diculty in handling secretions (peritonsillar abscess) • Diculty in swallowing (Ludwig’s angina) • Severe pain in the absence of erythema (supraglottitis/epiglottitis) • Palpable mass (neoplasm) • Blood in the pharynx or ear (trauma)

FM51 Family Medicine

Toronto Notes 2023

Table 24. Modified Centor Score: Approach to Diagnosis and Management of GABHS CRITERIA

POINTS

Cough absent?

1

History of fever >38ºC?

1

Tonsillar exudate?

1

Swollen, tender anterior nodes?

1

Ages 5-14

1

Ages 15-44

0

Ages >45

–1

In communities with moderate levels of strep infection (10-20% of sore throats): SCORE

0-2

3 or more

Risk of GABHS

1-17%

28-53%

Suggested action

No further testing or antibiotics

Perform rapid antigen detection test (RADT) and treat with antibiotics if positive. For negative RADT and patient 24 mo, treat with antibiotics if worsens after 24-48 h 10 d course if ages 1 week) or chronic change, and can detect lucencies surrounding infected orthopedic hardware ■ MRI is more sensitive, with loss of normal fatty T1 marrow signal diagnostic of esteomyelitis, and can also assess for extra-osseous so tissue involvement or spread • nuclear medicine ( 99 mTc, followed by 111In-labeled white cell scan or gallium radioisotope scan) may be used where available, or in the setting of hardware Septic Arthritis • surgical emergency in large joints (i.e. hip) • x-ray usually normal early • aspiration required if concern for septic arthritis • imaging modalities can detect joint uid in some points, but imaging cannot rule out septic arthritis Necrotizing Fasciitis • surgical emergency • X-ray can detect gas, but absence does not rule out necrotizing fasciitis • in the perineum, referred to as Fournier’s gangrene • surgical referral required

Metabolic Bone Disease Osteoporosis • reduction in amount of normal bone mass; fewer and thinner trabeculae; diuse process aecting all bones ■ typical sites of fragility fracture: spine, hip, pelvis, wrist, humerus, rib • DEXA: gold standard for measuring bone mineral density, typically measured hip and lumbar spine • CAROC guidelines for use of DEXA: diagnosis, determining fracture risk/therapy, and monitoring ■ diagnosis driven by T-score: the number of standard deviations from the young adult mean, most clinically valuable ◆ osteopenia: –2.5< T-score anterior circulation, deep/eloquent location, basilar artery bifurcation/ apex, older age, presence of comorbidities, presence of vasospasm ◆ clipping: dicult endovascular access, broad aneurysmal base, branching arteries at the aneurysm base, tortuosity/atherosclerosis of aerent vessels, dissection, hematoma, acute brainstem compression • unruptured aneurysms ■ average 1.4% annual risk of rupture; predictors include: age, HTN, history of SAH, aneurysm size and location, and geographical region (Finnish people = 3.6 times increased risk; Japanese people = 2.8 times increased risk) ■ no clear evidence on when to operate; need to weigh life expectancy ■ risk of morbidity/mortality of SAH (20-50%) vs. risk of coiling (~2%) ■ generally treat unruptured aneurysms >10 mm ■ treatment guided by balance of risks of SAH per ISUIA and PHASES and of intervention per centre experience and outcomes ■ follow smaller aneurysms with serial angiography

The Unruptured Intracranial Aneurysm Treatment Score Neurology 2015;85(10):881-889 Purpose: To develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus method. Results: The UIATS accounts for 29 key factors in UIA management. Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty.

See Landmark Neurosurgery Trials table for more information on the natural history of unruptured intracranial aneurysms and the risk associated with the repair.

Intracerebral Hemorrhage Definition • hemorrhage within brain parenchyma, accounts for ~10% of strokes • can dissect into ventricular system (IVH) or through cortical surface (SAH) Etiology • HTN (usually causes bleeds at putamen, thalamus, pons, and cerebellum) • hemorrhagic transformation (reperfusion post-stroke, surgery, strenuous exercise, etc.) • vascular anomalies ■ aneurysm, AVMs, and other vascular malformations (see Vascular Malformations, NS27) ■ venous sinus thrombosis ■ arteriopathies (cerebral amyloid angiopathy, lipohyalinosis, vasculitis)

Location of ICH • Basal ganglia/internal capsule (50%) • Thalamus (15%) • Cerebral white matter (15%) • Cerebellum/brainstem – usually pons (15%) • Other (5%)

NS26 Neurosurgery

• • • • •

tumours (1%): oen malignant (e.g. GBM, lymphoma, metastases) drugs (amphetamines, cocaine, alcohol, anticoagulants, etc.) coagulopathy (iatrogenic, leukemia, thrombotic thrombocytopenic purpura, aplastic anemia) CNS infections (fungal, granulomas, herpes simplex encephalitis) post-trauma (immediate or delayed, frontal and temporal lobes most commonly injured via coupcontrecoup mechanism) • eclampsia • postoperative (post-carotid endarterectomy cerebral reperfusion, craniotomy) • idiopathic

Toronto Notes 2023

ICH Score Components • GCS score (3-4=2 pts; 5-12=1 pt, 13-15=0 pt) • ICH volume (≥30 cm=1 pt, White • previous cerebrovascular accident of any type (23 times risk) • both acute and chronic heavy EtOH use; cocaine, amphetamines • liver disease • anticoagulants Clinical Features • TIA-like symptoms oen precede ICH, can localize to site of impending hemorrhage • gradual onset of symptoms over minutes-hours, usually during activity • H/A, N/V, and decreased LOC are common • specic symptoms/decits depend on location of ICH Investigations • baseline severity score such as the ICH Score should be performed as part of the initial workup • hyperdense blood on non-contrast CT • CTA routine, if spot sign (contrast in the hematoma) demonstrated there is high likelihood of clot growth

Surgical Decision Making in Brain Hemorrhage: New Analysis of the STICH, STICH II and STITCH ( Trauma) Randomized Trials Stroke 2019;50:1108-1115 Summary: The STICH (Surgical Trial in Lobar Intracerebral Hemorrhage) I (n=1033 patients) and II (n=601 patients) trials randomized patients with spontaneous intracerebral hemorrhage (ICH) to early surgery or initially conservative treatment. The STITCH (Trauma) trial investigated these options in the context of head-injured patients (n=170 patients). Meta-analysis of spontaneous ICH patients suggests that those presenting with a GCS of 10-13 and a large ICH are more likely to benefit from early surgery than those presenting with a GCS outside this range. Surgical treatment of traumatic ICH with GCS 10-13 may have similarly beneficial outcomes. Refer to the Landmark Neurosurgery Trials table for details of STICH.

Spetzler-Martin AVM Grading Scale Item

Score

Size

Treatment • patients should be transferred to and managed in a neuro-ICU or stroke unit • medical ■ decrease MAP to pre-morbid level or by ~20% (target BP 140/90) in emergency department ■ check partial thromboplastin time/international normalized ratio (PTT/INR), and correct coagulopathy (immediate reversal of anticoagulation) ■ control raised ICP (see Intracranial Pressure Dynamics, NS4) ■ corticosteroids should NOT be used for elevated ICP in ICH ■ levetiracetam/phenytoin for seizure prophylaxis ■ follow electrolytes (SIADH common) ■ angiogram to rule out vascular lesion unless >45 yr, known HTN, and putamen/thalamic/ posterior fossa ICH (yield ~0%) • surgical ■ craniotomy with evacuation of clot, treatment of source of ICH (i.e. AVM, tumour, cavernoma), ventriculostomy to treat hydrocephalus ■ indications ◆ symptoms of raised ICP or mass eect ◆ rapid deterioration (especially if signs of brainstem compression) ◆ favourable location (e.g. cerebellar, non-dominant hemisphere) ◆ young patient (10 ◆ poor prognosis: massive hemorrhage (especially dominant lobe), low GCS/coma, lost brainstem function ◆ medical reasons (e.g. advanced age, severe coagulopathy, dicult location (e.g. basal ganglia, thalamus)) Prognosis • 30 d mortality rate 44%, mostly due to cerebral herniation • rebleed rate 2-6%, higher if HTN poorly controlled

0-3 cm

1

3.1-6.0 cm

2

>6 cm

3

Location Non-eloquent

0

Eloquent

1

Deep Venous Drainage Not present

0

Present

1

AVM grades are calculated by adding the 3 individual Spetzler-Martin Scale scores from the above table. e.g. a 2 cm tumour in non-eloquent location without deep venous drainage = Grade I

Vascular Malformations NS27 Neurosurgery

Toronto Notes 2023

Vascular Malformations Types • AVMs • cavernous malformations (cavernomas, cavernous hemangiomas/angiomas) • venous angioma • capillary telangiectasias • AVF (carotid-cavernous stula, dural AVF, vein of Galen aneurysm) • “angiographically occult vascular malformations” (any type, 10% of malformations)

Arteriovenous Malformations, Cavernous Malformations, and Dural Arteriovenous Fistulas Table 17. Comparison of Pathoetiology, Clinical Features, and Treatment of Arteriovenous Malformations, Cavernous Malformations, and Dural Fistulas Arteriovenous Malformations

Cavernous Malformations

Dural Fistulas

Definition

Tangle of abnormal vessels/arteriovenous Benign vascular hamartoma shunts, with no intervening capillary beds consisting of irregular sinusoidal or brain parenchyma; usually congenital vascular channels located within the brain without intervening neural tissue or associated large arteries/ veins Several genes now described: CCM1, CCM2, CCM3

Fistulas connecting dural arteries to dural veins or the dural sinus Frequently occur at the transverse and cavernous sinuses, but can be found at every cranial dural sinus Hypothesized to be related to venous sinus thrombosis formation, and subsequent microvascular shunt formation within the dura between arteries and veins

Epidemiology

Prevalence ~0.14%, M:F=2:1, average age Prevalence of 0.1-0.2%, both at diagnosis=33 yr sporadic and hereditary forms 15-20% of patients with hereditary described hemorrhagic telangiectasia (Osler-WeberRendu syndrome) will have cerebral AVMs

Unknown true incidence Constitute 10-15% of all intracranial vascular abnormalities

Clinical Features Hemorrhage (40-60%): small AVMs are more likely to bleed due to direct high pressure AV connections Seizures (50%): more common with larger AVMs Mass eect Focal neurological signs secondary to ischemia (high flow → “steal phenomena”) Localized H/A, increased ICP Bruit (especially with dural AVMs) May be asymptomatic (“silent”)

Seizures (60%), progressive neurological deficit (50%), hemorrhage (20%), H/A Often an incidental finding Hemorrhage risk less than AVM, usually minor bleeds

Asymptomatic, pulsatile tinnitus if involving sigmoid or transverse sinuses, bruits, H/A Carotid cavernous involvement classically produces proptosis, chemosis, and bruits Symptoms of SAH, SDH, or ICH

Investigations

MRI (flow void), MRA Angiography (7% will also have one or more associated aneurysms)

T2-weighted image MRI (nonenhancing) Gradient echo sequencing (best for diagnosis)

Angiography remains the gold standard Non-enhanced CT to rule out hemorrhage MRI; however, this does not demonstrate the arterial supply to the fistula

Treatment

Surgical excision: Decreases risk of future hemorrhage Only appropriate for symptomatic and seizure lesions that are surgically Surgical excision is treatment of choice accessible (supratentorial lesions even in Spetzler-Martin grades I – II with are less likely to bleed than general good health infratentorial lesions) SRS is preferred for small (2 wk, spontaneous leaks, delayed onset of leak aer trauma or surgery, leaks complicated by meningitis

EXTRACRANIAL PATHOLOGY Approach to Limb/Back Pain • see Orthopaedic Surgery

Extradural Lesions Post. circulation Ant. circulation

AXIAL SECTION OF THORACIC SPINE Dorsal funiculus

Posterior spinal artery

Fasciculus gracilis Fasciculus cuneatus

Dorsal horn (sensory)

Lateral corticospinal tract (efferent)

Lateral horn (autonomic)

Posterior spinal aa.

Anterior segmental medullary a.

*only present T1-L2, S2-S5

Lateral funiculus

Ventral horn (motor)

Spinothalamic tract (afferent)

Anterior spinal artery

Ventral Anterior corticospinal funiculus tract (efferent)

Arachnoid mater Dura mater Anterior spinal a.

Post. & ant. reticular aa.

Branch to vertebral body & dura mater Dorsal branch of intercostal a. Thoracic aorta

Spinal a.

Intercostal a.

Figure 22. Vascular supply of spinal cord

© Natalie Cormier 2015, after Takami Iijima

Suspect CSF fistula in patients with otorrhea or rhinorrhea after head trauma or recurrent meningitis

Ring Sign: If CSF is mixed with blood. Allow CSF to drain onto the surrounding sheets; positive if clear in centre with surrounding blood coloured ring (double ring sign) Reservoir Sign: Gush of CSF leaks out in certain head positions (i.e. teapot sign); not specific or sensitive

Red Flags for Back Pain BACK PAIN Bowel/Bladder (retention or incontinence) Anesthesia (saddle) Constitutional symptoms “K”hronic disease Parasthesia Age >50 or 50, previous Hx of cancer, pain unrelieved by bed rest, constitutional symptoms Infection Increased ESR, IV drug use, immunosuppressed, fever Compression Fracture Age >50, trauma, prolonged steroid use

Root Compression NS29 Neurosurgery

Toronto Notes 2023

Root Compression • radiculopathy is a pain and/or sensorimotor decit syndrome that involves compression of a nerve root. Nerve compression generally occurs as a result of disc herniation, degenerative disc diseases (spondylosis), instability, and masses (rare) • patients generally present with referred pain, sensory changes (numbness and/or tingling) or weakness. Whereas patients might sometimes describe sensory changes in a dermatomal distribution, the referred pain will not be in a dermatomal distribution. e areas of pain and altered sensorium may be incongruent • muscle innervation has less overlap than sensory innervation and hence is a better predictor of level of pathology

Sensory Fibres • Fasciculus gracilis/cuneatus: proprioception, fine touch, vibration • Spinothalamic tract: pain and temperature Motor Fibres • Corticospinal tract: skilled movements

Dierential Diagnosis • herniated disc • neoplasm (neurobroma, schwannoma) • synovial cyst, abscess • hypertrophic bone/spur

Cervical Disc Syndrome Etiology • nucleus pulposus herniates through annulus brosus and impinges upon nerve root, most commonly at C6-C7 (C7 root) Clinical Features • pain in arm follows nerve root distribution, worse with neck extension, ipsilateral rotation, and lateral exion (all compress the ipsilateral neural foramen) • LMN signs and symptoms (diminished reexes, non-spastic motor weakness) • central cervical disc protrusion may cause myelopathy as well as nerve root decits Investigations • if red ags: cervical spine (C-spine) x-ray, CT, MRI (imaging of choice) • only consider EMG/nerve conduction studies if diagnosis uncertain and presenting more as peripheral nerve issue Treatment • nonsurgical ■ no bed rest unless severe radicular symptoms ■ activity modication, patient education (reduce sitting, liing) ■ physiotherapy, exercise programs focus on strengthening core muscles ■ analgesics; NSAIDs are more ecacious ■ avoid cervical manipulation like traction • surgical indications ■ anterior cervical discectomy is the usual approach (posterior foraminotomy with discectomy is the other option) ■ intractable pain despite adequate conservative treatment for >3 mo ■ progressive neurological decit Prognosis • 95% improve spontaneously in 4-8 wk Table 18. Lateral Cervical Disc Syndromes C4-5

C5-6

C6-7

Root Involved

C5

C6

C7

C7-T1 C8

Incidence

2%

19%

69%

10%

Sensory

Shoulder

Thumb

Middle finger

Ring finger, 5th finger

Motor

Deltoid, biceps, supraspinatus

Biceps, wrist extensors

Triceps

Digital flexors, intrinsics

Reflex

No change

Biceps, brachioradialis

Triceps

Finger jerk (Homann’s sign)

Disc herniations impinge the nerve root at the level below the interspace (i.e. C5-6 disc aects the C6 nerve root)

Degenerative Cervical Myelopathy NS30 Neurosurgery

Toronto Notes 2023

Degenerative Cervical Myelopathy Definition • progressive degenerative process of cervical spine leading to canal stenosis; congenital spinal stenosis; degeneration of intervertebral discs; hypertrophy of dura or ligaments; subluxation; altered mobility; telescoping of the spine due to loss of height of vertebral bodies; alteration of normal lordotic curvature • resultant syndromes: mechanical neck pain, radiculopathy (root compression), myelopathy (spinal cord compression) Epidemiology • typically begins at age 40-50, M>F, most commonly at the C5-C6 > C6-C7 levels Pathogenesis • any of: disc degeneration/herniation, osteophyte formation, ossication, and hypertrophy of ligaments • pathophysiology includes static compression, dynamic compression, and vascular compromise Clinical Features • insidious onset of mechanical neck pain exacerbated by excess vertebral motion (particularly rotation and lateral bending with a vertical compressive force Spurling’s test) • the earliest symptoms are gait disturbance and lower extremity weakness or stiness • occipital H/A is common • radiculopathy may involve 1 or more roots, and symptoms include neck, shoulder, and arm pain; paresthesias; and numbness • cervical spondylotic myelopathy may present with: ■ weakness (upper > lower extremity), lower extremity weakness (corticospinal tracts) is most worrisome complaint ■ decreased dexterity, loss of ne motor control ■ sensory changes ■ UMN ndings such as hyperreexia, clonus, and Babinski reex ■ funicular pain, characterized by burning and stinging ± Lhermitte’s sign (lightning-like sensation down the back with neck exion) Investigations • x-ray of cervical spine ± exion/extension (alignment, fractures) • MRI most useful for determination of compression of the neural element • CT is only used for better determination of bony anatomy (i.e. OPLL) • EMG/nerve conduction studies reserved for peripheral nerve investigation

Figure 23. CT (left) and MRI (right) representations of cervical spondylosis Images courtesy of Dr. Eric Massicotte

Treatment • nonsurgical: physiotherapy, anti-inammatory medications • surgical: anterior approach (anterior cervical discectomy or corpectomy), posterior approach (decompressive cervical laminectomy) • in multilevel degenerative cervical myelopathy (DCM), both anterior and posterior options are acceptable approaches with generally comparable outcomes ■ with kyphosis → anterior approach generally preferred

Cervical spondylotic myelopathy is the most common cause of spinal cord impairment

Clinical Grading Scores to Assess CSM • Modified Japanese Orthopaedic Association (mJOA) • Nurick Grade • Neck Disability Index

A Clinical Practice Guideline for the Management of Patients with Degenerative Cervical Myelopathy (DCM): Recommendations for Patients with Mild, Moderate, and Severe Disease and Nonmyelopathic Patients with Evidence of Cord Compression Global Spine Journal 2017;7(3S):70S-83S Severe and moderate DCM: Moderate evidence suggesting strong recommendation of surgical intervention. Mild DCM: Very low to low evidence suggesting oering surgical intervention or a structured rehabilitation and if non-operative management initially pursued, consider operative intervention if evidence of neurological deterioration. Non-myelopathic patients without radiculopathy: In such patients with imaging evidence of cervical cord compression, suggestion of not oering prophylactic surgery; counsel, educate, and follow clinically. Non-myelopathic patients with radiculopathy: Such patients with imaging evidence of cervical cord compression are at a higher risk of developing myelopathy and should be counselled. Oer surgical or nonoperative treatment with appropriate follow-up and structured rehabilitation.

Lumbar Disc Syndrome NS31 Neurosurgery

Toronto Notes 2023

■ with preserved cervical lordosis → posterior approach generally preferred • surgical indications: myelopathy with motor impairment, progressive neurologic impairment, intractable pain • complete remission almost never occurs; surgical decompression stops progression of disease in almost all cases; 80% of patients experience neurological improvement Table 19. 2017 Summary AO Spine-CSRS Guideline for the Management of Degenerative Cervical Myelopathy Patient Population

Level of Recommendation

Guideline/Recommendation

Severe DCM (mJOA 0-11)

Strong

Surgical intervention is recommended

Moderate DCM (mJOA 12-14)

Strong

Surgical intervention is recommended

Mild DCM (mJOA 15-17)

Weak

Surgical intervention or structured rehabilitation is recommended; consider surgery if with neurologic deterioration or failure to improve

Non-myelopathic patients with cord compression and without radiculopathy

Weak

Prophylactic surgery is not recommended

Non-myelopathic patients with cord compression and with radiculopathy

Weak

Either surgical intervention or nonoperative treatment (close follow-up or structured rehabilitation)

Lumbar Disc Syndrome Definition • compression of nerve roots caused by herniation of the nucleus pulposus through the annulus brosus of an intervertebral disc in the lumbar spine Etiology • posterolaterally herniated disc compressed nerve root exiting BELOW the level of the disc or the traversing nerve root • far lateral disc herniation compressed nerve root AT the level of the disc or the exiting nerve root • central herniation may cause cauda equina compression or lumbar stenosis (neurogenic claudication) Clinical Features • initially back pain, then leg pain > back pain • limited back movement (especially forward exion) due to pain • motor weakness, dermatomal sensory changes, decreased reexes • exacerbation with Valsalva; relief with exing the knee or thigh • nerve root tension signs ■ straight leg raise (SLR) (Lasegue’s test) or crossed SLR (pain should occur at less than 60º) suggests L5, S1 root involvement ■ femoral stretch test suggests L2, L3, or L4 root involvement Investigations • MRI is modality of choice • x-ray spine (only to rule out other lesions), CT (bony anatomy) • myelogram and post-myelogram CT (only if MRI is contraindicated)

Figure 24. T2-weighted MRI of lumbar disc herniation

See Landmark Neurosurgery Trials table for more information on the SPORT trial for outcomes of surgery vs. nonoperative care for lumbar disc herniation.

Treatment • nonsurgical (same as cervical disc disease) • surgical indications: same as cervical disc and cauda equina syndrome Prognosis • 95% improve spontaneously within 4-8 wk • those who do not improve with conservative treatment achieve symptom relief quicker with surgery than continuation of conservative management; however, the long-term outcome aer surgery is comparable to conservative therapy • do not follow patients with serial MRIs; clinical status is more important at guiding management Table 20. Lateral Lumbar Disc Syndromes L3-4

L4-5

Root Involved

L4

L5

L5-S1 S1

Incidence

loss of vibration and proprioception

Posterior Cord

Posterior spinal artery infarction, trauma

Preserved

Bilateral loss of vibration, proprioception, light touch at and below the lesion Preserved pain and temperature

Motor

Etiology Hemisection of cord

Pain/Temp

Syndrome Brown-Séquard

Brown-Séquard

Table 22. Comparison Between Incomplete Spinal Cord Lesion Syndromes

Posterior Cord

Grade

Central Cord

Incomplete Spinal Cord Lesion • any residual function at ≥4 segments below lesion • signs include sensory/motor function in lower limbs and “sacral sparing” (perianal sensation, voluntary rectal sphincter contraction)

American Spinal Injury Association Impairment Scale

Anterior Cord

Complete Spinal Cord Lesion • bilateral loss of motor/sensory and autonomic function at ≥4 segments below lesion/injury, with UMN signs • about 3% of patients with complete injuries will develop some recovery within 24 h; beyond 24 h, no distal function will recover

Peripheral Nerves

Vibr/Prop

• see Neurology, N38 Classification Table 23. Seddon’s Classification of Peripheral Nerve Injury Nerve Injury

Description

Recovery

Neurapraxia (class I)

Axon structurally intact but fails to function

Within h to mo (average 6-8 wk)

Axonotmesis (class II)

Axon and myelin sheath disrupted but endoneurium and Spontaneous axonal recovery at 1 mm/d, max at 1-2 yr supporting structures intact → Wallerian degeneration of axon segment distal to injury

Neurotmesis (class III)

Nerve completely transected

Need surgical repair for possibility of recovery

Etiology • ischemia • nerve entrapment (compression) by nearby anatomic structures, oen secondary to localized, repetitive mechanical trauma with additional vascular injury to nerve • direct trauma (e.g. transection) • iatrogenic Investigations • clinical exam: muscle bulk and tone, power, sensation, reexes, localization via Tinel’s sign (paresthesias elicited by tapping along the course of a nerve) • electrophysiological studies: EMG/nerve conduction study (assess nerve integrity and monitoring recovery aer 2-3 wk post-injury) • labs: blood work (e.g. CBC, TSH, vitamin B12), CSF • imaging: C-spine, chest/bone x-rays, myelogram, CT, magnetic resonance neurography, angiogram if vascular damage is suspected Treatment • early neurosurgical consultation if injury is suspected

© Jenna Rebelo 2010

Figure 26. Spinal cord lesion syndromes

SPECIALTY TOPICS NS35 Neurosurgery

Toronto Notes 2023

Table 24. Treatment by Injury Type Injury

Treatment

Entrapment

Nonsurgical: Prevent repeated stress/injury, physiotherapy, NSAIDs, local anesthesia/steroid injection Surgical: Nerve decompression ± transposition for progressive deficits, muscle weakness/atrophy, failure of medical management

Stretch/Contusion

Follow-up clinically for recovery; exploration if no recovery in 3 mo

Axonotmesis

If no evidence of recovery, resect damaged segment Prompt physical therapy and rehabilitation to increase muscle function, maintain joint ROM, maximize return of useful function Recovery usually incomplete

Neurotmesis

Surgical repair of nerve sheath unless known to be intact (suture nerve sheaths directly if ends approximate or nerve graft (usually sural nerve)) Clean laceration: early exploration and repair Contamination or associated injuries: tag initially with nonabsorbable suture, reapproach within 10 d

Complications • loss of function (temporarily or permanently) • neuropathic pain: with neuroma formation • complex regional pain syndrome: with sympathetic nervous system involvement

Blood vessels

Epineurium Perineurium

SPECIALTY TOPICS

Endoneurium

Fascicle

Neurotrauma

Myelin sheath

Trauma Management • see Emergency Medicine, ER7 Axon © Andreea Margineanu 2012

Indications for Intubation in Trauma 1. depressed or decreasing loss of consciousness (patient cannot protect airway): usually GCS ≤8 2. need for hyperventilation 3. severe maxillofacial trauma: patency of airway is doubtful 4. need for pharmacologic paralysis for evaluation or management ■ if basal skull fracture suspected, avoid nasotracheal intubation as may inadvertently enter brain ■ note: intubation prevents patient’s ability to verbalize for determining GCS

Schwann cell

Schwann cell nucleus

Trauma Assessment Initial Management

Figure 27. Peripheral nerve structure

ABCs of Trauma Management • see Emergency Medicine, ER2 NEUROLOGICAL ASSESSMENT Mini-History • period of loss of consciousness, post-traumatic amnesia, loss of bowel/bladder control, loss of sensation, weakness, type of injury/accident • in urgent situations, remember “SAMPLE-F”: signs/symptoms, allergies, medications, past medical history, last meal, events leading up to the trauma, and baseline functioning Neurological Exam • ABCs • vital signs • GCS • brainstem reexes (if appropriate) • cranial nerve exam • motor and sensory exam, including peripheral reexes • spine (pain/tenderness, palpable deformity) • sphincter tone and saddle sensation • record and repeat neurological exam at regular intervals, as appropriate

Glasgow Coma Scale Eye Response

Verbal Response

Motor Response

4 spontaneous 5 oriented

6 obeys commands

3 opens eyes to voice

4 confused

5 localizes to pain

2 opens eyes to pain

3 inappropriate words

4 withdraws from pain

1 no eye opening

2 incomprehensible 3 flexion to pain sounds (decorticate posturing) 1 no response

2 extension to pain (decerebrate posturing)

T intubated

1 no response

Best response for each component recorded individually (e.g. E3V3M5) ≥13 is mild injury; 9-12 is moderate injury; ≤8 is severe injury

Head Injury NS36 Neurosurgery

Investigations • spinal injury precautions (cervical collar) are continued until C-spine is cleared • C,T,L-spine and head CT scan ■ AP, lateral, odontoid views for C-spine (must see from C1 to T1; swimmer’s view if necessary) ■ look for fractures, loss of mastoid or sinus air spaces, blood in cisterns, pneumocephalus ■ ~50% of injuries happen at the junction of the cervical and thoracic spines, T1 should be well visualized in the image to detect this occurrence ■ rarely done: oblique views looking for pars interarticularis fracture (“Scottie dog” sign) ■ if CT is unavailable, can do C-spine x-ray with T1 well visualized, but not recommended since injuries at C and T spine junction are seldom adequately visible with x-ray • cross and type, arterial blood gas (ABG), CBC, drug screen (especially alcohol) • chest and pelvic x-ray as indicated

Toronto Notes 2023

• Never do LP in head injury unless increased ICP has been ruled out • All patients with head injury have C-spine injury until proven otherwise • Suspect hematoma in alcoholicrelated injuries • Low BP after head injury means injury elsewhere • Must clear spine both radiologically AND clinically

TREATMENT

Treatment for Moderate (GCS 9-12) and Severe Head Injury (GCS ≤8) • clear airway and ensure breathing; intubate if necessary • secure C-spine • maintain adequate BP • monitor for clinical deterioration • monitor and manage increased ICP if present (see Herniation Syndromes, NS7) Admission required if: • skull fracture (indirect signs of basal skull fracture, see Head Injury) • confusion, impaired consciousness, concussion with >5 min amnesia • focal neurological signs, extreme H/A, vomiting, seizures • unstable spine • use of alcohol • poor social support

Head Injury Epidemiology • M:F=2-3:1 Pathogenesis • acceleration/deceleration: contusions, SDH, axon and vessel shearing/mesencephalic hematoma • impact: skull fracture, concussion, epidural hematoma • penetrating: worse with high velocity and/or high missile mass ■ low velocity: highest damage to structures on entry/exit path ■ high velocity: highest damage away from missile tract Scalp Injury • rich blood supply • considerable blood loss (vessels contract poorly when ruptured) • minimal risk of infection due to rich vascularity Skull Fractures • depressed fractures: double density on skull x-ray (outer table of depressed segment below inner table of skull), CT with bone window is gold standard • simple fractures (closed injury): no need for antibiotics, no surgery • compound fractures (open injury): increased risk of infection, surgical debridement within 24 h is necessary ■ internal fractures into sinus may lead to meningitis, pneumocephalus ■ risk of operative bleed may limit treatment to antibiotics • basal skull fractures: not readily seen on x-ray, rely on clinical signs ■ retroauricular ecchymosis (Battle’s sign) ■ periorbital ecchymosis (raccoon eyes) ■ hemotympanum ■ CSF rhinorrhea, otorrhea (suspect CSF if halo or target sign present); suspect with Lefort II/III midface fracture

Comparative Eectiveness of Using Computed Tomography Alone to Exclude Cervical Spine Injuries in Obtunded or Intubated Patients: MetaAnalysis of 14327 Patients with Blunt Trauma J Neurosurg 2011;115:541-549 Purpose: To determine the eectiveness of helical CT alone (vs. CT and adjuvant imaging such as MR) to diagnose acute unstable C-spine injury following blunt trauma. Methods: Meta-analysis comparing modern CT with adjunctive imaging modalities. Results: 17 studies with 14327 patients total. Sensitivity and specificity for modern CT were both >99.9% (95% CI 0.99 -1.00 for both). The negative predictive value of a normal CT scan was 100% (95% CI 0.96-1.00) and accuracy was not aected by the global severity of injury, CT slice thickness, or study quality. Conclusions: CT alone is sucient to detect unstable C-spine injuries in trauma patients and adjuvant imaging is unnecessary with a negative CT scan result. Consequently, if a CT scan is negative for acute injury, the cervical collar may be removed from obtunded or intubated trauma patients.

The Canadian CT Head Rule for Patients with Minor Head Injury Lancet 2001;357:1391-1396 CT Head is only required for patients with minor head injuries with any one of the following: High-Risk (for neurological intervention) • GCS score 30 min • Dangerous mechanism (pedestrian struck by motor vehicle, occupant ejected from motor vehicle, fall from height >3 feet or five stairs) Minor Head Injury is defined as witnessed LOC, definite amnesia, or witnessed disorientation in a patient with a GCS score of 13-15.

Periorbital ecchymosis (racoon eyes)

Retroauricular ecchymosis (Battle’s sign)

Figure 28. Signs of basal skull fractures

© Ke Er Zhang 2022

Treatment for Minor Head Injury (GCS 13-15) • observation over 24-48 h • wake every hour • judicious use of sedatives or pain killers during monitoring period • outpatient: advise patients to undergo stepwise approach to return to play and return to school (for latest recommendations, refer to 2019 Parachute Canada Concussion Guidelines)

Brain Injury NS37 Neurosurgery

Cranial Nerve Injury • most traumatic causes of cranial nerve injury do not warrant surgical intervention • surgical intervention ■ CN II: local eye/orbit injury ■ CN III, IV, VI: if herniation secondary to mass ■ CN VIII: repair of ossicles • CN injuries that improve ■ CN I: recovery may occur in a few months; most do not improve ■ CN III, IV, VI: majority recover ■ CN VII: recovery with delayed lesions ■ CN VIII: vestibular symptoms improve over weeks, deafness usually permanent (except when resulting from hemotympanum)

Toronto Notes 2023

AAN Concussion Classification Grade 1: altered mental status 15 min Grade 3: any loss of consciousness

Concussion Grades AAN Management Options Grade

Arterial Injury • e.g. carotid-cavernous (C-C) stula, carotid/vertebral artery dissection

1

15 min for amnesia and other symptoms Return to normal activity if symptoms clear within 15 min

Intracranial Bleeding • see Blood, NS20 and Cerebrovascular Disease, NS21

2

Remove from activity for 1 d, then re-examine CT or MRI if H/A or other symptoms worsen or last >1 wk Return to normal activity after 1 wk without symptoms

3

Emergent neurological exam and imaging; if initial exam is normal, may go home with close follow-up Admit if any signs of pathology or persistent abnormal mental status CT or MRI if H/A or other symptoms If brief loss of consciousness (1 min), return to normal activity only after 2 wk without symptoms

Brain Injury Primary Impact Injury • mechanism of injury determines pathology: penetrating injuries, direct impact ■ low velocity: local damage ■ high velocity: distant damage possible (due to wave of compression), concussion • concussion: a trauma-induced alteration in mental status ■ refer to American Academy of Neurology (AAN) guidelines for classication and management ■ no parenchymal abnormalities on CT • coup (damage at site of blow) and contrecoup (damage at opposite site of blow) ■ acute decompression causes cavitation followed by a wave of acute compression • contusion (hemorrhagic) ■ high density areas on CT ± mass eect ■ commonly occurs with brain impact on bony prominences (inferior frontal lobe, pole of temporal lobe) • diuse axonal injury/shearing ■ wide variety of damage results ■ may tear blood vessels (hemorrhagic foci) ■ oen the cause of decreased loss of consciousness if no space-occupying lesion on CT Secondary Pathologic Processes • same subsequent biochemical pathways for each traumatic etiology • delayed and progressive injury to the brain due to ■ high glutamate release → NMDA receptor activation → cytotoxic cascade ■ cerebral edema ■ intracranial hemorrhages ■ ischemia/infarction ■ raised ICP, intracranial HTN ■ hydrocephalus Extracranial Conditions • hypoxemia ■ due to trauma to the chest, upper airway, brainstem ■ extremely damaging to vulnerable brain cells ■ leads to ischemia, raised ICP • hypercarbia ■ leads to raised ICP (secondary to vasodilation) ■ systemic hypotension ■ caused by blood loss (e.g. ruptured spleen) ■ loss of cerebral autoregulation leads to decreased CPP, ischemia • hyperpyrexia ■ leads to increased brain metabolic demands → ischemia ■ caused by severe infections (e.g. meningitis, sepsis) • uid and electrolyte imbalance ■ iatrogenic (most common) ■ SIADH caused by head injury ■ DI ■ may lead to cerebral edema and raised ICP • coagulopathy

Coup

Contrecoup

Figure 29. CT showing coupcontrecoup injury

A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury NEJM 2012;367:2471-2481 Background: ICP monitoring is frequently used to monitor severe TBI, but controversy exists over whether it is beneficial. Methods: Study sample (n=324 patients, ≥13 yr) consisted of those who had severe TBI and were being treated in ICU in Bolivia or Ecuador. Patients were randomly assigned to one management group: 1. ICP-monitoring based management. 2. Management based on imaging and clinical examination. Primary outcome was a composite of survival time, impaired consciousness, functional status (at 3, 6 mo), and neuropsychological status (at 6 mo). Results: No significant dierence between management groups based on primary outcome, 6 mo mortality, median length of ICU stay, or occurrence of serious adverse events. However, duration of brainspecific treatments (e.g. use of hyperosmolar fluids or hyperventilation) was higher in the imaging-clinical examination group (4.8 d vs. 3.4 d, P=0.002). Conclusion: Maintaining monitored ICP at 20 mmHg or less is not superior to care based on imaging and clinical examination.

Spinal Cord Injury NS38 Neurosurgery

Toronto Notes 2023

Intracranial Conditions • raised ICP due to traumatic cerebral edema OR traumatic intracranial hemorrhage Brain Injury Outcomes • mildly traumatic (GCS 13-15): post-concussive symptoms: H/A, fatigue, dizziness, nausea, blurred vision, diplopia, memory impairment, tinnitus, irritability, low concentration; 50% at 6 wk, 14% at 1 yr • moderately traumatic (GCS 9-12): outcome proportional to age (>40) and CT ndings; 60% good recovery, 26% moderately disabled, 7% severely disabled, 7% vegetative/dead • severe (GCS ≤8): dicult to predict, correlates with post-resuscitation GCS (especially motor) and age

SIADH → hyponatremia DI → hypernatremia

2 11

3 4

Late Complications of Head/Brain Injury • seizures: 5% of head injury patients develop seizures ■ incidence related to severity and location of injury (increased with local brain damage or intracranial hemorrhage) ■ post-traumatic seizure may be immediate, early, or late ■ presence of early (within rst wk) post-traumatic seizure raises incidence of late seizures • meningitis: associated with CSF leak from nose or ear • hydrocephalus: acute hydrocephalus or delayed NPH • Post-Concussion Syndrome: H/A, dizziness, cognitive changes, psychological symptoms, and behavioural symptoms

• see Orthopaedic Surgery, OR25 and Emergency Medicine, ER9 Neurogenic and Spinal Shock 1. neurogenic shock: hypotension that follows SCI (sBP usually ≤80 mmHg) caused by ■ interruption of sympathetics (unopposed parasympathetics) below the level of injury, usually with injuries above T6 level ■ loss of muscle tone due to skeletal muscle paralysis below level of injury → venous pooling (relative hypovolemia) ■ neurogenic shock is to be distinguished from hemodynamic shock due to blood loss from associated wounds (true hypovolemia) ◆ neurogenic shock → hypotension, bradycardia, warm and well-perfused extremities ◆ hemodynamic shock → suspect in multisystem trauma and if there is peripheral vascular shut-down 2. spinal shock: transient loss of all neurologic function below the level of the SCI, associated with loss of bulbocavernosus reex, accid paralysis and areexia for variable periods Whiplash-Associated Disorders • denition: traumatic injury to the so tissue structures in the region of the cervical spine due to hyperexion, hyperextension, or rotational injury to the neck

ABCDS Alignment columns anterior vertebral line (1) posterior vertebral line (2) spinolaminar line (3) posterior spinous line (4) Bone vertebral bodies facets spinous processes Cartilage Disc disc space interspinous space Soft tissues

Pre-vertebral soft tissues (A)

Initial Management of Spinal Cord Injury • major causes of death in SCI are aspiration and shock • the following patients should be treated as having a SCI until proven otherwise: ■ all victims of signicant trauma ■ minor trauma patients with decreased LOC or complaints of neck or back pain, weakness, abdominal breathing, numbness/tingling, or priapism Stabilization and Initial Evaluation in the Hospital 1. ABCs, immobilization (backboard/head strap), oxygenation, Foley catheter to urometer, temperature regulation 2. hypotension: maintain sBP >90 mmHg with pressors (dopamine), hydration, and atropine ◆ deep vein thrombosis (DVT) prophylaxis 3. monitor CBC/electrolytes 4. perform a mental status and cranial nerve function assessment as many patients with SCI have cooccurring traumatic brain injury 5. focused history and exam as the patient is being immobilized (see Trauma Assessment, NS35) 6. spine palpation: point tenderness or deformity 7. motor level assessment (including rectal exam for voluntary anal sphincter contraction) 8. sensory level assessment: pinprick, light touch, and proprioception 9. evaluation of reexes 10. signs of autonomic dysfunction: altered level of perspiration, bowel or bladder incontinence, priapism 11. radiographic evaluation ◆ 3 views C-spine x-rays (AP, lateral, and odontoid) to adequately visualize C1 to C7-T1 junction ◆ exion-extension views to disclose occult instability ◆ CT scan (bony injuries) typically most trauma centres use CT as the modality of choice for looking at fractures, very sensitive with the high-resolution scanners ◆ MRI mandatory if neurological decits (so tissue injuries)

11

2

3

AA

Figure 30. Assessment of spine CT/X-Ray (parasagittal view) Images used with permission from Dr. Ferco Berger and Dr. Michael O’Keee

© Yu Xiang Ren 2021

Spinal Cord Injury

Fractures of the Spine NS39 Neurosurgery

Toronto Notes 2023

Medical Management Specific to Spinal Cord Injury • option: methylprednisolone (given within 8 h of injury) is controversial; must confer with Neurosurgery service • ± decompression in acute, non-penetrating SCI

Resolution of spinal shock is indicated by the return of reflexes (most commonly the bulbocavernosus reflex)

Fractures of the Spine FRACTURES AND FRACTURE-DISLOCATIONS OF THE THORACIC AND LUMBAR SPINE • assess ligamentous injury/instability using MRI ± exion/extension x-ray views • thoracolumbar spine unstable if 4/6 segments disrupted (3 columns divided into le and right) ■ anterior column: anterior half of vertebral body, disc, and anterior longitudinal ligament ■ middle column: posterior half of vertebral body, disc, and posterior longitudinal ligament ■ posterior column: posterior arch, facet joints, pedicle, lamina and supraspinous, interspinous, and ligamentum ligaments

See Landmark Neurosurgery Trials table for more information on the STASCIS trial for eectiveness of early vs. late decompressive surgery for traumatic cervical spinal cord injury.

Type 1

Types of Injury Table 25. AO Spine Classification System for Subaxial Cervical Spine Injury and Thoracolumbar Spine Injury Type

Description

A

Compression fractures Involves anterior elements (vertebral body and/or disc) 0

No injury/process fracture

1

Wedge compression (fracture of single endplate w/o involvement of posterior vertebral body wall)

2

Split/pincer type (fracture of both endplates w/o involvement of posterior vertebral body wall)

3

Incomplete burst (involvement of posterior vertebral body wall and only a single endplate)

4

Complete burst (involvement of posterior vertebral body wall and both endplates) Tension band injuries

1

Posterior transoesseous disruption

2

Posterior ligamentous disruption

3

Anterior ligamentous disruption

C

Type 3

Translation injuries (displacement/dislocation)

F (only for subaxial cervical spine injury)

Facet injuries

1

Non-displaced facet fracture (fragment 40% lateral mass or displaced)

3

Floating lateral mass (disconnection of superior and inferior articular processes)

4

Pathologic subluxation or dislocated facet

Management of Thoracolumbar Injury • severity and management based on thoracolumbar injury classication and severity (TLICS) classication FRACTURES OF THE CERVICAL SPINE Types of Injury Table 26. AO Spine Upper Cervical Spine Injury Classification System Type

Description

1

Occipital condyle and occipital cervical joint complex injuries

2

C1 ring and C1-2 joint complex injuries

3

C2 and C2-3 joint complex injuries

*A, B, and C sub-categorizations apply to each type of injury A → bony injuries only (stable) B → tension band injuries (potentially unstable) C → translational injuries (unstable)

Figure 31. Odontoid fracture classification

© Hidenori Miyagawa 2006

B

Type 2

Neurologically Determined Death NS40 Neurosurgery

Toronto Notes 2023

Table 27. Fracture Patterns of the Cervical Spine Fracture Type

Description

C1 Vertebral Fracture (Jeerson fracture)

Vertical compression forces the occipital condyles of the skull down on the C1 vertebra (atlas), pushing the lateral masses of the atlas outward and disrupting the ring of the atlas Also can cause an occipital condylar fracture

Odontoid Fracture

Causes C1 and odontoid of C2 to move independently of C2 body This occurs because Normally C1 vertebra and odontoid of C2 are a single functional unit Alar and transverse ligaments on posterior aspect of odontoid usually remain intact after injury Patients often report a feeling of instability and present holding their head with their hands Type II fracture the most common

C2 Vertebral Fracture (hangman fracture)

Bilateral fracture through the pars interarticularis of C2 with subluxation of C2 on C3 (spondylolisthesis of axis) Usually neurologically intact

Clay-Shoveler Fracture

Avulsion of spinous process, usually C6 or C7

*The AOSpine classification is preferred to characterize fractures of the cervical spine, but the terminology described above may still be encountered on the wards

Imaging • AP spine x-ray (open-mouth and lateral view), CT Treatment • immobilization in cervical collar or halo vest until healing occurs (usually 2-3 mo) • type II and III odontoid fractures: consider surgical xation for comminution, displacement, or inability to maintain alignment with external immobilization ■ type II odontoid fractures more likely to require surgery than type III due to higher risk of nonunion (fracture line in watershed zone) • conrm stability aer recovery with exion-extension x-rays

Thoracolumbar Injury Classification and Severity Scoring Parameter

Points

Morphology

Neurologically Determined Death Definition • irreversible and diuse brain injury resulting in absence of clinical brain function • cardiovascular activity may persist for up to 2 wk Criteria of Diagnosis • prerequisites: no CNS depressant drugs/neuromuscular blocking agents, no drug intoxication/ poisoning, temperature >32ºC, no electrolyte/acid-base/endocrine disturbance • absent brainstem reexes: pupillary light reex, corneal reexes, oculocephalic response, caloric responses (e.g. no deviation of eyes to irrigation of each ear with 50 cc of ice water allow 1 min aer injection, 5 min between sides), pharyngeal and tracheal reexes, cough with tracheal suctioning, absent respiratory drive at PaCO2 ≥60 mmHg, ≥20 mmHg rise above baseline, and pH ≤7.28 (apnea test) • 2 evaluations separated by time, usually performed by two specialists (e.g. anesthetist, neurologist, neurosurgeon) • conrmatory testing: at EEG, absent perfusion assessed with cerebral angiogram

Coma Definition • an unrousable state in which patients show no meaningful response to environmental stimuli Pathophysiology • lesions aecting the cerebral cortex bilaterally, the reticular activating system, or their connecting bres • focal supratentorial lesions do not alter consciousness except by herniation (compression on the brainstem or on the contralateral hemisphere) or by precipitating seizures Classification • structural lesions (tumour, pus, blood, infarction, CSF): 1/3 of comas ■ supratentorial mass lesion: leads to herniation ■ infratentorial lesion: compression of or direct damage to the reticular activating system (RAS) or its projections • metabolic disorders/diuse hemispheric damage: 2/3 of comas ■ deciency of essential substrates (e.g. oxygen, glucose, vitamin B12) ■ exogenous toxins (e.g. drugs, heavy metals, solvents) ■ endogenous toxins/systemic metabolic diseases (e.g. uremia, hepatic encephalopathy, electrolyte imbalances, thyroid storm) ■ infections (meningitis, encephalitis) ■ trauma (concussion, diuse shear axonal damage)

Compression fracture

1

Burst fracture

2

Translational/rotational fracture

3

Distraction

4

Neurologic Status Intact

0

Nerve root injury

2

Spinal Cord Status Incomplete

3

Complete

2

Cauda equina

3

Posterior Ligamentous Complex Intact

0

Injury suspected/indeterminate

2

Injured

3

TLICS scoring based on morphology of injury, status of posterior ligamentous complex, and neurological status Non-operative management if TLICS = 0-3, operative management if TLICS = 5+, either operative or nonoperative if TLICS = 4

Prenatal vs. Postnatal Repair of Myelomeningocele (MMC) NE JM 2011;364:993-1004 Purpose: To compare outcomes of in utero repair of myelomeningocele with standard postnatal repair of myelomeningocele. Methods: RCT comparing prenatal surgery (before 26 wk of gestation) and standard postoperative surgery. 12 mo outcomes included death or need for placement of a CSF shunt. 30 mo outcomes included mental development and motor function. Results: 40% of prenatal-surgery patients, compared to 82% of postnatal-surgery patients, required CSF shunt (P80 (but most are 8095), 40-85% ambulatory, 3-10% have normal urinary continence Early mortality: usually due to Chiari malformation complications (respiratory arrest, aspiration), late mortality: due to shunt malfunction

Spinal cord

0.1-0.2% of live births

Meninges Spinal cord Roots

Plain films, CT, MRI, U/S, echo, GU investigations Subarachnoid space

Spinal cord

© Savanna Jackson 2016

Investigations

Subarachnoid space

© Savanna Jackson 2016

Meningocele (Spinal Bifida Aperta)

© Jen Polk 2002

Spina Bifida Occulta

Figure 32. Spina bifida occulta, meningocele, myelomeningocele

Intraventricular Hemorrhage NS42 Neurosurgery

Toronto Notes 2023

Intraventricular Hemorrhage Definition • hemorrhage originating in the periventricular subependymal germinal matrix Epidemiology • incidence and severity increases as gestational age (GA) and birth weight (BW) decrease • 50% of IVH occurs within 8 h of birth; 90% occurs by day 3 Risk Factors • prematurity (40

DDx of Increased MSAFP • Incorrect GA • >1 fetus (e.g. twins) • Fetal loss • ONTD • Abdominal wall defects (e.g. omphalocele)

OB8 Obstetrics

Toronto Notes 2023

ULTRASOUND SCREENING • 8-12 wk GA: dating U/S (most accurate form of pregnancy dating) ■ measurement of crown-rump length (margin of error: ± 5 d) ■ EDD should be based on T1 U/S if available • 11-14 wk GA: U/S for NT ■ measures the amount of uid behind the neck of the fetus ■ early screen for trisomy 21 (may also detect cardiac anomalies and other aneuploidies like Turner syndrome) ■ NT measurement is necessary for the FTS and IPS Part 1 • 18-20 wk GA: growth and anatomy U/S (margin of error: ± 10 d) ■ earlier or subsequent U/S performed when medically indicated NON-INVASIVE PRENATAL TESTING (NIPT) • analyze maternal blood for circulating cell-free fetal DNA (ccDNA) at 9 wk GA onwards. Requires dating U/S for accuracy Advantages • increased accuracy (high detection rate (DR), low false positive rate (FPR)) ■ trisomy 21 (DR 99%, FPR 0.1%), highly sensitive ■ trisomy 18 (DR 96%, FPR 0.1%) ■ trisomy 13 (DR 91%, FPR 0.1%) ■ Turner syndrome (DR 90%, FPR 0.2%) ■ other disorders (DiGeorge syndrome, Cri Du Chat syndrome, Prader-Willi syndrome, Angelman syndrome, XY disorders) • earlier timing with results available in 1-2 wk where parents can potentially have a CVS at 10-12 wk GA for diagnosis over an amniocentesis aer 15 wk GA Disadvantages • does not screen for ONTD • not covered by most provincial health insurance systems • need to conrm with invasive testing (it is a screening test, not a diagnostic test) • obtaining a result depends on sucient fetal fraction (aected by the GA, maternal obesity, and presence of a chromosome aneuploidy in either the placenta or the mother) • does not test for all aneuploidies • gives no result in 1-5% of cases (insucient fetal fraction, more common with elevated BMI) Table 4. Comparison of FTS, MSS, and IPS eFTS

MSS

IPS

11-14 wk GA

15-20 wk GA

11-14 wk GA: U/S-nuchal translucency 11-14 wk GA: eFTS blood 15-20 wk GA: MSS blood including inhibin A

Risk estimate for 1. Trisomy 21 (Down syndrome): increased NT, increased β-hCG, decreased PAPP-A 2. Trisomy 18: increased NT, decreased PAPP-A

Risk estimate for 1. ONTD: increased MSAFP (sensitivity 80-90%) 2. Trisomy 21: decreased MSAFP, increased β-hCG, decreased E3 (sensitivity 65%) 3. Trisomy 18: decreased MSAFP, decreased Note: Useful when patient wants results β-hCG, decreased E3, decreased inhibin A within T1 (sensitivity 80%) more accurate estimate of trisomy 21 risk Only oered alone if patient missed the time than MSS, sensitivity ~85% (when combined window for IPS or eFTS with age) 8% baseline FPR for trisomy 21, lower for NTD 5% FPR and trisomy 18 Patients with positive screen should be oered Patients with positive screen should be oered CVS, amniocentesis, or NIPT (covered in some U/S, amniocentesis, or NIPT (covered in some provinces, self-pay in others) provinces, self-pay in others)

Risk estimate for ONTD, trisomy 21, trisomy 18 Sensitivity ~85-90% 2% FPR Patients with positive screen should be oered U/S and/or amniocentesis or NIPT (covered in some provinces, self-pay in others)

Note: In twins, eFTS, MSS, and IPS are not applicable; screen with NT, NIPT for chromosomal abnormalities, and MSAFP for ONTDs

Diagnostic Tests • diagnostic tests available: ■ amniocentesis ■ CVS Indications • age >35 yr (increased risk of chromosomal anomalies) • risk factors in current pregnancy • abnormal U/S • abnormal prenatal screen (IPS, eFTS, MSS, or NIPT) • past history/family history of: ■ chromosomal anomaly or genetic disease ■ either parent a known carrier of a genetic disorder or balanced translocation ■ consanguinity ■ >3 spontaneous abortions

OB9 Obstetrics

Toronto Notes 2023

AMNIOCENTESIS • U/S-guided transabdominal extraction of amniotic uid performed as early as 15 wk GA Indications • identication of genetic and chromosomal anomalies (15-16 wk GA) as per indications above • conrmation of positive NIPT testing • positive eFTS/IPS/MSS • assessment of fetal lung maturity (T3) via the L/S ratio ■ if >2:1, RDS is less likely to occur Advantages • also screens for ONTD (acetylcholinesterase and amniotic AFP) – 96% accurate • in women >35 yr, the risk of chromosomal anomaly (1/180) is greater than the risk of miscarriage from the procedure • more accurate genetic testing than CVS Disadvantages • 1/200 to 1/900 risk of procedure-related pregnancy loss, depending on local experience • results take 14-28 d; QF-PCR or FISH can be done on chromosomes X, Y, 13, 18, 21, 22 to give preliminary results in 48 h; chromosomal microarray also readily available CHORIONIC VILLUS SAMPLING • biopsy of fetal-derived chorion using a transabdominal needle or transcervical catheter at 10-12 wk GA

Compared to CVS, amniocentesis has a higher accuracy of prenatal cytogenetic diagnosis (99 .8% vs. 97.5%) and lower risk of spontaneous abortion (0.5% vs. 1-2%)

Risk Factors for Neural Tube Defects GRIMM Genetics: family history of NTD (risk of having second child with NTD is increased to 2-5%), consanguinity, chromosomal (characteristic of trisomy 13, 18, and 21) Race: Higher risk in Europeans and non-Hispanic whites than African Americans, 3-fold higher in Hispanics Insucient vitamins: zinc and folate Maternal chronic disease (e.g. DM) Maternal use of antiepileptic drugs General population risk for NTD is 0.1%

Advantages • enables pregnancy to be terminated earlier than with amniocentesis • rapid karyotyping and biochemical assay within 48 h, including FISH analysis • high sensitivity and specicity Disadvantages • 1% risk of procedure-related pregnancy loss • does not screen for ONTD • 1-2% incidence of genetic mosaicism “false negative” results ISOIMMUNIZATION SCREENING Definition • isoimmunization: antibodies (Ab) produced against a specic RBC antigen (Ag) as a result of antigenic stimulation with RBC of another individual Etiology • maternal-fetal circulation normally separated by placental barrier, but sensitization can occur and can aect the current pregnancy, or more commonly, future pregnancies • anti-Rh Ab produced by a sensitized Rh-negative mother can lead to fetal hemolytic anemia • risk of isoimmunization of an Rh-negative mother with an Rh-positive ABO-compatible infant is 16% • sensitization routes ■ incompatible blood transfusions ■ previous fetal-maternal transplacental hemorrhage (e.g. ectopic pregnancy, trauma, abruption) ■ invasive procedures in pregnancy (e.g. prenatal genetic diagnosis, cerclage, D&C) ■ any type of abortion ■ labour and delivery ■ trauma (e.g. car accident, fall, etc.) Investigations • screening with indirect Coombs test at rst visit for blood group, Rh status, and antibodies • Kleihauer-Betke test used to determine extent of fetomaternal hemorrhage by estimating volume of fetal blood volume that entered maternal circulation • detailed U/S for hydrops fetalis • middle cerebral artery Dopplers are done to assess degree of fetal anemia; if not available, bilirubin is measured by serial amniocentesis to assess the severity of hemolysis • cordocentesis for fetal Hb should be used cautiously (not rst-line) Prophylaxis • exogenous Rh IgG (Rhogam® or WinRho®) binds to Rh antigens of fetal cells and prevents them from contacting maternal immune system • Rhogam® (120-300 µg) given to all Rh-negative and antibody screen negative women in the following scenarios: ■ routinely at 28 wk GA (provides protection for ~12 wk) ■ within 72 h of the birth of a Rh-positive fetus ■ with any invasive procedure in pregnancy (CVS, amniocentesis)

Rh Antibody Titre A positive titre (≥1:16) indicates an increased risk of fetal hemolytic anemia

Standard dose of 300 g of Rhogam® sucient for 30 mL of fetal blood. Give additional 10 g of Rhogam® for every mL of fetal blood over 30 mL

Fetal Surveillance OB10 Obstetrics

Toronto Notes 2023

■ as part of management of ectopic pregnancy ■ with miscarriage or therapeutic abortion ■ with an antepartum hemorrhage ■ with trauma • Rhogam® 300 µg provides sucient prophylaxis for 30 mL fetal Rh-positive whole blood • a Kleihauer-Betke test or ow cytometry can be used to measure the relative quantity of fetal blood in maternal circulation to determine if additional Rhogam® is indicated (if >30 mL fetal blood) • if Rh-negative and Ab screen positive, follow mother with serial monthly Ab titres throughout pregnancy + U/S ± serial amniocentesis as needed (Rhogam® has no benet, as B cells/antibodies already in circulation) Treatment • falling biliary pigment warrants no intervention (usually indicative of either unaected or mildly aected fetus) • intrauterine transfusion between 18-35 wk GA of O-negative packed RBCs may be required for severely aected fetus • early delivery of the fetus for exchange transfusion following 35 wk GA Complications • anti-Rh IgG can cross the placenta and cause fetal RBC hemolysis resulting in fetal anemia, CHF, edema, and/or ascites • severe cases can lead to hydrops fetalis (edema in at least two fetal compartments due to fetal heart failure secondary to anemia) or erythroblastosis fetalis (moderate to severe immune-mediated hemolytic anemia)

Fetal Surveillance • patients will generally rst notice FM (“quickening”) at 18-20 wk GA in primigravidas; can occur 1-2 wk earlier in multigravidas; can occur 1-2 wk later if placenta is implanted on the anterior wall of uterus • if there is concern about decreased FM, the patient is counselled to choose a time when the fetus is normally active to count movements (usually recommended aer 26 wk GA) • all high-risk patients should be advised to do FM counts ■ should experience ≥6 perceived movements in 2 h period ■ if there is a subjective decrease in FM, time how long it takes to feel 10 discrete movements (laying on the le in a quiet setting may facilitate feeling subtle movements) ■ if 10 movements take more than 2 h, further assessment is indicated, and patient should present to labour and delivery triage for assessment

DDx of Decreased Fetal Movements DASH De ath of fetus Amniotic fluid decreased Sleep cycle of fetus Hunger/Thirst

NON-STRESS TEST Definition • FHR tracing ≥20 min using continuous external fetal monitoring to assess FHR and its relationship to FM (see Gynaecology, First and Second Trimester Bleeding, GY20)

Normal NST: 2 accelerations, >15 bpm from baseline, lasting >15 s in 20 min

Indication • any suggestion of uteroplacental insuciency or suspected compromise in fetal well-being Table 5. Classification of Intrapartum EFM Tracings Normal Tracing (Category 1) Atypical Tracing (Category 2)

Abnormal Tracing (Category 3)

Baseline

110-160 bpm

Bradycardia 160 for >80 min Erratic baseline

Variability

6-25 bpm (moderate) ≤5 (absent or minimal) for 40-80 ≤5 (absent or minimal) for 80 min ≥25 bpm for >10 min Sinusoidal

Decelerations

None Non-repetitive uncomplicated variable Early decelerations

Repetitive uncomplicated variables Non-repetitive complicated variables Intermittent late decelerations Single prolonged deceleration ≥2 min but 32 wk GA: at least 2 accelerations of FHR ≥15 bpm from the baseline lasting ≥15 s in 20 min • normal, 3), placenta previa aer 28 wk GA, persistent T2 or T3 bleeding, uncontrolled T1DM, uncontrolled thyroid disease, serious cardiovascular or respiratory disease, and other systemic disorders • relative contraindications of physical activity ■ recurrent pregnancy loss, gestational HTN, history of spontaneous preterm birth, mild/moderate cardiovascular or respiratory disease, symptomatic anemia, malnutrition, eating disorder, twin pregnancy aer 28 wk GA, and other signicant medical conditions • weight gain: optimal gain depends on pre-pregnancy BMI (varies from 6.8-18.2 kg) • work: strenuous work, extended hours, and shi work during pregnancy may be associated with greater risk of low birth weight, prematurity, and spontaneous abortion • air travel: acceptable in T2; airline cut o for travel is 36-38 wk GA depending on the airline, to avoid giving birth on the plane • sexual intercourse: may continue, except in patients at risk for: spontaneous abortion, PTL, or placenta previa; breast stimulation may induce uterine activity, and is discouraged in high-risk patients near term • smoking: assist/encourage to reduce or quit smoking (see Family Medicine, FM13) ■ increased risk of decreased birth weight, placenta previa/abruption, spontaneous abortion, PTL, and stillbirth ■ psychosocial interventions considered rst-line, nicotine replacement therapy, and/or pharmacotherapy if counselling unsuccessful ■ lowest eective dose to minimize fetal exposure, intermittent dosage preparations preferred ■ limited safety data for bupropion and varenicline use during pregnancy • alcohol: no amount of alcohol is safe in pregnancy; encourage abstinence from alcohol during pregnancy; alcohol increases incidence of spontaneous abortion, stillbirth, and congenital anomalies ■ fetal alcohol spectrum disorder (see Paediatrics, P29) • cocaine: microcephaly, growth retardation, prematurity, and placental abruption • cannabis: associated with low birth weight infants and risk of neurobehavioural abnormalities in childhood • biopsychosocial considerations: discuss adjustment to pregnancy (e.g. mood, work, stress, family) and birth plan, refer to counselling or community resources as necessary

Weight Gain in Pregnancy BMI

Total Gain in T2 & T3

Weekly Gain

30

11-20 lb

0.4-0.6 lb/wk

Medications OB13 Obstetrics

Toronto Notes 2023

Medications • • • •

most drugs cross the placenta to some extent very few drugs are teratogenic, but very few drugs have proven safety in pregnancy use any drug with caution and only if necessary analgesics: acetaminophen preferable to ASA or ibuprofen Table 7. Documented Adverse Eects, Weigh Benefits vs. Risks, and Consider Medication Change Contraindicated Medication

Adverse Eect

ACE Inhibitor

Fetal renal defects, IUGR, oligohydramnios

Carbamazepine

ONTD in 1-2%

Chloramphenicol

Grey baby syndrome (fetal circulatory collapse 2° to toxic accumulation)

Lithium

Ebstein’s cardiac anomaly, goitre, hyponatremia

Misoprostol

Mobius syndrome (congenital facial paralysis with or without limb defects), spontaneous abortion, PTL

NSAIDs

Premature closure of the ductus arteriosus after 30 wk GA (prior to that, indomethacin used for tocolysis)

Phenytoin

Fetal hydantoin syndrome in 5-10% (IUGR, mental retardation, facial dysmorphogenesis, congenital anomalies)

Retinoids (e.g. Accutane®)

CNS, craniofacial, cardiac, and thymic anomalies

Sulpha drugs

Anti-folate properties, therefore theoretical risk in T1; risk of kernicterus in T3

Tetracycline

Stains infant’s teeth, may aect long bone development

Valproate

Congenital malformation (including ONTD) up to 9%

Warfarin

Increased incidence of spontaneous abortion, stillbirth, prematurity, IUGR, fetal warfarin syndrome (nasal hypoplasia, epiphyseal stippling, optic atrophy, mental retardation, intracranial hemorrhage)

Immunizations Intrapartum • administration is dependent on the risk of infection vs. risk of immunization complications • safe: tetanus toxoid, diphtheria, inuenza, hepatitis B, and pertussis • avoid live vaccines (risk of placental and fetal infection): polio, measles/mumps/rubella, and varicella • contraindicated: oral typhoid • the Public Health Agency of Canada recommends: ■ all pregnant women receive the inuenza vaccine ■ all pregnant women should be given Tdap every pregnancy irrespective of immunization history. Ideally between 27-32 wk GA but can be given at 13-26 wk GA if high-risk of PTL Postpartum • rubella vaccine for all non-immune mothers. If they have had an adult booster and remain nonimmune, they should not be revaccinated and pregnancy should be deferred for at least 1 mo following vaccination • hepatitis B vaccine should be given to infants within 12 h of birth if maternal status unknown or positive or if father is known to have chronic hepatitis B infection – follow-up doses at 1 and 6 mo • any vaccine required/recommended is generally safe postpartum • delayed postpartum vaccination is recommended if patient receives immunoglobulin or blood products (e.g. RhIg or packed red blood cells)

Radiation • ionizing radiation exposure is considered teratogenic at high doses ■ if indicated for maternal health, should be done • imaging not involving direct abdominal/pelvic high dosage radiation is not associated with adverse eects ■ higher dosage of radiation to fetus occurs with plain x-ray of lumbar spine/abdomen/pelvis, barium enema, CT abdomen/pelvis/lumbar spine • radioactive isotopes of iodine are contraindicated • no known adverse eects from U/S or MRI (long-term eects of gadolinium unknown, avoid if possible)

Drug Resources During Pregnancy and Breastfeeding • Hale T. Medications and mothers’ milk, 18th ed. Springer Publishing Company, 2019 • Lactmed: https://toxnet.nlm.nih.gov/ newtoxnet/lactmed.htm

Antepartum Hemorrhage OB14 Obstetrics

Toronto Notes 2023

Table 8. Approximate Fetal Doses from Common Diagnostic Procedures Examination

Estimated Fetal Dose (cGy)

Number of Exams Safe in Pregnancy

Plain Film Abdomen Pelvis Lumbar spine Thoracic spine Chest (2 views)

0-14 0-11 0-17 0.009 5 cGy • Necessary amount to cause malformations: >20-30 cGy

Adapted from: Cohen-Kerem, et al. 2005 and Valentin 2000

Antepartum Hemorrhage • see Gynaecology, First and Second Trimester Bleeding, GY20 Definition • vaginal bleeding from 20 wk GA to term Dierential Diagnosis • bloody show (represents cervical changes/early stages of dilation) – most common physiologic etiology in T3 • placenta previa • placental abruption – most common pathological etiology in T3 • vasa previa • cervical lesion (cervicitis, polyp, ectropion, cervical cancer) • uterine rupture • other: bleeding from bowel or bladder, abnormal coagulation Table 9. Comparison of Placenta Previa and Abruptio Placentae Placenta Previa

Abruptio Placentae

Definition

Abnormal location of the placenta near, partially, or completely over the internal cervical os

Premature separation of a normally implanted placenta after 20 wk GA

Etiology

Idiopathic

Idiopathic

Epidemiology

0.5-0.8% of all pregnancies

1-2% of all pregnancies

Risk Factors

History of placenta previa (4-8% recurrence risk) Multiparity Increased maternal age Multiple gestation Uterine tumour (e.g. fibroids) or other uterine anomalies Uterine scar due to previous abortion, CD, D&C, myomectomy

Previous abruption (recurrence rate 5-16%) Maternal HTN (chronic or gestational HTN in 50% of abruptions) or vascular disease Cigarette smoking (>1 pack/d), excessive alcohol consumption, cocaine Multiparity and/or maternal age >35 yr PPROM Rapid decompression of a distended uterus (polyhydramnios, multiple gestation) Uterine anomaly, fibroids Trauma (e.g. motor vehicle collision, maternal battery)

Bleeding

PAINLESS

Usually PAINFUL

Placenta Previa Definition • placenta implanted in the lower segment of the uterus covering the internal cervical os (either fully or partially) • placental location is described in relation to the internal os as “mm away” or “mm of overlap” Clinical Features • PAINLESS bright red vaginal bleeding (recurrent), may be minimal and cease spontaneously but can become catastrophic • mean onset of bleeding is 30 wk GA, but onset depends on degree of previa • physical exam ■ do not perform digital vaginal exam until ruled out placenta previa (speculum and transvaginal probe are safe) ■ uterus so and non-tender ■ presenting fetal part high or displaced ■ FHR usually normal ■ shock/anemia correspond to degree of apparent blood loss

Do NOT perform a vaginal exam until placenta previa has been ruled out by U/S

Placental Abruption OB15 Obstetrics

Toronto Notes 2023

• complications ■ fetal ◆ perinatal mortality low but still higher than with a normal pregnancy ◆ prematurity (bleeding oen dictates early CD) ◆ intrauterine hypoxia (acute or IUGR) ◆ fetal malpresentation ◆ PPROM ◆ risk of fetal blood loss from placenta, especially if incised during CD ■ maternal ◆ 34 wk GA • optimize fetus with betamethasone valerate (Celestone®), MgSO 4 for neuroprotection, early GBS swab, and paediatrics consult if anticipated preterm delivery • as IUGR fetuses are less likely to withstand stresses of labour, they are more likely to be delivered by CD

Macrosomia Definition • infant weight ≥90th percentile for a particular GA or >4000 g Etiology/Risk Factors • maternal obesity, gestational and pre-gestational DM, past history of macrosomic infant, prolonged gestation, multiparity, excessive maternal weight gain during pregnancy Clinical Features • increased risk of perinatal mortality • CPD and birth injuries (shoulder dystocia, fetal bone fracture) more common • complications of DM in labour (see Table 14, OB30) Investigations • serial SFH • U/S for EFW if mother at high-risk or SFH >2 cm ahead of GA Management • prevent hyperglycemia in patients with DM, optimize pre-pregnancy weight, and limit excessive pregnancy weight gain in patients with increased BMI • planned CD is a reasonable option where EFW >5000 g in non-diabetic patients and EFW >4500 g in diabetic patients

Toronto Notes 2023

Polyhydramnios/Oligohydramnios OB22 Obstetrics

Toronto Notes 2023

Polyhydramnios/Oligohydramnios Table 11. Polyhydramnios and Oligohydramnios Polyhydramnios

Oligohydramnios

Definition

AFI >25 cm U/S: single deepest pocket >8 cm

AFI 30%) ■ BPP • may attempt vaginal delivery (if dichorionic diamniotic or monochorionic diamniotic) if twin A presents as vertex and growth discrepancy 30% discordance in EFW Clinical Features • donor twin: IUGR, hypovolemia, hypotension, anemia, and oligohydramnios • recipient twin: hypervolemia, HTN, CHF, polycythemia, edema, polyhydramnios, and kernicterus in neonatal period Investigations • detected by U/S screening, Doppler ow analysis Management • fetoscopic laser ablation of placental vascular anastomoses (preferred between 16-26 wk GA) • therapeutic serial amniocentesis to decompress polyhydramnios of recipient twin and decrease pressure in cavity and on placenta • intrauterine blood transfusion to donor twin if necessary

Breech Presentation Definition • fetal buttocks or lower extremity is the presenting part as determined on U/S • complete (10%): hips and knees both exed • frank (60%): hips exed, knees extended, buttocks present at cervix ■ most common type of breech presentation ■ most common breech presentation to be delivered vaginally • incomplete (30%): both or one hip partially exed and both or one knee present below the buttocks, feet or knees present rst (footling breech, kneeling breech) Epidemiology • occurs in 3-4% of pregnancies at term (25% at 36 wk GA • EFW 2500-3800 g based on clinical and U/S assessment (5.5–8.5 lb) • Fetal head flexed • Continuous fetal monitoring • Two experienced obstetricians, assistant, and anesthetist present • Ability to perform emergency CD within 30 min if required • Mother motivated for vaginal breech delivery and understands risks and benefits

Hypertensive Disorders of Pregnancy OB25 Obstetrics

Toronto Notes 2023

Risk Factors • maternal: pelvis (contracted), uterus (shape abnormalities, broids, previous breech), pelvic tumours causing compression, and grand multiparity • placental: placenta previa • fetal: prematurity, amniotic uid (poly-/oligohydramnios), multiple gestation, congenital malformations (found in 6% of breeches; 2-3% if in vertex presentations), abnormalities in fetal tone and movement, aneuploidy, hydrocephalus, and anencephaly

A. Complete Breech

B. Frank Breech

C. Incomplete Breech Figure 5. Types of breech presentation

Prognosis • regardless of route of delivery, breech infants have lower birth weights and higher rates of perinatal mortality, congenital anomalies, abruption, and cord prolapse

Hypertensive Disorders of Pregnancy Hypertension in Pregnancy • hypertensive disorders of pregnancy are classied as either pre-existing or de novo (gestational HTN or preeclampsia) and exist on a spectrum PRE-EXISTING HYPERTENSION Definition • sBP ≥140 mmHg or dBP ≥90 mmHg prior to 20 wk GA; BP should be elevated on ≥2 occasions at least 15 min apart on the same arm, seated with appropriate sized cu • essential HTN is associated with an increased risk of gestational HTN, abruptio placentae, IUGR, and IUFD GESTATIONAL HYPERTENSION Definition • sBP ≥140 mmHg or dBP ≥90 mmHg aer 20 wk GA without proteinuria in a patient known to be normotensive before pregnancy

Ominous Symptoms of HTN in Pregnancy Right upper quadrant pain Headache Visual disturbances

© Crista Mason 2004

Management • pre- or early-labour U/S to assess type of breech presentation, fetal growth, estimated weight, placenta position, attitude of fetal head (exed is preferable); if U/S unavailable, recommend CD • ECV and elective CD should be presented as options with the risks and benets outlined; obtain informed consent • ECV: procedure that is performed with external pressure on the uterus to encourage a non-vertex fetus (breech, transverse, or oblique) to turn into vertex presentation ■ overall success rate of ~40-60% ■ criteria: >36 wk GA, singleton, unengaged presenting part, reactive NST, intact membrane ■ contraindications: ◆ absolute: where CD is required (placenta previa, previous classical CD), previous myomectomy, PROM, uteroplacental insuciency, non-reactive NST, multiple gestation ◆ relative: mild/moderate oligohydramnios, suspected IUGR, HTN, previous T3 bleed, nuchal cord ■ risks: abruption, cord compression, cord accident, ROM, labour, fetal bradycardia requiring CD (30 mg/ mmol) or adverse conditions (end organ dysfunction) ECLAMPSIA Definition • the occurrence of ≥1 generalized convulsion and/or coma in the setting of preeclampsia and in the absence of other neurologic conditions Etiology • placental malperfusion → soluble factors released into circulation → maternal vascular endothelial injury → hypertension + multi-organ injury Epidemiology of Eclampsia • an eclamptic seizure occurs in approximately 0.5% of mildly preeclamptic patients and 2-3% of severely preeclamptic patients Clinical Manifestation of Eclampsia • eclampsia is a clinical diagnosis • typically tonic-clonic and lasting 60-75 s • symptoms that may occur before the seizure include persistent frontal or occipital headache, blurred vision, photophobia, right upper quadrant or epigastric pain, and altered mental status • in up to one third of cases, there is no proteinuria or hypertension prior to the seizure • approx 25% of cases will present in the postpartum period • in general, women with typical eclamptic seizures who do not have focal neurologic decits or prolonged coma do not require diagnostic evaluation, including imaging Risk Factors for Hypertensive Disorders in Pregnancy • maternal factors: ■ primigravida (80-90% of gestational HTN), rst conception with a new partner, PMHx or FMHx of gestational HTN, or preeclampsia/eclampsia ■ DM, chronic HTN, or renal insuciency ■ obesity ■ APS or inherited thrombophilia ■ extremes of maternal age (35 yr) ■ previous stillbirth or IUFD ■ vascular or connective tissue disease • fetal factors: ■ IUGR or oligohydramnios ■ GTN ■ multiple gestation ■ fetal hydrops “mirror syndrome” ■ abruptio placentae Clinical Evaluation of Hypertensive Disorders in Pregnancy • in general, clinical evaluation should include the mother and fetus • evaluation of mother: ■ body weight ■ central nervous system ◆ presence and severity of headache ◆ visual disturbances (blurring, scotomata) ◆ tremulousness, irritability, and somnolence ◆ hyperreexia ■ hematologic (bleeding, petechiae) ■ hepatic (right upper quadrant or epigastric pain, severe N/V) ■ renal (urine output, colour) • evaluation of fetus: ■ FM ■ FHR tracing – NST ■ U/S for growth ■ BPP ■ Doppler ow studies Laboratory Evaluation of Hypertensive Disorders in Pregnancy • CBC • PTT, INR, brinogen – if abnormal LFTs or bleeding • ALT, AST • creatinine, uric acid • 24 h urine collection for protein or albumin:creatinine ratio • may consider placental growth factor (PlGF) testing or sFlt-1:PlGF ratio as an early screening test for suspected preeclampsia

Eclampsia prior to 20 wk GA is rare and should raise the possibility of an underlying molar pregnancy or APS

Hypertension in Pregnancy Adverse Maternal Conditions • sBP >160 mmHg • dBP >100 mmHg • HELLP • Cerebral hemorrhage • Renal dysfunction: oliguria 40% Fourth Stage of Labour • rst postpartum hour • monitor vital signs and bleeding, repair lacerations • ensure uterus is contracted (palpate uterus and monitor uterine bleeding) • inspect placenta for completeness and umbilical cord for presence of 2 arteries and 1 vein • 3rd and 4th stages of labour most dangerous to the mother (i.e. hemorrhage)

Continuous Support for Women During Childbirth Cochrane DB Syst Rev 2017;7:CD003766 Study: Systematic review of 27 trials from 17 countries involving a total of 15858 women Intervention: Continuous support vs. usual care during labour Outcome: Eects on mothers and their babies Results: Women receiving continuous support were slightly more likely to have a spontaneous vaginal birth (RR 1.08, 95% CI 1.04 to 1.12) and shorter labour (mean dierence -0.69 h, 95% CI -1.04 to -0.34) and were less likely to use intrapartum analgesia (RR 0.90, 95% CI 0.84 to 0.96), report dissatisfaction with their childbirth experience (RR 0.69, 95% CI 0.59 to 0.79), and have a baby with a low 5 min APGAR score (RR 0.62, 95% CI 0.46 to 0.85)

The Cardinal Movements of the Fetus During Delivery

5. Complete extension

2. Engagement, descent, flexion

6. Restitution (external rotation)

3. Further descent, internal rotation

7. Delivery of anterior shoulder

Figure 8. Cardinal movements of fetus during delivery Adapted from illustration in Williams Obstetrics, 19th ed

Analgesic and Anesthetic Techniques in Labour and Birth • pain or anxiety leads to high endogenous catecholamines, which produce a direct inhibitory eect on uterine contractility Non-Pharmacologic Pain Relief Techniques • reduction of painful stimuli ■ maternal movement, position change, counter-pressure, and abdominal compression • activation of peripheral sensory receptors ■ supercial heat and cold ■ immersion in water during labour ■ touch and massage, acupuncture, and acupressure ■ TENS ■ intradermal injection of sterile water ■ aromatherapy • enhancement of descending inhibitory pathways ■ attention focusing and distraction ■ hypnosis ■ music and audio analgesia ■ biofeedback

4. Complete rotation, beginning extension

8. Delivery of posterior shoulder

© Danielle Bader

1. Head floating, before engagement

Fetal Monitoring in Labour OB36 Obstetrics

Toronto Notes 2023

Pharmacologic Methods (see Anesthesia, A26) • nitrous oxide (e.g. self-administered Entonox®) • narcotics (usually combined with anti-emetic) • pudendal nerve block • perineal inltration with local anesthetic • regional anesthesia (epidural block, combined spinal-epidural, and spinal)

Fetal Monitoring in Labour • see online Fetal Heart Rate Tutorial Vaginal Exam • membrane status, as indicated by amniotic uid (clear, pink, bloody, and meconium) • cervical eacement (thinning), dilatation, consistency, position, and application • fetal presenting part, position, and station • bony pelvis size and shape • monitor progress of labour at regular intervals and document in a partogram Intrapartum Fetal Monitoring • intermittent fetal auscultation with Doppler device q15-30 min for 1 min in active phase of rst stage following a contraction, q5 min during second stage when pushing has begun • continuous electronic FHR monitoring reserved for abnormal auscultation, prolonged labour, labour which is induced or augmented, meconium present, multiple gestation/fetal complication, and concerns about the fetus tolerating labour ■ use of continuous electronic monitoring shown to lead to higher intervention rates and no improvement in outcome for the neonate when used routinely in all patients (i.e. no risk factors) ■ techniques for continuous monitoring include external (Doppler) vs. internal (fetal scalp electrode) monitoring • fetal scalp sampling should be used in conjunction with electronic FHR monitoring and contraction monitoring (CTG) to resolve the interpretation of abnormal or atypical patterns Electronic FHR Monitoring • FHR measured by Doppler; contractions measured by tocometer • described in terms of baseline FHR, variability (short-term, long-term), and periodicity (accelerations, decelerations) • see Table 5, OB10 • Baseline FHR ■ normal range is 110-160 bpm ■ parameter of fetal well-being vs. distress • Variability ■ physiologic variability is a normal characteristic of FHR ■ variability is measured over a 15 min period and is described as: absent, minimal (25 bpm) ■ normal variability indicates fetal acid-base status is acceptable ■ can only be assessed by electronic contraction monitoring (CTG) ■ variability decreases intermittently even in a healthy fetus • Periodicity ■ accelerations: increase of ≥15 bpm for ≥15 s (or ≥10 bpm for ≥10 s if 160 bpm)

Fetal Bradycardia (FHR 15 bpm below baseline (>15 s, 60 s in duration with slow return to baseline Late Deceleration

BPM Onset of deceleration

160

Nadir of deceleration

140

FHR

120 100

30 seconds of lag time

Recovery time

Acme of contraction Onset of contraction

Uterine contraction End of contraction

Fetal Scalp Blood Sampling • cervix must be adequately dilated • indicated when atypical or abnormal FHR is suggested by clinical parameters including heavy meconium or moderately to severely abnormal FHR patterns (including unexplained low variability, repetitive late decelerations, complex variable decelerations, and fetal cardiac arrhythmias) • done by measuring pH or more recently fetal lactate ■ pH ≥7.25, lactate 4.8 mmol/L indicates fetal acidosis, delivery is indicated • contraindications: ■ known or suspected fetal blood dyscrasia (hemophilia, VWD) ■ active maternal infection (HIV, genital herpes, Hep B) Fetal Oxygenation • uterine contractions during labour decrease uteroplacental blood ow, which results in reduced oxygen delivery to the fetus • most fetuses tolerate this reduction in ow and have no adverse eects • fetal response to hypoxia/asphyxia: ■ decreased movement, tone, and breathing activities ■ anaerobic metabolism (decreased pH) ■ transient fetal bradycardia followed by fetal tachycardia ■ redistribution of fetal blood ow • increased ow to brain, heart, and adrenals • decreased ow to kidneys, lungs, gut, liver, and peripheral tissues • increase in blood pressure

Induction and Augmentation of Labour OB38 Obstetrics

Toronto Notes 2023

Table 19. Factors Aecting Fetal Oxygenation Factor

Mechanism

Example

Maternal

Decreased maternal oxygen carrying capacity

Significant anemia (iron deficiency, hemoglobinopathies), carboxyhemoglobin (smokers)

Decreased uterine blood flow

Hypotension (blood loss, sepsis), regional anesthesia, maternal positioning

Uteroplacental

Fetal

Chronic maternal conditions

Vasculopathies (SLE, T1DM, chronic HTN), APS, cyanotic heart disease, COPD

Uterine hypertonus

Placental abruption, tachysystole secondary to oxytocin, prostaglandins, or normal labour

Uteroplacental dysfunction

Placental abruption, placental infarction (dysfunction marked by IUGR, oligohydramnios, abnormal Doppler studies), chorioamnionitis, placental edema (DM, hydrops), placental senescence (post-dates)

Cord compression

Oligohydramnios, cord prolapse, or entanglement

Decreased fetal oxygen carrying capacity

Significant anemia (isoimmunization, fetomaternal bleed), carboxyhemoglobin (exposure to smokers)

Induction and Augmentation of Labour Induction of Labour Definition • articial initiation of labour in a pregnant woman prior to spontaneous initiation to deliver the fetus and placenta Prerequisites for Labour Induction • capability for CD if necessary • maternal: ■ inducible/ripe cervix: short, thin, so, anterior cervix with open os ■ if cervix is not ripe, use prostaglandin vaginal insert (Cervidil®), prostaglandin gel (Prepidil®), misoprostol (Cytotec®), or Foley catheter • fetal: ■ normal fetal heart tracing ■ cephalic presentation ■ adequate fetal monitoring available • likelihood of success determined by Bishop score: ■ cervix considered unfavourable if 40 yr): consideration should be given to IOL due to increased risk of stillbirth • >41 wk GA: oer IOL if vaginal delivery is not contraindicated ■ IOL shown to decrease CD, FHR changes, meconium staining, macrosomia, and death when compared with expectant management • >41 wk GA and expectant management elected: serial fetal surveillance ■ FM count by the mother ■ BPP q3-4 d • maternal factors: ■ DM = second most common reason for induction ■ gestational HTN ≥38 wk GA ■ preeclampsia ≥37 wk GA ■ other maternal medical problems, (e.g. renal or lung disease, chronic HTN, and cholestasis) ■ signicant but stable antepartum hemorrhage ■ labour induction may be oered to patients age ≥40 at ≥39 wk GA due to increased risk of stillbirth

Induction is indicated when the risk of continuing pregnancy exceeds the risks associated with induced labour and delivery

Induction vs. Augmentation Induction is the artificial initiation of labour Augmentation promotes contractions when spontaneous contractions are inadequate

Consider the Following Before Induction • Indication for induction • Contraindications • GA • Cervical favourability • Fetal presentation • Potential for CPD • Fetal well-being/FHR • Membrane status

Methods for Induction of Labour OB39 Obstetrics

• maternal-fetal factors: ■ isoimmunization, PROM, and chorioamnionitis • fetal factors: ■ suspected fetal jeopardy as evidenced by biochemical or biophysical indications ■ macrosomia, fetal demise, IUGR, oligo/polyhydramnios, anomalies requiring surgical intervention, and twins ■ previous stillbirth or low PAPP-A Risks • failure to achieve labour and/or vaginal birth • tachysystole with fetal compromise or uterine rupture • maternal side eects to medications • uterine atony and PPH if labour is prolonged Contraindications • maternal ■ prior classical or inverted T-incision CD or uterine surgery (e.g. myomectomy) ■ unstable maternal condition ■ active maternal genital herpes ■ invasive cervical carcinoma ■ pelvic structure deformities ■ previous uterine rupture • maternal-fetal ■ placenta previa or vasa previa ■ cord presentation • fetal ■ fetal distress or malpresentation/abnormal lie

Methods for Induction of Labour

Toronto Notes 2023

Evidence for Cervical Ripening Methods (SOGC Guidelines) • Meta-analysis of five trials has concluded that the use of oxytocin to ripen the cervix is not eective • Since the best dose and route of misoprostol for labour induction with a live fetus are not known and there are concerns regarding hyperstimulation, the use of misoprostol for IOL should be in cases of IUFD to initiate labour

Vaginal Prostaglandin (PGE2 and PGF2a) for Induction of Labour at Term Cochrane DB Syst Rev 2014;6:CD003101 This analysis examined the results of 70 RCTs (n=11487 women). Use of vaginal PGE2 increased the risk of uterine hyperstimulation with FHR changes (RR 3.16; 95% CI 1.67-5.98) and likely reduces the CD rate slightly (RR 0.91; 95% CI 0.81-1.02) compared to placebo or no treatment. There were no detectable dierences in eectiveness between gel or tablet forms of PGE2 or between sustained release pessaries and PGE2 gel/tablets Theoretical advantages between intravaginal PGE2 (Cervidil®) compared to Intravaginal Prostaglandin Gel: • Slow, continuous release • Ability to use oxytocin 30 min after removal vs. 6 h for gel • Ability to remove insert if required (e.g. excessive uterine activity)

CERVICAL RIPENING Definition • use of medications or other means to soen, eace, and dilate the cervix; increases likelihood of successful induction • ripening of an unfavourable cervix (Bishop score 10%) in the past six months • repeated unplanned/crisis admissions • sentinel event (e.g. serious fall, bereavement, transfer to nursing home) • serum albumin 18 yr who have made a decision to withdraw or withhold life support. Patients were randomized to receive standard of care support and communication, or a physician-driven, nurse-aided, three-step support strategy. The outcome of interest was the proportion of relatives with prolonged grief as indicated by a score ≥30 on the Prolonged Grief Scale (PG-13), 6 mo after the death. Results: A smaller proportion of relatives randomized to receive the involved communication strategy experienced prolonged grief (15%) when compared to the control group (21%). Associated PG-13 scores were also comparatively lower in the group that received the involved communication strategy. Conclusions: A physician-driven, nurse-aided, three-step support strategy is eective at reducing prolonged grief in relatives coping with the loss of a family member.

ENABLE II

JAMA 2009;302:741–749

Title: Eects of a Palliative Care Intervention on Clinical Outcomes in Patients with Advanced Cancer: the Project ENABLE II Randomized Controlled Trial Purpose: To determine the eect of a nursing-led intervention on QoL, symptom intensity, mood, and use of resources in patients with advanced cancer. Methods: Patients were randomized to receive multi-component intervention vs. usual care (n=322). Intervention included telephonebased care by advanced palliative care trained nurses, who provide structured educational and problem-solving sessions, to encourage patient activation, self-management, empowerment and follow-up at least monthly with every patient. Primary outcomes included QoL, symptom intensity, and mood. Intensity of service was measured using days in the hospital and number of ED visits. Results: Longitudinal intention-to-treat analyses for the total sample revealed higher QoL, lower depressed mood, and a trend toward lower symptom intensity. Similar results were seen among patients who passed away, except there was no change in symptom intensity. No dierences were noted in the number of days in the hospital, ICU, or ED visits. Conclusions: A nurse-led, palliative care-focused intervention addressing physical and psychosocial care along with oncology care improved scores for QoL and mood.

ENABLE III

J Clin Oncol. 2015 May 1;33(13):1438-45

Title: Early vs. Delayed Initiation of Concurrent Palliative Oncology Care Purpose: To determine the impact of early vs. delayed initiation of concurrent palliative oncology care on mood, symptom impact, quality of life, and 1-yr survival rate. Methods: RCT consisting of 207 patients with advanced cancer. Patients were randomized to receive in-person palliative care (PC) consultation, structured PC telehealth nurse coaching sessions, and monthly follow-ups upon admission or within 3 mo of admission. The outcomes of interest were quality of life, symptom impact, mood, 1-yr survival, hospital/intensive care unit days, emergency room visits, chemotherapy in the last 14 d, and death location. Results: Mood and quality of life were not significantly dierent between the two groups. 1-yr survival rates were greater in the early intervention compared to the delayed intervention. Relative rates of hospital days, ICU days, emergency room visits, and chemotherapy in the last 14 d of life were similar between the two groups. Conclusions: Although, self-reported outcomes, and resource use were not significantly dierent between the two groups, there was an improvement in 1-yr survival rates.

Back et al., 2007

JAMA Intern. Med. 2007; 167:453-460

Title: Ecacy of Communication Skills Training for Giving Bad News and Discussing Transitions to Palliative Care Purpose: To evaluate the ecacy of a residential communication skills workshop (Oncotalk) for medical oncology fellows in changing observable communication behaviours. Methods: A cohort of 115 medical oncology fellows took part in Oncotalk which emphasized skills practice in small groups. The primary outcomes included participant communication skills measured during standardized patient encounters before and after the workshop in giving bad news and discussing transitions to palliative care. Comparisons were made using each participant as his or her own control. Results: Post-workshop encounters showed that participants improved in bad news skills (P20 mm trunk, >6 mm face, hands, and feet), poorly defined borders, recurrent lesion, poor dierentiation, and type of lesion (e.g. sclerosing, morpheaform)

Table 4. Surgical Margins for Squamous Cell Carcinoma Type of Lesion

Surgical Margins

Low-Risk

4 mm

High-Risk*

6 mm

*High-risk features include: immunosuppressed patient, depth >6 mm, ear/lip, non-sun exposed sites, poorly defined borders, recurrent lesion, poor dierentiation, and histologic features (acantholytic, spindle, desmoplastic, perineural invasion)

© Julian Kirk-Elleker 2006

9

Basic Surgical Techniques PL6 Plastic Surgery

Toronto Notes 2023

Table 5. Surgical Margins for Malignant Melanoma Depth of Lesion*

Surgical Margins

In situ

5 mm

20 mm

*Determined via excisional biopsy **With or without ulceration

Basic Surgical Techniques Sutures and Suturing ANESTHESIA • irrigate before injecting anesthetic, followed by debridement and more vigorous irrigation Table 6. Toxic Limit and Duration of Action (1 cc of 1% solution contains 10 mg lidocaine) Without Epinephrine

With Epinephrine (vasoconstrictor, limits bleeding)

Lidocaine (Xylocaine®)*

5 mg/kg, lasts 45-60 min

7 mg/kg, lasts 2-6 h

Bupivicaine (Marcaine®)

2 mg/kg, lasts 2-4 h

3 mg/kg, lasts 3-7 h

* Lidocaine toxicity symptoms include: circumoral numbness, light-headedness, and drowsiness followed by tremors and seizures. Cardiac and respiratory signs are late findings

Traumatic tattoos are permanent discolourations resulting from new skin growth over foreign material or dirt left behind in the dermis. Copious irrigation and debridement should be done A SAP in order to prevent traumatic tattoos, as they are very dicult to treat later

• e.g. when using 1% lidocaine without epinephrine in a 70 kg patient: ■ 1% = 1g/100 cc = 1000 mg/100 cc = 10 mg/cc ■ toxic limit = 5 mg/kg x 70 kg = 350 mg ■ max bolus injection = 350 mg ÷ 10 mg/cc = 35 cc (may add more aer 30 min) IRRIGATION AND DEBRIDEMENT • irrigate copiously with a physiologic solution such as RL or NS to remove surface clots, foreign material, and bacteria • debride all obviously devitalized tissue; irregular or jagged wounds must be excised to produce sharp wound edges that will assist healing when approximated • there is high-risk of infection for any wound closed primarily aer 8 h SUTURES • use of a particular suture material is dependent on surgeon preference; however, skin should be closed with a non-absorbable, monolament suture material when traumatic mechanisms are involved to prevent harboring bacteria in suture material

Simple Interrupted

Sub-cuticular

Table 7. Suture Materials: Absorbable vs. Non-absorbable and Monofilament vs. Multifilament Uses

Examples

Notes

Deep sutures under short-term tension Skin closure in children

Plain gut®, Vicryl®, Polysorb®, Biosyn®, Monocryl®, Caprosyn®, chromic gut, fast absorbing gut

Loses at least 50% of their strength in 4 wk; eventually absorbed

Non-Absorbable

Skin closure Sites of long-term tension

Nylon, polypropylene (Prolene®), stainless steel, silk, Ticron®, Ethibond®

Lower likelihood of wound dehiscence, more dicult to tie, makes track marks

Monofilament

Everyday use and optimal for contaminated and infected wounds (lower likelihood of bacterial trapping in suture material)

Monosof®, Monocryl®, Biosyn®, Prolene®

Slides through tissue with less friction; more memory/stiness; more dicult to tie; requires multiple throws (lower knot security)

Multifilament

Used to close deep layers, such as in traumatic degloving injuries

Vicryl® and silk, Ticron®, Ethibond®

Less memory/stiness, thus easier to work with (higher knot security); greater infection risk

BASIC SUTURING TECHNIQUES

Horizontal Mattress

Vertical Mattress

Basic Suture Methods • simple interrupted: can be used in almost all situations • sub-cuticular: good cosmetic result but weak, used in combination with deep sutures; not used in trauma Deep Dermal Figure 11. Basic suture methods

© Baseer Khan, Tabby Lulham 2010

Suture Materials Absorbable

Excision PL7 Plastic Surgery

• vertical/horizontal mattress: for areas dicult to evert (e.g. volar hand) • continuous over and over (i.e. “running,” “baseball stitch”): time-saving, good for hemostasis • deep/buried dermal: simple interrupted sutures placed in dermal layer, reduces skin tension for improved healing and are the only sutures that close the wound Other Skin Closure Materials • tapes: (e.g. steri-strips) may be indicated for supercial wounds and those with opposable edges; tape cannot be used on actively bleeding wounds; when placed across the incision, will prevent surface marks and can be used as the primary closing material or as additional reinforcement aer primary surface sutures have been removed • skin adhesives: (e.g. 2-octyl cyanoacrylate, Dermabond®) works well on small areas without much tension or shearing; may cause irreversible tattooing • staples: steel-titanium alloys that incite minimal tissue reaction (healing is comparable to wounds closed by suture)

Excision • plan your incision along relaxed skin tension lines to minimize appearance of scar • use elliptical incision to prevent standing cone deformity (heaped up skin at end of incision), so the length of the ellipse should be approximately 3x the width • if needed, undermine skin edges (separate skin from underlying fascia to allow wound edge manipulation and decrease tension) • use layered closure including deep dermal sutures (decreases tension)

Skin Biopsy Types and Techniques SHAVE BIOPSY • used for supercial lesions where sampling of the full thickness of the dermis is not necessary or practical • most suitable lesions for shave biopsies are benign lesions either elevated above the skin or have pathology conned to the epidermis (e.g. seborrheic or actinic keratoses, skin tags, and warts) • high-risk of recurrence with shave biopsy for any lesions, including actinic or seborrheic keratoses • rapid, requires little training, and does not require sutures for closure (caution in patients on anticoagulant treatment) • heals by secondary intent (moist dressings should be used) • should not be used for pigmented lesions – an unsuspected melanoma cannot be properly staged if partially removed NEEDLE BIOPSY • 21 G for lymph node biopsy • Trucut® needle biopsy for breast masses suspected for carcinoma ■ needle biopsy has fallen out of favour for lymph node biopsies; excisional biopsy is the preferred method in this circumstance INCISIONAL BIOPSY • can be a punch biopsy, or an ellipse within the lesion (normal tissue must be included in biopsy) • gives pathologists a portion of the lesion and the border with normal skin • punch biopsies involve the removal of a full thickness core of tissue to allow sampling of the epidermis, dermis, fat, and potentially muscle depending on the area; performed with a round, disposable circular cutting surface on a plastic handle ranging in diameter from 2-10 mm • punch biopsy wounds can be closed with suture or le to heal by secondary intention EXCISIONAL BIOPSY • performed for lesions that require complete removal for diagnostic purposes • performed for lesions that cannot be adequately punch biopsied due to depth of lesion below surface • for small pigmented lesions and atypical moles; if concerned about melanoma, can do a narrow margin excision for diagnosis and treatment (depending on depth in the case of melanoma) • best for small lesions that are easily removed and primarily closed • requires the greatest amount of expertise and time • always requires sutures for closure TECHNIQUE General • all shave and punch biopsies performed in clinic are done using aseptic technique, but are not sterile • sterile gloves are indicated for biopsies and excisions in all patients Preparing the Site • common skin antiseptics (Betadine®, chlorhexidine) can be used to prepare the biopsy site

Toronto Notes 2023

Steps to Ensuring an Optimized Scar • Incisions should be made along resting skin tension lines • Attain close apposition of wound edges • Minimize tension on skin by closing in layers • Evert wound edges • Use appropriately sized suture for skin closure (5-0 on face; 3-0, 4-0 elsewhere) • Ensure equal width and depth of tissue on both sides • Remove sutures within 5-7 d from the face, 10-14 d from scalp/torso/ extremities

Relaxed Skin Tension Lines Natural skin/wrinkle lines with minimal linear tension. Placing incisions parallel to resting skin tension lines minimizes widening/hypertrophy and helps to camouflage scars. Relaxed skin tension lines are usually parallel to any existing wrinkle lines and perpendicular to the orientation of underlying muscle fibres (perpendicular to lines of maximum extensibility)

Incision Lesion Relaxed skin tension line ©Amy Cao 2019

Figure 12. Incision of lesions along relaxed skin tension lines

Wounds PL8 Plastic Surgery

Toronto Notes 2023

• chlorhexidine is used in concentrations ranging from 0.5-4%. It is not typically used on the face, as it could get into the eyes or ears and may burn or cause damage. Most chlorhexidine preps also contain alcohol, which can be ammable, so allow to dry before the biopsy and certainly before using any cautery • Betadine® (7.5% povidone–iodine) is safer for the head and neck (as to avoid the above problems with chlorhexidine) and around the eyes and ears. It is also used in “contaminated” areas such as the feet and groin • mark the intended lesion and surgical margins with a surgical marker as the rst step, since they may be temporarily obliterated following injection of the anesthetic • for all biopsies, a sterile drape technique is indicated. Sterile towels are placed around the biopsy site aer the area is cleansed and anesthetized Anesthesia • most commonly used local anesthetic is 1% or 2% lidocaine (with epinephrine) • small amounts of epinephrine are added to constrict blood vessels, decrease bleeding, prolong anesthesia, and limit lidocaine toxicity. e local with epinephrine can be injected directly into the lesion • local anesthetics with epinephrine may be used anywhere in the body, including the digits

Wounds • wound: disruption of the normal anatomical relationships of tissue as a result of injury

Types of Wounds • laceration: sharply cut tissue • abrasion: supercial skin layer is removed, variable depth • contusion: injury caused by forceful blow to the skin and so tissue; entire outer layer of skin intact, yet injured • avulsion: skin and so tissue forcefully separated from deeper structures, potentially compromising blood supply or resulting in full detachment (amputation) • puncture wounds: cutaneous opening relatively small as compared with depth (e.g. needle), including bite wounds • crush injuries: caused by compression • burns: thermal, chemical, electrical • ulcers: an open wound that develops on skin as a result of injury, poor circulation, or pressure Principles of Wound Healing Table 8. Factors Influencing Wound Healing Local

General

Mechanical (local trauma, significant crush, avulsion, tension)

Age (aects healing rate)

Blood supply (ischemia/circulation)

Nutrition

Technique and suture materials

Tobacco smoking

Retained foreign body

Alcohol consumption

Infection

Chronic illness (e.g. DM, cancer, dyslipidemia, renal failure, stroke)

Venous HTN

Immunosuppression (steroids, chemotherapy)

PVD

Tissue irradiation Genetic predisposition to abnormal healing (e.g. hypertrophic or keloid scarring, collagen vascular disease) Skin type

STAGES OF WOUND HEALING • growth factors released by tissues play an important role • scar is mature once it has completed the nal stage, usually aer 1-2 yr

PL9 Plastic Surgery

Toronto Notes 2023

PHASE

PROCESS

1. Inflammatory Phase (Reactive) (Days 1-6) • Limits damage, prevents further injury • Debris and organisms cleared via inflammatory response: • Neutrophils (24-48 h) • Macrophages: critical to wound healing by orchestrating growth factors for collagen production (48-96 h) • Lymphocytes: role poorly defined (5-7 d)

1. Hemostasis – vasoconstriction + platelet plug 2. Chemotaxis – migration of macrophages and PMN

2. Proliferative Phase (Regenerative) (Day 4 – Week 3) • Fibroblasts attracted and activated by macrophage growth factors • Reparative process: re-epithelialization, matrix synthesis, angiogenesis (relieves ischemia) • Tensile strength begins to increase at 4-5 d

1. Collagen synthesis (mainly type III) 2. Angiogenesis 3. Epithelialization

3. Remodeling Phase (Maturation) (Week 3 – Year 1) • Increasing collagen organization and stronger crosslinks • Type I collagen replaces Type III until normal 4:1 ratio achieved • Peak tensile strength at 60 d – 80% of pre-injury strength

1. Contraction 2. Scarring 3. Remodeling of scar

Figure 13. Stages of wound healing

TYPES OF WOUND HEALING Primary (1°) Healing (First Intention) • denition: wound closure by direct approximation of edges within hours of wound creation (i.e. with sutures, staples, skin gra, etc.) • indication: recent (6-8 h, longer with facial wounds) wounds • contraindications: animal/human bites, crush injuries, infection, long time lapse since injury (>6-8 h), retained foreign body Secondary (2°) Healing/Spontaneous Healing (Second Intention) • denition: wound le open to heal spontaneously (epithelialization occurs at 1 mm/d from wound margins in concentric pattern, contraction (myobroblasts), and granulation)– maintained in inammatory phase until wound closed; requires dressing changes • indication: when 1° closure not possible or indicated (see Primary Healing) Tertiary (3°) Healing/Delayed Primary Healing (Third Intention) • denition: intentionally interrupt healing process (e.g. with packing, sharp debridement), then wound can be closed primarily at 4-10 d post-injury aer granulation tissue has formed and there is 105 microorganisms in a wound without intact epithelium or small amounts of a very virulent organism (e.g. GBS); have delayed healing and exhibit classic signs of infection ◆ signs of infection: redness, swelling, pain, clinically unwell Management of Acute Contaminated Wounds (8 h, severely contaminated, immunocompromised, involvement of deeper structures (e.g. joints, fractures) ■ use systemic antibiotics if wound cultures are positive and there are signs of infection; tailor antibiotics as cultures return Management of Late Contaminated Wounds (>24 h) • tetanus prophylaxis • irrigation and debridement • systemic antibiotics if there are clinical signs of infection • closure: nal closure via secondary intention (most common), delayed wound closure (3° closure), skin gra, or ap Table 9. Risks for Tetanus Infection Wound Characteristics

Tetanus-Prone

Not Tetanus-Prone

Time Since Injury

>6 h

1 cm

65 years of age; • Tdap for persons 10-64 years of age if using Adacel™ ‡or > 10 years of age if using Boostrix™‡ , unless the person has received a prior dose of Tdap* 3 No vaccine or TIG is recommended for infants 65 years of age if only Adacel™‡is available, or those who have received a Tdap previously. If TT is administered, an adsorbed TT product is preferred to fluid TT (all DTaP/DTP/Tdap/DT/Td products contain adsorbed tetanus toxoid) 5 Give TIG 250 U IM for all ages. It can and should be given simultaneously with the tetanus-containing vaccine 6 For infants 10 years of age ‡

Brand names are used for the purpose of clarifying product characteristics and are not in any way an endorsement of either product

Figure 14. Tetanus immunization recommendations

BITES • see Emergency Medicine, ER47 Dog and Cat Bites • pathogens: Pasteurella multocida, Staphylococcus aureus, Streptococcus viridans, Moraxella species, and Corynebacterium species • investigations ■ radiographs prior to therapy to rule out foreign body (e.g. tooth) or fracture ■ culture for aerobic and anaerobic organisms, Gram stain • treatment: Clavulin® (amoxicillin + clavulanic acid) 500 mg PO q8 h started immediately ■ consider rabies prophylaxis if animal has symptoms of rabies or unknown animal ◆ ± rabies Ig (20 IU/kg around wound, or IM) and 1 of the 3 types of rabies vaccines (1.0 mL IM in deltoid, repeat on days 3, 7, 14, 28) • irrigation with debridement • healing by secondary intention is mainstay of treatment • only consider primary closure for bite wounds on the face if large and done in OR; otherwise primary closure is contraindicated • contact Public Health if animal status unknown Human Bites • pathogens: Staphylococcus aureus > GAS> Eikenella corrodens > Bacteroides • serious condition, as mouth has 10 9 microorganisms/mL, which can get trapped in joint space when the overlying skin forms and air-tight covering ideal for anaerobic growth (e.g. ght bite injury when st unclenches) - can lead to septic arthritis • investigations ■ radiographs prior to therapy to rule out foreign body (e.g. tooth) or fracture ■ culture for aerobic and anaerobic organisms, Gram stain

Dressings PL12 Plastic Surgery

Toronto Notes 2023

• treatment ■ if joint infected, urgent surgical exploration of joint, drainage, and debridement of infected tissue ■ otherwise, can be managed with I & D and antibiotic treatment in ER ■ if due to MSSA, Cefazolin 2 g IV q8h or (if penicillin allergy or MRSA) vancomycin 15 mg/kg IV q12h + secondary closure ■ splint

Dressings • dressing selection depends on the wound characteristics, goal of dressing, and surgeon preference ■ as the wound progresses through healing, it will require dierent types of dressings; therefore, routine inspection is recommended ◆ principles of dressing clean vs. infected wounds – clean wounds can be dressed with non-adherent dressing (which is non-adhering to epithelialising tissue); requires secondary dressing – infected wounds may need debridement, antibiotics, and antimicrobial dressings (i.e. iodine gauze and silver-containing dressings) ◆ moist vs. dry wounds – purpose of dressings should be to promote moist wound healing i.e. moistening dry wounds or drying (removing excess exudate/blood) wet wounds ◆ wide-based vs. cavitary/tunneling wounds – cavitary or tunneling wounds (i.e. through a fascial layer) can be packed with loose, large, and radiopaque packing materials ◆ negative pressure wound therapy uses wound dressings that apply subatmospheric pressure to the wound site to promote blood ow to the region and enhance the healing process. e resultant pressure gradient promotes uid transport from the wound bed and interstitial space to reduce wound edema ◆ indications: diabetic foot ulcers, reconstructive surgery, and following debridement of acute or chronic wounds ◆ contraindications: wounds with exposed vital structures (i.e. organs, blood vessels, vascular gras) and malignant tissue Table 10. Wound Dressings and Their Use Dressing Type

Example

Use

Low adherent dressings

Jelonet, tullegras, mepilex, mepitel

Flat and shallow wounds with low exudates

Semipermeable films

Mefilm, Tegaderm, Bioclusive

Wounds in dicult anatomic sites (ex: over joints)

Hydrocolloids

CombiDERM, Tegasorb, Aquacel

Hydrocolloid sheets: flat, shallow wounds with low exudate; dicult areas (elbow, heel, etc.) Hydrofibre: flat wounds, cavities, sinuses; medium – high exudate wounds

Antimicrobial

Acticoat, Avance, Iodosorb

Locally infected wounds

Reconstruction RECONSTRUCTION LADDER Definition • an approach to wound management with successively more complex methods of treatment • surgeons should start with the least complex method and progressively increase in complexity as appropriate SKIN GRAFTS

Reconstruction Ladder Vascularized composite allotransplantation Free flap Pedicle flap Random pattern flap Tissue expansion

Definition • tissue composed of epidermis and varying degrees of dermis, that does not carry its own blood supply. Survival requires the generation of new blood vessels from the recipient site bed Donor Site Selection • must consider size, hair pattern, texture, thickness of skin, and colour (facial gras best if taken from “blush zones” - harvest sites above clavicle where colour match for full thickness gras is optimized (e.g. pre/post auricular or neck)) • partial thickness gras usually taken from inconspicuous areas (e.g. buttocks, lateral thighs, etc.)

Full thickness graft Split thickness graft Delayed closure Primary closure Healing by secondary intention ©Tiffany Ni 2T4 2022

Figure 15. Reconstructive ladder - in order of increasing complexity

Meshed Grafts PL13 Plastic Surgery

Toronto Notes 2023

Partial Thickness Skin Graft Survival • initial stabilization of gra provided by brin network between recipient site and gra • 3 phases of skin gra “take” 1. plasmatic imbibition: diusion of nutrition from recipient site (rst 48 h) 2. inosculation: growth of vessels from bed and gra toward each other (d 2-3) 3. neovascular ingrowth: growth of new vessels which vascularize gra (d 3-5) • requirements for gra survival ■ well-vascularized bed (recipient site). Examples of unsuitable beds include heavily irradiated wounds and infected wounds ■ coagulation begins as soon as gra is placed on bed ■ good contact between gra and recipient bed. Staples, sutures, splinting, and pressure dressings are used to prevent movement/shearing of gra and hematoma or seroma formation ■ low bacterial count at recipient site (5 s

50 yr, peripheral vascular disease, and malnutrition Clinical Features • pain out of proportion to clinical ndings and beyond border of erythema • edema, tenderness, ± crepitus (subcutaneous gas from anaerobes), ± sepsis-type symptoms (e.g. nausea, fever, diarrhea, dizziness, malaise) • overlying skin changes including blistering and ecchymoses • patients may look deceptively well at rst, but have some physiological abnormalities on initial labs and may rapidly become very sick/toxic • late ndings: ■ skin turns dusky blue and black (secondary to thrombosis and necrosis) ■ induration, formation of bullae ■ cutaneous gangrene, subcutaneous emphysema Investigations • a clinical diagnosis • CT scan only if suspect it is not necrotizing fasciitis (looking for abscess, gas collection, myonecrosis and possible source of infection) • severely elevated CK: usually means myonecrosis (late sign) • bedside incision, exploration, and incisional biopsy when ruling out conditions, clinical feature is not supportive, or dicult exam • during incisional biopsy, oen see “dishwater pus” (GAS) and a hemostat easily passed along fascial plane (fascial biopsy to rule out in equivocal situations)

Toronto Notes 2023

Ulcers PL17 Plastic Surgery

Toronto Notes 2023

Treatment • vigorous resuscitation (ABCs) • urgent surgical debridement: remove all necrotic tissue, copious irrigation with plans for repeat surgery in 24-48 h • IV antibiotics: as appropriate for clinical scenario; consider penicillin 4 million IU IV q4 h and clindamycin 900 mg IV q6 h until nal cultures available (the combination can be synergistic if GAS) or vancomycin and clindamycin • postoperative ICU admission and infectious disease consult aer urgent surgical debridement by plastic surgery

Ulcers Lower Limb Ulcers Traumatic Ulcers (Acute) • failure of wound to heal, usually due to compromised blood supply and unstable scar, secondary to pressure or bacterial colonization/infection • usually over bony prominence ± edema ± pigmentation changes ± pain • treatment, in consultation with vascular surgery ■ any debridement of ulcer and compromised tissues must be preceded by ABIs and vascular Doppler ■ ulcers or compromised tissues le to heal by secondary intention with dressings may need reconstruction with local or distant ap in select cases; vascular status of limb must be assessed clinically and via vascular studies (i.e. ABI, duplex Doppler) Table 14. Venous vs. Arterial vs. Diabetic Ulcers Characteristic

Venous (70% of vascular ulcers)

Arterial

Diabetic

Cause

Valvular incompetence Venous HTN

2° to small and/or large vessel disease (be aware of risk factors)

Peripheral neuropathy: decreased sensation Atherosclerosis: microvascular disease

History

Dependent edema, trauma Rapid onset ± thrombophlebitis, varicosities

Arteriosclerosis, claudication Usually >45 yr Slow progression

DM Peripheral neuropathy Trauma/pressure

Common Distribution

Medial malleolus (“Gaiter” locations)

Distal locations (e.g. lower limb, feet)

Pressure point distribution (more likely metatarsal heads)

Appearance

Yellow exudates Granulation tissue Varicose veins Brown discolouration of surrounding skin

Pale/white, necrotic base ± dry eschar covering

Necrotic base

Wound Margins

Irregular

Even (“punched out”)

Irregular or “punched out” or deep

Depth

Superficial

Deep

Superficial/deep

Surrounding Skin

Venous stasis discolouration (brown) Thin, shiny, dry skin; hairless, cool

Thin, dry skin ± hyperkeratotic border Hypersensitive/ischemic

Pulses

Normal distal pulses

Decreased or no distal pulses

Decreased pulses likely (take caution in calcified vessels)

Vascular Exam

ABI >0.9 Doppler; abnormal venous system

ABI 6 h of pressure 4. ulcer: necrotic area breaks down Classification (National Pressure Ulcer Advisory Panel 2014) • Stage I: non-blanchable erythema present >1 h aer pressure relief, skin intact • Stage II: partial-thickness skin loss • Stage III: full-thickness skin loss into subcutaneous tissue • Stage IV: full-thickness skin loss into muscle, bone, tendon, or joint ■ if an eschar is present, must fully debride before staging possible • Stage X: unstageable Prevention • clean and dry skin, frequently reposition, special beds or pressure relief surface, proper nutrition, activity, early identication of individuals at risk (e.g. immobility, incontinence, paraplegia, immunocompromised, DM, etc.), treatment of underlying medical conditions Treatment • treatment plan individualized to patient • 4 main principles: ■ preventative measures (pressure relief, assess for pressure points e.g. wheelchairs; manage continence issues, divert contaminants e.g. urine and feces, ensure appropriate nutrition) ■ treatment of underlying medical issues including nutrition ■ moisture reduction and pressure relief ■ wound bed preparation and treatment • systemic antibiotics for infections • assess for possible reconstruction

A Nutritional Formula Enriched with Arginine, Zinc, and Antioxidants for the Healing of Pressure Ulcers: A Randomized Trial Ann Intern Med 2015;162(3):167-174 Purpose: To determine whether supplementation with arginine, zinc, and antioxidants within a high-calorie, high-protein formula improves pressure ulcer healing. Methods: 200 adult patients from long-term care and home care services with stage II, III, and IV pressure ulcers received either an energy-dense, protein-rich oral formula enriched with arginine, zinc, and antioxidants or an equal volume of an isocaloric, isonitrogenous formula for 8 wk. Results: Supplementation with the enriched formula resulted in a greater reduction in pressure ulcer area. A more frequent reduction in area of 40% or greater at 8 wk was also seen. Conclusion: Among malnourished patients with pressure ulcers, 8 wk of supplementation with an oral nutritional formula enriched with arginine, zinc, and antioxidants improves pressure ulcer healing.

Complications • cellulitis, osteomyelitis, sepsis, gangrene

Burns Burn Injuries Causal Conditions • thermal (ame contact, scald) • chemical • radiation (UV, medical/therapeutic) • electrical

Skin surface Epidermis

Zone of hyperemia

Table 15. Skin Function and Burn Injury

Zone of stasis

Skin Function

Consequence of Burn Injury

Intervention Required

Thermoregulation

Prone to lose body heat

Must keep patient covered and warm

Control of Fluid Loss

Loss of large amounts of water and protein from the skin and other body tissues

Adequate fluid resuscitation is imperative

Mechanical Barrier to Bacterial Invasion and High-risk of infection Immunological Organ

Antimicrobial dressings (systemic antibiotics if signs of specific infection present) Tetanus prophylaxis if not already administered

Zone of coagulation

Blood vessels and most nerves are found in the dermis

Figure 18. Zones of thermal injury

© Gail Rudakewich

Dermis: Nerves Vessels

Most Common Etiologies • children: scald burns • adults: ame burns

Pathophysiology of Burn Wounds PL19 Plastic Surgery

Toronto Notes 2023

Pathophysiology of Burn Wounds • amount of tissue destruction is based on temperature, time of exposure, and specic heat of the causative agent • zone of hyperemia: vasodilation from inammation; entirely viable, cells recover within 7 d; contributes to systemic consequences seen with major burns • zone of stasis (edema): decreased perfusion; microvascular sludging and thrombosis of vessels results in progressive tissue necrosis → cellular death in 24-48 h without proper treatment ■ factors favouring cell survival: moist, aseptic environment, rich blood supply ■ zone where appropriate early intervention has most profound eect in minimizing injury • zone of coagulation (ischemia): no blood ow to tissue → irreversible cell damage → cellular death/ necrosis

Diagnosis and Prognosis • burn size ■ % of TBSA burned: rule of 9s for 2° and 3° burns only (children 80% TBSA ■ 4° burns ■ associated traumatic injury ■ electrical burn ■ inhalation injury ■ delayed start of resuscitation ■ paediatric burns • monitor resuscitation ■ urine output is best measure: maintain at >0.5 cc/kg/h (adults) and 1.0 cc/kg/h in children 10% TBSA, or deeper than supercial-partial thickness, need 0.5 cc tetanus toxoid ■ also give 250 U of tetanus Ig if prior immunization is absent/unclear, or the last booster >10 yr ago • baseline laboratory studies (Hb, U/A, BUN, CXR, electrolytes, Cr, glucose, CK, ECG, cross-match if traumatic injury, ABG, carboxyhemoglobin) • cleanse, debride, and treat the burn injury (antimicrobial dressings) • early excision and graing are standard of care and important for outcome Respiratory Problems • 3 major causes ■ burn eschar encircling chest ◆ distress may be apparent immediately ◆ perform escharotomy to relieve constriction ■ CO poisoning ◆ may present immediately or later ◆ treat with 100% O2 by facemask (decreases half-life of carboxyhemoglobin from 210 to 59 min) until carboxyhemoglobin Hour 30

D5W at rate to maintain normal serum sodium

* Remember to add maintenance fluid to resuscitation

Inhalation Injuries 101 Indicators of Inhalation Injury • Injury in a closed space • Facial burn • Singed nasal hair/eyebrows • Soot around nares/oral cavity • Hoarseness • Conjunctivitis • Tachypnea • Carbon particles in sputum • Elevated blood CO levels (i.e. brighter red) • Suspected inhalation injury requires immediate intubation due to impending airway edema; failure to diagnose inhalation injury can result in airway swelling and obstruction, which, if untreated, can lead to death • Neither CXR or ABG can be used to rule out inhalation injury • Direct bronchoscopy now used for diagnosis • Signs of CO poisoning (headache, confusion, coma, arrhythmias)

PL22 Plastic Surgery

Toronto Notes 2023

Table 18. Burn Wound Healing Depth

Healing

First Degree

No scarring; complete healing

Second Degree (superficial partial)

Spontaneously re-epithelialize in 7-14 d from retained epidermal structures ± Residual skin discolouration Hypertrophic scarring uncommon; grafting rarely required

Deep Second Degree (deep partial)

Re-epithelialize in 14-35 d from retained epidermal structures Hypertrophic scarring frequent Grafting recommended to expedite healing

Third Degree (full thickness)

Re-epithelialize from the wound edge

Fourth Degree

Often results in amputations

Grafting/flap necessary to replace dermal integrity and limit hypertrophic scarring If not requiring amputation, needs flap for coverage after debridement (does not re-epithelialize, cannot graft)

Treatment • three stages 1. assessment: depth determined 2. management: specic to depth of burn and associated injuries 3. rehabilitation • rst degree ■ treatment aimed at comfort ■ topical creams (pain control, keep skin moist) ± aloe ■ oral NSAIDs (pain control) • supercial second degree/partial thickness ■ daily dressing changes with topical antimicrobials (such as Polysporin®); leave blisters intact unless impaired or over joint and inhibiting motion • deep second degree/deep partial thickness and third degree/full thickness ■ prevent infection and sepsis (signicant complication and cause of death in patients with burns) ◆ most common organisms: S. aureus, P. aeruginosa, and C. albicans – day 1-3 (rare): Gram-positive – day 3-5: Gram-negative (Proteus, Klebsiella) ◆ topical antimicrobials: treat colonized wounds (from skin ora, gut ora, or caregiver) ■ remove dead tissue • surgically debride necrotic tissue, excise to viable (bleeding) tissue Table 19. Antimicrobial Dressings for Burns Antibiotic

Pain with Application

Penetration

Adverse Eects

Silver Nitrate (0.5% solution)

None

Minimal

May cause methemoglobinemia, stains (black), leeches sodium from wounds

Nanocrystalline Silver-Coated Dressing (Acticoat®)

None or transient

Medium, does not penetrate eschar

May stain, producing a pseudoeschar or facial discolouration (bluish-gray discolouration; raised liver enzymes

Silver Sulfadiazine (cream) (Flamazine®, Silvadene®)

Minimal

Medium, penetrates eschar

Slowed healing, leukopenia, mild inhibition of epithelialisation; pseudoeschar must be washed o prior to each application

Sulfamylon®

Moderate

Well, penetrates eschar; only used on ears

Mild inhibition of epithelialization, may cause metabolic acidosis with wide application

• early excision and graing is the mainstay of treatment for deep/full thickness burns • initial dressing should decrease bacterial proliferation Other Considerations in Burn Management Altered Hemodynamics ( CO,  SVR) Vascular Permeability and Edema Hypermetabolism Immunosuppression

SEVERE BURN Progressive Pulmonary Insufficiency

Renal Failure (2º to  Renal Blood Flow) Increased Gut Mucosal Permeability (GI Bleed Risk)

Figure 21. Systemic eects of severe burns

• nutrition ■ hypermetabolism: TBSA >40% have BMR 2-2.5x predicted ■ consider nutritional supplementation (e.g. calories, vitamin C, vitamin A, Ca 2+, Zn 2+, Fe 2+)

Risk Factors for Infection of Burn Wounds Patient Related Extent >30% TBSA • Depth: full thickness and deep partial thickness • Patient age (higher risk with very young and very old) • Comorbidities • Wound dryness • Wound temperature • Secondary impairment of blood flow to wound • Acidosis Microbial Factors • Density >105 organisms per gram of tissue • Motility • Virulence and metabolic products (endotoxin, exotoxin, permeability factors, other factors) • Antimicrobial resistance

Special Considerations PL23 Plastic Surgery

Toronto Notes 2023

• immunosuppression and sepsis ■ must keep bacterial count 48 h post-burn, mental status changes, azotemia, thrombocytopenia, hypobrinogenemia, hyper/hypoglycemia (especially if burn >40% TBSA) • GI bleed may occur with burns >40% TBSA (usually subclinical) ■ treatment: tube feeding or NPO if there is a GI bleed, antacids, H2 blockers (preventative) • renal failure secondary to under resuscitation, drugs, myoglobin, etc. • progressive pulmonary insuciency ■ can occur aer: smoke inhalation, pneumonia, cardiac decompensation, sepsis • wound contracture and hypertrophic scarring ■ outcomes optimized with timely wound closure, splinting, pressure garments, and physiotherapy

Special Considerations CHEMICAL • major categories: acid burns, alkaline burns, phosphorus burns, chemical injection injuries • common agents: cement, hydrouoric acid, phenol, tar • mechanism of injury: chemical solutions coagulate tissue protein leading to necrosis ■ acids → coagulation necrosis ■ alkalines → saponication followed by liquefactive necrosis • severity related to: type of chemical (alkali worse than acid), temperature, volume, concentration, contact time, site aected, mechanism of chemical action, degree of tissue penetration • burns are deeper than they initially appear and may progress with time Treatment (General) • ABCs, monitoring • remove contaminated clothing and brush o any dry powders before irrigation • irrigation with water for 1-2 h under low pressure (contraindicated in elemental metal burns, such as sodium, potassium, magnesium, and lithium; in these cases, soak in mineral oil instead) • inspect eyes; if aected, wash with saline and refer to ophthalmology • inspect nails, hair, and webspaces • correct metabolic abnormalities and provide tetanus prophylaxis if necessary • contact poison control line if necessary • local wound care 12 h aer initial dilution (debridement) • wound closure same as for thermal burn • beware of underestimated uid resuscitation, renal, liver, and pulmonary damage Table 20. Special Burns and Treatments Burns

Treatment

Acid Burn

Water irrigation, followed by dilute solution of sodium bicarbonate

Hydrofluoric Acid

Water irrigation; clip fingernails to avoid acid trapping; topical calcium gel ± subcutaneous injection of calcium gluconate ± 10% calcium gluconate IV depending on amount of exposure and pain

Sulfuric Acid

Treat with soap/lime prior to irrigation as direct water exposure produces extreme heat

Tar

Remove with repeated application of petroleum-based antibiotic ointments (e.g. Polysporin®)

ELECTRICAL BURNS • injury occurs due to ow of current through body, arc ash, or clothing catching on re • depth of burn depends on voltage and resistance of the tissue (injury more severe in tissues with high resistance) • oen presents as small punctate burns on skin, with extensive deep tissue damage which requires debridement • electrical burns require ongoing monitoring (ECG and neurovascular status), as latent injuries can occur • watch for system-specic damages and abnormalities ■ abdominal: intraperitoneal damage ■ bone: fractures and dislocations especially of the spine and shoulder ■ cardiopulmonary: anoxia, ventricular brillation, arrhythmias ■ muscle: myoglobinuria indicates signicant muscle damage → compartment syndrome ■ neurological: seizures and spinal cord damage ■ ophthalmology: cataract formation (late complication) ■ renal: acute tubular necrosis resulting from toxic levels of myoglobin and hemoglobin ■ vascular: vessel thrombosis → tissue necrosis (increased Cr, K+, and acidity), decrease in RBC count (beware of hemorrhages/delayed vessel rupture)

Hand PL24 Plastic Surgery

Toronto Notes 2023

Treatment • ABCs, primary and secondary survey, treat associated injuries • beware of cardiac arrhythmias (continue cardiac monitoring) • monitor: hemochromogenuria, compartment syndrome, urine output • wound management: topical agent with good penetrating ability (silver sulfadiazine or mafenide acetate) • debride nonviable tissue early and repeat prn (every 48 h) to prevent sepsis • amputations frequently required FROSTBITE • see Emergency Medicine, ER46

Hand Traumatic Hand Table 21. Key Features of the History and Physical Exam of the Injured Hand HISTORY Key Questions

Age

Tetanus status

Hand dominance

Diabetes

Occupation

Smoking status

Time and place of accident

Last oral intake

Mechanism of injury

Previous history of hand injury

Initial treatment received PHYSICAL EXAM Observation

Vascular Status

Sensory (see Figure 3, PL3)

Motor Function

Structure

Examination

Position of finger

Abnormal cascade (fingers normally slightly flexed and point towards scaphoid), scissoring

Deformity

Bony protrusions or specific deformities (e.g. mallet, boutonnière, and swan neck deformity)

Bruising or swelling

May indicate underlying skeletal injury

Approach to Hand Lacerations

Sweating pattern (usually felt more so than from observation)

May indicate denervation

Anatomical structures beneath

If open laceration, need to explore within wound (under sterile conditions)

Radial and ulnar arteries

Palpate pulses Allen’s test

Digital arteries

Assess capillary refill (30-40 mmHg). Of note, upper and lower extremity pressures are dierent and comorbidities can result in variability in measured pressures. As such, indication for an emergent fasciotomy is based on clinical diagnosis; if untreated, end result is ischemic contracture of the extremity (Volkmann’s contracture)

Allen’s Test: You need to exsanguinate the hand by having the patient open and close the hand. Then, while patient’s hand is firmly closed, occlude both radial and ulnar arteries. Once fist is open, release one artery and assess collateral flow. The process should be repeated for the other artery

Tissue Resistance to Electrical Current Nerve < vessel/blood < muscle < skin < tendon < fat < bone

General Management of Hand Injuries (Categorized by Tissue) PL25 Plastic Surgery

Toronto Notes 2023

General Management of Hand Injuries (Categorized by Tissue) Nerves • test the nerve function BEFORE putting in local anesthesia • primary repair for a clean injury within 2 wk and without concurrent major injuries; secondary repair if >2 wk (may require nerve gra) • epineurial repair of all digital nerves with minimal tension • postoperative: dress wound, elevate hand, and immobilize • Tinel’s sign (cutaneous percussion over the repaired nerve) produces paresthesias and denes level of nerve regeneration ■ Wallerian degeneration occurs in the rst 2 wk, which is why there is no Tinel’s sign until aer this time period ■ a peripheral nerve regenerates at 1 mm/d ■ paresthesias felt at area of percussion because regrowth of myelin (Schwann cells) is slower than axonal regrowth → percussion on exposed free-end of axon generates paresthesia Vessels • oen associated with nerve injury in the digits (anatomical proximity) • control bleeding with direct pressure and hand elevation • if digit devascularized, optimal repair within 6 h • close skin, then dress, immobilize, and splint hand with ngertips visible • monitor colour, capillary rell, skin turgor, ngertip temperature post-revascularization Tendons • most tendon lacerations require repair • most extensors are repaired in the emergency room, exors are repaired in the operating room within 2 wk • see Tendons, PL27 Bones • see Fractures and Dislocations, PL28 Nailbed • subungual hematomas >50% of the nail surface area need to be drained (trephination), done under a digital block by puncturing nail plate • if suspecting greater severity of injury (e.g. distal phalanx displaced fracture, laceration of nail bed), remove nail plate to examine underlying nailbed under digital block anesthesia • irrigate wound and nail thoroughly • suture repair of nailbed with chromic suture • replace cleaned nail, which acts as a splint for any underlying distal phalangeal fracture and prevents adhesion formation between nail fold and nailbed

Hand Infections Principles • trauma is most common cause • 90% caused by Gram-positive organisms • most common organisms (in order): S. aureus, S. viridans, GAS, S. epidermidis, and Bacteroides melaninogenicus (MRSA is becoming more common) TYPES OF INFECTIONS Deep Space Infections • abscess formation in deep spaces of the hand, parona’s space, web spaces, or most commonly thenar or midpalmar space Felon • denition: abscess in the pulp of a ngertip or thumb that occurs following a puncture wound into the pad of the digit; may be associated with osteomyelitis • treatment: elevation, warm soaks, cloxacillin 500 mg PO q6 h (if in early stage); if obvious abscess or pressure on the overlying skin or failure to resolve with conservative measures, then I&D, take cultures/Gram stain, and adjust antibiotics to culture results

Hand Exam • Never blindly clamp a bleeding vessel as nerves are often found in close association with vessels • Never explore any volar hand wound in the ER • Arterial bleeding from a volar digital laceration is likely associated with a nerve laceration (nerves in digits are superficial to arteries)

Amputations PL26 Plastic Surgery

Flexor Tendon Sheath Infection • Staphylococcus > Streptococcus > Gram-negative rods • denition: abscess within the exor tendon sheath (exor tenosynovitis), commonly caused by a penetrating injury and can lead to tendon necrosis and rupture if not treated • clinical features: Kanavel’s 4 cardinal signs 1. point tenderness along exor tendon sheath from A1 pulley onwards 2. severe pain on passive extension of digit 3. fusiform swelling of entire digit 4. exed posture (increased comfort) • treatment ■ non-suppurative: antibiotics, resting hand splint and elevation until infection resolves, hand therapy aer ■ suppurative (produces pus): I&D in OR Herpetic Whitlow • HSV-1, HSV-2 • denition: painful vesicle(s) around ngertip or thumb ■ oen found in medical/dental personnel and children • clinical features: can be associated with fever, malaise, and lymphadenopathy, prodromal phase ■ patient is infectious until lesion has completely healed • treatment: diagnosed clinically, if in doubt conrm with viral culture/PCR or Tzanck smear, usually self-limited, consider oral acyclovir in severe cases; debridement of these lesions is contraindicated Paronychia • acute = Staphylococcus; chronic = Candida • denition: infection (granulation tissue) of so tissue around ngernail (within the paronychium and/or beneath eponychial fold) • etiology ■ acute paronychia: a “hangnail,” articial nails, and nail biting ■ chronic paronychia: prolonged exposure to moisture • treatment ■ acute paronychia: warm compresses and oral antibiotics if caught early; if abscess present, drainage with blade (avoid hitting nail bed) and oral/IV antibiotics; if abscess extends to below nail plate, nail plate removal may be required ■ chronic paronychia: antifungals, eponychial marsupialization; nail plate removal may be required

Amputations Hand or Finger • emergency management: injured patient and amputated part requires attention ■ patient: x-rays (stump and amputated part), NPO, clean wound and irrigate with NS, dress stump with non-adherent dressing, cover with dry sterile dressing, tetanus and antibiotic prophylaxis (cephalosporin/erythromycin) ■ amputated part: x-rays, gently irrigate with RL, wrap amputated part in a NS/RL soaked sterile gauze and place inside waterproof plastic bag, place in a container, then place container on ice • indications for replantation ■ age: children oen better results than adults ■ level of injury: thumb and multiple digit amputations are higher priority; multiple level amputation is a contraindication to replant ■ nature of injury: clean cut injuries have greater success; avulsion and crush injuries are relative contraindications to replant • if replant contraindicated, manage stump with revision amputation ■ involves debriding stump of wound, trimming back the bone and nerve endings, and gently closing the skin ■ commonly done in the ER under digital block

Toronto Notes 2023

Tendons PL27 Plastic Surgery

Toronto Notes 2023

Tendons Common Extensor Tendon Deformities Table 22. Extensor Tendon Deformities Injury

Definition

Zone

Etiology/Clinical Features

Treatment

Mallet Finger

DIP flexed with loss of active extension

1

There are bony and non-bony mallets Bony: fracture of distal phalanx distal to tendon insertion Non-bony: forced flexion of the extended DIP leading to extensor tendon rupture at DIP (e.g. sudden blow to tip of the finger)

Splint DIP in extension for 6 wk, followed by 2 wk of night splinting; if inadequate improvement after 6 wk, check splinting routine and recommend 4 more wk of continuous splinting

Boutonnière Deformity

PIP flexed, DIP hyperextended

3

Injury or disease aecting the extensor tendon insertion into the dorsal base of the middle phalanx Associated with RA or trauma (laceration, volar dislocation, acute forceful flexion of PIP)

Splint PIP in extension and allow active DIP motion

A

PIP hyperextended, DIP 1,3 flexed

B

Corrective procedures Trauma (PIP volar plate injury) Associated with RA and old, untreated involve tendon rebalancing or arthrodesis/arthroplasty mallet deformity Splint to prevent PIP hyperextension or DIP flexion

C

DIP

Zone 1 Zone 2

© Jackie Robers | Erina He 2016

Swan Neck Deformity

PIP

Zone 3 Zone 4 Zone 5

DIP flexion

Zone 6 ET

PIP hyperextension

Zone 7 Zone 8

© Emily Taylor 2020 after Jackie Robers

Figure 22. Extensor tendon deformities: (A) Mallet finger deformity (B) Boutonnière deformity (C) Swan neck deformity

Figure 23. Zone of extensor tendon injury (odd numbered zones fall over a joint)

De Quervain’s Tenosynovitis • denition: tenosynovitis is inammation of the tendon and/or its sheath. Most common is De Quervain’s tenosynovitis (inammation of the extensor tendons in the 1st dorsal compartment (APL and EPB)) • clinical features ■ positive Finkelstein’s test (pain over the radial styloid induced by making st, with thumb in palm, and ulnar deviation of wrist) ■ pain localized to the 1st extensor compartment ■ tenderness and crepitation over radial styloid may be present ■ dierentiate from CMC joint arthritis (CMC joint arthritis will have a positive grind test, whereby crepitus and pain are elicited by axial pressure to the thumb) • treatment ■ mild: NSAIDs, splinting, and steroid injection into the tendon sheath ■ severe: surgery to open 1st dorsal compartment and release stenotic tendon sheaths of APL and EPB Ganglion Cyst • denition ■ uid-lled synovial lining that protrudes between carpal bones or from a tendon sheath; most commonly carpal in origin ■ most common so tissue tumour of hand and wrist (60% of masses) • clinical features ■ most commonly on the dorsal wrist overlying the scapholunate ligament, followed by the volar surface of the wrist overlying the radioscaphoid or scaphotrapezial joints ■ 3 times more common in women than in men ■ more common in younger individuals (2nd to 4th decades) ■ can be large or small (may drain internally so size may wax and wane) ■ oen non-tender, although tenderness increased when cyst is smaller (from increased pressure within smaller cyst sac) • treatment ■ conservative treatment: observation and reassurance; advise patient against rupturing cyst ■ aspiration (recurrence rate 30-60% within one yr, risk of damaging nearby neurovascular structures) ■ steroid injection if painful (done in combination with aspiration, as results alone are no better than aspiration) ■ consider operative excision of cyst and stalk (recurrence rate 5.9% for dorsal wrist ganglion, 30% for volar)

I

II

III

IV

V

©Ava Schroedl 2021 after Shelley Wall 2003

Figure 24. Zones of the flexor tendons

A-2 and A-4 pulleys are most important for function; prevent bowstringing of tendons

Fractures and Dislocations PL28 Plastic Surgery

Common Flexor Tendon Deformities • exor tendon zones (important for prognosis of tendon lacerations) • “no-man’s land” (zone 2) ■ between distal palmar crease and mid-middle phalanx ■ zone where supercialis and profundus lie ensheathed together ■ recovery of glide very dicult aer injury Stenosing Tenosynovitis (Trigger Finger/Thumb) • denition: inammation and thickening of tendon or tendon sheath/pulley (most commonly at A-1 pulley near MCP), preventing smooth gliding of tendon through the sheath/pulley and resulting in locking of thumb or nger in exion/extension • etiology: idiopathic or associated with RA, DM, hypothyroidism, gout, and pregnancy • clinical features ■ ring nger is most commonly aected, then long nger and thumb ■ patient complains of catching, snapping, or locking of aected nger ■ tenderness to palpation/nodule at palmar aspect of MCP over A-1 pulley ■ women are 4 times more likely to be aected than men • non-surgical treatment ■ NSAIDs ■ steroid injection; injections less likely to be successful in patients >60 yr, or symptoms greater than 6 mo ■ splint • surgical treatment ■ indicated if no relief of symptoms or minimal relief with steroids ■ incise A-1 exor pulley to permit unrestricted, full active nger motion

Fractures and Dislocations • for fracture principles, see Orthopaedic Surgery, OR5 FRACTURES • about 90% of hand fractures are stable in exion (splint to prevent extension) • position of safety ■ wrist extension 0-30° ■ MCP exion 70-90° ■ IP full extension ■ this is done if you want to immobilize a fracture but are not sure whether there are other injuries • stiness secondary to immobilization is the most important complication Distal Phalanx Fractures • most commonly fractured bone in the hand • usual mechanism is crush injury, and thus accompanied by so tissue injury • subungual hematoma is common and must be decompressed, especially if there is involvement of >50% of the nail surface area, see General Management of Hand Injuries (Categorized by Tissue), PL25 • treatment: 3 wk of digital splinting (immobilize the DIP with a STAX™ splint); if intra-articular fracture displaced >30%, then percutaneous pinning (K-wires) and splint, or ORIF Proximal and Middle Phalanx Fractures • check for: rotation, scissoring (overlap of ngers on making a st), shortening of digit • non-displaced or minimally displaced: closed reduction (if extra-articular), buddy tape to neighbouring stable digit, elevate hand, careful motion of extremity with splint to prevent reinjury, splinted for 2-3 wk • displaced, non-reducible, not stable with closed reduction, or rotational or scissoring deformity: percutaneous pinning (K-wires) or ORIF, and splint Metacarpal Fractures • generally accept varying degrees of deviation before reduction required: up to 10° (D2), 20° (D3), 30° (D4), or 40° (D5) • Boxer’s fracture: acute angulation of the neck of the 5th metacarpal into palm ■ mechanism: blow on the distal-dorsal aspect of closed st ■ loss of prominence of metacarpal head, volar displacement of head ■ up to 30-40° angulation may be acceptable ■ closed reduction should be considered to decrease the angle ■ if stable, ulnar gutter splint for 4-6 wk • Bennett’s fracture: two-piece fracture/dislocation of the base of the thumb metacarpal, usually intraarticular ■ unstable fracture ■ APL pulls MC sha proximally and radially, causing adduction of thumb ■ treat with percutaneous pinning or ORIF, followed by thumb spica for 6 wk • Rolando fracture: T- or Y-shaped fracture of the base of the thumb metacarpal ■ treated like a Bennett’s fracture

Toronto Notes 2023

A5 A4 A3 A2 A1 Nodule Synovial sheath Flexor digitorum superficialis Flexor digitorum profundus ©Cassie Hillock-Watling 2021

Figure 25. Digital flexor pulley system

Dupuytren’s Disease PL29 Plastic Surgery

Toronto Notes 2023

DISLOCATIONS • treatment: must be reduced as soon as possible • dislocation vs. subluxation ■ dislocation: severe injury where articular surfaces of a joint are no longer in contact with one another ■ subluxation: articular surfaces of a joint are partially out of place (i.e. “partial dislocation” – oen unstable and requires reduction) PIP and DIP Dislocations (PIP more common than DIP) • usually dorsal dislocation (commonly from hyperextension) • 3 views of hand needed with x-ray imaging to assess degree of dislocation (posteroanterior, oblique, and lateral) • if closed dislocation: closed reduction and splinting in position of function for 1 wk or buddy taping, and early mobilization (prolonged immobilization causes stiness) • open injuries are treated with wound care, irrigation, and debridement, followed by closed or open reduction and antibiotics MCP Dislocations (relatively rare) • dorsal dislocations much more common than volar dislocations • dorsal dislocation of proximal phalanx on metacarpal head; most commonly index nger (hyperextension) • two types of dorsal dislocation ■ simple (reducible with manipulation): treat with closed reduction and splinting for 2-4 wk at 6070° MCP exion ■ complex (irreducible, most commonly due to volar plate blocking the reduction): treat with open reduction UCL Injury of the Hand • forced abduction of thumb (e.g. ski pole injury) • skier’s thumb: acute UCL injury; if stable (elbow valgus stress test), treated with splint x 6-8 wk; if unstable, patient may have Stener lesion • Gamekeeper’s thumb: chronic UCL injury, oen requires open repair and tendon gra for stabilization • Stener lesion: the distal portion of the UCL can detach and ip supercial to the adductor aponeurosis and will not appropriately heal; requires open repair (requires x-ray imaging to diagnose) • evaluation: radially deviate thumb MCP joint in full extension and at 30° exion and compare with non-injured hand. UCL rupture is presumed if injured side deviates more than 30° in full extension or more than 15° in exion

Dupuytren’s Disease

Epidemiology • unusual in Asian patients or patients of African descent, high incidence in northern European patients, men > women, oen presents in 5th-7th decade of life; associated with but not caused by alcohol use, smoking, and DM Clinical Features • nodules, cords, and contractures of MCP, PIP, and DIP • order of digit involvement (most common to least common): ring > little > long > thumb > index • risk of recurrence Treatment • palmar pit or nodule: no surgery (steroid injections for pain) • palpable band/cord with no limitation of extension (i.e. no contracture) of either MCP or PIP: no surgery • MCP contracture >30° or PIP contracture of any degree: needle aponeurotomy, collagenase Clostridium histolyticum (Xiaex®) injection (indicated if cord is palpable), or surgical fasciectomy • contractures impeding function and/or hygiene: needle aponeurotomy, collagenase injection, or surgical fasciectomy • MCP joints have better outcomes than PIP joints post-treatment (achievement of near full extension, lower risk of recurrence)

© Monika Musial

Definition • proliferative disorder of the palmar fascia, forming nodules (usually painless), brous cords, and exion contractures at the MCP and interphalangeal joints • exor tendons not involved • Dupuytren’s diathesis: male sex, early age of onset, strong family history (autosomal dominant inheritance), involvement of multiple digits, bilateral involvement, and involvement of sites other than palmar aspect of hand, including the plantar fascia (Ledderhose’s) and the penis (Peyronie’s; see Urology, Table 24, U33)

Cord Nodule Palmar aponeurosis

Figure 26. Dupuytren’s disease

Carpal Tunnel Syndrome PL30 Plastic Surgery

Toronto Notes 2023

Carpal Tunnel Syndrome Definition • median nerve compression at the level of the exor retinaculum/transverse carpal ligament Etiology • median nerve entrapment at wrist • primary cause is idiopathic • secondary causes: space occupying lesions (tumours, hypertrophic synovial tissue, fracture callus, and osteophytes); metabolic and physiological (pregnancy, hypothyroidism, acromegaly, and RA); job/ hobby-related repetitive trauma, especially forced wrist exion Epidemiology • F:M=4:1, most common entrapment neuropathy Clinical Features • classically, patient awakened at night with numb/painful hand, relieved by shaking/dangling/rubbing • on exam, sensory loss in median nerve distribution (see Figure 3, PL3), but thenar eminence sensory loss is spared (palmar cutaneous branch given o prior to carpal tunnel) • decreased light touch and 2-point discrimination at DIP radial and ulnar creases; discriminative touch oen lost rst • advanced cases: thenar wasting/weakness due to involvement of the motor branch of the median nerve • ± Tinel’s sign (paresthesia on percussion of nerve) • ± Durkan’s sign (paresthesia aer pressure over carpal tunnel 1 cm sensation Necrosis of graft or donor nipple

Table 31. Types of Areolar Reconstruction Description

Advantages

Disadvantages

Tattoo*

Conducted 3-4 mo after nipple reconstruction when most of the projection has stabilized

Can provide more accurate colour matching with limited morbidity

May require touch-ups due to pigment fading over time with skin sloughing

Skin Graft*

Full thickness skin grafts, commonly from inner aspect of thigh or opposite areola

Provides texture and pigment resembling a natural areola

Donor site morbidity

* Tattoo and skin grafting can be used in conjunction

Aesthetic Surgery Aesthetic Procedures Table 32. Aesthetic Procedures Location Head/Neck

Skin

Other

Procedure

Description

Hair transplants

Aesthetic improvement of hair growth patterns using hair follicle grafts or flaps

Otoplasty

Surgical reconstruction of external ear

Forehead/brow lift

Surgical procedure to lift the forehead and eyebrows

Rhytidectomy

Surgical procedure to reduce wrinkling and sagging of the face and neck; “face lift”

Blepharoplasty

Surgical procedure to shape or modify the appearance of eyelids by removing excess eyelid skin ± fat pads

Rhinoplasty

Surgical reconstruction of the nose ± nasal airway

Genioplasty

Chin augmentation via osteotomy or synthetic implant to improve contour

Chemical peel

Application of one or more exfoliating agents to the skin resulting in destruction of portions of the epidermis and/or dermis with subsequent tissue regeneration

Dermabrasion

Skin resurfacing with a rapidly rotating abrasive tool; often used to reduce scars, irregular skin surfaces, and fine lines

Laser resurfacing

Application of laser to the skin which ultimately results in collagen reconfiguration and subsequent skin shrinking and tightening; often used to reduce scars and wrinkles

Injectable fillers

An injectable substance is used to decrease facial rhytids; can augment lips to create fuller appearance; substances include: collagen, fat, hyaluronic acid, and calcium hydroxyapatite (most common substances include hyaluronic acid and fat)

Abdominoplasty

Removal of excess skin and repair of rectus muscle laxity (rectus diastasis); “tummy tuck”

Calf augmentation

Augmentation of calf muscle with implants

Liposuction

Surgical removal of adipose tissue for body contouring (not a weight loss procedure)

Gender-Affirming Surgery (Transition-Related Surgery) PL41 Plastic Surgery

Toronto Notes 2023

Gender-Arming Surgery (Transition-Related Surgery) • ensure appropriate use of gender pronouns • some procedures require 1 yr trial of hormone therapy, preoperative letters of evaluation and documentation from mental health professionals as outlined by the World Professional Association for Transgender Health Standards of Care – Version 7 guidelines Table 33. Surgical Options for Transgender Women Procedure

Description

Follow-Up

Breast Augmentation

Implant-based, fat-grafting, or combined surgery to increase breast size

Surveillance for implant rupture Adhere to breast cancer screening guidelines in addition to gender-specific medical maintenance

Contouring Procedures

Altering fat distribution in distinguishing regions of the body (abdomen, flank, hip, and buttock) using liposuction or fat-grafting (limited by availability of autologous fat)

Short-term restrictions on placing body weight on fatgrafted areas (M 4% chance of cleft if one parent or sibling have cleft 17% chance of cleft if both sibling and parent have cleft

Classified as incomplete/ complete and unilateral/ bilateral Isolated (common in females) or in conjunction with cleft lip (common in males)

Special bottles for feeding SLP Surgery (6-9 mo): Von Langenbeck or Furlow Z-Plasty ENT consult – often recurrent otitis media, requiring myringotomy tubes

1 in 2000 live newborns; M:F=52:48 Syndromes include: Crouzon’s, Apert’s, Saethre-Chotzen, Carpenter’s, Pfeier’s, Jackson-Weiss, and Boston-type syndromes

Primary (no known cause), or secondary (associated with a known cause or syndrome)

Multidisciplinary team (including neurosurgery, ENT, genetics, dentistry, paediatrics, SLP) The type, timing, and procedure are dependent on which sutures (lambdoid, sagittal, etc.) are involved Early surgery prevents secondary deformities

Craniosynostosis

Congenital Hand Anomalies Table 36. American Society for Surgery of the Hand (ASSH) Classification of Congenital Hand Anomalies Classification

Example

Features

Treatment

Failure of Formation

Transverse absence (congenital amputation)

At any level (often below elbow/ wrist)

Early prosthesis

Longitudinal absence (phocomelia)

Absent humerus Thalidomide association

Radial deficiency (radial club hand)

Radial deviation Thumb hypoplasia M>F

Physiotherapy + splinting Soft tissue release if splinting fails Distraction osteogenesis (Ilizarov distraction) ± wedge osteotomy Tendon transfer Pollicization

Thumb hypoplasia

Syndromes include: Fanconi anemia, Holt-Ogram, and CHARGE syndromes. Degree ranges from small thumb with all components to complete absence

Depends on degree – may involve no treatment, webspace deepening, tendon transfer, or pollicization of index finger

Ulnar club hand

Rare, compared to radial club hand Stable wrist

Splinting and soft tissue stretching therapies Soft tissue release (if above fails) Correction of angulation (Ilizarov distraction)

Cleft hand

Autosomal dominant Often functionally normal (depending on degree)

First web space syndactyly release Osteotomy/tendon transfer of thumb (if hypoplastic)

Syndactyly

Syndromes include: Apert, Poland, and Holt-Oram syndromes 1 in 3000 live births M:F=2:1

Surgical separation before 6-12 mo of age May require a skin graft to cover the fingers Usually good result

Symbrachydactyly

Short fingers with short nails at fingertips

Digital separation Webspace deepening

Camptodactyly

Congenital flexion contracture (usually at PIP, especially 5th digit)

Early splinting Volar release Arthroplasty (rarely)

Clinodactyly

Radial or ulnar deviation Often middle phalanx

None (usually); if severe, osteotomy with grafting

Failure of Dierentiation/ Separation

Figure 38. Veau classification of cleft lip and palate © Image reproduced with permission from Medscape Drugs & Diseases (https://emedicine.medscape.com/), Cleft Lip and Palate and Mouth and Pharynx Deformities, 2021, available at: https://emedicine.medscape.com/ article/837347-overview

References PL43 Plastic Surgery

Toronto Notes 2023

Table 36. American Society for Surgery of the Hand (ASSH) Classification of Congenital Hand Anomalies Classification

Example

Features

Treatment

Duplication

Polydactyly

Congenital duplication of digits May be radial (increased in Asian individuals and Indigenous peoples) or central or ulnar (increased in individuals of African descent)

Amputation of least functional digit Usually >1 yr of age (when functional status can be assessed)

Overgrowth

Macrodactyly

Rare

None (if mild) Soft tissue/bony reduction

Undergrowth

Brachydactyly

Short phalanges

Removal of nonfunctional stumps Osteotomies/tendon transfers Distraction osteogenesis

Symbrachydactyly

Short webbed fingers

As above + syndactyly release

Variety of presentations

Urgent release for acute, progressive edema distal to band in newborn Other reconstruction is case specific

Variety of presentations

Treatment depends on etiology

Phalangeal/free toe transfer Brachysyndactyly Constriction Band Syndrome

i.e. amniotic (annular) band syndrome

Generalized Skeletal Achondroplasia, Marfan Abnormality syndrome, Madelung’s deformity

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Francis KR, Lamaute HR, Davis JM, et al. Implications of risk factors in necrotizing fasciitis. Am Surg 1993;59:304-308. Georgiade GS, Rieohl R, Levin LS. Georgiade plastic, maxillofacial and reconstructive surgery, 3rd ed. Baltimore: Williams & Wilkins, 1997. Giladi M, Malay S, Chung KC. A systematic review of the management of acute pyogenic flexor tenosynovitis. J Hand Surg-Eur Vol 2015;40(7):720-728. Giure JL, Kakar S, Bishop AT, et al. Current concepts of the treatment of adult brachial plexus injuries. J Hand Surg Am 2010;35:678-688. Gourgiotis S, Villias C, Germanos S, et al. Acute limb compartment syndrome: a review. J Surg Educ 2007;64:178-186. Graham B, Regehr G, Naglie G, et al. Development and validation of diagnostic criteria for carpal tunnel syndrome. J Hand Surg 2006;31(6):919-924. Greene FL, Page DL, Fleming ID, et al. AJCC cancer staging handbook: from the AJCC cancer staging manual, 6th ed. Chicago: Springer, 2002. Gulleth Y, Goldberg N, Silverman R, et al. What is the best surgical margin for a basal cell carcinoma: a meta-analysis of the literature. Plast Reconstr Surg 2010;126:1222-1231. Guo S, DiPietro LA. Factors Aecting Wound Healing. J Dent Res 2010;89:219-229. Harrison V. The newborn baby, 5th ed. Juta & Company, 2008. Chapter: Congenital Abnormalities. Holtmann H, Eren H, Sander K, et al. Orbital floor fractures - short- and intermediate-term complications depending on treatment procedures. Head Face Med 2016;12:1. Huang CC, Boyce SM. Surgical margins of excision for basal cell carcinoma and squamous cell carcinoma. Semin Cutan Med Surg 2004;23:167-173. Hunt TK, Doherty GM, Way LW (editors). Current surgical diagnosis and treatment, 12th ed. Norwalk: McGraw-Hill, 2006. Chapter: Wound Healing. Janis JE. Essentials of plastic surgery: a UT Southwestern Medical Center handbook. St. Louis: Quality Medical, 2007. Jarbrink K, Ni G, Sonnergren H, et al. Prevalence and incidence of chronic wounds and related complications: a protocol for a systematic review. Syst Rev 2016, 5(1):152. Johnson RE, Murad MH. Gynecomastia: pathophysiology, evaluation, and management. Mayo Clin Proc 2009;84:1010-1015. Jones V, Grey JE, Harding KG. Wound dressings. BMJ. 2006;332(7544):777-80. Kargül G, Deutinger M. Reconstruction of breast areola complex. Comparison of dierent techniques. Handchir Mikrochir 2001;33:133-137. Kaufman CL, Marvin MR, Chilton PM, et al. Immunobiology in VCA. Transplant International. 2016;29(6):644-654. Khalifian S, Brazio PS, Mohan R, et al. Facial transplantation: the first 9 years. Lancet 2014;384:2153-2163. Koshy JC, Feldman EM, Chike-Obi CJ, et al. Pearls of mandibular trauma management. Semin Plast Surg 2010;24:357-374. Kraft R, Herndon DN, Al-Mousawi AM, et al. Burn size and survival probability in paediatric patients in modern burn care: a prospective observational cohort study. Lancet 2012;379:1013-1021. Kraut RY, Brown E, Korownyk, et al. The impact of breast reduction surgery on breastfeeding: systematic review of observational studies. PLoS One 2017;12:e0186591 Kuhn JE, Lebus V GF, Bible JE. Thoracic outlet syndrome. J Am Acad Orthop Surg 2015;23:222-232. Lavigne E, Holowaty EJ, Pan SY, et al. Breast cancer detection and survival among women with cosmetic breast implants: systematic review and meta-analysis of observational studies. BMJ 2013;346:f2399. Liu C, Bayer A, Cosgrove SE, et al. Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. Merrell GA, Barrie KA, Katz DL, et al. Results of nerve transfer techniques for restoration of shoulder and elbow function in the context of a meta-analysis of the English literature. J Hand Surg Am 2001;26:303-314. Miller TJ, Wilson SC, Massie JP, et al. Breast augmentation in male-to-female transgender patients: technical considerations and outcomes. J Plast Reconstr Aes 2019;21:63-74. Morrison SD, Vyas KS, Motakef S, et al. Facial feminization: systematic review of the literature. Plast Reconstr Surg. 2016;137(6):1759-1770. Muangman P, Chuntrasakul C, Silthram S, et al. Comparison of ecacy of 1% silver sulfadiazine and Acticoat for treatment of partial thickness burn wounds. J Med Assoc Thailand 2006;89:953-958. Nahhas AF, Scarbrough CA, Trotter S. A review of the global guidelines on surgical margins for nonmelanoma skin cancers. J Clin Aesthet Dermatol. 2017 Apr;10(4):37-46. Neal SL, Fields KB. Peripheral nerve entrapment and injury in the upper extremity. Am Fam Physician. 2010;81(2):147-155. Noble J. Textbook of primary care medicine, 3rd ed. St. Louis: Mosby, 2001. Ong YS, Samuel M, Song C. Meta-analysis of early excision of burns. Burns 2006;32:145-150. Patel BC, Skidmore K, Hutchison J, et al. Cauliflower Ear. [Updated 2021 Feb 25, cited 2021 Jun 6]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK470424/. Patil RK, Koul AR. Early active mobilisation vs. immobilisation after extrinsic extensor tendon repair: a prospective randomised trial. Indian J Plast Surg 2012;45(01):29-37. Peterson LJ. Peterson’s principles of oral and maxillofacial surgery. Vol 1. Shelton: People’s Medical Publishing House, 2011. Chapter: Maxillofacial Trauma. Richards AM. Key notes in plastic surgery. Great Britain: Blackwell Science, 2002. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant staphylococcus aureus infections: a revised consensus guideline and review by the American Society of

PL44 Plastic Surgery

Toronto Notes 2023

Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases and Pharmacists. Am J Health Syst Pharm 2020; 77:835. Salzberg CA, Ashikari AY, Koch RM, et al. An 8-year experience of direct-to-implant immediate breast reconstruction using human acellular dermal matrix (Allo Derm). Plast Reconstr Surg 2011;127:514-524. Schechter LS. Gender confirmation surgery. Springer Nature Switzerland AG, 2020. Sermer NB. Practical plastic surgery for nonsurgeons. Philadelphia: Hanley & Belfus, 2001. Sibbald RG, Williamson D, Orsted HL, et al. Preparing the wound bed – debridement, bacterial balance, and moisture balance. Ostomy Wound Manage 2000;46:14-35. Simonacci F, Bertozzi N, Grieco MP, et al. Surgical therapy of cutaneous squamous cell carcinoma: our experience. Acta Bio Medica Atenei Parm. 2018;89(2):242–8. Singer AJ, Hollander JE, Subramanian S, et al. Pressure dynamics of various irrigation techniques commonly used in the emergency department. Ann Emerg Med 1994;24:36-40. Sisti A, Grimaldi L, Tassinari J, et al. Nipple-areola complex reconstruction techniques: a literature review. Eur J Surg Oncol 2016;42:441-465. Shahriari N, Ferenczi K, Heald PW. Breast implant-associated anaplastic large cell lymphoma: a review and assessment of cutaneous manifestations. Int J Womens Dermatology 2017;3:140-144. Smith DJ, Brown AS, Cruse CW, et al. Plastic and reconstructive surgery. Chicago: Plastic Surgery Educational Foundation, 1987. Smith JM, Broyles JM, Guo Y, et al. Human acellular dermis increases surgical site infection and overall complication profile when compared with submuscular breast reconstruction: an updated meta-analysis incorporating new products. J Plast Reconstr Aesthet Surg 2018;71:1547-1556. Spear SL, Parikh PM, Reisin E, et al. Acellular dermis-assisted breast reconstruction. Aesthetic Plast Surg 2008;32:418-425. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e10-e52. Stone C. Plastic surgery: facts. London: Greenwich Medical Media, 2001. Sun G, Wu Z, Wang X, et al: Nerve transfer helps repair brachial plexus injury by increasing cerebral cortical plasticity. Neural Regen Res 2010;9:2111-2114. Tchernev G, Chokoeva AA. New safety margins for melanoma surgery: nice possibility of drinking “just that cup of coee?” Open Access Maced J Med Sci 2016;5:352-358. Thorne CH. Grabb & Smith’s plastic surgery, 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2007. Townsend CM. Sabiston textbook of surgery – the biological basis of modern surgical practice, 16th ed. Philadelphia: WB Saunders, 2001. Chapter: plastic and reconstructive surgery. Wang, T., Regmi, S., Liu, H. et al. Free lateral tarsal artery perforator flap with functioning extensor digitorum brevis muscle for thenar reconstruction: a case report. Arch Orthop Trauma Surg 137, 273–276 (2017). Wol K, Johnson RA. Fitzpatrick’s colour atlas and synopsis of clinical dermatology, 6th ed. New York: McGraw-Hill, 2009. Weinzweig J. Plastic surgery secrets. Philadelphia: Hanley and Belfus, 1999. Wilson SC, Morrison SD, Anzai L, et al. Masculinizing top surgery: a systematic review of techniques and outcomes. Ann Plas Surg 2018;80(6):679-683. Zingg M, Laedrach K, Chen J, et al. Classification and treatment of zygomatic fractures: a review of 1,025 cases. J Oral Maxillofac Surg 1992;50:778-790.

Psychiatry

PS

Psychiatry Tania Da Silva, Rawaan Elsawi, and Rachel Goud, chapter editors Ming Li and Dorrin Zarrin Khat, associate editors Vijithan Sugumar, EBM editor Dr. Saulo Castel, Dr. Tamara Milovic, and Dr. Jerome Perera, sta editors Acronyms.............................................................................PS2 Psychiatric Assessment....................................................... PS2 History Mental Status Exam Assessment and Plan...........................................................PS4 Suicide.................................................................................PS5 Psychotic Disorders............................................................. PS7 Dierential Diagnosis of Psychosis Schizophrenia Schizophreniform Disorder Brief Psychotic Disorder Schizoaective Disorder Delusional Disorder Mood Disorders ................................................................. PS10 Mood Episodes Depressive Disorders Postpartum Mood Disorders Bipolar Disorders Anxiety Disorders.............................................................. PS15 Panic Disorder Agoraphobia Generalized Anxiety Disorder Social Anxiety Phobic Disorders Obsessive-Compulsive and Related Disorders.................. PS19 Obsessive-Compulsive Disorder Related Disorders Trauma- and Stressor-Related Disorders...........................PS20 Post-Traumatic Stress Disorder Adjustment Disorder Bereavement.....................................................................PS22 Neurocognitive Disorders..................................................PS23 Delirium Major Neurocognitive Disorder (Dementia) Substance-Related and Addictive Disorders Nicotine Alcohol Opioids Cocaine Amphetamines Cannabis Hallucinogens “Club Drugs”

Eating Disorders ................................................................PS39 Anorexia Nervosa Bulimia Nervosa Binge-Eating Disorder Avoidant/Restrictive Food Intake Disorder Personality Disorders........................................................PS42 Child Psychiatry.................................................................PS44 Developmental Concepts Mood Disorders in Children and Adolescents Anxiety Disorders in Children and Adolescents Neurodevelopmental Disorders.........................................PS46 Autism Spectrum Disorder Attention Deficit Hyperactivity Disorder Disruptive, Impulse Control, and Conduct Disorder..........PS48 Oppositional Defiant Disorder Conduct Disorder Intermittent Explosive Disorder Psychotherapy...................................................................PS49 Pharmacotherapy...............................................................PS51 Antipsychotics Antidepressants Mood Stabilizers Anxiolytics Somatic Therapies.............................................................PS60 Repetitive Transcranial Magnetic Stimulation (rTMS) Magnetic Seizure Therapy (Experimental) Neurosurgical Treatments Other Therapy Modalities Canadian Legal Issues.......................................................PS62 Common Forms Consent Community Treatment Order (CTO) Duty to Inform/Warn Landmark Psychiatry Clinical Trials...................................PS64 References.........................................................................PS64

Somatic Symptom and Related Disorders..........................PS33 Somatic Symptom Disorder Illness Anxiety Disorder Conversion Disorder (Functional Neurological Symptom Disorder) Dissociative Disorders....................................................... PS35 Dissociative Identity Disorder Dissociative Amnesia Depersonalization/Derealization Disorder Sleep Disorders.................................................................PS36 Sexuality and Gender........................................................ PS37 Gender Dysphoria Paraphilic Disorders Sexual Addiction Sexual Dysfunction

PS1 Psychiatry

Toronto Notes 2023

Acronyms PS2 Psychiatry

Toronto Notes 2023

Acronyms 5-HT ACh ACT ADHD ADL AN ASD ASPD BN CBT CD CRA CTO DA

serotonin acetylcholine assertive community treatment attention deficit hyperactivity disorder activities of daily living anorexia nervosa autism spectrum disorder antisocial personality disorder bulimia nervosa cognitive behavioural therapy conduct disorder community reinforcement approach community treatment order dopamine

DBT DZ ECT EPS ERP GAD GMC IPT IADL MBCT MBSR MDD MDE

dialectical behavioural therapy dizygotic electroconvulsive therapy extrapyramidal symptoms exposure with response prevention generalized anxiety disorder general medical condition interpersonal therapy instructional activities of daily living mindfulness-based cognitive therapy mindfulness-based stress reduction major depressive disorder major depressive episode

MET MI MSE MST MZ NA NMS NOS OCD OCP OCPD ODD PCP PD

motivational enhancement therapy motivational interviewing mental status examination magnetic stimulation therapy monozygotic Narcotics Anonymous neuroleptic malignant syndrome not otherwise specified obsessive-compulsive disorder oral contraceptive pill obsessive-compulsive personality disorder oppositional defiant disorder phencyclidine personality disorder

PDD PTSD rTMS SGA SIADH SNRI SS SSRI TCA TD XR

pervasive developmental disorder post-traumatic stress disorder repetitive transcranial magnetic stimulation second generation antipsychotics syndrome of inappropriate antidiuretic hormone secretion serotonin and norepinephrine reuptake inhibitors serotonin syndrome selective serotonin reuptake inhibitor tricyclic antidepressant tardive dyskinesia extended-release

Psychiatric Assessment History Introduction • name, role, purpose, circumstances (i.e. approximate time) • limits of condentiality (i.e. safety of dependents, harm to self or others) Identifying Data • necessary: name, age, gender (preferred pronouns), living situation (accommodation, independently, or with others), marital/relationship status, children, source of income/support, or occupation • adjunct: outpatient/inpatient, referral source, known/unknown to provider Chief Complaint • in patient’s own words, with duration of symptoms History of Present Illness • context: events, problems, stressors, losses, changes • symptoms: onset, duration, intensity, progression, uctuation with day/season • impact on functioning: social, occupational, ADL/IADLs, personal care/survival • coping strategies, treatments, personal/professional supports • reason for seeking help that specic day • prior episodes/experiences, longitudinal course (duration/frequency) • last period of wellness, changes to usual personality when unwell • opinions about cause/nature of concerns, willingness to engage, hopes/expectations of treatment Psychiatric Functional Inquiry • mood: depression, mania • other: trauma, obsessions/compulsions, disordered eating • anxiety: worries, panic attacks, phobias, or social anxiety • psychosis: hallucinations, delusions • safety/risk: self (suicidal ideation/intent/plan (see Suicide, PS5), self-harm, neglect), others (homicide, aggression, violence), dependents (children, elderly, disabled, pets), driving, cooking/res Past Psychiatric History • previous psychiatric diagnoses and mental health contacts • hospitalizations: approximate total, date of last discharge • emergency department visits (for mental health crisis) • suicide attempts: number, severity, medical intervention, most recent • self-harming behaviour (cutting) • aggression/violence, legal (charges) • treatments: pharmacological and non-pharmacological (eectiveness, side eects) Substance Use History • type: tobacco, cannabis, alcohol, other (stimulants, hallucinogens, prescription drugs, gambling/ online) • use: rst, typical, last, periods of abstinence • withdrawal symptoms (i.e. seizures, delirium tremens) • previous treatments: counselling, detox, groups • impact on symptoms, motivation to change

Screening Questions for Major Psychiatric Disorders • Have you been feeling down, depressed, or hopeless? • Do you feel anxious or worry about things? • Has there been a time in your life where you have felt euphoric, extremely talkative, had a lot of energy, and a decreased need for sleep? • Do you see or hear things that you think other people cannot? • Have you ever thought of harming yourself or killing yourself?

Psychiatric Functional Inquiry MOAPS Moo d Other (medical problems and substance use) Anxiety Psychosis Safety

Mental Status Exam PS3 Psychiatry

Toronto Notes 2023

Past Medical/Surgical History • all medical, surgical, neurological (i.e. head trauma, seizures) conditions/illnesses • allergies Medications • names, doses, frequency • adherence, eectiveness, side eects • over the counter, supplements Family Psychiatric/Medical History • diagnoses, treatments, hospitalizations, suicide attempts, substance use, legal • perceptions regarding mental illness, engagement with treatments • if relevant: any past medical or genetic illness

Always Remember to Ask About Abuse See Family Medicine, FM30

Past Personal/Developmental History (as relevant) • birthplace, immigration history (if applicable), ethnicity/nationality, religion/spirituality • family members: ages, occupations, personalities, quality of relationships • history of verbal, physical, or sexual abuse • prenatal and perinatal history: desired vs. unplanned pregnancy, maternal and fetal health, domestic violence, maternal substance use and exposures, complications of pregnancy/delivery • early childhood to age 3: developmental milestones, temperament, family stability, primary caregivers/attachment gures • middle childhood to age 11: school performance, peer relationships, bullying, activity/attention level, behavioural challenges • late childhood to adolescence: school performance, drugs/alcohol, legal problems, peer and family relationships, extra-curriculars • sexuality: puberty, gender identity, sexual orientation, sexual functioning/experiences, romantic relationships • adulthood: education, employment, relationships • hobbies, interests, sources of meaning, strengths, accomplishments, aspirations, hopes Collateral History • source, details provided

Mental Status Exam General Appearance • age (chronological vs. apparent), gender, ethnicity • posture, grooming, hygiene, manner of dress, body habitus, distinguishing features • eye contact, facial expression, alertness • attitude: polite, friendly, collaborative, uncooperative, guarded/suspicious, evasive, agitated, aggressive/hostile • reliability (consistency, congruent with collateral), ease of building rapport • gait, psychomotor changes (slowing/agitation), tics, tremors, tardive dyskinesia, dystonia, catatonia Speech • rate (i.e. pressured, slowed), rhythm, volume, tone, quantity, spontaneity, latency, language uency, articulation Mood and Aect • mood: subjective emotional state (in patient’s own words) • aect: objective emotional state inferred from emotional responses to stimuli; described in terms of ■ quality (euthymic, depressed, elevated, anxious, irritable) ■ range (full, restricted, at, blunted) ■ stability (continuum from xed to labile) ■ mood congruence (inferred by comparing the patient’s subjective mood with their aect) • many clinicians use a 0-10 scale (0: worst; 10: best) when rating mood to get a subjective norm for each patient that can help to monitor changes over time and with treatment Perception • hallucination: sensory perception in the absence of appropriate stimuli that is similar in quality to a true perception ■ auditory (most common), visual, gustatory, olfactory, tactile • illusion: misperception of a real external stimulus (i.e. mistaking a coat on a rack as a person late at night) • depersonalization: change in self-awareness such that the person feels unreal, distant, or detached from their body, and/or unable to feel emotion • derealization: feeling that the world/outer environment is unreal

Mental Status Exam ASEPTIC Ap pearance and behaviour Speech Emotion (mood and aect) Perception Thought content and process Insight and judgment Cognition

The MSE is analogous to the physical exam. It focuses on current signs, aect, behaviour, and cognition

Spectrum of Aect Full > Restricted > Blunted > Flat; quality (euthymic, depressed, anxious, elated)

There is poor correlation between clinical impression of suicide risk and frequency of attempts

Assessment and Plan PS4 Psychiatry

Thought Process/Form • coherence (coherent, incoherent) • stream ■ goal-directed: clearly answers questions in a linear, organized, logical fashion ■ circumstantial: speech that is indirect and delayed in reaching its goal; eventually comes back to the point ■ tangential: speech is oblique or irrelevant; does not come back to the original point ■ loosening of associations/derailment: illogical shiing between topics ■ ight of ideas: quickly skipping from one idea to another where the ideas are marginally connected, usually associated with racing thoughts in mania ■ word salad: jumble of words lacking meaning or logical coherence • perseveration: repetition of the same verbal or motor response to stimuli • echolalia: repetition of phrases or words spoken by someone else • thought blocking: sudden cessation of ow of thought and speech • clang associations: speech based on sound such as rhyming or punning • neologism: use of novel words or of existing words in a novel fashion Thought Content • major themes discussed by patient • suicidal ideation/homicidal ideation: frequency and pervasiveness of thoughts, plan, intent, active vs. passive, protective factors • preoccupations, ruminations: reections/thoughts at length, not xed or false • obsession: recurrent and persistent thought, impulse, or image which is intrusive or inappropriate and unwanted ■ cannot be stopped by logic or reason ■ causes marked anxiety and distress ■ common themes: contamination, orderliness, sexual, pathological doubt/worry/guilt • magical thinking (i.e. superstition, belief that thinking something will make it happen), normal in children and certain cultures • ideas of reference: similar to delusion of reference, but less xed (the reality of the belief is questioned) • overvalued ideas: unusual/odd beliefs that are not of delusional proportions • rst rank symptoms of schizophrenia: thought insertion/withdrawal/broadcasting (all delusional ideas) • delusion: a xed false belief that is out of keeping with a person’s cultural or religious background and is rmly held despite incontrovertible proof to the contrary Insight • ability to realize that they have a mental health concern and to appreciate its implications as it relates to functioning and benets of treatment: none, limited, partial, or full

Toronto Notes 2023

Cognitive Assessment Use MMSE to assess • Orientation (time and place) • Memory (immediate and delayed recall) • Attention and concentration • Language (comprehension, reading, writing, repetition, naming) • Spatial ability (intersecting pentagons) Gross screen for cognitive dysfunction: Total score is out of 30; 75 yr ■ sex: male ■ race/ethnic background: White people or Indigenous peoples in Canada ■ marital status: widowed/divorced ■ living situation: alone; no children 6 mo Disorder 1-6 mo 1 mo

Delusional Disorder

≥1 delusions (if hallucinations, related to delusional theme)

>1 mo

Substance-Induced Psychotic Disorder

Delusions or hallucinations

Onset during intoxication/withdrawal, resolve in 50% use tobacco) • anxiety disorders • reduced life expectancy secondary to medical comorbidities (i.e. obesity, diabetes, metabolic syndrome, CV/pulmonary disease) Management of Schizophrenia • biological/somatic ■ acute treatment and maintenance: antipsychotics (risperidone, aripiprazole, haloperidol, paliperidone; clozapine if resistant); regimens of IM q2-4 wk. Long-acting injectables (LAI or depot) shown to be more eective in reducing relapse and rehospitalization compared with oral alternatives ■ adjunctive: ± mood stabilizers (for aggression/impulsiveness - lithium, valproate, carbamazepine) ± anxiolytics ± ECT ■ maintenance treatment for at least 1-2 yr aer the rst episode, at least 5 yr aer multiple episodes (relapse causes severe deterioration) • psychosocial ■ psychotherapy (individual, family, group), supportive, CBT (see Table 14, PS50) ■ ACT (Assertive Community Treatment): mobile mental health teams that provide individualized treatment in the community and help patients with medication adherence, basic living skills, social support, job placements, resources ■ social skills training, employment programs, disability benets ■ housing (group home, boarding home, transitional home) Course and Prognosis • majority of individuals display some type of prodromal phase • course is variable: some individuals have exacerbations and remissions while others remain chronically ill; accurate prediction of the long-term outcome is not possible • positive symptoms typically diminish with treatment; negative symptoms tend to be most persistent and cognitive symptoms may not improve • over time: 1/3 improve, 1/3 remain the same, 1/3 worsen

Toronto Notes 2023

Cannabis Use and Earlier Onset of Psychosis Arch Gen Psychiatry 2011;68:555-561 Purpose: To examine the extent to which cannabis, alcohol, and other psychoactive drugs aect the age of onset of psychosis. Method: A systematic review and meta-analysis. English studies were included that compared two cohorts: patients who used substances vs. patients who did not use substances. Results: 83 studies were included. The age of onset in cannabis users was 2.7 yr younger than in nonusers. For broadly defined substance use, age of onset of psychosis was 2.0 yr earlier than for nonusers. Alcohol use was not associated with significantly earlier age of psychosis. Conclusions: These results provide evidence that cannabis plays a role in earlier onset of psychosis.

Good Prognostic Factors • Acute onset • Later age of onset • Shorter duration of prodrome • Female gender • Good cognitive functioning • Good premorbid functioning • No family history • Presence of aective symptoms • Absence of structural brain abnormalities • Good response to drugs • Good support system

Schizophreniform Disorder Diagnosis • criteria A, D, and E of schizophrenia are met; an episode of the disorder lasts for >1 mo but 65 y/o; up to 50% in nursing homes • high suicide risk due to social isolation, chronic medical illness, and decreased independence • suicide peak: males ages 80-90, females ages 50-65 • low mood or dysphoria may not be a reliable indicator of depression in those >70 y/o • oen present with somatic complaints (i.e. changes in weight, sleep, energy; chronic pain) or anxiety symptoms • may have prominent cognitive changes aer onset of mood symptoms (dementia syndrome of depression) • see Table 3, PS26, for a comparison of delirium and dementia Treatment • lifestyle: increased aerobic exercise, mindfulness-based stress reduction, sleep hygiene • biological: SSRIs, SNRIs, other antidepressants, somatic therapies (see Pharmacotherapy, PS51 and Somatic erapies, PS60) ■ for MDE of moderate or greater severity, 1st line pharmacotherapy are used: most 2nd generation antidepressants, with escitalopram, mirtazapine, sertraline, venlafaxine, agomelatine, and citalopram showing evidence for superiority ■ for non or partial response, optimize the dose, switch to antidepressant with superiority, or add augmenting agent (i.e. aripiprazole, quetiapine, risperidone) ■ typical response to antidepressant treatment: physical symptoms improve at 2 wk, mood/ cognition by 4 wk; if no improvement aer 4 wk at the highest tolerated therapeutic dosage, alter regimen

Antidepressants for Depression in Physically Ill People Cochrane DB Syst Rev 2010;CD007503 Purpose: To determine the ecacy of antidepressants in treating depression in people with comorbid physical illness. Methods: Systematic review of RCTs comparing the ecacy of antidepressants vs. placebo in the treatment of major depression, adjustment disorder, and dysthymia in adults with comorbid depression and physical illness. Physical illness was defined as any medical condition known to have a biological underpinning where diagnosis is not purely symptom based. Results: Fifty-one studies including 3603 participants were included in this review. Both tricyclic antidepressants and selective serotonin reuptake inhibitors were more eective than placebo at treating depression in adults with concurrent physical illness. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant.

PS13 Psychiatry

Toronto Notes 2023

■ ECT: currently fastest and most eective treatment for MDD. Consider in severe, psychotic, or treatment-resistant cases ■ rTMS: 1st line treatment for MDD for patients who have failed at least 1 antidepressant treatment. Ecacy equivalent to medications (but not to ECT) with good safety and tolerability ■ phototherapy: especially if seasonal component, shi work, sleep dysregulation • psychological ■ individual therapy (CBT, interpersonal, behavioural activation, dynamic), group therapy, family therapy • social: vocational rehabilitation, social skills training • experimental: magnetic seizure therapy, deep brain stimulation, ketamine Prognosis • 1 yr aer diagnosis of MDD without treatment: 40% of individuals will still have symptoms that are suciently severe to meet criteria for MDD, 20% will continue to have some symptoms that no longer meet criteria for MDD, 40% will have no symptoms PERSISTENT DEPRESSIVE DISORDER DSM-5 DIAGNOSTIC CRITERIA FOR PERSISTENT DEPRESSIVE DISORDER Note: in DSM-IV-TR this was referred to as Dysthymic Disorder

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013. American Psychiatric Association

A.depressed mood for most of the day, for more days than not, as indicated either by subjective account or observation by others, for ≥2 yr Note: In children and adolescents, mood can be irritable and duration must be at least 1 yr B. presence, while depressed, of ≥2 of the following ■ poor appetite or overeating ■ insomnia or hypersomnia ■ low energy or fatigue ■ low self-esteem ■ poor concentration or diculty making decisions ■ feelings of hopelessness C. during the 2 yr period (1 yr for children or adolescents) of the disturbance, the person has never been without the symptoms in criteria A and B for more than 2 mo at a time D.criteria for a major depressive disorder may be continuously present for 2 yr E. there has never been a manic episode or a hypomanic episode, and criteria have never been met for cyclothymic disorder F. the disturbance is not better explained by a persistent schizoaective disorder, schizophrenia, delusional disorder, or other specied or unspecied schizophrenia spectrum and other psychotic disorder G.the symptoms are not due to the direct physiological eects of a substance or another medical condition H.the symptoms cause clinically signicant distress or impairment in social, occupational, or other important areas of functioning • speciers: ■ with anxious distress, mixed features, melancholic features, atypical features, mood-congruent psychotic features, mood-incongruent psychotic features, catatonia, peripartum onset, seasonal pattern ■ partial remission, full remission ■ early onset (21 y/o) ■ with pure dysthymic syndrome (full criteria for MDE have not been met in at least preceding 2 yr), with persistent MDE (full criteria for MDE have been met throughout preceding 2 yr) ■ with intermittent MDEs, with current episode: full criteria for a MDE are currently met, but there have been periods of at least 8 wk in at least the preceding 2 yr with symptoms below the threshold for a full MDE ■ with intermittent MDEs, without current episode: full criteria for a MDE are not currently met, but there has been one or more MDEs in at least the preceding 2 yr ■ specify current severity: mild, moderate, severe Epidemiology • lifetime prevalence: 2-3%; M=F Treatment • psychological ■ traditionally, psychotherapy was the principal treatment for persistent depressive disorder; recent evidence suggests some (but generally inferior) benet for pharmacological treatment. Combinations of the two may be most ecacious • biological ■ antidepressant therapy: SSRIs (e.g. sertraline, escitalopram), TCAs (e.g. nortriptyline)

See Landmark Psychiatry Trials table for more information on TRANSFORM-2, which details the use of esk etamine nasal spray for patients with treatmentresistant depression.

Postpartum Mood Disorders PS14 Psychiatry

Toronto Notes 2023

Postpartum Mood Disorders Postpartum “Blues” • transient period of mild depression, mood instability, anxiety, decreased concentration; considered to be normal in response to uctuating hormonal levels, the stress of childbirth, and the increased responsibilities of motherhood • occurs in 50-80% of mothers; begins 2-4 d postpartum, usually lasts 48 h, can last up to 10 d • does not require psychotropic medication • usually mild or absent: feelings of inadequacy, anhedonia, thoughts of harming baby, suicidal thoughts

Selective Serotonin Reuptake Inhibitors in Pregnancy and Infant Outcomes Paediatr Child Health 2011;16:562-63 Canadian Paediatric Society (CPS) clinical practice guideline recommendations: It is important to treat depression in pregnancy. There is no evidence that SSRIs increase the risk of major malformations. There is conflicting evidence concerning the association of paroxetine and cardiac malformations. SSRIs are not contraindicated while breast-feeding.

MAJOR DEPRESSIVE DISORDER WITH PERIPARTUM ONSET (POSTPARTUM DEPRESSION) Clinical Features • this specier can apply to a MDE with onset during pregnancy or within 4 wk following delivery • typically lasts 2-6 mo; residual symptoms can last up to 1 yr • may present with psychosis (rare, 0.2% – more frequent with prior postpartum mood episodes and postpartum mania) • severe symptoms may include complete disinterest in baby, suicidal and infanticidal ideation Epidemiology • occurs in up to 3-6% of mothers, up to 50% risk of recurrence Risk Factors • previous history of a mood disorder (postpartum or otherwise), family history of mood disorder • psychosocial factors: stressful life events, unemployment, marital conict, lack of social support, unwanted pregnancy, colicky or sick infant Treatment • psychotherapy (CBT or IPT) • short-term safety of maternal SSRIs for breastfeeding infants established; long-term eects unknown • if depression severe or psychotic symptoms present, consider ECT Prognosis • impact on child development: increased risk of cognitive delay, insecure attachment, behavioural disorders • treatment of mother improves outcome for child at 8 mo through increased mother-child interaction

Bipolar Disorders

Antidepressant Use in Pregnancy and the Risk of Cardiac Defects NEJM 2014 Jun 19;370(25):2397-2407 Purpose: It is uncertain whether selective serotoninreuptake inhibitors (SSRIs) and other antidepressants during pregnancy are associated with increased risk of congenital cardiac defects. There are concerns about an association between paroxetine use and right ventricular outflow tract obstruction, and between sertraline use and ventricular septal defects. Methods: Cohort study including 949504 women enrolled in Medicaid for a 7 yr period. The risk of major cardiac defects among infants born to women who took antidepressants during the 1st trimester was compared with the risk among infants born to women who did not use antidepressants. An unadjusted analysis was used, possible confounders were considered. Results: Overall, the chance of infants not exposed to antidepressants born with a cardiac defect was 72.3 per 10000 infants, and infants with exposure was 90.1 per 10000 infants. The relative risks of any cardiac defect with the use of SSRIs were 1.06 (95% CI, 0.93 to 1.22) in the fully adjusted analysis restricted to women with depression. No significant association was found between the use of paroxetine and right ventricular outflow tract obstruction (RR, 1.07) or between the use of sertraline and ventricular septal defects (RR, 1.04). Conclusions: No substantial increase in risk of cardiac malformations attributable to antidepressant use during the 1st trimester.

BIPOLAR I/BIPOLAR II DISORDER Definition • Bipolar I Disorder ■ disorder in which at least one manic episode has occurred ■ if manic symptoms lead to hospitalization, or if there are psychotic symptoms, the diagnosis is bipolar I ■ commonly accompanied by at least 1 MDE but not required for diagnosis ■ time spent in mood episodes: 53% asymptomatic, 32% depressed, 9% cycling/mixed, 6% hypo/ manic • Bipolar II Disorder ■ disorder in which there is at least 1 MDE, 1 hypomanic episode, and no manic episodes ■ while hypomania is less severe than mania, bipolar II is not a “milder” form of bipolar I ■ time spent in mood episodes: 46% asymptomatic, 50% depressed, 1% cycling/mixed, 2% hypo/ manic ■ bipolar II is oen missed due to the severity and chronicity of depressive episodes and low rates of spontaneous reporting and recognition of hypomanic episodes Classification • classication of BD involves describing the disorder (I or II) and the current or most recent mood episode as either manic, hypomanic, or depressed • speciers: with anxious distress, hypo/manic/depressed with mixed features, rapid cycling, melancholic features, atypical features, mood-congruent or -incongruent psychotic features, catatonia, peripartum onset, seasonal pattern, rapid cycling (≥4 mood episodes in 1 yr) Epidemiology • lifetime prevalence: 1% BD I, 1.1% BD II, 2.4% Subthreshold BD; M:F=1:1 • mean age of onset: 25 yr, usually MDE rst, manic episode 6-10 yr aer; average age of rst manic episode: 32 yr

Bipolar II is quite often missed and many patients are symptomatic for up to a decade before accurate diagnosis and treatment

Patients with bipolar disorder are at higher risk for suicide when they switch from mania to depression, especially as they become aware of consequences of their behaviour during the manic episode

Lithium is among few agents with proven ecacy in preventing suicide attempts and completions

Anxiety Disorders PS15 Psychiatry

Risk Factors • genetic: 60-65% of bipolar patients have family history of a major mood disorder, especially bipolar disorder • clinical features of MDE history favouring bipolar over unipolar diagnosis: early age of onset (2 mo • have never met criteria for MDE, manic, or hypomanic episodes • symptoms are not due to the direct physiological eects of a substance or GMC • symptoms cause clinically signicant distress or impairment in social, occupational, or other important areas of functioning Treatment • similar to Bipolar I: mood stabilizer ± psychotherapy

Anxiety Disorders Definition • fear is a universal human experience which can serve as an adaptive mechanism to facilitate appropriate reactions to external threat • anxiety may be seen as pathological fear when: ■ fear is greatly out of proportion to risk/severity of threat ■ response continues beyond existence of threat (prolonged, excessive, etc.) or becomes generalized to other similar or dissimilar situations ■ social or occupational functioning is impaired

Toronto Notes 2023

Monotherapy with antidepressants should be avoided in patients with bipolar depression as patients can switch from depression into mania

The 4 L’s for Bipolar Depression Lithium, Lamotrigine, Lurasidone, SeroqueL

A Randomized Controlled Trial of Cognitive Therapy for Bipolar Disorder: Focus on Long-Term Change J Clin Psychiatry 2006;67:277-86 Purpose: To evaluate long-term change with cognitive therapy plus emotive techniques for the treatment of bipolar disorder. Methods: Blinded RCT including patients with DSM-IV bipolar I or II disorder allocated to either a 6 mo trial of cognitive therapy (CT) with emotive techniques or treatment as usual. Both groups received mood stabilizers. Main outcomes were relapse rates, dysfunctional attitudes, psychosocial functioning, hopelessness, self-control, and medication adherence. Patients were assessed by independent raters blinded to treatment group. Results: At 6 mo, CT patients experienced fewer depressive symptoms and fewer dysfunctional attitudes. There was a non-significant (p=0.06) trend to greater time to depressive relapse. At 12 mo followup, CT patients had lower Young Mania Rating scores and improved behavioural self-control. At 18 mo, CT patients reported less severity of illness. Conclusions: CT appears to provide benefits in the 12 mo after completion of therapy.

Ecacy of Cognitive-Behavioural Therapy in Patients with Bipolar Disorder: A Meta-Analysis of Randomized Controlled Trials PLoS One 2017;12(5):e0176849 Purpose: To determine the ecacy of cognitive behavioural therapy (CBT) in the treatment of type I and II bipolar disorder. Methods: A systematic review and meta-analysis of RCTs of CBT in the treatment of adults with bipolar disorder. Results: Nineteen RCTs including 1284 patients with type I or II BD were included. CBT lowered the relapse rate (pooled OR=0.506; 95% CI=0.278 −0.921) and improved depressive symptoms (g=−0.494; 95% CI=−0.963 to −0.026), mania severity ( =−0.581; 95% CI=−1.127 to −0.035), and psychosocial functioning (g=0.457; 95% CI=0.106–0.809). Greater eects were seen with CBT treatment duration >90 min. Relapse rates were lower in people with type I bipolar disorder.

PS16 Psychiatry

Toronto Notes 2023

• manifestations of anxiety are a result of the activation of the sympathetic nervous system and can be described through: ■ physiology: main brain structure involved is the amygdala; neurotransmitters involved include 5-HT, cholecystokinin, epinephrine, norepinephrine, and DA ■ psychology: one’s thoughts about a given situation or stimulus contribute to the feeling of fear and perception of threat ■ behaviour: anxiety can lead to avoidance which can perpetuate the fear/avoidance ■ oen comorbid with substance use and depression; more than 50% have multiple anxiety disorders ■ when starting medication for anxiety: start low, go slow, aim high, and explain symptoms to expect prior to initiation of therapy to prevent non-adherence due to side eects ■ psychotherapy: individual or group CBT Dierential Diagnosis Table 2. Dierential Diagnosis of Anxiety Disorders Cardiovascular

Post-MI, arrhythmia, congestive heart failure, pulmonary embolus, mitral valve prolapse

Respiratory

Asthma, COPD, pneumonia

Endocrine

Hyperthyroidism, hypoglycemia, hyperadrenalism, hyperparathyroidism

Metabolic

Vitamin B12deficiency, folate deficiency, porphyria, hypoxemia, hypercalcemia

Neurologic

Neoplasm, vestibular dysfunction, encephalitis, trauma (contusion or hematoma), MS, temporal lobe epilepsy, migraine

Infectious

Cerebral (meningitis, HIV, syphilis) or systemic

GI

Gastritis, esophageal spasm

Substance-Induced

Intoxication (caeine, cannabis, amphetamines, cocaine, thyroid replacement, OTC for colds/decongestants, steroids), withdrawal (benzodiazepines, alcohol)

Medical Workup of Anxiety Disorder • only proceed with medical workup as clinically indicated • routine screening: vitals, physical exam, CBC, electrolytes, thyroid function test, glucose, ECG • additional screening: extended electrolytes, vitamin B12, β-HCG, folate, chest x-ray, any other tests as per DDx in Table 2 Risk Factors for the Development of Anxiety Disorders • biological ■ endocrine disorders (i.e. hyperthyroidism), respiratory conditions (i.e. asthma), CNS conditions (i.e. temporal lobe epilepsy), substances/medications (i.e. excessive stimulant use), chronic medical illness ■ personal or family history of anxiety or mood disorder ■ XX>XY chromosomes • psychological ■ current stress, early childhood adversity or trauma, early parental loss, parental factors

Panic Disorder DSM-5 DIAGNOSTIC CRITERIA FOR PANIC DISORDER Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013. American Psychiatric Association

A.recurrent unexpected panic attacks; a panic attack is an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and during which time four (or more) of the following symptoms occur ■ palpitations, pounding heart, or accelerated heart rate ■ sweating ■ trembling or shaking ■ sensations of shortness of breath or smothering ■ feelings of choking ■ chest pain or discomfort ■ nausea or abdominal distress ■ feeling dizzy, unsteady, light-headed, or faint ■ chills or heat sensations ■ paresthesias (numbness or tingling sensations) ■ derealization (feelings of unreality) or depersonalization (being detached from oneself) ■ fear of losing control or “going crazy” ■ fear of dying B. at least one of the attacks has been followed by 1 mo (or more) of one or both of the following: ■ persistent concern or worry about additional panic attacks or their consequences ■ a signicant maladaptive change in behaviour related to the attacks C. the disturbance is not attributable to the physiological eects of a substance or another medical condition D. the disturbance is not better explained by another mental disorder

Situational trigger

Panic attack

Increased anxiety and generalization to other situations

Mentally associated with situation

Figure 2. Mechanism of panic attacks

Criteria for Panic Attack (≥4) STUDENTS FEAR the 3 Cs Sweating Trembling/shaking Unsteadiness, dizziness Depersonalization, Derealization Excessive heart rate, palpitations Nausea/abdominal distress Tingling/numbness Shortness of breath Fear of dying, losing control, going crazy 3 Cs: Chest pain, Chills/hot flashes, Choking Duration typically 5-10 min

Agoraphobia PS17 Psychiatry

Toronto Notes 2023

Epidemiology • lifetime prevalence: 5% (one of the top ve most common reasons to see a family physician); M:F=1:23 • onset: average early-mid 20s, familial pattern • comorbidities: depression, agoraphobia, medical comorbidity Treatment • pharmacological and psychological treatment together can be very eective • psychological ■ CBT: exposure (graduated exposure to unpleasant sensations of arousal associated with a panic attack for experiential disconrmation of their fears), cognitive restructuring (addressing underlying beliefs regarding the panic attacks), relaxation techniques (visualization, boxbreathing), psychoeducation • pharmacological (rst line agents) ■ SSRIs: uoxetine, citalopram, escitalopram, paroxetine, sertraline, uvoxamine ■ SNRI: venlafaxine extended release ■ with SSRI/SNRIs, start with low doses and titrate up as tolerated ■ anxiety disorders oen require treatment at higher doses for a longer period of time than depression (full response may take up to 12 wk) ■ treat for up to 1 yr aer symptoms resolve to avoid relapse ■ explain expected adverse eects prior to initiation of therapy to prevent non-adherence ■ other antidepressants: (mirtazapine, TCAs) ■ benzodiazepines considered 2nd line (short-term, lowest eective dose, helpful while titrating antidepressant) Prognosis • 85% can achieve good results, 10-20% continue with signicant symptoms. Longer term, 65% achieve remission • clinical course: chronic, but episodic with psychosocial stressors

Agoraphobia DSM-5 DIAGNOSTIC CRITERIA FOR AGORAPHOBIA

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013. American Psychiatric Association

A. marked fear or anxiety about two (or more) of the following ve situations: ■ using public transportation ■ being in open spaces ■ being in enclosed places ■ standing in line or being in a crowd ■ being outside of the home alone B. the individual fears or avoids these situations because of thoughts that escape might be dicult or help might not be available in the event of developing panic-like symptoms or other incapacitating or embarrassing symptoms C. the agoraphobic situations almost always provoke fear or anxiety D. the agoraphobic situations are actively avoided, require the presence of a companion, or are endured with intense fear or anxiety E. the fear or anxiety is out of proportion to the actual danger posed by the agoraphobic situations and to the sociocultural context F. the fear, anxiety, or avoidance is persistent, typically lasting ≥6 mo G. the fear, anxiety, or avoidance causes clinically signicant distress or impairment in social, occupational, or other important areas of functioning H. if another medical condition is present, the fear, anxiety, or avoidance is clearly excessive I. the fear, anxiety, or avoidance is not better explained by the symptoms of another mental disorder and are not related exclusively to obsessions, perceived defects or aws in physical appearance, reminders of traumatic events, or fear of separation Note: agoraphobia is diagnosed irrespective of the presence of panic disorder. If an individual’s presentation meets criteria for panic disorder and agoraphobia, both diagnoses should be assigned Treatment • as per specic panic disorder

Panic Attack vs. Panic Disorder • Panic disorder requires recurrent, unexpected panic attacks + fear of another panic attack • Panic attacks can occur in the context of many dierent disorders

Starting Medication for Anxiety Start low, go slow, aim high, and explain symptoms to e xpect prior to initiation of therapy to prevent non-adherence due to side eects

Generalized Anxiety Disorder PS18 Psychiatry

Toronto Notes 2023

Generalized Anxiety Disorder DSM-5 DIAGNOSTIC CRITERIA FOR GENERALIZED ANXIETY DISORDER

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013. American Psychiatric Association

A.excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 mo, about a number of events or activities (such as work or school performance) B. the individual nds it dicult to control the worry C. the anxiety and worry are associated with three (or more) of the following six symptoms (with at least some symptoms having been present for more days than not for the past 6 mo) 1. restlessness or feeling keyed up or on edge 2. being easily fatigued 3. diculty concentrating or mind going blank 4. irritability 5. muscle tension 6. sleep disturbance (diculty falling or staying asleep, or restless, unsatisfying sleep) D.the anxiety, worry, or physical symptoms cause clinically signicant distress or impairment in social, occupational, or other important areas of functioning E. the disturbance is not attributable to the physiological eects of a substance or another medical condition F. the disturbance is not better explained by another mental disorder Epidemiology • 1 yr prevalence: 1-4%, lifetime prevalence 6%; M:F=1:2 ■ 8% of all who seek primary care treatment (WHO) ■ in primary care: 70% initially present with physical symptoms as main concern • bimodal age of onset: before 20 or middle adulthood Source: Depression and other common mental disorders: Global health estimates. Geneva: World Health Organization, 2017.

Treatment • lifestyle: avoid caeine and EtOH, sleep hygiene • psychological: CBT (cognitive restructuring), muscle relaxation techniques, mindfulness • biological ■ 1st line: SSRIs (escitalopram, sertraline, paroxetine), SNRIs (venlafaxine XR, duloxetine), pregabalin ■ benzodiazepines considered 2nd line (short-term, lowest eective dose, helpful while titrating antidepressant) ■ β-blockers not recommended Prognosis • good with treatment • depends on pre-morbid personality functioning, stability of relationships, work, and severity of environmental stress

Social Anxiety • denition: marked and persistent (>6 mo) fear of social or performance situations in which one is exposed to unfamiliar people or to possible scrutiny by others. ey fear that they will be negatively evaluated in a way that may be humiliating, embarrassing, or lead to rejection (e.g. public speaking, initiating or maintaining conversation, dating, eating in public) • situations are avoided or endured with intense anxiety and causes signicant distress or impairment in functioning • lifetime prevalence 8-12%; M:F ratio approximately equal

Phobic Disorders Specific Phobias • denition: marked and persistent (>6 mo) fear that is excessive or unreasonable, cued by presence or anticipation of a specic object or situation • lifetime prevalence 10-13%; M:F ratio variable • types: animal/insect, environment (e.g. heights, storms), blood/injection/injury, situational (e.g. airplane, closed spaces), other (e.g. loud noise, clowns), multiple fears Diagnostic Criteria for Phobic Disorders • marked fear/anxiety about a specic object/situation • exposure to stimulus almost invariably provokes an immediate fear/anxiety response; may present as a panic attack • phobic object/situation is actively avoided or endured with intense anxiety. • fear/anxiety out of proportion to actual danger/sociocultural context and persistent (lasting 6 mo or more) • person recognizes fear as excessive or unreasonable • signicant impact on daily routine, occupational/social functioning, and/or marked distress

Criteria for GAD (≥3) C-FIRST Concentration issues Fatigue Irritability Restlessness Sleep disturbance Tension (muscle)

Obsessive-Compulsive and Related Disorders PS19 Psychiatry

Treatment • psychological: psychoeducation, CBT (focusing on both in vivo and virtual exposure therapy, gradually facing feared situations) • biological: minimal role for medications

Obsessive-Compulsive and Related Disorders Obsessive-Compulsive Disorder DSM-5 DIAGNOSTIC CRITERIA FOR OBSESSIVE-COMPULSIVE DISORDER

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013. American Psychiatric Association

A.presence of obsessions, compulsions, or both ■ obsessions are dened by (1) and (2) 1. recurrent and persistent thoughts, urges, or images that are experienced, at some time during the disturbance, as intrusive and unwanted, and that in most individuals cause marked anxiety or distress 2. the individual attempts to ignore or suppress such thoughts, urges, or images, or to neutralize them with some other thought or action (i.e. by performing a compulsion) ■ compulsions are dened by (1) and (2) 1. repetitive behaviours (e.g. hand washing, ordering, checking) or mental acts (e.g. praying, counting, repeating words silently) that the individual feels driven to perform in response to an obsession or according to rules that must be applied rigidly 2. the behaviours or mental acts are aimed at preventing or reducing anxiety or distress, or preventing some dreaded event or situation; however, these behaviours or mental acts are not connected in a realistic way with what they are designed to neutralize or prevent, or are clearly excessive B. the obsessions or compulsions are time-consuming (e.g. take >1 h/d) or cause clinically signicant distress or impairment in social, occupational, or other important areas of functioning C. the obsessive-compulsive symptoms are not attributable to the physiological eects D.the disturbance is not better explained by the symptoms of another mental disorder • speciers: with good or fair insight, with poor insight, with absent insight/delusional beliefs, ticrelated • most common obsessions: contamination fear, pathological doubts, harm (sex, aggression), somatic dysfunctions, need for symmetry, religious • most common compulsions: checking, washing, repeating, ordering, counting, need to ask, and hoarding • rituals serve to counteract the anxiety induced by the obsessive thoughts Epidemiology • lifetime prevalence 3% • mean age of onset: 20 yr; onset aer 35 yr rare • rate of OCD in rst-degree relatives is higher than in the general population • common comorbidities: anxiety disorders (>75%), depressive or bipolar disorder (>60%), obsessivecompulsive PD, tic disorders, substance use disorder, body dysmorphic disorder, trichotillomania, and excoriation disorder Risk Factors • etiology unknown but linked with: ■ neurological abnormalities: neurological dysfunction (brain injury, Sydenham’s or Huntington’s chorea), abnormal EEG, and abnormal evoked auditory potentials ■ family history of OCD or Tourette’s disorder ■ paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) in children following group A β-streptococcal infection; also linked to D8/17 antigen positivity ■ social isolation, physical abuse, negative emotionality Treatment • CBT: ERP which involves exposure to feared situations using various techniques (e.g. imaginal exposure, systematic desensitization, ooding) with the addition of preventing the compulsive behaviours; cognitive strategies include challenging underlying beliefs • pharmacotherapy: SSRIs (12-16 wk potential delay until response, higher therapeutic dosages than used for depression), clomipramine; adjunctive antipsychotics (risperidone, aripiprazole) for refractory OCD • neurosurgery or neurostimulation: anterior cingulotomy for severe refractory OCD, two techniques: radiofrequency thermolesion and gamma knife capsulotomy or cingulotomy (50-70% response rate); ECT (particularly for those with comorbid severe depression) Prognosis • may be refractory and chronic with waxing and waning symptoms (65 yr, 35-50% in patients >85 yr • probability of dementia in an older person with reported memory loss is estimated to be 60% • prevalence is increased in people with Down’s syndrome and head trauma • Alzheimer’s disease comprises >50% of cases; vascular causes comprise approximately 15% of cases (other causes of dementia neurocognitive disorder – see Neurology, N23) • disease course: insidious onset, usually leading to death within 8-10 yr of rst symptoms Subtypes • with or without behavioural disturbance (e.g. wandering, agitation) • early-onset: 65 yr Assessment and Investigations (to rule out reversible causes) • history: consider the 7 A’s of dementia, signicant changes in ADLs and IADLS, medication compliance and substance use, risk factors for dementia and delirium, mood/anxiety and psychotic symptoms, screen for non-Alzheimer’s dementias, assess safety and consent/capacity issues • cognitive tests (e.g. MMSE, Rowland Universal Dementia Assessment Scale, Frontal Assessment Battery, MoCA) • MoCA 18-25 suggestive of mild neurocognitive disorder (NCD), 30 d for heavy users) • limitations: negative tests cannot rule out substance use, and positive results cannot determine how much or frequency of use General Approach to Treatment • approach must be appropriate to the patient’s current state of change (see Public Health and Preventive Medicine, Health Promotion Strategies, PH11) • patients will change when the pain of change appears less than the pain of staying the same • provider can help by providing psychoeducation (emphasize neurobiologic model of addiction), motivation, and hope • principles of motivational interviewing (see Psychotherapy, PS49) ■ non-judgmental stance ■ space for patient to talk and reect ■ oer accurate empathic reections back to patient to help frame issue • encourage and oer referral to evidence based services ■ social: 12-step programs (alcoholics anonymous, narcotics anonymous), family education, and support ■ psychological therapy: addiction counselling, MET, CBT, contingency management, group therapy, family therapy, marital counselling ■ medical management (diers depending on substance): acute detoxication, pharmacologic agents to aid maintenance. Ontario has the RAAM- Rapid Access to Addiction Medicine clinics that oer timely, low barrier, specialized services by self-referral • harm reduction whenever possible: safe-sex practices, avoid driving while intoxicated, avoid substances with child care, safe needle practices/exchange, pill-testing kits, reducing tobacco use • comorbid psychiatric conditions: many will resolve with successful treatment of the substance use disorder but patients who meet full criteria for another disorder should be treated for that disorder with psychological and pharmacologic therapies • always consider duty to inform Ministry of Transportation for risk of driving or operating other vehicles

Nicotine • see Family Medicine, FM13 Confabulations: the fabrication of imaginary experiences to compensate for memory loss

Alcohol • see Family Medicine, FM15 and Emergency Medicine, ER54 History • Validated screening questionnaire for alcohol use disorders C ever felt the need to Cut down on your drinking? A ever felt Annoyed at criticism of your drinking? G ever feel Guilty about your drinking? E ever need a drink rst thing in the morning (Eye opener)? ◆ for men, a score of ≥2 is a positive screen; for women, a score of ≥1 is a positive screen ◆ if positive CAGE, then assess further to distinguish between problem drinking and alcohol use disorder Canada’s Low-Risk Alcohol Drinking Guidelines Moderate Drinking Men: 3 or less/d (≤15/wk)

Women: 2 or less/d (≤10/wk)

Elderly: 1 or less/d

Biochemical Markers of Prolonged Alcohol Use • elevated liver function tests (AST, ALT, GGT), MCV, and carbohydrate-decient transferrin (CDT) • AST:ALT ratio >2:1 and elevated GGT are suggestive of alcohol use Alcohol Intoxication • throughout Canada, the legal limit for impaired driving is a BAC ≥0.08% (≥80 mg/dL or 17.4 mmol/L) which is typically reached aer 4 drinks in women and 5 drinks in men in a 2 h period

Make sure to ask about other alcohols: mouthwash, rubbing alcohol, methanol, ethylene glycol, aftershave (may be used as a cheaper alternative)

A “Standard Drink” (SD) Spirit (40%): 1.5 oz. or 43 mL T able Wine (12%): 5 oz. or 142 mL Fortified Wine (18%): 3 oz. or 85 mL Regular Beer (5%): 12 oz. or 341 mL OR 1 pint of beer = 1.5 SD 1 bottle of wine = 5 SD 1 “mickey” = 8 SD (375 mL) “26-er” = 17 SD (750 mL) “40 oz.” = 27 SD

PS29 Psychiatry

Toronto Notes 2023

• most signs of intoxication are present at over >21.7 mmol/L (100 mg/dL): altered perception, impaired judgement, ataxia, hyper-reexia, impaired coordination, changes in mood/personality, prolonged reaction time, and slurred speech • respiratory depression and arrest can occur with >60 mmol/L (non-tolerant drinkers) and 90-120 mmol/L (tolerant drinkers) Management of Alcohol Intoxication • stabilize patient if there is reduced level of consciousness or vomiting; assess airways and respiratory function • administer IV crystalloid uids if evidence of volume depletion or shock; correct electrolytes and hypoglycemia • monitor for signs of alcohol withdrawal following detoxication in patients with alcohol use disorder Alcohol Withdrawal • medical emergency: occurs within 12-48 h aer prolonged heavy drinking and can be life-threatening • ~50% of middle-class, functional individuals with alcohol use disorder have experienced alcohol withdrawal; 80% in hospitalized/homeless individuals ■ alcohol withdrawal can be described as having 4 stages, however not all stages may be experienced: ◆ stage 1 (onset 4-12 h aer last drink): “the shakes” tremor, sweating, agitation, anorexia, cramps, diarrhea, sleep disturbance, anxiety, insomnia, headache. e majority of alcohol withdrawal presentations are mild to moderate (stage 1) ◆ stage 2 (onset 12-24 h): alcoholic hallucinosis: visual, auditory, olfactory, or tactile hallucinations ◆ stage 3 (onset 12-48 h): alcohol withdrawal seizures, usually tonic-clonic, non-focal, and brief (can occur as early as 2 h aer alcohol consumption) ◆ stage 4 (onset 48-96 h): delirium tremens, confusion/disorientation, delusions, hallucinations, agitation, tremors, autonomic hyperactivity (diaphoresis, fever, tachycardia, HTN) • course: almost completely reversible in young; elderly oen le with cognitive decits • 20% mortality rate of severe presentations (delirium tremens) if untreated Management of Alcohol Withdrawal • monitor using the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-A) scoring system ■ areas of assessment include (SHANT AS TAV): ◆ physical (5): paroxysmal Sweats, Headache/fullness in head, Agitation, Nausea and vomiting, Tremor ◆ psychological/cognitive (2): Anxiety, orientation/clouding of Sensorium ◆ perceptual (3): Tactile disturbances, Auditory disturbances, Visual disturbances ◆ all categories are scored from 0-7 (except: orientation/sensorium 0-4), maximum score of 67 ◆ mild 20 • check for signs of hepatic failure (e.g. ascites, jaundice, and coagulopathy) Table 5. CIWA-A Scale Treatment Protocol for Alcohol Withdrawal Basic protocol

Diazepam 20 mg PO q1-2 h PRN until CIWA-A 65 or patient has severe liver disease, Use a short acting benzodiazepine severe asthma or respiratory failure Lorazepam 1-4 mg PO/SL/IM q1-2 h If hallucinations are present

Haloperidol 2-5 mg IM/PO q1-4 h – max 5 doses/d or atypical antipsychotics (olanzapine, risperidone) Diazepam 20 mg x 3 doses as seizure prophylaxis (haloperidol lowers seizure threshold)

Admit to hospital if

Still in withdrawal after >80 mg of diazepam Delirium tremens, recurrent arrhythmias, or multiple seizures Medically ill or unsafe to discharge home

Wernicke-Korsako Syndrome • alcohol-induced amnestic disorders due to thiamine deciency (poor nutrition or malabsorption) • necrotic lesions: mammillary bodies, thalamus, brainstem • Wernicke’s encephalopathy (acute and reversible): triad of oculomotor dysfunction such as nystagmus (CN VI palsy (eye pointing inwards)), gait ataxia, and confusion. If untreated, may progress to Korsako’s syndrome • Korsako’s syndrome (chronic and only 20% reversible with treatment): anterograde amnesia and compensatory confabulation; cannot occur only during an acute delirium or dementia and must persist beyond usual duration of intoxication/withdrawal • management ■ Wernicke’s preventative treatment (any patient in withdrawal): thiamine 100-250 mg IM/IV x 1 dose ■ Wernicke’s acute treatment: thiamine 500 mg IV BID/TID x 72 h, then reassess ■ Korsako’s: IV treatment as for Wernicke’s followed by thiamine 100 mg PO TID x 3-12 mo

Delirium Tremens (alcohol withdrawal delirium) • Autonomic hyperactivity (diaphoresis, tachycardia, increased respiration) • Hand tremor • Insomnia • Psychomotor agitation • Anxiety • Nausea or vomiting • Tonic-clonic seizures • Visual/tactile/auditory hallucinations • Persecutory delusions

Opioids PS30 Psychiatry

Toronto Notes 2023

Treatment of Alcohol Use Disorder • non-pharmacological ■ see General Approach to Treatment, PS28 • pharmacological ■ naltrexone (Revia®): opioid antagonist, shown to be successful in reducing the “high” associated with alcohol, moderately eective in reducing cravings, frequency or intensity of alcohol binges; can be started if still consuming alcohol or abstinent but can precipitate withdrawal in those with physical opioid dependence ■ acamprosate (Campral®): NMDA glutamate receptor antagonist; useful in maintaining abstinence and decreasing cravings ■ disulram (Antabuse®): prevents oxidation of alcohol (blocks acetaldehyde dehydrogenase) and causes an adverse reaction to alcohol (nausea/vomiting, tachycardia, shortness of breath, headache); if patient relapses, must wait 48 h before restarting Antabuse®; prescribed only when treatment goal is abstinence; RCT evidence is generally poor or negative due to poor medication adherence; contraindicated in severe renal disease, pregnancy, psychoses, and cardiac disease ■ some evidence for the use of gabapentin, topiramate, and ondansetron as anti-craving agents, but not approved by Health Canada approved for this indication (currently under investigation)

Opioids • types of opioids: heroin, morphine, oxycodone, Tylenol #3® (codeine), hydromorphone, fentanyl, methadone, meperidine (Demerol®) • in addition to working on opiate receptors, opiates also act on the dopaminergic system, which mediates their addictive properties • most commonly used are: Percocet® (oxycodone/acetaminophen), Vicodin® (hydrocodone/ acetaminophen), and OxyContin® (oxycodone) • major risks associated with the use of contaminated needles: increased risk of hepatitis B and C, bacterial endocarditis, and HIV/AIDS • recent considerations of inadvertent overdose secondary to contamination with fentanyl in the drug supply “opioid crisis” leading to 9000 deaths in Canada between January 2016 and June 2018 Acute Intoxication • direct eect on receptors in CNS resulting in decreased pain perception, sedation, decreased sex drive, nausea/vomiting, decreased GI motility (constipation and anorexia), pupil constriction (e.g. pinpoint pupils; exception is meperidine), and respiratory depression (can be fatal) • medical emergency: typical syndrome includes shallow respirations, miosis, bradycardia, hypothermia, decreased level of consciousness • management ■ ABCs ■ IV glucose ■ naloxone hydrochloride (Narcan®): 0.4 mg up to 2 mg IV for diagnosis ■ treatment: intubation and mechanical ventilation, ± naloxone drip, until patient alert without naloxone (up to >48 h with long-acting opioids) • caution: opioids have a longer half-life than naloxone; may need to observe for toxic reaction for at least ≥24 h Withdrawal • symptoms: dysphoric mood, insomnia, drug-craving, myalgias, nausea or vomiting, yawning, chills, lacrimation, rhinorrhea, pupillary dilation, piloerection, sweating, diarrhea, fever; withdrawal symptoms can be severe but are not life threatening • onset: 6-12 h (depending on half-life of opioid used); duration: 5-10 d • complications: loss of tolerance (overdose on relapse), miscarriage, premature labour • management: long-acting oral opioids (methadone, buprenorphine), α-adrenergic agonists (clonidine for symptomatic management of autonomic signs and symptoms of withdrawal) • monitor withdrawal severity using Clinical Opioid Withdrawal Scale (COWS) Treatment of Opioid Use Disorder • see General Approach to Treatment, PS28 • long-term treatment may include maintenance treatment with methadone (opioid agonist) or buprenorphine (mixed agonist-antagonist) • caution: methadone can cause QTc interval prolongation, screening ECG recommended • Suboxone® formulation includes naloxone in addition to buprenorphine, in an eort to prevent injection of the drug. When naloxone is injected, it will precipitate opiate withdrawal and block the opiate eect of buprenorphine. However, it will not have this antagonist action when taken sublingually • decreasing risk of overdose: patients with a history of opiate use, and/or friends, family members and co-workers working with people using opiates should be encouraged to carry a naloxone kit and educated on ways to limit overdose risk (i.e. use with a friend, avoid mixing drugs). It is a life-saving strategy

Opioid Antagonists Naltrexone vs. Naloxone Naltrexone (Revia®) • Can be used for EtOH dependence (although not routinely used) • Long half-life (>1 h) Naloxone (Narcan®) • Used for life-threatening CNS/ respiratory depression in opioid overdose • Short half-life ( explanation of symptoms)

Emerging Medical Uses of Hallucinogens Many hallucinogens are currently under investigation for therapeutic benefit; LSD & psilocybin for end of life anxiety, MDMA for PTSD, ketamine for rapid treatment of depression, ibogaine derivatives for addiction

Malingering: intentional production of false or grossly exaggerated physical or psychological symptoms, motivated by secondary gain/external reward (e.g. avoiding work, obtaining financial compensation, or obtaining drugs) Factitious Disorder: intentional production or feigning of physical or psychological signs or symptoms. Unlike malingering, patients are not motivated by secondary gain but rather may seek sympathy, nurturance, and attention

Somatic Symptom Disorder PS34 Psychiatry

Toronto Notes 2023

• focus on functional improvement (physiotherapy, occupational therapy) and provide psychoeducation to validate suering in the face of medically unexplained symptoms • psychotherapy: CBT, psychodynamic therapy, mindfulness interventions, biofeedback • minimize psychotropic drugs: anxiolytics for short-term use only (associated with worse outcomes), antidepressants for comorbid depression and anxiety

Somatic Symptom Disorder DSM-5 DIAGNOSTIC CRITERIA FOR SOMATIC SYMPTOM DISORDER

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. 2013. American Psychiatric Association

A.one or more somatic symptoms that are distressing or result in signicant disruption of daily life B. excessive thoughts, feelings, or behaviours related to the somatic symptoms or associated health concerns as manifested by at least one of the following: 1. disproportionate and persistent thoughts about the seriousness of one’s symptoms 2. persistently high level of anxiety about health or symptoms 3. excessive time and energy devoted to these symptoms or health concerns C. although any one somatic symptom may not be continuously present, the state of being symptomatic is persistent (typically >6 mo) • somatic symptom disorder with predominant pain (previously pain disorder) for those whose somatic symptom is primarily pain • patients have physical symptoms and believe these symptoms represent the manifestation of a serious illness • persistent belief despite negative medical investigations and may develop dierent symptoms over time • lifetime prevalence may be around 5-7% in the general adult population • females tend to report more somatic symptoms than males do; cultural factors may inuence sex ratio • other risk factors include: history of sexual abuse, lower education and socioeconomic status, and concurrent psychiatric/chronic physical illnesses • complications: anxiety and depression commonly comorbid (up to 80%), unnecessary medications, or surgery • oen a misdiagnosis for an insidious illness, so rule out all organic illnesses (e.g. multiple sclerosis) • DDx: GAD, depressive disorder, delusional disorder, body dysmorphic disorder, obsessive compulsive disorder, other medical condition

Illness Anxiety Disorder • preoccupation with fear of having, or the idea that one has a serious disease to the point of causing signicant impairment • convictions persist despite negative investigations and medical reassurance; however, able to acknowledge the possibility that feared disease is not present, unlike a delusion, which is xed and rm • somatic symptoms are mild or not present (not acute) • there is a high level of anxiety about health and the individual is easily alarmed about personal health status • person engages in maladaptive behaviour such as excessive physical checking or total healthcare avoidance • duration is ≥6 mo; onset in 3rd-4th decade of life • epidemiology: 3-5% of patients seen by primary care physicians; increased risk of substance use problems • possible role for SSRIs as treatment due to generally high level of anxiety • speciers: care-seeking type or care-avoidant type

Conversion Disorder (Functional Neurological Symptom Disorder) • one or more symptoms or decits aecting voluntary motor or sensory function that mimic a neurological or GMC (e.g. impaired coordination, local paralysis, double vision, seizures, or convulsions) • does not need to be preceded by a psychological event as per previous DSM criteria; however this is still worth exploring as many patients will present aer such an event or are related to a medical diagnosis in a rst-degree relative • incidence of 2-5 in 100000 in general population; up to 20-25% of neurology inpatients and 5% of psychiatry inpatients • more common in rural populations and in individuals with little medical knowledge • spontaneous remission in 95% of acute cases, 50% of chronic cases (>6 mo) • incompatible ndings detected from specic neurological testing can help dierentiate between functional and neurological origin (e.g. Hoover’s sign and dermatome testing) • for more details about Conversion Disorder, please consult the DSM-5

Screening questions for somatic disorders 1. When did the symptoms start? 2. Have you been frustrated with getting no answers? 3. What has been your experience with other physicians? 4. What is your understanding of your symptoms? 5. How have the symptoms aected your life?

Dissociative Disorders PS35 Psychiatry

Toronto Notes 2023

Table 7. Dierential of Somatic Symptom and Related Disorders

Somatic Symptoms

Somatic Symptom Illness Anxiety Disorder Disorder

Conversion Disorder

Factitious Disorder

Malingering

Present

Mild or absent

Neurologic, voluntary Psychological or motor or sensory physical

Psychological or physical

Symptoms Produced

Unconsciously

Unconsciously

Unconsciously

Consciously

Consciously

Physical Findings

Absent

Absent

Incompatible

Possible, attempts to falsify

Possible, attempts to falsify

La belle indierence: an inappropriately cavalier patient attitude in the face of serious symptoms; classically associated with conversion disorder but is not diagnostic Hoover’s sign: involuntary extension of the “normal” leg occurs when flexing the contralateral leg against resistance

Dissociative Disorders General Characteristics • severe dissociation resulting in breakdown of integrated functions of consciousness and perception of self • severe stress or traumas are predisposing factors for dissociative disorders (e.g. survivors of signicant or chronic trauma, child abuse) • result in signicant distress or impairment in social/occupational functioning • psychotherapy (psychodynamic, CBT) are the mainstays of treatment; lack of evidence for use of medications • DDx: PTSD, acute stress disorder, borderline personality disorder, somatic symptom disorder, substance use disorder, GMC (various neurologic disorders including complex/partial seizures, migraine, Cotard syndrome)

Dissociative Identity Disorder • disruption of identity characterized by ≥2 distinct personality states or an experience of possession • can manifest as sudden alterations in sense of self and agency (ego-dystonic emotions, behaviours, speech) • features recurrent episodes of amnesia (declarative or procedural) as well as episodes of depersonalization and derealization • rare (17 kg/m 2 , moderate = BMI 16-16.99 kg/m2 , severe = BMI 15-15.99 kg/m 2, extreme = BMI 90 d, more commonly yr

Treatment

Acute: benztropine or diphenhydramine, usually IM

Acute: lorazepam, propranolol, benztropine, or diphenhydramine; best approach: reduce dose or change antipsychotic to lower potency

Acute: benztropine; reduce dosage or change antipsychotic to low potency atypical antipsychotic

Tardive: no good treatment; may try clozapine; discontinue drug or reduce dosage Recently the FDA approved valbenazine and deutetrabenazine for the treatment of tardive dyskinesia

Anticholinergic Agents • types ■ benztropine (Cogentin®) 2 mg PO, IM, or IV once daily (1-6 mg) ■ diphenhydramine (Benadryl®) 25-50 mg PO/IM QID • do not routinely prescribe with antipsychotics ■ give anticholinergic agents only if at high-risk for acute EPS or if acute EPS develops • do not give these for tardive syndromes because they worsen the condition

Antidepressants • onset of eect ■ relief of neuro-vegetative/physical symptoms: 1-3 wk ■ relief of emotional/cognitive symptoms: 2-6 wk • tapering of most antidepressants is usually required to avoid withdrawal reactions; speed of taper is based on the medication’s half-life and the patient’s individual sensitivity (i.e. uoxetine does not require a taper due to its long half-life; paroxetine and venlafaxine require a slower taper than sertraline or citalopram) • must be vigilant over the rst 2 wk of therapy; neuro-vegetative symptoms may start to resolve while emotional and cognitive symptoms may not (patients may be at risk for suicidal behaviour during this time, particularly in children/adolescents) • treatment of bipolar depression • patients with bipolar disorder (bipolar depression) should not be treated with an antidepressant as the rst-line therapy ■ patients with bipolar disorder should only be treated with an antidepressant if combined with a mood stabilizer or antipsychotic; monotherapy with antidepressants is not advisable as the depression can switch to mania ■ maintenance of patients with bipolar disorder with antidepressants is not advisable except in specic cases

PS55 Psychiatry

Toronto Notes 2023

Table 19. Common Antidepressants Class

Drug

Daily Starting Dose (mg)*

Therapeutic Dose (mg)

Comments

SSRI

fluoxetine (Prozac®) fluvoxamine (Luvox®) paroxetine (Paxil®) sertraline (Zoloft®) citalopram (Celexa®) escitalopram (Cipralex®)

20 50-100 10 50 20 10

20-80 150-300 20-60 50-200 20-40 10-20

Useful for typical and atypical depression, seasonal depression, anxiety disorders, OCD, eating disorders All SSRIs have similar eectiveness but consider side eect profiles and half-lives Citalopram and escitalopram have the fewest drug interactions and are sleepwake neutral Sertraline is the safest SSRI in pregnancy and breastfeeding Fluoxetine is the most activating SSRI (recommend taking in the AM) Fluoxetine does not require a taper due to long half-life and is the most used in children and adolescents as it has most evidence Fluvoxamine is sedating (should be taken in PM) and can be involved in many drug-drug interactions For OCD, aim for maximum doses, sometimes higher

SNRI

venlafaxine (Eexor®) desvenlafaxine (Pristiq®) duloxetine (Cymbalta®)

37.5-75 50 30

75-225 50-100 30-60

Useful for depression, anxiety disorders, neuropathic pain

NDRI

bupropion (Wellbutrin®)

100

300-450

Useful for depression, seasonal depression; not recommended for anxiety disorder treatment because of stimulating eects Causes less sexual dysfunction (may reverse eects of SSRIs/SNRIs), weight gain, and sedation Increased risk of seizures at higher doses Contraindicated with history of seizure, stroke, brain tumour, brain injury, closed head injury Important to specify formulation, as available in IR, SR, XL (longest)

TCA (3º Amines)

amitriptyline (Elavil®) imipramine (Tofranil®) clomipramine (Anafranil®)

25-50 25-50 25-50

150-300 150-300 100-250

Useful for OCD (clomipramine is gold standard), melancholic depression, can also be used in other types of depression and anxiety disorders Requires ECG monitoring Check blood levels if using higher dosage Highly lethal in overdose

TCA (2º Amines)

nortriptyline (Aventyl®) desipramine (Norpramin®)

25-50 25-50

75-150 150-300

Preferred to tertiary amines because of lower propensity for anticholinergic adverse eects Requires ECG monitoring Check blood levels if using higher dosage Highly lethal in overdose

MAOI

phenelzine (Nardil®) tranylcypromine (Parnate®)

15 20

60-90 10-60

Useful for moderate/severe depression that does not respond to other antidepressants; atypical depression; anxiety disorders Requires strict adherence to MAOI diet, (low tyramine)

RIMA

moclobemide (Manerix®)

300

300-600

Useful for some anxiety disorders (e.g. social phobia) and depression

NaSSA

mirtazapine (Remeron®)

15

15-45

Useful in depression with prominent features of insomnia, agitation, or cachexia

SPARI

vilazodone (Viibryd®)

10

10-40

Useful in those with constipation as diarrhea is a common side eect

Serotonin Receptor Modulator

vortioxetine (Trintellix®)

5

5-20

May improve cognitive function

*for depression (star t with ½ this dose for treatment of anxiety disorders) MAOI = monoamine oxidase inhibitors; NaSSA = noradrenergic and specific serotonergic agent; NDRI = norepinephrine and dopamine reuptake inhibitors; RIMA = reversible inhibition of MAO-A; SNRI = serotonin and norepinephrine reuptake inhibitors; SSRI = selective serotonin reuptake inhibitors; TCA = tricyclic antidepressants; SPARI = serotonin partial agonist and reuptake inhibitor

PS56 Psychiatry

Toronto Notes 2023

Treatment Approach for Depression Select and initiate a first-line antidepressant

Psychopharmacology of SSRIs

Monitor Early improvement after 2-4 wk?

NO

Optimize dose

Consider factors for switch vs. adjunct Early treatment failure

Switch to a 2nd or 3rd line antidepressant

YES

Switch to another first-line antidepressant, preferably with superior efficacy

Post-Synaptic Serotonin Receptor Stimulated

Eect/Side Eect

5HT1A centrally

Relief of depression Anxiolytic eect

5HT2A in spinal cord

Sexual dysfunction: delayed ejaculation, anorgasmia, decreased interest/ libido

5HT2C/5HT2A in brain

Activation: anxiety, insomnia Worst with fluoxetine, paroxetine Warn patients anxiety may worsen in first 1-2 wk of treatment

5HT3A in gut

GI upset: nausea, vomiting, bloating Take with food

Add adjunctive medication

Monitor: consider longer evaluation period for more persistant depression Continue treatment for 6-8 wk

YES Optimize dose

Symptom remission?

Early improvement after 2-4 wk?

NO

NO

YES Risk factors for recurrence?

NO

Maintain treatment for 6-9 mo

YES Maintain treatment for 2 yr or longer

Figure 3. Depression treatment algorithm Adapted from: Sidney H. Kennedy, Raymond W. Lam, Roger S. McIntyre, et al, The Canadian Journal of Psychiatry (61, 9), p. 21, copyright © 2020, Modified by Permission of SAGE Publications, Inc.

• optimization: increase dosage to maximum tolerated or highest therapeutic dosage • augmentation: the addition of a medication that is not considered an antidepressant to an antidepressant regimen (i.e. thyroid hormone, lithium, atypical antipsychotics (aripiprazole, quetiapine, olanzapine, risperidone)) • combination: the addition of another antidepressant to an existing treatment regimen (i.e. the addition of bupropion or mirtazapine to an SSRI or SNRI) • switch: change of the primary antidepressant (within or outside a class) • note: it is important to fully treat depression symptoms (i.e. to remission) to decrease relapse rates Serotonin Syndrome • thought to be due to over-stimulation of the serotonergic system • can result from medication combinations such as more than one SSRI, SSRI + SNRI, SSRI or SNRI + MAOI, SSRI + tryptophan, MAOI + meperidine, MAOI + tryptophan • rare but potentially life-threatening adverse reaction to SSRIs and SNRIs • symptoms include: nausea, diarrhea, palpitations, chills, diaphoresis, restlessness, confusion, and lethargy, but can progress to myoclonus, hyperthermia, rigor, and hypertonicity • treatment: discontinue medication and administer emergency medical care as needed • important to distinguish from NMS Discontinuation Syndrome • caused by the abrupt cessation of some antidepressants; most commonly with paroxetine, uvoxamine, and venlafaxine (drugs with shortest half-lives) • symptoms usually begin within 1-3 d and can include anxiety, insomnia, irritability, mood lability, N/V, dizziness, headache, dystonia, tremor, chills, fatigue, lethargy, and myalgia (“u-like symptoms”) • treatment: symptoms may last between 1-3 wk, but can be relieved within 24 h by restarting antidepressant at the same dosage the patient was taking initially and initiating a slower taper over several weeks • consider avoiding drugs with a short half-life

Symptoms of Antidepressant Discontinuation (mainly from serotonin reuptake inhibition activity) FINISH Flu-like symptoms Insomnia Nausea Imbalance Sensory disturbances Hyperarousal (anxiety/agitation)

PS57 Psychiatry

Toronto Notes 2023

Table 20. Features of Commonly Used Antidepressant Classes SSRI

SNRI

TCA

MAOI

NDRI

RIMA

NaSSA

SPARI

Serotonin receptor modulator

Examples

fluoxetine, sertraline, citalopram

venlafaxine, duloxetine

amitriptyline, clomipramine

phenelzine

bupropion

moclobemide

mirtazapine

vilazodone

vortioxetine

Mode of Action

Block serotonin reuptake only

Block norepinephrine and serotonin reuptake

Block norepinephrine reuptake (clomipramine also blocks serotonin reuptake)

Irreversible inhibition of MAO A and B increases duration that NE, dopamine, and 5HT are in the synaptic cleft by preventing their degradation

Block norepinephrine and dopamine reuptake

Reversible inhibitor of monoamine oxidase A leads to increased duration of norepinephrine, dopamine, and 5HT in the synaptic cleft by preventing their degradation

Enhance central noradrenergic and serotonergic activity by inhibiting presynaptic α-2 adrenergic receptors

5HT1A partial agonism causes downregulation of presynaptic 5HT1A receptors to disinhibit serotonin release, and 5HT4 agonism treats constipation

5HT1A agonism downregulates presynaptic 5HT1A receptors to disinhibit serotonin release, and 5HT7 antagonism theoretically enhances cognitive function

Side Eects

CNS: restlessness, tremor, insomnia, headache, drowsiness, EPS GI: N/V, diarrhea, abdominal cramps, weight gain Sexual dysfunction: erectile dysfunction, anorgasmia CVS: increased HR, increased QTc, serotonin syndrome, SIADH, decreased platelet aggregation – increased risk of bleeding

Low dose side eects similar to SSRIs (serotonergic) Higher dose side eects: tremors, tachycardia, sweating, insomnia, orthostatic hypotension, increase in BP (noradrenergic) SIADH

Anticholinergic eects: (see Table 17, PS53 ) Noradrenergic eects: tremors, tachycardia, sweating α-1 adrenergic eects: orthostatic hypotension, falls QRS prolongation

Antihistamine eects (minimal): sedation, weight gain CVS: orthostatic hypotension, hypertensive crises with tyramine rich foods (e.g. wine, cheese), or combination with serotonergic or adrenergic medications, headache, flushes, reflex tachycardia, postural hypotension, insomnia Minimal anticholinergic eects

CNS: dizziness, headache, tremor, insomnia, agitation, anxiety, lower seizure threshold CVS: dysrhythmia, HTN GI: dry mouth, N/V, constipation, decreased appetite

CNS (usually minor): dizziness, headache, tremor, insomnia CVS: dysrhythmia, hypotension GI: dry mouth, N/V, diarrhea, abdominal pain, dyspepsia GU: delayed ejaculation Other: diaphoresis

CNS: sedation, dizziness Endocrine: increase in cholesterol, increase in triglycerides, weight gain GI: constipation, ALT elevation

CNS: sedation GI: nausea, diarrhea

GI: nausea

Risk in Overdose

Relatively safe in overdose

Tachycardia and N/V seen in acute overdose

Toxic in overdose 3 times therapeutic dose may be lethal Presentation: anticholinergic eects, CNS stimulation, then depression and seizures ECG: prolonged QRS and QTc (reflect severity) Treatment: activated charcoal, cathartics, supportive treatment, IV diazepam for seizure, physostigmine salicylate for coma Do not give ipecac, as can cause rapid neurologic deterioration and seizures

Toxic in overdose, but wider margin of safety than TCA

Tremors and seizures seen in overdose

Risk of fatal overdose when combined with SSRIs, SNRIs, or clomipramine

Relatively safe in overdose

Relatively safe in overdose

Relatively safe in overdose

MAOI, SSRI Low inhibition of cytochrome P450 compounds

MAOI, SSRI EtOH

Hypertensive crises with noradrenergic medications (i.e. TCA, decongestants, amphetamines) Serotonin syndrome with serotonergic drugs (i.e. SSRI, SNRI, tryptophan, dextromethorphan)

MAOI MAOI, paroxetine MAOI, RIMA Drugs that reduce Opioids seizure threshold: antipsychotics, systemic steroids, quinolone antibiotics, antimalarial drugs

MAOI

MAOI No inhibition of cytochrome P450

Drug MAOI, SNRI Interactions Some SSRIs (fluoxetine, fluvoxamine, paroxetine) strongly inhibit cytochrome P450 enzymes, therefore will aect levels of drugs metabolized by P450 system

Mood Stabilizers PS58 Psychiatry

Toronto Notes 2023

Mood Stabilizers General Prescribing Information • examples: lithium, divalproex, lamotrigine, carbamazepine • used mainly for long-term stabilization of bipolar disorder, also used as rst-line monotherapy or in conjunction with atypical antipsychotics for acute episodes of bipolar disorder (i.e. depression and mania) • vary in their ability to “treat” (i.e. reduce symptoms acutely) or “stabilize” (i.e. prevent relapse and recurrence) manic and depressive symptoms; multi-agent therapy can be avoided in many patients but it is common • before initiating, get baseline: CBC with dierential and platelets, ECG (if patient >45 y/o or cardiovascular risk), BUN, creatinine, extended electrolytes, TSH, LFTs for divalproex and carbamazepine • screening for: pregnancy, thyroid disease, neurological, renal, liver, cardiovascular diseases • full eects may take 2-4 wk, thus may need acute coverage with benzodiazepines or antipsychotics Specific Prescribing Information • detailed pharmacological guidelines available online from the Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) • for clinical information for treating bipolar disorder (see Mood Disorders, PS10) • be mindful that divalproex and carbamazepine are teratogenic thus if prescribed for women at reproductive age, a reliable contraceptive strategy is required Table 21. Commonly Used Mood Stabilizers Lithium

Lamotrigine (Lamictal®)

Divalproex (Epival®)

Carbamazepine (Tegretol®)

1st line Acute mania (monotherapy or with adjunct SGA) Bipolar I depression (monotherapy or in combination with divalproex, SSRI, or bupropion) Bipolar disorder maintenance (monotherapy or with adjunct SGA)

1st line Bipolar I depression (monotherapy) Bipolar disorder maintenance (limited ecacy in preventing mania, more eective when combined with lithium)

1st line Acute mania (monotherapy or with adjunct SGA) Bipolar I depression (combination with lithium or SSRI) Bipolar disorder maintenance (monotherapy or with adjunct SGA)

2nd line Acute mania (monotherapy) Bipolar disorder maintenance (monotherapy or in combination with lithium)

Other uses Bipolar II depression Augmentation of antidepressants in MDD and OCD Schizoaective disorder Chronic aggression, antisocial behaviour Recurrent depression

Not recommended for acute mania

Mode of Action

Unknown Therapeutic response within 7-14 d

May inhibit 5-HT3 receptors May potentiate DA activity

Depresses synaptic transmission Raises seizure threshold

Depresses synaptic transmission Raises seizure threshold

Dosage

Adult: 600-1500 mg/d Geriatric: 150-600 mg/d Usually daily dosing Blood levels monitored and dose adjusted accordingly

Note: very slow titration required due to risk of Stevens-Johnson Syndrome Dose adjusted in patients taking other anticonvulsants such as divalproex Daily dose: 100-200 mg/d

750-2500 mg/d Usually daily dosing with ER preparation

400-1600 mg/d Usually BID or TID dosing

Therapeutic Level

Adult: 0.8-1.0 mmol/L (1.0-1.25 mmol/L for acute mania) Geriatric: 0.6-0.8 mmol/L

Therapeutic plasma level not established Dosing based on therapeutic response

17-50 mmol/L Same therapeutic levels as used for seizure prophylaxis (no data specific for mood stabilizing eect)

350-700 µmol/L Same therapeutic levels as used for seizure prophylaxis (no data specific for mood stabilizing eect)

Monitoring

Monitor serum levels every 5-7 d until therapeutic (always 12 h after dose) Then monitor monthly, then q2-3 mo Monitor thyroid function, creatinine q6 mo

Monitor for skin rash and suicidality when initiating treatment

Monitor serum levels every 5-7 d until therapeutic LFTs weekly x 1 mo, then monthly, then q2-3 mo due to risk of liver dysfunction Watch for signs of liver dysfunction: nausea, edema, malaise Check platelets and monitor levels to adjust dosage and confirm adherence

Monitor serum levels every 5-7 d until therapeutic Weekly blood counts for 1st mo, due to risk of agranulocytosis Watch for signs of blood dyscrasias: fever, rash, sore throat, easy bruising

Side Eects

GI: N/V, diarrhea, stomach pain GU: polyuria, polydipsia, nephrogenic diabetic insipidus, glomerulonephritis, renal failure, decreased glomerular filtration rate CNS: fine tremor, headache, fatigue, lethargy Hematologic: reversible benign leukocytosis Other: teratogenic (Ebstein’s anomaly), hypothyroidism, weight gain, edema, worsening of psoriasis, bradycardia, ECG changes

Skin: rash (consider discontinuing due to risk of Steven-Johnson syndrome which is an emergency), slow dose titration to reduce risk Otherwise, usually well tolerated (GI: N/V, diarrhea CNS: ataxia, dizziness, diplopia, headache, somnolence Other: anxiety)

GI: liver dysfunction, N/V, diarrhea CNS: ataxia, drowsiness, tremor, sedation, cognitive blurring Other: hair loss, weight gain, thrombocytopenia, neural tube defects when used in pregnancy, polycystic ovarian syndrome

GI: N/V, diarrhea, hepatic toxicity CNS: ataxia, dizziness, slurred speech, drowsiness, confusion, nystagmus, diplopia Hematologic: transient leukopenia (10%), rare agranulocytosis, aplastic anemia Skin: rash (5% risk; consider discontinuing drug because of risk of Stevens-Johnson syndrome) Other: neural tube defects when used in pregnancy

Interactions

NSAIDs, thiazides, ACEI, and metronidazole decrease clearance, risk for lithium toxicity

OCP

OCP

Indications

Other uses Bipolar II depression

Other uses Rapid cycling bipolar disorder

Other uses Bipolar II depression Rapid cycling bipolar disorder Mixed phase/dysphoric mania

Anxiolytics PS59 Psychiatry

Lithium Toxicity • clinical diagnosis as toxicity can occur at therapeutic levels • common causes: overdose, sodium/uid loss, concurrent medical illness or initiation of NSAIDs, diuretics, or ACEI • clinical features ■ GI: severe nausea/vomiting and diarrhea ■ cerebellar: ataxia, slurred speech, lack of coordination ■ cerebral: drowsiness, myoclonus, tremor, upper motor neuron signs, seizures, delirium, coma • management ■ discontinue lithium for several days and begin again at a lower dose when lithium level has fallen to a non-toxic range ■ monitor serum lithium levels, creatinine, BUN, electrolytes ■ IV saline ■ hemodialysis if lithium >2 mmol/L, coma, shock, severe dehydration, failure to respond to treatment aer 24 h, or deterioration

Toronto Notes 2023

Long-term lithium use can lead to a nephropathy and diabetes insipidus in some patients

Anxiolytics • anxiolytics mask or alleviate symptoms • indications ■ short-term treatment of anxiety disorders, insomnia, alcohol withdrawal (especially delirium tremens), barbiturate withdrawal, akathisia due to antipsychotics, seizure disorders, musculoskeletal disorders, agitation or aggression associated with acute mania, or psychosis • relative contraindications ■ major depression (except as an adjunct to other treatment), history of drug/alcohol misuse, caution in pregnancy/breastfeeding ■ myasthenia gravis is a relative contraindication for benzodiazepines • mechanism of action ■ benzodiazepines: potentiate binding of GABA to its receptors; results in decreased neuronal activity ■ buspirone: partial agonist of 5-HT1A receptors Benzodiazepines • should be used for limited periods (i.e. days-weeks) to avoid tolerance and dependence • all benzodiazepines are sedating, decrease respiratory drive, and increase risk for falls, confusion, and motor vehicle accidents; be wary with use in the elderly, especially in combination with other psychotropic medications • have similar ecacy, so choice depends on half-life, metabolites, and route or schedule of administration • taper slowly over weeks-months because they can cause withdrawal reactions (see below) • beware of use with alcohol and other CNS depressants because of potentiation of CNS depression; caution with drinking and driving/machinery use • side eects ■ CNS: drowsiness, cognitive impairment, reduced motor coordination (falls), memory impairment ■ dependence, tolerance, withdrawal • withdrawal ■ low dose withdrawal symptoms: tachycardia, HTN, panic, rebound insomnia, anxiety, impaired memory and concentration, perceptual disturbances ■ high dose or rapid withdrawal symptoms: hyperpyrexia, seizures, death ■ onset: 1-2 d (short-acting), 2-4 d (long-acting) ■ duration: days-weeks ■ complication with above 50 mg diazepam/d or abrupt withdrawal: autonomic hyperactivity, seizures, delirium, arrhythmias ■ management: taper slowly; may need to switch to a long-acting benzodiazepine ■ similar to but less severe than alcohol withdrawal; can be fatal • overdose ■ overdose is common but rarely fatal unless combined with other substances ■ more dangerous or potentially fatal when combined with alcohol, other CNS depressants, opioids, or TCAs Buspirone (Buspar®) • primary use: GAD • may be preferred over benzodiazepines because it is non-sedating, has no interaction with alcohol, does not alter seizure threshold, not prone to abuse • onset of action: 2 wk • side eects: dizziness, drowsiness, nausea, headache, nervousness, EPS Z-drugs for Sleep • non-benzodiazepine sedatives indicated for short-term management of insomnia • examples include zopiclone (Imovane®), eszopiclone (Lunesta®), and zolpidem (Sublinox®) • anecdotally provide a more restful sleep than benzodiazepines • similar side eect prole and warnings to benzodiazepines • should not be used long-term due to side eects and likelihood of dependency

Benzodiazepine Antagonist – Flumazenil (Anexate®) Use for suspected benzodiazepine overdose Specific antagonist at the benzodiazepine receptor site

Benzodiazepines That are Safe for Patients with Impaired Liver Function LOT Lorazepam Oxazepam Temazepam

Somatic Therapies PS60 Psychiatry

Toronto Notes 2023

Table 22. Dosing and Indications for Common Anxiolytics Class

Drug

Dose Range (mg/d)

t1/2 (h)

tmax (h)

Appropriate Use

Clonazepam (Rivotril®)

0.25-4

18-50

1-4

Seizure prevention, akathisia, generalized anxiety disorder, panic disorder

Diazepam (Valium®)

2-40

30-100

1-2

Seizure prevention, muscle relaxant, alcohol withdrawal, generalized anxiety

Chlordiazepoxide (Librium®)

5-300

30-100

1-4

Alcohol withdrawal

Flurazepam (Dalmane®)

15-30

50-160

0.5-1

Should be avoided

Alprazolam (Xanax®)

0.25-4.0

6-20

1-2

Should be avoided due to high dependency rate

Lorazepam (Ativan®)

0.5-6.0

10-20

1-4

Alcohol withdrawal (no first-pass liver metabolism), akathisia, short-term sedation for anxiety during procedures (e.g. CT or MRI), generalized anxiety; sublingual or IM for rapid action

Oxazepam (Serax®)

10-120

8-12

2-3

Alcohol withdrawal (no first-pass liver metabolism), generalized anxiety disorder

Temazepam (Restoril®)

7.5-30

8-20

2-5

Should be avoided

Triazolam (Halcion®)

0.125-0.5

1.5-5

1-2

Shortest t1/2, rapid sleep without daytime sedation (e.g. overnight plane travel), but risk of rebound insomnia

Buspirone (Buspar®)

15-30

2-3

1-1.5

Generalized anxiety disorder

Benzodiazepines Long-acting

Short-acting

Azapirones

Somatic Therapies Electroconvulsive Therapy • the fastest and most eective acute treatment of depression • ECT is a safe and controlled way of producing seizures to treat mental illness • various methodological improvements have been made since the rst treatment in 1938 to reduce adverse eects • modern ECT: induction of a generalized seizure using an electrical pulse through scalp electrodes while the patient is under general anesthesia with a muscle relaxant • considerations: unilateral vs. bilateral electrode placement, pulse rate, energy, number, and spacing of treatments • usual course is 6-12 treatments, 2-3 treatments per wk • indications ■ treatment-resistant depression (unipolar, bipolar I, bipolar II): psychotic features, catatonic features, when medications may be unsafe or rapid response is needed (e.g. cachexia, severe dehydration, frail elderly, high suicide risk, pregnancy) ■ catatonia: refractory, severe, or life-threatening ■ schizophrenia: treatment-resistant, acute symptoms, catatonia, history of NMS ■ mania: refractory, severe or life-threatening situation ■ personal or family history of good response to ECT ■ inconclusive evidence for OCD • adverse eects: risk of anesthesia (equal to risk of ECT), memory loss (may be retrograde and/or anterograde, tends to resolve by 6-9 mo, permanent impairment controversial), transient headaches, transient myalgias • unilateral ECT causes less memory loss than bilateral but may not be as eective • contraindications: no absolute contraindications; relative contraindications: increased intracranial pressure, recent (65 yr

Elder abuse Lack of emotional support Isolation

Low hazard tolerance Higher rates of institutionalization Mobility issues

Inactivity Polypharmacy Medical comorbidities

Aging in place of choice Falls and injury prevention Mental health promotion Preventing abuse and neglect

Individuals/Children in Poverty

Low income Family dysfunction Lack of educational LICO is an income threshold below which a family will likely opportunities devote a larger share of its income on the necessities of food, shelter, and clothing than the average family

Housing availability Unsafe housing Lack of recreational space

Poor supervision Food insecurity High-risk behaviours

Improvements in family income most significant Access to early childhood education Access to safe housing

People with Disabilities

Includes impairments, activity limitations, and participation restrictions

Low income Low education status Discrimination Stigma

Institutionalization Barriers to access Transportation challenges

Substance misuse Poor nutrition Inactivity Dependency for ADLs

Transportation support Multidisciplinary care Unique support for individuals with specific disabilities (e.g. Trisomy 21)

New Immigrants

Person born outside of Canada who has been granted the right to live in Canada permanently by immigration authorities

Access to community services Cultural perspectives (including reliance on alternative health practices) Unstable or precarious housing

Exposure to diseases and conditions in country of origin, in current country of residence, or during immigration process (e.g. smoke from wood fires, incidence of TB)

Barriers finding employment that matches skills and qualifications Exposure to cultural discrimination and isolation which can impact health English language learner Healthy immigrant eect (health worsens over time to match that of the general population) Cultural or religious expectations

Women’s health Mental health Comprehensive medical exam Dental and vision screening Vaccinations Cancer screening Receive language and employment training Support integrating into local community Benefit from culturally appropriate and culturally safe interventions, ideally developed in collaboration with the specific target communities

Based on LICOs

Note: this chart delineates the major challenges faced by each group, but the issues listed are not unique to each population. Sources: Shah, CP. The Health of Vulnerable Groups. Public Health and Preventive Medicine in Canada, 5e. Toronto: Elsevier, 2003.

PH6 Public Health and Preventive Medicine

Toronto Notes 2023

Table 2. Equity-Seeking Groups Facing Systemic Barriers Definition

Physical

Environmental

Personal Risk Factors

Population-Specific Interventions

Persons Experiencing Homelessness

An individual who lacks permanent housing or adequate housing

Low income Food insecurity Mental illness

A history of colonial subjugation and land expropriation Exposure to temperature extremes Exposure to communicable diseases in shelters

Higher rates of adverse childhood events and subsequent substance use Greater risk of experiencing violence due to lack of housing and protection

Housing First policies Safe housing Addictions support Mental health

Refugees

Forced to flee country of origin because of a well-founded fear of persecution and given protection by the Government of Canada Refugee claimant: arrive in Canada and ask to be considered refugee

Post-traumatic stress disorders Depression Adjustment problems Partial health coverage via Interim Federal Health Program

Diseases and conditions in country of origin (e.g. malaria, TB, onchocerciasis, etc.) Direct and indirect eects of war

Employment English language learner Longstanding prior lack of access to health care (chronically neglected problems) Cultural or religious expectations

Vaccinations Women’s health Mental health Comprehensive medical exam Dental and vision screening Political advocacy Language training Support for transitioning into the workplace Support integrating into local community

Religious Minorities

Religious minorities are those who do not practice the statistically dominant faith It varies by country, but in Canada, religious minorities are currently those who are not aliated with one of the major Christian denominations Not all members of a minority faith practice and degree of identification varies by individual

Reduced employment options in Quebec due to laws banning government workers such as teachers, police ocers, publicly employed lawyers, and court workers from wearing religious symbols like hijabs, turbans, and kippahs

At risk of experiencing hate Poorer mental health crimes, especially those who Suboptimal health and carewear visible religious symbols, seeking behaviours such as Muslim women, Sikh men, and Jewish men

If possible and when requested, oer patients a healthcare provider of the same gender Provide accessible multi-faith spaces and chaplain services in the hospital Instill a culture of inclusion beyond tolerance and provide religious accommodation where possible Proactively consult healthcare workers if they require alternative scheduling for religious holidays or fasting Collaborate with religious leaders and chaplains in supporting the health of their respective communities

LGBTIQ2S Individuals

Those who identify as lesbian (a homosexual woman), gay (a homosexual person irrespective of gender), bisexual (a person who is attracted to both genders), trans (a person whose core gender identity and/or gender expression does not align with the sex-assigned gender at birth; the sexuality of trans persons is independent of their gender diversity), intersex (an umbrella term to describe bodies that fall outside the strict male/female binary), questioning (regarding one’s sexual or gender identity), queer (a historically reclaimed pejorative that is an umbrella term to encompass all sexual and gender diversities), two-spirited (a pan-indigenous term acknowledging gender diversity in uniquely traditional roles as distinct from western gender diverse identities), and asexual (a person who does not experience sexual attraction to others as distinct from celibacy; asexual individuals may still have sex

Family violence Lower income Identity documents lacking correct name or sex designations Victims of hate crimes motivated by sexual orientation and/or gender identity; higher prevalence of hate crimes against racialized communities with greater fatality

Over-representation in youth homeless population Violence, harassment, and discrimination when seeking stable housing, employment, health, or social services

Apply an intersectional lens to understand LGBTIQ2S populations (racialized, gender-diverse, traditional/ cultural roles as in 2S) Gender-neutral language and the avoidance of heteronormative assumptions to invite patients to selfidentify as gender or sexual minorities Increased awareness of the broader social, legal, and medical context in which LGBTIQ2S individuals live Improve recognition that individuals who belong to multiple marginalized communities may face additional barriers to maintaining good health

Note: this chart delineates the major challenges faced by each group, but the issues listed are not unique to each population. Sources: Shah, CP. The Health of Vulnerable Groups. Public Health and Preventive Medicine in Canada, 5e. Toronto: Elsevier, 2003.

Higher rates of depression, anxiety, obsessive-compulsive and phobic disorders, suicidality, and self-harm Increased risk of alcohol, tobacco, and other substance misuse Double the risk for posttraumatic stress disorder than heterosexual people Greater participation in highrisk sexual practices related to HIV infection Deterioration of mental health due to multiple factors (internalized queerphobia, limited sociomedical infrastructure perpetuating/ instigating underlying comorbidities)

Indigenous Health in Canada PH7 Public Health and Preventive Medicine

Screening for Poverty • poverty is not always apparent despite being widespread (20% of families in Ontario live in poverty) • poverty is a risk factor for many chronic diseases, cancer, and mental illness • women, Indigenous peoples, new immigrants, and LGBTQ+ are some of the groups at highest risk of living in poverty • primary healthcare providers should intervene, such as by asking the following two questions: ■ step 1: “Do you ever have diculty making ends meet at the end of the month?” ◆ for living below the poverty line, sensitivity 98% and specicity 40% ■ step 2: “Have you lled out and sent in your tax forms?” ◆ tax returns are required for accessing many income security benets like GST/HST credit, working income tax benets, property tax credits, child benets, etc. ◆ connect your patients to a free community tax clinic to assist them

Indigenous Health in Canada Definitions • Indigenous peoples represent approximately 4.9% of the total population of Canada in 2016 and speak over 70 Indigenous languages • 3 distinct groups of Indigenous peoples in Canada (per sec. 35 of the Constitution Act 1982): First Nations (status and non-status), Métis, and Inuit ■ First Nations: includes over 600 diverse communities in Canada; status vs. non-status refers to the registration of First Nations peoples under the Indian Act (1876), which, in addition to the establishment of the Department of Indian Aairs, was originally established by the government to administer/manage Treaty commitments, and to remove self-governing and traditional practice rights. e Indian Act impacts the lives of countless Indigenous peoples, families and communities from birth to death ■ Métis: descendants of the First Nations and European settlers; nearly 2/3 residing in cities, greatest percentage in Ontario ■ Inuit: roughly 75% of this population of 70000 resides in the 4 Canadian Regions known as Inuit Nunangat, the Inuit Homeland. ese include: Nunavut, Nunavik (N. Quebec), Nunatsiavut (Labrador), and Inuvialuit (Northwest Territories). e majority of Inuit live in Nunavut (30135), followed by Nunavik (11800), Inuvialuit (3110), and Nunatsiavut (2285). Another 17690 Inuit live outside of Inuit Nunangat, many in urban centres in southern Canada, including Ottawa, Edmonton, and Montréal Young and Growing Populations • between 2006-2016 the Indigenous populations have increased by 42.5%, 4 times that of nonIndigenous Canadian population growth • 32.1 is the average age of the Indigenous population, about 8 yr younger than the non-Indigenous Canadian population • the aging Indigenous population is also growing, with anticipated doubling of >65 age group by 2036 Colonization and Healthcare Colonizers have perpetrated specic acts throughout Canadian history that have greatly impacted the physical, mental, emotional, and spiritual health of Indigenous peoples. Physicians should therefore be aware of the historical (and current) underpinnings of Indigenous health disparities, and the way in which health care professionals, including physicians, have acted as agents of the colonial agenda historically, which are discussed here, and their responsibility to redress previously damaged healthcare relationships (see Ethical, Legal, and Organizational Medicine, Resources in Indigenous Health, ELOM29). Despite institutionalized abuse and assimilation, Indigenous people have survived remarkable injustice and have built resilience through traditional knowledge and practices. Residential Schools (1870s-1996) e residential school era is well-known for its lasting and damaging eects on many generations of Indigenous people. Many Indigenous students suered from poor nutrition, hygiene, and living conditions, as well as physical, sexual, and psychological abuse from teachers and others in power. e intent of residential schools to assimilate Indigenous people also led to spiritual harms through signicant loss of traditional language and culture. Residential school survivors report poorer general and self-rated health as well as increased rates of chronic and infectious diseases, mental distress, depression, substance use, and suicide. Importantly, many of these outcomes extend to subsequent generations (i.e. intergenerational trauma). e term “residential school syndrome” has been proposed to better characterize the traditional DSM-V denition of post-traumatic stress disorder with additional criteria specic to residential school survivors, such as tendency to misuse alcohol and drugs (oen at a young age), loss of cultural knowledge, violent or angry outbursts, and diculty parenting. Treatment approaches must take into account a holistic view of all these criteria, rather than simply focusing on one aspect, like substance use, which oen perpetuates negative stereotypes. e Truth and Reconciliation Commission (TRC) (2015) is a document jointly created by the Canadian government and residential school survivors that preserves in writing the truth of residential schools

Toronto Notes 2023

New Immigrants to Canada • Mandatory medical exams on entry to Canada by a designated medical practitioner • Complete medical examination for persons of all ages • Chest x-ray and report for persons ≥11 yr • Urinalysis for persons ≥5 yr • Syphilis serology for persons ≥15 yr • HIV testing for applicants ≥15 yr, as well as for those children who have received blood or blood products, have a known HIV-positive mother, or have an identified risk. An ELISA HIV screening test should be done for HIV 1 and HIV 2 • Serum creatinine for persons ≥15 yr, and children with a history of HTN (resting BP >150/90 mmHg), DM, kidney disease, or signs of impaired renal function • Provide compassionate psychosocial assessment, be aware of increased prevalence of mental health issues (e.g. PTSD, depression, intimate partner violence) • Assess immunization documents and develop catch-up schedule Source: Citizenship and immigration Canada handbook [Internet]. Government of Canada [modified 2022 Sept 20]. Available from https://www.canada.ca/en/ immigration-refugees-citizenship/corporate/publicationsmanuals.html

Traditional and Complementary Medicine Use Among Indigenous Cancer Patients in Australia, C anada, New Zealand, and the United States: A Systematic Review Integr Cancer Ther 2018;17(3): 568-581 Purpose: To systematically review the use of traditional Indigenous and complementary medicines among Indigenous cancer patients in Australia, Canada, New Zealand, and the United States. Methods: Studies on the use of traditional Indigenous and complementary medicines among Indigenous cancer patients in Australia, Canada, New Zealand, and the United States published between January 2000 and October 2017 were eligible for inclusion. Results: 21 articles based on 18 studies were included. Traditional Indigenous and complementary medicines were used by between 19% to 57.7% of Indigenous patients. These modalities were most often used in combination with conventional cancer treatments to meet spiritual, emotional, and cultural needs. These treatments had multiple perceived spiritual, emotional, and cultural benefits. Traditional Indigenous and complementary medicine use was influenced by a patient’s perceptions of their healthcare practitioner’s attitudes towards these modalities.

In Canada, many Indigenous healing practices include drumming, singing, smudging, herbal teas, sweat lodges, and other ceremonies. Healthcare providers are encouraged to research and explore these options as an additional therapeutic tool for Indigenous patients requesting them. Not all Indigenous patients will request such treatments and so perhaps first ask patients, “What do I need to know about you as a person to give you the best care possible?”

PH8 Public Health and Preventive Medicine

and delineates recommendations for reconciliation. Many TRC recommendations pertain directly to health and healthcare providers. Unfortunately, seven years later they remain recommendations and have not become Calls to Action. Nutrition Trials From 1942 to 1952, nutritional scientists in conjunction with the Canadian government performed unethical research on Indigenous people with the aim of “studying the state of nutrition of the Indian.” e James Bay Survey is perhaps the most well-known of these studies conducted on the Attawapiskat and Rupert’s House Cree First Nations, though many were conducted on residential school children as well. One of the lead physician-scientists was Dr. Frederick Tisdall (inventor of Pablum), former president of the Canadian Paediatric Society and paediatrician at the Hospital for Sick Children in Toronto, Ontario. Some unethical and arguably criminal acts committed by researchers were: • lack of informed consent from parents or children • Indigenous children were kept malnourished over a two-year period to establish a baseline • one group of children received a our mix not yet approved for sale that caused them to develop anemia, contributing to greater morbidity and mortality in this group with no therapeutic intervention • in an eort to control as many factors as possible, dental care was denied to observe the progression of dental cavities and gingivitis in the setting of malnutrition Impact of Sustained Caloric Restriction on Residential School Survivors and Other Generations • sustained caloric restriction can cause height stunting, induce physiological changes to prioritize fat over lean mass, and higher risk of developing type 2 diabetes • stunting negatively impacts neurological, psychological, and immune systems • due to sustained starvation, “the child’s physiology is essentially ‘programmed’ by hunger to continue the cycle of worsening eects, with their bodies displaying a rapid tendency for fat-mass accumulation when nutritional resources become available” • other generations are at risk of having a higher BMI and developing obesity Tuberculosis, Tuberculosis Sanatoriums, and “Indian Hospitals” European colonizers brought tuberculosis (TB) to Indigenous populations as early as the 1700s. Indigenous communities, particularly the Inuit, already had risk factors predisposing the spread of TB. For example, there was malnutrition from food scarcity and overcrowding on federally mandated reserves aer forced relocation from traditional territories. From 1930-1940, death rates from TB in Inuit populations were roughly 700 per 100000, among the highest ever recorded in a human population. For comparison, TB was the tenth leading cause of death globally in 2016 at a crude death rate of 17 per 100000, while ischemic heart disease was the rst at 126 per 100000. is led the Canadian government to forcibly relocate many Indigenous people to TB sanatoriums and “Indian hospitals,” oen hundreds of kilometres away. e average length of stay at these institutions was 2.5 yr and many patients never returned home. e TB health crisis persists today; in 2016, the average annual incidence rate of TB among the Inuit in Canada was roughly 296 times higher than Canadian-born non-Indigenous people. In March 2018, the national representational organization for Inuit people in Canada, called Inuit Tapiriit Kanatami (ITK), and the Government of Canada committed to reduce TB rates across Inuit communities by 50% by 2025 and to eliminate TB by 2030 in a project called the Inuit Tuberculosis Elimination Framework. It is worth noting that “Indian hospitals” were initially welcomed by many First Nations who were under the impression that reasonable healthcare was part of treaty terms. In reality, “Indian hospitals” were crowded, underfunded, and poorly staed, serving to segregate sick Indigenous people from the rest of the population. ey were also the site of the cycle of apprehension, coercive sterilization, chemical and physical restraints, and scientic experimentation, all of which inicted signicant morbidity and mortality. When the Canadian government began closing these hospitals in the 1960s, Indigenous people continued to ght for their right to healthcare, which was nally recognized in the Indian Health Policy of 1979. Coerced Sterilizations roughout the twentieth century, eugenics programs existed across the country. In the 1920s-1930s, both Alberta and British Columbia legalized eugenic policies in the Sexual Sterilization Acts which were not repealed until the 1970s. To limit reproduction of “unt” people in the eyes of the government, Indigenous women were disproportionately targeted. is is referred to as forced or coerced sterilization and, according to various accounts by Indigenous women across the country, involved any number of the following: • tubal ligations being performed without consent • being falsely told that a procedure is reversible • being pressured into signing consent forms while actively in labour or on operating tables • being given an ultimatum to undergo a tubal ligation or risk child apprehension It is important to note that many sterilizations also occurred outside legislation, in federally run “Indian hospitals,” and some have been documented as recently as 2018. At least 100 Indigenous women have come forward with accounts of coerced sterilization by physicians and nurses, spanning from the 1970s until 2018.

Toronto Notes 2023

Disease Prevention PH9 Public Health and Preventive Medicine

Sixties Scoop and Indigenous Child Welfare e “Sixties Scoop” (Johnson, 1983) (1951-1980s) refers to the government-mandated practice of removing Indigenous children from their families without consent for placement in foster care or adoption. As residential schools started to close, many children were transitioned to child welfare facilities as the state deemed Indigenous parents unt to care for their children – a legacy that persists today. Similar to the Indian Residential School system, the goal was to assimilate Indigenous children into a non-Indigenous family, rather than to directly provide child welfare to Indigenous communities. ough Indigenous bands have increasingly been allowed to provide their own child welfare, Indigenous children are still overrepresented in foster care. In 2016, Indigenous youth ages 0 to 4 made up about half of all foster children in private households, despite being only 8% of total youth in this age group in Canada. Youth with a history in government care may be at greater risk for substance misuse, street involvement, and incarceration. To this day, Indigenous children are disproportionately represented in the child welfare system and are oen apprehended for reasons directly related to the routine conditions of poverty. e apprehensions that continue today echo the practices of the Sixties Scoop and residential school eras; the displacement of Indigenous children separates them from their language and culture and hinders the ability of Indigenous families to build resilience. Importantly, many Indigenous mothers and families avoid accessing healthcare services for fear of their children being apprehended. Indigenous Approaches to Health and Wellness • it is important to recognize the signicant diversity amongst Indigenous nations in the land now known as Canada. Even within the same nation or language group, there will be variability in practices. Despite this diversity, there are some ideas that recur across many nations • restoring balance in the four realms of spiritual, emotional, mental, and physical health of a person acting as an individual, as well as a member of a family, community, and nation ■ ideas represented by the medicine wheel of First Nations peoples, the Learning Blanket of Inuit peoples, and the Métis tree model all share a worldview based on holistic lifelong learning and wellness ■ Indigenous medicines may take many forms (song, dance, smudge, ceremonies, plant medicines, etc.) ■ practiced by experts who have decades of apprenticeship ■ while allopathic medicine oen focuses on treating illness (like HTN or DM), Indigenous medicine may understand the cause of a condition and the approach to healing in a dierent way than a biomedical guideline ■ Indigenous medicine may focus on quality of life and not just cure ■ cultural humility ◆ cultural humility is a respectful, person-centered way of bringing curiosity and compassion when a patient is willing to come for support ◆ it takes courage to be humble enough to admit that we do not know what we do not know ◆ Indigenous medicine is thousands of years old and eludes randomized controlled trials ◆ Traditional Medicine is unlikely to interfere with Western erapies ◆ Latin root of “curiosity” is “cura,” which means “to care.” Caring about someone’s healing and their beliefs about what may help them heal is a powerful act of witnessing and honouring. Beginning with the belief that a person has wisdom about themselves that no one else does and that we can be supporters of their healing, if they consent, can be a way to honour the inherent wholeness of a person seeking care. is is especially true of Indigenous patients for whom regaining self-determination is tantamount to regaining their wellness. ■ before assuming that an Indigenous person is interested in using traditional medicine, it is important to begin with questions and curiosity. Dr. Chantal Perrot speaks about the Patient Dignity Questionnaire which advises healthcare workers to rst ask patients, “What do I need to know about you as a person to give you the best care possible?” ■ National Indigenous Health Organization (NIHO) oers 8 guidelines on practicing culturally safe health care for Indigenous patients including the need to allow Indigenous patients to access ceremony, song, and prayer; the need for information and for family support; guidelines for the appropriate disposal of body parts and for handling death

Disease Prevention Natural History of Disease • course of a disease from onset to resolution 1. pathological onset 2. presymptomatic stage: from onset to rst appearance of symptoms/signs 3. clinical manifestation of disease: may regress spontaneously, be subject to remissions and relapses, or progress to death Surveillance • the continuous, systematic collection, analysis, and interpretation of health-related data needed for the planning, implementation, and evaluation of public health practice Sources: Public health surveillance [Internet]. World Health Organization. Available from https://www.who.int/topics/public_health_surveillance/en/

Toronto Notes 2023

PH10 Public Health and Preventive Medicine

Toronto Notes 2023

• types of surveillance ■ passive surveillance: reporting of disease data by all institutions that see patients, relying solely on the cooperation of healthcare providers (laboratories, hospitals, health facilities, and private practitioners) ◆ most common, least expensive, but dicult to ensure completeness and timeliness of data ■ active surveillance: regular visits to health facilities for reviewing medical records to identify suspected cases of disease under surveillance, or active testing of a population for the presence of a disease ◆ resource-intensive, used when a disease is targeted for eradication where every possible case must be investigated, or for outbreak investigations ■ sentinel surveillance: selective reporting of disease data from a limited network of carefully selected reporting sites with a high probability of seeing cases in question ◆ well-designed system can be used to signal trends, identify outbreaks, and monitor the burden of disease in a community in a timely and cost-eective manner compared to other kinds of surveillance ◆ may not be as eective in identifying rare diseases, or diseases that occur outside the catchment area of sentinel sites Sources: World Health Organization. Public Health Surveillance. Accessed from: https://www.who.int/immunization/monitoring_surveillance/burden/vpd/ surveillance_type/passive/en/; https://www.who.int/immunization/monitoring_surveillance/burden/vpd/surveillance_type/active/en/; https://www.who. int/immunization/monitoring_surveillance/burden/vpd/surveillance_type/sentinel/en/

Disease Prevention Strategies • measures aimed at preventing the occurrence, interrupting through early detection and treatment, or slowing the progression of disease/mitigating the sequelae Table 3. Levels of Disease Prevention Level of Prevention

Goal

Examples

Primordial

Preventing the development of risk factors

Education that begins in childhood about behaviour that can harm health Programs that encourage physical activity

Primary

Protect health and prevent disease onset Reducing exposure to risk factors

Immunization programs (e.g. measles, diphtheria, pertussis, tetanus, polio, see Paediatrics, P5) Smoking cessation Seatbelt use See Landmark Public Health and Preventive Medicine Trials, PH32for more information on VAXICOL, which details the impact of influenza vaccination of nursing home sta on mortality of residents

Secondary

Early detection of (subclinical) disease to minimize morbidity and mortality

Mammography Routine Pap smears FIT (vs.FOBT vs. colonoscopy)

Tertiary

DM monitoring with HbA1c, eye exams, foot exams Treatment and rehabilitation of disease to prevent progression, permanent disability, and Medication to manage chronic conditions future disease

Source: Basic Concepts in Prevention, Surveillance, and Health Promotion. AFMC Primer on Population Health. http://phprimer.afmc.ca/Part1TheoryThinkingAboutHealth Chapter4BasicConceptsInPreventionSurveillanceAndHealthPromotion/Thestagesofprevention

Screening (Secondary Prevention) • “screening is a strategy used in a population to identify the possible presence of an as-yet-undiagnosed disease in individuals without signs or symptoms” ■ screening vs. case nding: screening tests are not diagnostic tests ■ the primary purpose of screening tests is to detect early disease or risk factors for disease in large numbers of apparently healthy individuals. e purpose of a diagnostic test is to establish the presence (or absence) of disease as a basis for treatment decisions in symptomatic or screen positive individuals (conrmatory test). Both screening and case nding seek to risk stratify for further investigation ■ to minimize biases and harms, and maximize benets, screening is best done at the population level, not the individual clinical level, as part of a screening program (e.g. provincial breast cancer screening program vs. screening by primary care/family physicians) • types of screening ■ universal screening: screening all members of a population for a disease (e.g. phenylketonuria (PKU) and hypothyroidism in all newborns) ■ selective screening: screening of targeted subgroups of the population at risk for a disease (e.g. mammography in women >50 yr) ■ multiphasic screening: the use of many measurements and investigations to look for many disease entities (e.g. periodic health exam) • types of bias in screening ■ lead-time bias: overestimation of survival time ‘from diagnosis’ when the estimate is made from the time of screening, instead of the later time when the disease would have been diagnosed without screening ■ length-time bias: overestimation of the survival time due to screening at one time point including more stable cases than aggressive cases of disease, which may have shorter survival times

Passive Prevention Measures that operate without the person’s active involvement (e.g. airbags in cars) are more eective than active prevention, measures that a person must do on their own (e.g. wearing a seatbelt)

Example of Primary Prevention HPV 9-Valent Vaccine and Its Ecacy in the Prevention of Cervical Cancer • This is a nonavalent HPV vaccine covering strains 6, 11, 16, 18, 31, 33, 45, 52, and 58 • The ecacy of this vaccine was studied in 4 randomized, doubleblind, placebo-controlled trials on females between 11 and 26 yr and was found to prevent nearly 100% of precancerous cervical changes for up to 4 yr after vaccination

Does Evidence Support Supervised Injection Sites? Can Fam Physician 2017;63(11):866 • Clinical question: Do supervised injection sites (SISs) reduce mortality, hospitalizations, ambulance calls, or disease transmission? • Bottom line: The best evidence from cohort and modelling studies suggests that SISs are associated with lower overdose mortality (88 fewer overdose deaths per 100000 person-years (PYs)), 67% fewer ambulance calls for treating overdoses, and a decrease in HIV infections. Eects on hospitalizations are unknown

Smoking Cessation: Vaping Compared with Traditional Nicotine Replacement Therapies: a Systematic Review and Meta-analysis BMJ Open 2021;11:e044222 Pooled results from six randomized controlled trials identified no dierence in smoking cessation, the proportion of participants reducing smoking consumption, mean reduction in cigarettes smoked per day, or harms, between e-cigarettes and traditional nicotine replacement therapy. Most studies were judged to have a high risk of bias, resulting in the overall quality of evidence as low. More research is necessary prior to establishing recommendations related to e-cigarettes as smoking cessation tools.

PH11 Public Health and Preventive Medicine

Toronto Notes 2023

Occult Disease

Onset of Disease

Overt Disease

Death from Disease

Lead Time Screen Detected Clinically Detected

Figure 2. Lead-time bias

Table 4. Ideal Criteria for Screening Tests Disease

Test

Health Care System

Causes significant suering and/or death Natural history must be understood Must have an asymptomatic stage that can be detected by a test Early detection and intervention must result in improved outcomes

High sensitivity Safe, rapid, easy, relatively inexpensive Acceptable to providers and the population Continuously utilized

Adequate capacity for reporting, follow-up, and treatment of positive screens Cost eective Sustainable program Clear policy guidelines on who to treat

Adapted from: Shah CP. Public Health and Preventive Medicine in Canada, 5th ed. Toronto: Elsevier, 2003

Health Promotion Strategies Table 5. Disease Prevention vs. Health Promotion Approach Disease Prevention

Health Promotion

Health = absence of disease

Health = positive and multidimensional concept

Medical model (passive role)

Participatory model of health

Aimed mainly at high-risk groups in the population

Aimed at the population in its total environment

One-shot strategy aimed at a specific pathology

Diverse and complementary strategies aimed at a network of issues/ determinants

Directive and persuasive strategies enforced in target groups

Facilitating and enabling approaches by incentives oered to the population

Focused mostly on individuals

Focused on a person’s health status and environment

Led by professional groups from health disciplines

Led by non-professional organizations, civic groups, local, municipal, regional, and national governments

Source: Shah CP. Public Health and Preventive Medicine in Canada, 5th ed. Toronto: Elsevier, 2003

Healthy Public Policy

• purpose: to create a supportive environment to enable people to lead healthy lives, thereby making healthy choices easier for citizens • governments and non-governmental agencies need to consider the cost and acceptability of proposed public health interventions (e.g.. more invasive or costly measures should be justied by the extent of benecial impacts on people’s lives) • the Nueld Intervention Ladder provides one way of ranking the level of intrusion and hence a need for proportionate benet of health promotion interventions at a population level • methods ■ scal: imposing additional costs (e.g. taxes on tobacco and alcohol) ■ legislative: implementing legal deterrents (e.g. smoking bans, legal alcohol drinking age) ■ social: improving health beyond providing universally funded health care (e.g. providing aordable housing) Source: International Conference on Health Promotion, Adelaide, South Australia (1998)

Behaviour Change • behaviour is a result of three factors 1. predisposing factors: knowledge, attitude, beliefs, values, intentions 2. enabling factors: skills, supports 3. reinforcing factors: health care professionals and the social context of family and community • health education serves to: increase knowledge and skills and promote healthy behaviours Health Belief Model (1975) • a psychological model that explains and predicts individual short- and long-term health behaviours based on one’s beliefs and attitudes • based on the assumption that one will adopt a benecial health behaviour if the following three beliefs are present: ■ the negative health outcome is avoidable ■ expects that the health outcome can be prevented if the recommended health behaviour is adopted ■ the individual can be successful in adopting the health behaviour • six concepts: ■ four concepts inuencing one’s “readiness to act” – perceived susceptibility, perceived severity, perceived benets, perceived barriers ■ cues to action: stimuli that can trigger health action ■ self-ecacy: condence in one’s ability to take a health action

A Snapshot of the Opioid Crisis in Canada Canada is experiencing a crisis of opioidrelated overdose and death. Between January 2016 and September 2019, there were more than 14700 deaths in Canada related to opioids. There were also 19490 hospitalizations and 17000 emergency services. Individuals 25-34 y/o are at the greatest risk of overdose death (1 in 6 deaths), but rates have increased for all adult ages. Deaths are most commonly unintentional. Heroin, fentanyl, and hydromorphone are most commonly involved. The highest rates of opioid-related overdose and death are found in British Columbia. An estimated 300 per million British Columbians died in relation to opioid use in 2017. More died from opioids than homicide, motor vehicle accidents, and suicide combined. In 2017, deaths from opioids in Ontario were ~1250, while deaths from motor vehicle accidents were ~450. Fentanyl or a fentanyl analogue were involved in more than 70% of cases, increased from 55% in 2016. Sources: J Addict Med. Measuring the Burden of Opioidrelated Mortality in Ontario, Canada. Latest Trends in Opioid-Related Deaths in Ontario: 1991 to 2015, Toronto: Ontario Drug Policy Research Network. Health Canada. March 2018. Opioid-related harms in Canada. Health Canada. March 2020

See Landmark Public Health and Preventive Medicine Trials table for more information on the Swedish TwoCounty Trial, which details the long-term eect of mammographic screening on breast cancer mortality.

Transtheoretical Model Stages of Change for Dietary and Physical Exercise Modification in Weight Loss Management for Overweight and Obese Adults Cochrane DB Syst Rev 2014:CD008066 Purpose: To explore the ecacy of dietary and physical activity interventions based in the transtheoretical model of change for sustained weight loss after one yr in overweight or obese adults. Methods: RCTs comparing the use of weight loss or physical activity intervention grounded in the transtheoretical model of change to usual care for weight loss in adults who were overweight or obese were eligible for inclusion. Interventions had to be carried out by healthcare professionals or trained lay people. Weight loss or change in BMI was required as an outcome measure. Results: Three studies including a total of 2971 participants were included in this review. Interventions grounded in this model did have positive eects on physical activity and dietary habits that included increased exercise duration and frequency, reduced fat intake, and increased fruit and vegetable consumption. The evidence for sustained weight loss at one yr was inconclusive (mean dierence in favour of the transtheoretical model was between 2.1 kg and 0.2 kg at 24 mo).

Measurements of Health and Disease in a Population PH12 Public Health and Preventive Medicine

Toronto Notes 2023

Stages of Change Model • provides a framework in which the Health Belief Model is applied to facilitating behaviour change (e.g. quitting smoking) 1. Precontemplation: the individual is not seriously considering change (for various reasons) and is not interested in any kind of intervention 2. Contemplation: the individual begins to seriously consider making the change within the foreseeable future (often defined as six months) 3. Preparation: the individual begins experimenting, making small changes; he or she resolves to make a serious attempt in the future (usually defined as 30 days)

Relapse: possible at any stage

4. Action: the individual is actively involved in making the change, using different techniques 5. Maintenance: the individual must learn to successfully cope with temptations to return to the previous behaviour pattern

Figure 3. Stages of change model Source: Prochaska JO, DiClemente CC, and Norcross JC. In search of how people change. Applications to Addictive Behaviours. Am Psychol 1992;47:1102-1114

Risk Reduction Strategies • risk reduction: lower the risk to health without eliminating it (e.g. avoiding sun to lower risk of skin cancer) • harm reduction: a set of strategies aimed to reduce the negative consequences of drug use and other risky behaviours (e.g. needle exchange programs) Source: Shah, CP. Concepts, Determinants, and Promotion of Health. Public Health and Preventive Medicine in Canada, 5e. Toronto: Elsevier, 2003

Community Needs Assessment • a community needs assessment studies a community’s health gaps and pairs identication of that community’s existing resources and strengths to nd solutions to address those gaps. is assessment strongly values interviewing community members to gather their concerns and proposed solutions. Steps include: 1. dene the community and understand its history and demographic characteristics to formulate context for subsequent data collection 2. understand what matters to community stakeholders (e.g. interviews, surveys, focus groups) 3. use evidence (e.g. mortality rate, feasibility), prioritize each concern 4. identify barriers that may prevent a concern from being addressed and propose solutions using community-based resources

Measurements of Health and Disease in a Population MEASURES OF DISEASE OCCURRENCE Rates, Ratios, and Proportions • a rate measures the frequency of an event in a dened population over a specic period of time (e.g. number of opioid overdoses in Canada in one year) • a ratio compares the magnitude of one quantity to another (e.g. ratio of women to men with lupus) • a proportion is a ratio where the numerator is a part of the denominator (e.g. proportion of deliveries complicated by placental abruption) Incidence Rate • number of new cases in a population over a specic period of time Prevalence • total number of cases in a population over a dened period of time • two forms of prevalence ■ point prevalence: assessed at one point in time ■ period prevalence: assessed over a period of time, therefore including new cases and excluding cases that terminate (cure or death) • a function of the incidence rate and disease duration from onset to termination • favours the inclusion of chronic over acute cases and may underestimate disease burden if those with short disease duration are missed • prevalence estimates are useful for measuring disease burden and therefore help in the planning of facilities and services

Principles of Standardization • When comparing a health measure (e.g. mortality) between two populations (or the same population at dierent time points) that dier in characteristics known to influence that outcome (e.g. age), standardization is used to control for the eect of that factor • Standardization is either direct or indirect • Indirect standardization is expressed as standardized outcome ratio. For example, Standardized Mortality Ratio (SMR) is calculated using age specific rates for a reference population, as well as age structure and total cases for a sample/ known population. (e.g. an SMR of 100 signifies that deaths are at the expected level, a SMR of 110 indicates a death rate 10% higher than expected) • Direct standardization is expressed as a rate (i.e. using age specific rates in a known/sample population against a standard population)

Epidemiology PH13 Public Health and Preventive Medicine

Toronto Notes 2023

Age-Standardized Rate • adjustment of the crude rate of a health-related event using a “standard” population • standard population is one with a known number of persons in each age and sex group • standardization prevents bias that can occur when crude rates from two dissimilar populations are compared (e.g. crude death rates over a number of decades are not comparable as the population age distribution has changed with time) • this allows for the calculation of a Standardized Mortality Ratio (SMR), where SMR = (observed number of deaths)/(expected number of deaths) MEASURES OF MORTALITY Life Expectancy • the expected number of years to be lived by a newborn based on age-specic mortality rates at a selected time Crude Death Rate • mortality from all causes of death per 1000 in the population Infant Mortality Rate (IMR) • number of reported deaths among children 600 mL/24 h or bleeding rate of >100 mL/h

Most Common Causes of Chronic Cough in the Non-smoking Patient (Cough >3 mo with Normal CXR) • GERD • Asthma • Postnasal drip • ACEI

© Andrew Q. Tran 2015

Dierential Diagnoses of Common Presentations

Pulmonary Function Tests R4 Respirology

Toronto Notes 2023

Pulmonary Function Tests FEV1

IC

VOLUME

• useful in dierentiating the pattern of lung disease (obstructive vs. restrictive) • assess lung volumes, ow rates, and diusion capacity • note: normal values for FEV1 are approximately ±20% of the predicted values (for age, sex, and height); “Race” dierences in predicted values are recognized but are not fully understood and likely represent genetic ancestry and the eects of the social determinants of health

FVC TLC VT

RV

TIME

Table 5. Comparison of Lung Flow and Volume Parameters in Lung Disease Obstructive

Figure 4A. Lung volumes and capacities

Restrictive

Decreased flow rates (most marked during expiration)

Decreased lung compliance

Air trapping (increased RV/TLC)

Decreased lung volumes 8

Asthma, COPD, bronchiolitis, bronchiectasis/CF*

FEV1 /FVC

ILD, pleural disease, neuromuscular disease, chest wall disease

Reduced

TLC

Elevated or normal

Elevated or normal

Reduced

FLOW RATE (L/sec)

Hyperinflation (increased TLC) DDx

ERV

1SEC

FRC

6 4

RV

Elevated or normal

Reduced, normal or elevated

Elevated or normal

Normal or elevated (neuromuscular disease may have elevated RV/TLC ratio)

DLCO

Normal or reduced depending on disease state

Reduced or normal depending on whether parenchymal or extraparenchymal restriction is present

*Bronchiectasis can be obstructive or mixed

Restrictive

2 0

RV/TLC

Normal Obstructive

FEV1 FVC 86420 LUNG VOLUME (L)

1 second time marker

Figure 4B. Expiratory flow volume curves Adapted with permission from Elsevier. Weinberger SE. Principles of pulmonary medicine, 5th ed. 2008

Table 6. Common Respirology Procedures Technique

Purpose

Description

Plethysmography (“body box”)

Measure FRC

After a normal expiration, the patient inhales against a closed mouthpiece Resultant changes in the volume and pressure of the plethysmograph are used to calculate the volume of gas in the thorax Useful for patients with air trapping

He Dilution

Measure FRC

A patient breathes from a closed circuit containing a known concentration and volume of helium Since the amount of helium remains constant, FRC is determined based on the final concentration of the helium in the closed system Only includes airspaces that communicate with the bronchial tree and is dependent on airflow – may underestimate volumes in patients with gas trapping

Bronchoscopy

Diagnosis and therapy

A flexible or rigid bronchoscope is used for visualization of a patient’s airways allows for: Bronchial and broncho-alveolar lavage (washings) for culture, cell count analysis, and cytology Endobronchial or transbronchial tissue biopsies Removal of secretions/foreign bodies/blood Laser resections Airway stenting Mediastinal lymph nodes can also be sampled using a special bronchoscope equipped with an U/S probe (EBUS)

Pulmonary Function Tests (PFTs)

FEV1/FVC LLN

Lung volumes normal

Lung volumes low, especially TLC, RV

Give bronchodilator

DLCO DLCO Normal

Low Low

Normal PFT

ANEMIA, PULMONARY VASCULAR DISEASE, INTERSTITIAL DISEASE (EARLY), EMPHYSEMA (EARLY)

Figure 5. Interpreting PFTs

Rise in FEV1>12% and >200 cc and/or positive methacholine test

INTERSTITIAL LUNG DISEASE

Decreased TLC and FRC + increased RV (and low MIP and MEP)

*LLN = lower limit of normal

Normal

NEUROMUSCULAR DISEASE

ASTHMA

Decreased TLC and FRC + normal RV

CHEST WALL DISEASE

No significant change in FEV1

Flow volume loop, lung volumes, DLCO

Normal TLC and DLCO

High TLC + low DL CO

CHRONIC BRONCHITIS, BRONCHIOLITIS, BROCHIECTASIS

EMPHYSEMA

Lung Volumes ERV – Expiratory Reserve Volume FEF – Forced Expiratory Flow Rate FEV – Forced Expiratory Volume (in one second) FRC – Functional Residual Capacity IC – Inspiratory Capacity RV – Residual Volume TLC – Total Lung Capacity FVC – Forced Vital Capacity VT – Tidal Volume

Chest X-Rays R5 Respirology

Toronto Notes 2023

Chest X-Rays • see Medical Imaging, MI4 Table 7. CXR Patterns and Dierential Diagnosis Pattern

Signs

Common DDx

Consolidation (“Airspace disease”)

Air bronchogram Silhouette sign Less visible blood vessels

Acute: water (CHF), pus (pneumonia), blood (hemorrhage) Chronic: neoplasm (lymphoma, bronchioloalveolar carcinoma), inflammatory (eosinophilic pneumonia, organizing pneumonia), infection (TB, fungal)

Reticular (“Interstitial disease”)

Increased linear markings Fine or ground glass opacities Honeycombing (clustered cystic changes seen in IPF usually, but also in rheumatoid arthritis, asbestosis etc.)

ILD (IPF, collagen vascular disease, asbestos, drugs, HP)

Nodular

Cavitary vs. non-cavitary

Cavitary: neoplasm (primary – squamous cell carcinoma vs. metastatic cancer), infectious (anaerobic or Gram negative, TB, fungal), inflammatory (RA, sarcoidosis, granulomatosis with polyangiitis (GPA)) Non-cavitary: above + sarcoidosis, Kaposi’s sarcoma (in HIV), silicosis, and coal worker’s pneumoconiosis 100

Arterial Blood Gases • provides information on acid-base and oxygenation status • see Nephrology, NP17 Approach to Acid-Base Status 1. Is the pH acidemic (pH 7.45), or normal (pH 7.35-7.45)? 2. What is the primary disturbance? metabolic: change in HCO3- and pH in same directions respiratory: change in HCO3- and pH in opposite directions 3. Is there appropriate compensation? (see Table 8) metabolic compensation occurs over 2-3 d reecting altered renal HCO3- production and excretion respiratory compensation through ventilatory control of PaCO2 occurs immediately inadequate compensation may indicate a second acid-base disorder

% SaO2of Hb

80

CO pCO2 temperature pH 2,3-DPG

60

pCO 2 temperature pH 2,3-DPG

40 pH 7.40, T=38ºC 20 0

0 20 40 60 80 100

pO2 (mmHg)

Figure 6. Oxygen-Hb dissociation curve

Table 8. Expected Compensation for Specific Acid-Base Disorders Disturbance

PaCO (mmHg) (normal ~40)

HCO –(mmHg) (normal ~24) Factors that Shift the Oxygen-Hb Dissociation Curve to the Right

Respiratory Acidosis Acute Chronic

↑ 10 ↑10

↑1 ↑3

↓ 10 ↓ 10 ↓1 ↑5-7

↓2 ↓5 ↓1 ↑10

Respiratory Alkalosis Acute Chronic Metabolic Acidosis Metabolic Alkalosis

4. If the patient has metabolic acidosis, what is the anion gap and osmolar gap? ■ anion gap = [Na + ]–([Cl–]+[HCO3–]); normal 5-14 mmol/L ■ osmolar gap = measured osmolarity – calculated osmolarity = measured – (2[Na +] + glucose + urea); normal ≤10 mmol/L ■ abnormal osmolar gap indicates the presence of alcohols 5. If anion gap is increased, is the change in bicarbonate the same as the change in anion gap? ■ if not, consider a mixed metabolic picture

“ CADET, face right!” CO 2 Acid 2,3-DPG Exercise Temperature (increased) Note: 2,3-DPG (2,3-diphosphoglycerate) is now called 2,3-BPG (2,3-biphosphoglycerate)

Acidosis ←→ Hyperkalemia Alkalosis ←→ Hypokalemia

Note: Mixed acid-base disturbances can still have a “normal” pH

Table 9. Dierential Diagnosis of Respiratory Acidosis Increased PaCO 2secondary to hypoventilation Respiratory Centre Depression (Decreased RR) Drugs (anesthesia, sedatives, narcotics) Trauma Encephalitis Stroke Central apnea Supplemental O 2 in chronic CO2 retainers (e.g. COPD)

Neuromuscular Disorders (Decreased Vital Capacity) Myasthenia gravis Guillain-Barré syndrome Botulism Poliomyelitis Muscular dystrophies ALS Myopathies Chest wall disease (obesity, kyphoscoliosis)

Lung Disease Chronic: COPD, CF Acute: Asthma Pulmonary edema Pneumothorax Pneumonia ILD (late stage) ARDS

Mechanical Hypoventilation (Inadequate Mechanical Ventilation) Osmolar Gap = measured osmolarity – calculated osmolarity; for calculated osmolarity think “2 salts and a sticky BUN” (2Na + glucose + urea)

R6 Respirology

Toronto Notes 2023

Table 10. Dierential Diagnosis of Respiratory Alkalosis Decreased PaCO2 secondary to hyperventilation Systemic Diseases Pulmonary disease (pneumonia, edema, PE, interstitial fibrosis) Severe anemia Heart failure

Respiratory Centre Stimulation Drugs (ASA, progesterone, theophylline, catecholamines, psychotropics, nicotine, salicylates) Hepatic failure Gram-negative sepsis Pregnancy Anxiety Pain High altitude

Mechanical Hyperventilation (Excessive Mechanical Ventilation)

• see Nephrology, NP18 for dierential diagnosis of metabolic acidosis and alkalosis

Anion Gap Metabolic Acidosis MUDPILESCAT Methanol Uremia Diabetic ketoacidosis/starvation ketoacidosis Phenformin/Paraldehyde Isoniazid, Iron, Ibuprofen Lactic acidosis Ethylene glycol Salicylates Cyanide, Carbon dioxide Alcoholic ketoacidosis Toluene, Theophylline

What is the PaO2? (normal 95-100 mmHg) PaO 220 mmHg with a pulmonary arterial wedge pressure (PAWP) ≤15 mmHg and peripheral vascular resistance (PVR) ≥3 Wood units measured by right heart catheterization in supine position at rest • pulmonary HTN is grouped into 5 categories and classied based on etiology Table 19. World Health Organization Classification of Pulmonary Hypertension and their Treatment Options Classification

Some Causes

Treatment Options

I. Pulmonary Arterial HTN (PAH)

Idiopathic Hereditary mutations Collagen vascular disease (scleroderma, SLE, RA) Congenital heart disease (Eisenmenger syndrome) Persistent pulmonary hypertension of the newborn (PPHN) Portopulmonary HTN HIV infection Drugs and toxins (e.g. anorexigens) Schistosomiasis Pulmonary capillary hemangiomatosis Pulmonary veno-occlusive disease (PVOD)

CCBs for patients with vasoreactivity. Advanced therapy with single or combination prostanoids, endothelin receptor antagonists (ERA), PDE5 inhibitors. Lung transplantation for refractory advanced patients. Treatment of underlying condition if relevant

Related to heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF) Left-sided valvular heart disease (e.g. aortic stenosis, mitral stenosis) Congenital/acquired left heart inflow/ outflow tract obstruction and congenital cardiomyopathies

Treat underlying heart disease

Obstructive lung disease (COPD) Restrictive lung disease (e.g. ILD like idiopathic pulmonary fibrosis) Mixed restrictive/obstructive lung disease (e.g. lymphangioleiomyomatosis) Chronic alveolar hypoxia (chronic high altitude, alveolar hypoventilation disorders, sleep-disordered breathing, developmental lung disorders)

Treat underlying lung disease and/ or cause of chronic hypoxia and correct with supplemental oxygen (proven mortality benefit)

IV. Chronic Thromboembolic Pulmonary HTN (CTEPH)

Chronic PE, other pulmonary artery obstruction (e.g. tumours, parasites, congenital stenosis) Thromboembolic obstruction of proximal pulmonary arteries

Anticoagulation, pulmonary thromboendarterectomy, riociguat

V. Pulmonary HTN with Unclear Multifactorial Mechanisms

Hematologic disorders (e.g. sickle cell) Systemic disorders (e.g. sarcoidosis) Metabolic disorders Extrinsic compression of central pulmonary veins (tumour, adenopathy, fibrosing mediastinitis) Segmental pulmonary hypertension

Treat underlying cause

II. Pulmonary HTN due to Left Heart Disease

III. Pulmonary HTN due to Lung Disease and/or Hypoxia

Consider in All Patients with PH

Oxygen therapy Exercise Consider anticoagulation

Group I PH (PAH) therapies not applicable in Group II PH

Influenza and pneumococcal vaccines Counselling on pregnancy risks Diuretic therapy in patients with signs of right ventricular failure and fluid retention

Group I PH (PAH) therapies not applicable in Group III PH

Adapted: Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classifications of pulmonary hypertension. Eur Respir J 2019;53;1801913. Table 2

IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION (PRIMARY PULMONARY HYPERTENSION) Definition • pulmonary HTN in the absence of a demonstrable cause (i.e. Group I) • disease of the pulmonary artery vessel wall characterized by vasoconstriction, vascular proliferation, and obstructive remodeling leading to increased pulmonary vascular resistance Pathology • histology includes medial arterial hypertrophy, intimal brosis, and plexiform arteriopathy Epidemiology • usually older adults between the ages of 50 and 65, female predominance at younger ages • most cases are sporadic; familial predisposition in 6)

78%

Modified Wells’: >4 PE likely; ≤4 PE unlikely JAMA 2006

Both sensitive and specific for PE Diagnosis and management uncertain for small filling defects CT may identify an alternative diagnosis if PE is not present CT scanning of the proximal leg and pelvic veins can be done at the same time and may be helpful

Venous Duplex U/S or Doppler

With leg symptoms Positive test rules in proximal DVT Negative test rules out proximal DVT Without leg symptoms Positive test rules in proximal DVT Negative test does not rule out a DVT: patient may have non-occlusive or calf DVT

ECG

Findings not sensitive or specific Sinus tachycardia most common; may see non-specific ST segment and T wave changes RV strain, RAD, right bundle branch block (RBBB), S1-Q3-T3 with massive embolization

CXR

Frequently normal; no specific features Atelectasis (subsegmental), elevation of a hemidiaphragm Pleural eusion: usually small Hampton’s hump: cone-shaped area of peripheral opacification representing infarction Westermark’s sign: dilated proximal pulmonary artery with distal oligemia/decreased vascular markings (dicult to assess without prior films) Dilatation of proximal pulmonary artery: rare

Virchow’s Triad • Venous stasis • Endothelial cell damage • Hypercoagulable states

R21 Respirology

Toronto Notes 2023

Table 21. Common Investigations for Pulmonary Embolism Investigation

Purpose/Utility

V/Q Scan

Very sensitive but low specificity Order scan if: CXR normal, no COPD Contraindication to CT (contrast allergy, renal dysfunction, pregnancy) Avoid V/Q scan if: CXR abnormal or COPD Inpatient Suspect massive PE Results: Normal: excludes the diagnosis of PE High probability: most likely means PE present, unless pre-test probability is low 60% of V/Q scans are nondiagnostic

Echocardiogram

Useful to assess massive or chronic PE

PE Rule Out Criteria (PERC) Prospective Multicentre Evaluation of the Pulmonary Embolism Rule Out Criteria J Thromb Hemost 2008;6:772 • Age less than 50 yr • Heart rate less than 100 bpm • Oxyhemoglobin saturation ≥95 percent • No hemoptysis • No estrogen use • No prior DVT or PE • No unilateral leg swelling • No surgery or trauma requiring hospitalization within the past 4 wk Acute PE can probably be excluded without further diagnostic testing if the patient meets all PERC criteria AND there is a low clinical suspicion for PE, according to either the Wells’ criteria or a low gestalt probability determined by the clinician prior to diagnostic testing for PE.

Dependent on clinical status ABG

No diagnostic use in PE (insensitive and nonspecific) May show respiratory alkalosis (due to hyperventilation)

Treatment • admit for observation and stratify risk – in low-risk PE setting with no other indication for hospitalization and low-risk of early adverse outcomes, patients may be sent home with anticoagulation • oxygen: supplemental oxygen should be administered to target an oxygen saturation ≥90 percent • pain relief: analgesics if chest pain – narcotics or acetaminophen • acute anticoagulation: therapeutic-dose SC LMWH or fondaparinux or unfractionated heparin or oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) or direct thrombin inhibitors (dabigatran) – start ASAP ■ anticoagulation stops clot propagation, prevents new clots, and allows endogenous brinolytic system to dissolve existing thromboemboli over months; get baseline CBC, INR, aPTT ± renal function ± liver function ■ for SC LMWH: dalteparin 200 U/kg once daily, enoxaparin 1 mg/kg BID, or fondaparinux 5-10 mg once daily – no lab monitoring – avoid or reduce dose in renal dysfunction ■ for IV heparin: bolus of 75 U/kg (usually 5000 U) followed by infusion starting at 20 U/kg/h – aim for aPTT 2-3x control • long-term anticoagulation ■ for most nonpregnant patients who do not have renal insuciency or active cancer, rst-line is direct oral anticoagulants (rivaroxaban, apixaban, edoxaban, or dabigatran) rather than warfarin ■ if using warfarin instead of DOAC: start the same day as LMWH/heparin – overlap warfarin with LMWH/heparin for at least 5 d and until INR in target range of 2-3 for at least 2 d (use for patients with severe renal insuciency) ■ LMWH instead of warfarin for pregnancy, active cancer, or high bleeding risk patients • IV thrombolytic therapy ■ if patient has massive PE (hypotension or clinical right heart failure) and no contraindications ■ hastens resolution of PE but may not improve survival or long-term outcome and doubles risk of major bleeding ■ interventional thrombolytic therapy ■ massive PE may be treated with catheter-directed thrombolysis by an interventional radiologist ■ catheter-directed thrombolysis is not recommended over systemic thrombolysis • IVC lter: routine use is not indicated; use if recent proximal DVT and absolute contraindication to anticoagulation • duration of long-term anticoagulation: individualized, however generally ■ if reversible cause for PE (e.g. surgery, injury, pregnancy, etc.): 3-6 mo ■ if PE unprovoked: 6 mo to indenite ■ if ongoing major risk factor (active cancer, antiphospholipid antibody, etc.): indenite Thromboprophylaxis • mandatory for most hospital patients: reduces DVT, PE, all-cause mortality, cost-eective • start ASAP • continue at least until discharge or recommend extending for 35 d postoperatively, if major orthopaedic surgery

Evaluation of a Suspected Pulmonary Embolism Low clinical probability of embolism D-dimer (+ve) → CT scan (+ve) → ruled in (–ve) → ruled out Intermediate or high probability CT pulmonary angiography scan (–ve) → ruled out (+ve) → ruled in Notes: • Use D-dimers only if low clinical probability, otherwise, go straight to CT • If using V/Q scans (CT contrast allergy or renal failure): • Negative V/Q scan rules out the diagnosis • High probability V/Q scan only rules in the diagnosis if high clinical suspicion • Inconclusive V/Q scan requires leg U/S to look for DVT or CT

Workup for Idiopathic Venous Thromboembolism Thrombophilia workup: recurrent or idiopathic DVT/PE, age 0.6

>0.6

Pleural LDH

>2/3 upper limit of N serum LDH

>0.45 upper limit of N serum LDH

Exudate = any one criterion Ann Intern Med 1979;77:507-513 Chest 1997;111:970-980

Transudative Pleural Eusions • pathophysiology: alterations to Starling forces aects the rates of formation and absorption of pleural uid • etiology ■ CHF: usually bilateral, right-sided more than the le, can occasionally be isolated right-sided ■ cirrhosis leading to hepatic hydrothorax (diaphragmatic decit allows uid into chest cavity) ■ nephrotic syndrome, protein losing enteropathy ■ pulmonary embolism (may cause transudative but more oen causes exudative eusion) ■ peritoneal dialysis with transdiaphragmatic ow, hypothyroidism, urinothorax Exudative Pleural Eusions • pathophysiology: increased permeability of pleural capillaries or lymphatic dysfunction

Transudative eusions are usually bilateral, not unilateral Exudative eusions can be bilateral or unilateral

R24 Respirology

Toronto Notes 2023

Table 25. Exudative Pleural Eusion Etiologies Etiology

Examples

Infectious

Parapneumonic eusion (associated with bacterial pneumonia, or other process such as lung abscess) Empyema: bacterial, fungal, TB TB pleuritis Viral infection (rare) Fungal Parasitic

Malignancy

Lung carcinoma (35%) Lymphoma (10%)

Appearance of Pleural Fluid • Bloody: trauma, malignancy, traumatic tap • White: empyema, chylous, or chyliform eusion • Black: aspergillosis, amoebic liver abscess • Yellow-green: rheumatoid pleurisy • Viscous: malignant mesothelioma • Ammonia odour: urinothorax • Food particles: esophageal rupture

Metastases: breast (25%), ovary, kidney, other Mesothelioma Myeloma Inflammatory

Collagen vascular diseases: RA, SLE Pancreatitis Benign asbestos related eusion Pulmonary embolism Post-coronary artery bypass grafting or cardiac injury Drug reaction

Intra-Abdominal

Subphrenic abscess (sympathetic eusion) Pancreatic pseudocyst with fistula into pleural space (associated with elevated pleural fluid amylase) Meigs’ syndrome (ascites and hydrothorax associated with an ovarian fibroma or other pelvic tumour) (can also be a transudate)

Intra-Thoracic Trauma

Esophageal perforation (associated with elevated pleural fluid amylase) Hemothorax: rupture of a blood vessel, commonly by trauma or tumours Pneumothorax: spontaneous, traumatic Chylothorax (thoracic duct leak) Iatrogenic

Other

Drug-induced Hypothyroidism (can also be transudate)

Signs and Symptoms • oen asymptomatic • dyspnea: varies with size of eusion and underlying lung function • pleuritic chest pain, shoulder pain (referred pain from the phrenic nerve, C3-C5, which innervates the diaphragm) • inspection: ipsilateral decreased expansion; when accumulated rapidly, trachea can deviate away from eusion • palpation: decreased tactile fremitus • percussion: dullness • auscultation: decreased breath sounds; bronchial breathing and egophony just above uid level, sometimes pleural friction rub if inammatory cause and minimal uid Investigations • CXR ■ must have >200 mL of pleural uid for visualization on PA lm ■ PA: blunting of lateral costophrenic angle ■ lateral: >50 mL leads to blunting of posterior costophrenic angle ■ dense opacication of lower lung elds with concave meniscus as uid accumulates ■ decubitus: uid will layer out unless it is loculated ■ supine: uid will appear as general haziness over lung eld • CT: helpful in dierentiating parenchymal from pleural abnormalities; identifying loculation, measuring density of uid (higher density may indicate a hemothorax); contrast can detect pleural enhancement indicative of empyema and may identify underlying lung pathology causing eusion • U/S: detects small eusions and can guide thoracentesis • thoracentesis: indicated if pleural eusion is a new and concerning nding, if patient is unstable, and/ or if patient has pneumonia and there is a concern about infected parapneumonic eusion; order blood work (serum LDH, glucose, protein, albumin) at the same time for comparison ■ risk of re-expansion pulmonary edema if >1.5 L of uid is removed in one shot through a closed tap ■ inspect for colour, character, presence of pus, and odour of uid ■ send uid for analysis (see Table 26) • pleural biopsy: indicated if suspect TB, mesothelioma, or other malignancy (and if cytology nondiagnostic)

Role of CT in Pleural Eusion • To assess for fluid loculation, pleural enhancement, thickening and nodules, parenchymal abnormalities, and adenopathy • Can provide clues to help distinguish benign from malignant eusion • May not distinguish empyema from parapneumonic eusion Features of Mesothelioma • Multiple pleural nodules • Circumferential pleural thickening >1 cm • Mediastinal pleural involvement Imaging Features of Empyema • Parietal pleural thickening • Pleural enhancement • Concurrent thickening and enhancement of both the visceral and parietal pleural (split pleural sign)

Complicated Parapneumonic Effusion R25 Respirology

Toronto Notes 2023

Table 26. Analysis of Pleural Eusion Measure

Purpose

Always order: Protein, LDH

Transudate vs. exudate LDH especially high (>1000 IU/L) in empyema, rheumatoid, malignancy Protein especially high in TB, myeloma

Gram Stain, Ziehl-Neelsen Stain (TB), Culture

Looking for specific organisms (can add Ziehl-Neelsen Stain if TB suspected)

Cell Count Dierential

Neutrophils vs. lymphocytes (lymphocytic eusion in TB, cancer, lymphoma, RA) Eosinophilic (seen in pneumothorax, hemothorax, drug reactions, pulmonary embolism, eosinophilic granulomatosis with polyangiitis, asbestos-related, malignancy, parasitic, occasionally TB) High RBC count: mostly traumatic, malignancy, PE with infarction, TB, hemothorax

Cytology

Malignancy

Glucose

Low (fluid:serum 50 mmHg and pH 90% Anti-topoisomerase 1 (diuse) Anti-centromere (usually in CREST, see Sidebar, CREST Syndrome, RH14)

CK elevated in 80% ANA-positive in 33% Anti-Jo-1, anti-Mi-2 Muscle biopsy EMG MRI

Radiographs

Very early: normal Early: periarticular osteopenia Later: joint space narrowing Erosions Symmetric/concentric + ILD/lung nodules

Non-erosive ± Osteopenia ± Soft tissue swelling

± Pulmonary fibrosis/ILD ± Esophageal dysmotility ± Calcinosis

± Esophageal dysmotility ± ILD ± Calcifications

CLINICAL FEATURES

LABORATORY

Rheumatoid Arthritis Definition • chronic, symmetric, erosive synovitis of peripheral joints (e.g. wrists, MCPs, MTPs) • characterized by inammatory joint disease ± a number of extra-articular features • 1 joint with denite clinical synovitis (swelling) not explained by another disease Table 13. 2010 ACR/EULAR Classification Criteria for RA (score-based algorithm: add score of categories A-D; a score of 6/10 for definite RA) Criteria A. Joint involvement (swollen or tender) 1 large joint (shoulders, elbows, hips, knees, and ankles) 2-10 large joints 1-3 small joints (MCPs, PIPs, wrists, 2nd-5th MTPs) 4-10 small joints >10 joints (at least 1 small joint)

Score

0 2 3

C. Acute phase reactants Normal CRP and normal ESR Abnormal CRP and abnormal ESR

0 1

D. Duration of symptoms 1 h, improves with use • Symmetric joint involvement • Initially involves small joints of hands and feet • Constitutional symptoms

Toronto Notes 2023

Epidemiology • most common inammatory arthritis: prevalent in 1% of population • F:M=3:1 • age of onset 20-40 yr Clinical Presentation • variable course of exacerbations and remissions • morning stiness >1 h, improves with use, worsens with rest • polyarthritis: symmetric joint involvement (tender, swollen), small joints aected, most commonly in hands and feet (MCP, PIP, MTP) • constitutional symptoms: profound fatigue, depression, myalgia, weight loss • extra-articular features • limitation of function and decrease in global functional status • complications of chronic synovitis ■ signs of mechanical joint damage: loss of motion, instability, deformity, crepitus, joint deformities ◆ swan neck deformity, boutonnière deformity ◆ ulnar deviation and subluxation of MCP, radial deviation of wrist joint ◆ hammer toe, mallet toe, claw toe ◆ exion contractures ■ atlanto-axial and subaxial subluxation ◆ C-spine instability – neurological impingement (long tract signs) – dicult/dangerous intubation: risk of worsening subluxation and damage to spinal cord • limited shoulder mobility, spontaneous tears of the rotator cu leading to chronic spasm • tenosynovitis → may cause rupture of tendons • carpal tunnel syndrome • ruptured Baker’s cyst (outpouching of synovium behind the knee); presentation similar to acute deep vein thrombosis (DVT) • poor prognostic factors include: young age of onset, high RF titre, elevated ESR, activity of >20 joints, and presence of extra-articular features Table 14. Extra-Articular Features of RA Classified by Underlying Pathophysiology System

Vasculitic

Lymphocytic Infiltrate

Skin

Periungual infarction, cutaneous ulcers, palpable purpura

Rheumatoid nodules (may have vasculitic component)

Ocular

Episcleritis, scleritis

Keratoconjunctivitis sicca

Head and Neck

Xerostomia, Hashimoto’s thyroiditis (see Endocrinology, E31)

Cardiac

Peri-/myocarditis, valvular disease, conduction defects

Pulmonary

Pulmonary fibrosis, pleural eusion, pleuritis, pulmonary nodules

Neurologic

Peripheral neuropathy: sensory stockingglove, mononeuritis multiplex

Hematologic

Splenomegaly, neutropenia (Felty’s syndrome)

Renal

Amyloidosis – caused by accumulation of abnormal proteins

Classification of Global Functional Status in RA • Class I: able to perform usual activities of daily living (self-care, vocational, avocational) • Class II: able to perform self-care and vocational activities, restriction of avocational activities • Class III: able to perform self-care, restriction of vocational and avocational activities • Class IV: limited ability to perform self-care, vocational, and avocational activities

• • • • • • • • •

PIP MCP Wrist, not 1st CMC Elbow Shoulder Knee Ankle MTP C-spine

Figure 5. Common sites of joint involvement in RA

Boutonnière Deformity

Swan Neck Deformity

Claw Toe

Hammer Toe

Mallet Toe

© Elisheva Marcus and Gloria Situ © Jennifer Gu 2022

Pathophysiology • autoimmune disorder, unknown etiology; may have genetic and environmental component • complex genetic and environment interactions lead to disruption of immune tolerance, ultimately resulting in synovial inammation ■ genetic predisposition: HLA-DR4/DR1 association (93% of patients have either HLA type), cytokine promoters, T cell signaling ■ environmental predisposition: induction of enzymes that convert arginine to citrulline caused by environmental stress (cigarette smoking), propensity for immune reactivity to neoepitopes created by protein citrullination • inammatory process causes transformation of synovium into an invasive pannus tissue that degrades cartilage and bone with absence of repair ■ elevated TNF level increases osteoclasts and decreases osteoblasts at the site of inammation (results in periarticular osteopenia) ■ upregulation of RANK ligand increases osteoclast-mediated destruction

© Linda Colati

RH9 Rheumatology

Figure 6. Joint deformities

Syndromes in RA • SS (common): keratoconjunctivitis sicca and xerostomia (dry eyes and mouth) • Caplan’s syndrome (very rare): combination of RA + pneumoconiosis that manifests as multiple intrapulmonary nodules • Felty’s syndrome (rare): arthritis, splenomegaly, neutropenia

RH10 Rheumatology

Investigations • blood work ■ RF: 80% sensitivity but non-specic; may not be present at onset of symptoms; levels do not correlate with disease activity ◆ can be associated with more erosions, more extra-articular manifestations, and worse function ■ anti-CCP: 80% sensitivity but more specic (94-98%); may precede onset of symptoms • increased disease activity is associated with decreased Hb (anemia of chronic disease) and increased platelets, ESR, and CRP • imaging ■ bilateral hands/wrists, ankles/feet x-ray ◆ rst change is periarticular osteopenia, followed by erosions ■ C-spine x-ray (may be normal at onset, required for preoperative assessment in long-standing disease) ■ U/S (with power Doppler) – oen changes of synovitis/erosion noted in advance of those seen on plain x-ray ■ MRI may be used to image hands to detect early synovitis and erosions ■ MRI T1 inamed synovium is hypointense and hyperintense on T2; bone marrow edema can be seen as well as areas of increased uptake gadolinium contrast Treatment • goals of therapy: remission or lowest possible disease activity ■ key is early diagnosis and early intervention with DMARDs ■ “window of opportunity” = early treatment within rst 3 mo of disease may allow better control/ remission ■ assess poor prognostic factors at baseline (RF-positive, functional limitations, and extra-articular features) • behavioural ■ exercise program: active, gentle ROM and isometric exercise during ares; aquatic/aerobic/ strengthening exercise between ares ■ job modication, assistive devices as necessary ■ interventions to reduce cardiovascular disease, smoking cessation, lipid control • pharmacologic: alter disease progression ■ DMARDs and biologics (not analgesics or NSAIDs) can alter the course of RA ■ DMARDs ◆ treatment with DMARDs should be started as soon as RA diagnosis is made and should be aimed at reaching sustained remission ◆ MTX is the gold standard and is rst-line unless contraindicated – prior to MTX therapy: CBC prole, liver enzymes (ALT), Cr (Cr clearance), hepatitis B and C serology, and a CXR should be done – monitor and if inadequate response (3-6 mo) → combine or switch – consider combination therapy to MTX if patients have poor prognostic features or high disease activity – therapy includes: hydroxychloroquine, SSZ, leunomide, biologics – contraindications include liver disease, signicant alcohol intake, pregnancy, and lactation – if contraindication to MTX, then hydroxychloroquine, SSZ, and/or leunomide should be considered with the former being considered as a weaker agent and the latter as more potent ■ biologics (bDMARDs) ◆ should be used if inadequate response to DMARDs ◆ should be combined with DMARD therapy (initiating with combination therapy is associated with faster response rates and longer duration of eect) ◆ rst-line (anti-TNF) options: iniximab, etanercept, adalimumab, golimumab, and certolizumab ◆ non-anti-TNF agents include anakinra (almost never used for RA), abatacept, rituximab, and tocilizumab ◆ reassess every 3-6 mo and monitor disease activity (predominantly via assessing swollen joint count) ◆ JAK inhibitors (including tofacitinib and upacitinib) are oral small molecule synthetic DMARDs; used if other DMARDs and biologics fail • pharmacologic: supportive to reduce inammation and pain ■ NSAIDs ◆ individualize according to ecacy, tolerability, and comorbidities ◆ contraindicated/cautioned in some patients (e.g. PUD, ischemic cardiac disease, pregnancy, CKD, anticoagulant use) ◆ add acetaminophen for synergistic pain control ■ corticosteroids ◆ local: injections to control symptoms in a specic joint

Toronto Notes 2023

Poor prognostic features of RA include: young age of onset, high RF titre, elevated ESR, activity of >20 joints, and presence of e xtra-articular features

Side Eects of Steroids • Weight gain • Osteoporosis • AVN • Cataracts, glaucoma • PUD • Susceptibility to infection • Easy bruising • Acne • HTN • Hyperlipidemia • Hypokalemia, hyperglycemia • Mood swings

DMARDs, prednisone, and biologics (bDMARDs) but not analgesics or NS AIDs, alter the course of RA

Systemic Lupus Erythematosus RH11 Rheumatology

Toronto Notes 2023

◆ systemic (oral prednisone) or IM – low dose (5-10 mg/d) useful for short-term to improve symptoms if NSAIDs are ineective and to bridge gap until DMARDs take eect – do baseline DEXA bone density scan and consider bone supportive pharmacologic therapy (e.g. bisphosphonates) if using corticosteroids 7.5 mg/d >3 mo, particularly in those with other risk factors – cautions/contraindications: active infection, TB, osteoporosis, HTN, gastric ulcer, DM • surgical ■ indicated for structural joint damage ■ surgical options include: synovectomy, joint replacement, joint fusion, reconstruction/tendon repair Follow-Up Management and Clinical Outcomes • clinical reassessment every mo initially, then 3-6 mo if still ongoing activity, then 6-12 mo aer inammation has been suppressed • examine joints for active inammation – if active, consider adjusting medications, physical therapy/ occupational therapy (PT/OT) • RA patients should be screened and managed for cardiovascular disease given increased risk • if assessment reveals joint damage – consider analgesia, referral to PT/OT, surgical options • outcome depends on disease activity, joint damage, physical functional status, psychological health, and comorbidities • functional capacity is a useful tool for determining therapeutic eectiveness; many tools for evaluation have been validated • patients with RA have an increased prevalence of other serious illnesses: infection (e.g. pulmonary, skin, joint), osteoporosis, mental health disorders, renal impairment, lymphoproliferative disorders, cardiovascular disease (correlates with disease activity and duration) • risk of premature mortality, decreased life expectancy (most mortality not directly caused by RA)

Systemic Lupus Erythematosus • see Nephrology, NP26

Diagnostic Criteria of SLE

Definition • chronic autoimmune disease of unknown etiology resulting in multi-system inammation • characterized by production of autoantibodies and diverse clinical manifestations Table 15. Classification Criteria of SLE* Entry criterion: ANA at a titre of ≥1:80 and Additive Criteria 1. Do not count criterion if there is a more likely explanation than SLE 2. Occurrence of a criterion on at least one occasion is sucient 3. Within each domain, only the highest weighted criterion is counted towards the total score Clinical Domains and Criteria

Score

Constitutional

Fever

2

Hematologic

Leukopenia

3

Neuropsychiatric

Mucocutaneous

Thrombocytopenia

4

Autoimmune hemolysis

4

Delirium

2

Psychosis

3

Seizure

5

Non-scarring alopecia

2

Oral ulcers

2

Subacute cutaneous or discoid lupus

4

MD SOAP BRAIN Malar rash Discoid rash Serositis Oral ulcers ANA Photosensitivity Blood Renal Arthritis Immune Neurologic

A Systematic Review of Guidelines for Managing Rheumatoid Arthritis BMC Rheumatol 2019;3:42 Five general principles for management: • Start DMARDs as soon as possible following the diagnosis. • The best initial treatment is MTX. • Monitor disease activity regularly. • Biologics should be initiated in patients with persistently active disease despite MTX treatment. • Goals of treatment should be aimed at low disease activity or remission.

Acute cutaneous lupus

6

Pleural or pericardial eusion

5

Acute pericarditis

6

Musculoskeletal

Joint involvement

6

Renal

Proteinuria (>0.5 g/24 h)

4

Environment Stress, viruses, sun Genetic Hormonal HLA

Renal biopsy Class II or V lupus nephritis

8

T cells

Renal biopsy Class III or IV lupus nephritis

10

Serosal

Immunology Domains and Criteria

Score

Antiphospholipid antibodies

Anti-cardiolipin antibodies or Anti-β2PG1 antibodies or lupus anticoagulant

2

Complement proteins

Low C3 or low C4

3

SLE specific antibodies

Drugs

Low C3 and low C4

4

Anti-dsDNA or Anti-Sm antibodies

6

*Classification of SLE requires total score of ≥10 with ≥1 clinical criterion Sindhu R. Johnson, Thomas Dörner, Ray Naden, et al. Arthritis & Rheumatology (71, 9), p. 1400, copyright © 2020, Modified by Permission of John Wiley and Sons

Formation of Auto-Ab Cytotoxic Ab

Immune complexes

Cell damage/death

Inflammation

Figure 7. Multi-factorial etiology of SLE

RH12 Rheumatology

Toronto Notes 2023

Etiology and Pathophysiology • production of cytotoxic autoantibodies and immune complex formation • multi-factorial etiology • genetics ■ common association with HLA-B8/DR3; ~10% have positive family history ■ strong association with defects in apoptotic clearance → fragments of nuclear particles captured by antigen-presenting cells → develop ANAs ■ cytokines involved in inammatory process and tissue injury: BlyS, IL-6, IL-17, IL-18, TNF-α • environment ■ UV radiation, cigarette smoking, infection, vitamin D deciency, silica dust • estrogen ■ increased incidence aer puberty, decreased incidence aer menopause ■ men with SLE have higher concentration of estrogenic metabolites ■ increased risk of SLE associated with use of combined oral contraceptive pills and hormone replacement therapy • infection ■ viral (non-specic stimulant of immune response) • drug-induced ■ antihypertensives (hydralazine), anticonvulsants (phenytoin), antiarrhythmics (procainamide), isoniazid, biologics ■ anti-histone Abs are commonly seen in drug-induced SLE ■ symptoms resolve with discontinuation of oending drug

Drug-Induced SLE Often presents atypically with systemic features and serositis; usually associated with anti-histone Ab

Epidemiology • prevalence: 0.05% overall • F:M=10:1 • age of onset in reproductive yr (15-45) • more common and severe in Hispanic and Asian individuals, and individuals of African descent • bimodal mortality pattern ■ early (within 2 yr) ◆ active SLE, active nephritis, infection secondary to steroid use ■ late ◆ inactive SLE, inactive nephritis, atherosclerosis likely due to chronic inammation Clinical Presentation • characterized by periods of ares and remission Table 16. Signs and Symptoms of SLE System

Symptoms

Systemic

Fatigue, malaise, weight loss, fever, lymphadenopathy

Hematologic

Anemia of chronic disease, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia, pancytopenia, thrombosis, splenomegaly

Renal

Hematuria, proteinuria (glomerulonephritis), HTN, peripheral edema, renal failure

Dermatologic

Photosensitivity, malar rash, discoid rash, oral ulcers, alopecia (hair loss), purpura, panniculitis (inflammation of subcutaneous fat and muscle tissue), urticaria

Musculoskeletal

Polyarthralgias, polyarthritis, myalgias, AVN, reducible deformities of hand (Jaccoud’s arthritis)

Ophthalmic

Keratoconjunctivitis sicca, episcleritis, scleritis, cytoid bodies (cotton wool exudates on fundoscopy = infarction of nerve cell layer of retina)

Cardiac

Pericarditis, CAD, non-bacterial endocarditis (Libman-Sacks), myocarditis

Vascular

Note: SLE is an independent risk factor for atherosclerosis and CAD

Respiratory

Raynaud’s phenomenon, livedo reticularis (mottled discolouration of skin due to narrowing of blood vessels, characteristic lacy or net-like appearance), vasculitis

Gastrointestinal

Pleuritis, ILD, pulmonary HTN, PE, alveolar hemorrhage

Neurologic/Psychiatric

Pancreatitis, SLE enteropathy, hepatitis, hepatomegaly, dysphagia, esophagitis, intestinal pseudo-obstruction, peritonitis, mesenteric vasculitis

Life/Organ-Threatening

Cardiac: coronary vasculitis, malignant HTN, tamponade Hematologic: hemolytic anemia, neutropenia, thrombocytopenia, TTP, thrombosis Neurologic: seizures, CVA, stroke Respiratory: pulmonary HTN, pulmonary hemorrhage, emboli

Investigations • ANA (98% sensitivity, but poor specicity → used as a screening test; ANA titres are not useful to follow disease course, seeChoosing Wisely Recommendations, RH5) • anti-dsDNA and anti-Sm are specic (95-99%) • anti-dsDNA titre and serum complement (C3, C4) are useful to monitor treatment response in patients who are clinically and serologically concordant (anti-dsDNA increases, C3 and C4 decrease with disease activity) • APLA (anti-cardiolipin Ab, SLE anticoagulant, anti-β2 glycoprotein-I Ab), may cause increased risk of clotting and increased aPTT

Raynaud’s Phenomenon Vasospastic disorder characteristically causing discolouration of fingers and toes (white → blue → red) Classic triggers: cold and emotional stress

Consider SLE in a patient who has involvement of 2 or more organ systems

Antiphospholipid Antibody Syndrome RH13 Rheumatology

Toronto Notes 2023

Treatment • goals of therapy ■ aim for remission, prevention of ares ■ hydroxychloroquine ± glucocorticoid ■ treat early and avoid long-term steroid use, if unavoidable see Endocrinology, E46 for osteoporosis management ■ if high doses of steroids are necessary for long-term control, taper when possible and add immunosuppressive therapies (MTX, azathioprine, mycophenolate) ■ treatment is tailored to organ system involved and severity of disease ■ moderate refractory disease can be treated with belimumab ■ all medications used to treat SLE require periodic monitoring for potential toxicity • dermatologic ■ sunscreen, avoid UV light and estrogens ■ topical steroids, hydroxychloroquine • musculoskeletal ■ NSAIDs ± gastroprotective agent for arthritis (also benecial for pleuritis and pericarditis) ■ hydroxychloroquine improves long-term control and prevents ares ■ bisphosphonates, calcium, vitamin D to combat osteoporosis • other considerations ■ smoking cessation ■ immunizations (inuenza); live vaccines are generally not recommended ■ for women with APLA, avoid estrogen-containing contraceptives because of increased risk of thrombosis • organ-threatening disease ■ high-dose oral prednisone or IV methylprednisolone in severe disease ■ steroid-sparing agents: azathioprine, MTX, mycophenolate (can use mofetil or sodium) ■ IV cyclophosphamide for serious organ involvement (e.g. cerebritis or lupus nephritis) for clinical features of lupus nephritis ■ refractory disease can be treated with rituximab

The arthritis of SLE can be deforming but it is non-erosive (in contrast to RA) – called Jaccoud’s arthritis

Antiphospholipid Antibody Syndrome Definition • multi-system vasculopathy manifested by recurrent thromboembolic events, spontaneous abortions, and thrombocytopenia • circulating antiphospholipid autoantibodies interfere with coagulation • primary APS: occurs in the absence of other disease • secondary APS: occurs in the setting of a connective tissue disease (including SLE), malignancy, drugs (hydralazine, procainamide, phenytoin, interferon, quinidine), and infections (HIV, TB, hepatitis C, infectious mononucleosis) • catastrophic APS: development within 1 wk of small vessel thrombotic occlusion in ≥3 organ systems with positive APLA (high mortality) Table 17. Classification Criteria of APS* Criteria

Description

Manifestations of APLA • Thromboembolic events • Spontaneous abortions • Thrombocytopenia • Associated with livedo reticularis, migraine headaches

Arterial and venous thrombosis are usually mutually exclusive

CLINICAL Vascular thrombosis

One or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ Must be confirmed by imaging or histopathology

Pregnancy morbidity

1. ≥1 death of morphologically normal fetus (confirmed by U/S or fetal exam) at ≥10 wk gestation; OR 2. ≥1 premature birth of morphologically normal neonate before 34 wk gestation due to eclampsia, preeclampsia, or placental insuciency; OR 3. ≥3 consecutive spontaneous abortions 40 GPL or MPL, or >99th percentile), measured by ELISA

Anti-β2 glycoprotein-I Ab

IgG and/or IgM, plasma or serum, present in high titre (i.e. >99th percentile), measured by ELISA

* 1 clinical and 1 laboratory criteria must be present J Thromb Haemost 2006;4:295-306

Clinical Presentation • see clinical criteria ( Table 17) • hematologic ■ thrombocytopenia, hemolytic anemia, neutropenia • dermatologic ■ livedo reticularis, Raynaud’s phenomenon, purpura, leg ulcers, gangrene

See Landmark Rheumatology Trials, RH32 for more information on the TULIP-2 trial. It examined the ecacy of anifrolumab for the treatment of SLE.

Scleroderma (i.e. Systemic Sclerosis) RH14 Rheumatology

Toronto Notes 2023

Treatment • thrombosis ■ lifelong anticoagulation with warfarin ■ target INR 2.0-3.0 for rst venous event, >3.0 for recurrent event, target INR >3.0 for arterial event, or target INR 2.0-3.0 + ASA • recurrent fetal loss ■ heparin/low molecular weight heparin ± ASA during pregnancy • catastrophic APS ■ high-dose steroids, anticoagulation, cyclophosphamide, plasmapheresis

Scleroderma (i.e. Systemic Sclerosis) Definition • a non-inammatory autoimmune disorder characterized by widespread small vessel vasculopathy, production of autoantibodies, and broblast dysfunction causing brosis Scleroderma (i.e. systemic sclerosis)

Generalized

Localized (no involvement of internal organs) • Mostly children and young adults

Morphea • Hard oval patches on the skin

CREST Syndrome Cal cinosis Raynaud’s phenomenon Esophageal dysmotility Sclerodactyly Telangiectasia

Linear • Line of thickened skin

Diffuse systemic sclerosis • Widespread skin disease (proximal to wrist, can involve trunk), tendons • Early visceral involvement (renal, pulmonary fibrosis)

Limited systemic sclerosis • Skin sclerosis restricted to hands, face, neck • 3rd to 4th decade • Pulmonary HTN common • CREST

Scleroderma is the most common cause of secondary Raynaud’s phenomenon

Figure 8. Forms of scleroderma

Etiology and Pathophysiology • idiopathic vasculopathy (not vasculitis) leading to atrophy and brosis of tissues ■ characterized by several hallmark pathogenic features: small vessel vasculopathy resulting in tissue hypoxia, production of autoantibodies, and broblast dysfunction leading to increased deposition of extracellular matrix ■ resembles malignant HTN ■ lung disease is the most common cause of morbidity and mortality Table 18. The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Criteria for the Classification of Scleroderma* Item

Sub-item

1. Skin thickening of fingers of both hands extending proximal to the MCP (sucient criterion)

Score 9

2. Skin thickening of the fingers

Puy fingers Sclerodactyly

2

3. Fingertip lesions

Digital tip ulcers Fingertip pitting scars

4

4. Telangiectasia

2

5. Abnormal nailfold capillaries 6. Pulmonary arterial HTN ± ILD (max score 2)

3 Pulmonary arterial HTN ILD

2

Anti-centromere Anti-topoisomerase I Anti-RNA polymerase III

2

7. Raynaud’s phenomenon 8. Scleroderma-related Ab

2

* Score of ≥9 is sucient to classify a patient as having definite scleroderma (sensitivity 0.95, specificity 0.93)

Epidemiology • F:M=3-4:1, peaking in 5th decade • associated with HLA-DR1 and environmental exposures (silica, epoxy resins, toxic oil, aromatic hydrocarbons, polyvinyl chloride) • limited systemic sclerosis has a higher survival prognosis (>70% at 10 yr) than diuse systemic sclerosis (40-60% at 10 yr)

Cyclophosphamide vs. Mycophenolate Mofetil in Scleroderma Lung Disease L ancet Respir Med 2016;4:708-719 Study: Double-blind, randomized, parallel group trial. Purpose: To compare the toxicity and ecacy of cyclophosphamide vs. mycophenolate mofetil on lung function. Results: In both treatment groups, the adjusted percent predicted FVC improved from baseline to 24 mo. Mycophenolate mofetil was associated with less toxicity and was better tolerated. Conclusion: Treatment of SSc-ILD with mycophenolate mofetil for 2 yr or cyclophosphamide for 1 yr both result in improved lung function. However, mycophenolate mofetil is the current preference for treatment of SSc-ILD due to its better tolerability.

Raynaud’s Phenomenon DDx COLD HAND Cr yoglobulins/Cryofibrinogens Obstruction/Occupational Lupus erythematosus, other connective tissue disease DM/Drugs Hematologic problems (polycythemia, leukemia, etc.) Arterial problems (atherosclerosis)/ Anorexia nervosa Neurologic problems (vascular tone) Disease of unknown origin (idiopathic)

RH15 Rheumatology

Toronto Notes 2023

Clinical Presentation Table 19. Clinical Manifestations of Scleroderma System

Features

Dermatologic

Painless non-pitting edema → skin tightening Ulcerations, calcinosis, periungual erythema, hypo/hyperpigmentation, pruritus, telangiectasias Characteristic face: mask-like facies with tight lips, beak nose, radial perioral furrows

Vascular

Raynaud’s phenomenon → digital pits, gangrene Thrombosis

Gastrointestinal (~90%)

Distal esophageal hypomotility → dysphagia Loss of lower esophageal sphincter function → gastroesophageal reflux disease (GERD), ulcerations, strictures Small bowel hypomotility → bacterial overgrowth, diarrhea, bloating, cramps, malabsorption, weight loss Large bowel hypomotility → wide mouth diverticula are pathognomonic radiographic finding on barium study

Renal

Mild proteinuria, Cr elevation, HTN “Scleroderma renal crisis” (10-15%) may lead to malignant arterial HTN, oliguria, and microangiopathic hemolytic anemia

Pulmonary (~80%)

Interstitial fibrosis, pulmonary HTN, pleurisy, pleural eusions

Cardiac

Left ventricular dysfunction, pericarditis, pericardial eusion, arrhythmias

Musculoskeletal

Polyarthralgias “Resorption of distal tufts” (radiological finding) Proximal weakness 2º to disuse, atrophy, low grade myopathy, tendon friction rubs

Endocrine

Hypothyroidism

Investigations • blood work ■ CBC, Cr, ANA ■ anti-topoisomerase 1/anti-Scl-70 antibody: specic but not sensitive for diuse systemic sclerosis ■ anti-centromere antibody: favours diagnosis of CREST (limited systemic sclerosis) ■ anti-RNA polymerase III antibody: associated with severe skin involvement, increased risk of renal crisis • PFT ■ assess and monitor for ILD • echocardiogram ■ rule out pulmonary HTN • imaging ■ baseline CXR to rule out ILD Treatment • dermatologic ■ good skin hygiene ■ low-dose prednisone (>20 mg may provoke renal crisis if susceptible), MTX (limited evidence) • vascular ■ Raynaud’s: keep hands and body warm, smoking cessation ■ vasodilators (CCBs, local nitroglycerine cream, systemic PGE2 inhibitors, PDE5 inhibitors), fluoxetine • gastrointestinal ■ GERD: PPIs are first-line, then H2-receptor antagonists ■ small bowel bacterial overgrowth: broad spectrum antibiotics (tetracycline, metronidazole) ■ motilitydisturbances: prokinetics • renal disease ■ ACE inhibitor for hypertensive crisis ■ see Nephrology, NP35 for scleroderma renal crisis • pulmonary ■ early interstitial disease: mycophenolate mofetil (less toxicity) or cyclophosphamide ■ pulmonary HTN: vasodilators (e.g. bosentan, epoprostenol, and PDE5 inhibitors) ■ rapidly progressive disease at risk of organ failure: consider hematopoietic stem cell transplantation • cardiac ■ pericarditis: systemic steroids • musculoskeletal ■ arthritis: NSAIDs ■ myositis: systemic steroids

Features of Pathologic Raynaud’s Syndrome • New onset • Asymmetric • Precipitated by stimuli other than cold or emotion • Associated with distal pulp pitting or tissue reabsorption • Digit ischemia • Capillary dilatation by capillaroscopy

Inflammatory Myopathy RH16 Rheumatology

Toronto Notes 2023

Inflammatory Myopathy Definition • autoimmune diseases characterized by proximal muscle weakness ± pain • muscle becomes damaged by a non-suppurative lymphocytic inammatory process • associated with malignancy ■ increased risk of malignancy: age >50, DMM > PM, elevated CK, peak incidence of malignancy at onset of myositis or within 1st yr, dysphagia, ulcerative skin lesions, cutaneous vasculitis, anti-P155/140 antibody • associated with other CTDs, Raynaud’s phenomenon, autoimmune disorders Classification • PM/DMM • adult and juvenile forms • newly characterized entities: ■ focal necrotizing myopathy (secondary to statin) ■ amyopathic myopathy (anti-synthetase syndrome, MDA-5 syndrome) Inclusion Body Myositis • age >50, M>F, slowly progressive, vacuoles in cells on biopsy • patient unresponsive to treatment • distal and proximal muscle weakness • muscle biopsy positive for inclusion bodies POLYMYOSITIS/DERMATOMYOSITIS Definition • PM and DMM are idiopathic inammatory myopathies characterized by inammation and proximal skeletal muscle weakness • notably, DMM oen presents with characteristic skin manifestations Etiology and Pathophysiology • PM is a T cell-mediated process with myocytes being the primary target, characterized by focal endomysial inltrates (CD8+ T cells) surrounding muscle bres, found in adults • DMM is a complement mediated process with perivascular inammatory inltrates (CD4+ T cells > CD8+ T cells) leading to perifascicular atrophy of muscle bres Clinical Presentation • progressive symmetrical proximal muscle weakness (shoulder and hip) developing over wk to mo; diculty liing head o pillow, arising from chair, climbing stairs • dermatological ■ DMM has characteristic dermatological features (F>M, children and adults) ◆ Gottron’s papules – pink-violaceous, at-topped papules overlying the dorsal surface of the MCP and IP ◆ Gottron’s sign – erythematous, smooth or scaly patches over the extensor surface of elbows, knees, or medial malleoli ◆ heliotrope rash: violaceous rash over the eyelids; usually with edema ◆ shawl sign: poikilodermatous, erythematous rash over neck, upper chest, and shoulders ◆ mechanic’s hands: dry, crackled lesions on palmar and lateral surfaces of digits, especially over the pulp space, also seen in a subtype of myositis called anti-synthetase syndrome ◆ periungual erythema • cardiac ■ arrhythmias, congestive heart failure, conduction defect, ventricular hypertrophy, pericarditis • gastrointestinal ■ oropharyngeal and lower esophageal dysphagia, reux • pulmonary ■ weakness of respiratory muscles, ILD, aspiration pneumonia Investigations • general lab tests: CK, CBC, ESR and/or CRP, TSH • serologic tests: ANA, anti-Jo-1 (DMM), anti-Mi-2, anti-SRP (usually not available at commercial labs) • imaging: MRI may be used to localize biopsy site • EMG: characteristic ndings of muscle inammation and damage • muscle biopsy can aid in diagnosis, however not needed in those with classic skin ndings and muscle weakness

Signs of DMM Gottron’s papules and Gottron’s sign are pathognomonic of DMM (occur in 70% of patients)

Malignancies Associated with DMM • Breast • Lung • Colon • Ovarian

Sjögren’s Syndrome RH17 Rheumatology

Toronto Notes 2023

Treatment • non-pharmacological treatment ■ PT and OT, speech-language therapy for esophageal dysfunction • pharmacological treatment ■ high-dose glucocorticoid (e.g. prednisone 1 mg/kg/d) usually not exceeding 80 mg daily and slow taper aer patient improvement (~6 wk) ■ add immunosuppressive agents (azathioprine, MTX) ■ IVIG if severe or refractory ■ hydroxychloroquine for DMM rash • malignancy surveillance ■ detailed history and physical (breast, pelvic, and rectal exams) ■ CXR, abdominal and pelvic U/S, fecal occult blood, Pap test, mammogram ± CT scan (thoracic, abdominal, pelvic)

Sjögren’s Syndrome Definition • autoimmune condition characterized by dry eyes (keratoconjunctivitis sicca/xerophthalmia) and dry mouth (xerostomia), caused by lymphocytic inltration of salivary and lacrimal glands • exists on a spectrum and may evolve into a systemic disorder (20%) with diminished exocrine gland activity and extraglandular features • primary and secondary forms (associated with RA, SLE, DMM, and HIV) • prevalence 0.5%, F>>M at 10:1, 40-60 yr • increased risk of non-Hodgkin’s lymphoma (lifetime incidence 6-7%) Table 20. The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria for Primary Sjögren’s Syndrome (at least 1 inclusion criteria, no condition in exclusion criteria, score ≥4) Criteria

Score

Labial salivary gland biopsy with focal lymphocytic 3 sialadenitis with focus score ≥1 focus/4mm Anti-SSA- or Ro-positive

Comments Focus scores are histopathologic grading systems Strongly associated with phenotypic ocular and serological components of Sjögren’s

3

Ocular staining score ≥5 (or van Bijsterfeld score ≥4 1 on at least one eye) Schirmer’s test ≤5 mm/5 min on at least one eye

1

Unstimulated whole saliva flow rate ≤0.1 mL/min

1

Ocular staining score based on fluorescein dye examination of conjunctiva and cornea to determine clinical changes

Inclusion criteria (positive response to at least one question): 1) Have you had daily, persistent, troublesome dry eyes for more than 3 mo? 2) Do you have a recurrent sensation of sand or gravel in the eyes? 3) Do you use tear substitutes more than 3 times a d? 4) Have you had a daily feeling of dry mouth for more than 3 mo? 5) Do you frequently drink liquids to aid in swallowing dry food? Exclusion criteria include prior diagnosis of any of the following conditions: 1) History of head and neck radiation treatment, 2) Active hepatitis C infection (with confirmation by polymerase chain reaction, 3) AIDS, 4) Sarcoidosis, 5) Amyloidosis, 6) Graft-versus-host disease, 7) IgG4-related disease Arthritis Rheumatol. 2017;69:35-45

Clinical Presentation • “sicca complex”: dry eyes (keratoconjunctivitis sicca/xerophthalmia), dry mouth (xerostomia), complicated by staphylococcal blepharitis • dental caries, oral candidiasis, angular cheilitis (inammation and ssuring at the labial commissures of the mouth) • extra-glandular manifestations ■ fatigue, low-grade fever ■ autoimmune thyroid dysfunction ■ arthralgias, arthritis ■ subclinical diuse ILD, xerotrachea leading to chronic dry cough ■ renal disease, glomerulonephritis ■ palpable purpura, vasculitis ■ peripheral neuropathy ■ lymphoma risk greatly increased Treatment • ocular ■ articial tears/tear gel if severe, moisture retaining eyewear, humidiers, or surgical punctal occlusion for dry eyes • oral ■ good dental hygiene, hydration ■ avoid alcohol and tobacco ■ parasympathomimetic agents that stimulate salivary ow (e.g. pilocarpine) ■ topical nystatin or clotrimazole x4-6 wk for oral candidiasis • systemic treatments (e.g. hydroxychloroquine, corticosteroids) are ineective, rituximab can be used in severe organ-threatening disease (e.g. vasculitis)

Classic Triad (identifies 93% of Sjögren’s patients) • Dry eyes • Dry mouth (xerostomia) → dysphagia • Arthritis (small joint, asymmetrical, non-erosive) but may be associated with rheumatoid arthritis, in which case, the arthritis is erosive and symmetric

Mixed Connective Tissue Disease RH18 Rheumatology

Toronto Notes 2023

Mixed Connective Tissue Disease Definition • syndrome with features of 3 dierent CTDs (e.g. SLE, scleroderma, myositis) • common symptoms: Raynaud’s phenomenon, swollen ngers Investigations • blood work: anti-RNP (see Table 12, RH8) Treatment • treatment is generally guided by the severity of symptoms and organ system involvement Prognosis • prognosis is variable: some individuals go into remission, others develop a distinct connective tissue disease (e.g. SLE, SSc), and others develop a severe disease course ■ pulmonary arterial HTN is a major cause of death

Overlap Syndrome Definition • syndrome with sucient diagnostic features of 2+ dierent CTDs

Vasculitides • inammation and subsequent necrosis of blood vessels leading to tissue ischemia or infarction of any organ system • diagnosis ■ clinical suspicion: suspect in cases of unexplained multiple organ ischemia or systemic illness with no evidence of malignancy or infection; constitutional symptoms such as fever, weight loss, anorexia, fatigue ■ labs non-specic: anemia, increased WBC and CRP, abnormal U/A ■ investigations: biopsy if tissue accessible; angiography if tissue inaccessible • treatment generally involves corticosteroids and/or immunosuppressive agents Table 21. Classification of Vasculitis and Characteristic Features Classification

Features of Small Vessel Vasculitis • Palpable purpura • Vesicles • Chronic urticaria • Superficial ulcers (erosions)

Characteristic Features

SMALL VESSEL Non-ANCA-associated

Immune complex-mediated (most common mechanism)

Anti-GBM (Goodpasture’s disease)

Autoantibodies targeting type IV collagen in both glomerular basement membrane and alveoli causing glomerulonephritis and/or pulmonary findings

Anti-C1q vasculitis (hypocomplementemic urticarial vasculitis syndrome)

Specific autoimmune disorder with at least 6 mo of urticaria with C1q complement deficiency with various systemic findings

Predominantly cutaneous vasculitis

Also known as hypersensitivity/leukocytoclastic vasculitis

IgA vasculitis (formerly Henoch-Schönlein purpura (HSP)) (see Paediatrics, P98)

Vascular deposition of IgA causing systemic vasculitis (skin, GI, renal), usually self-limiting; most common in childhood

Cryoglobulinemic vasculitis (CV)

Systemic vasculitis caused by circulating cryoproteins forming immune complexes; 60-80% of cases are due to hepatitis C, 5-10% are due to a CTD (SLE, RA, SS), 5-10% are due to a lymphoproliferative disorder, and the remaining 5-10% are idiopathic or “essential.” CV may be associated with underlying infection (e.g. hepatitis C) or CTD

ANCA-associated (i.e. PR3-ANCA) Granulomatosis with polyangiitis (GPA, formerly Wegener’s) PR3 (c-ANCA) > MPO (p-ANCA)

Granulomatous inflammation of vessels of respiratory tract and kidneys leading to pulmonary hemorrhage and glomerulonephritis; initially may have upper respiratory tract infection (URTI) symptoms (sinusitis); most common in middle age

EGPA, formerly Churg-Strauss syndrome (50% ANCA positive)

Granulomatous inflammation of vessels with hypereosinophilia and eosinophilic tissue infiltration, frequent lung involvement (asthma, allergic rhinitis), associated with MPO-ANCA in 40-50% of cases. Other manifestations include peripheral neuropathy (70%), GI involvement, myocarditis, and rarely coronary arteritis; average age 40s

Microangiopathic polyangiitis (MPA) (70% ANCA positive, usually MPO)

Pauci-immune necrotizing vasculitis, aects kidneys (necrotizing glomerulonephritis), lungs (capillaritis and alveolar hemorrhage), and skin; most common in older age

• c-ANCA (e.g. pR3-ANCA): cytoplasmic anti-neutrophil cytoplasmic Ab associated with anti-PR3 • p-ANCA (e.g. MPO-ANCA): perinuclear anti-neutrophil cytoplasmic Ab associated with multiple antigens, e.g. myeloperoxidase, lactoferrin (IBD), cathepsin, elastase, etc. Of these, only antibodies to myeloperoxidase have been associated with the development of vasculitis

EGPA Triad • Allergic rhinitis and asthma (often quiescent at time of vasculitis) • Eosinophilic infiltrative disease resembling pneumonia • Systemic vasculitis often mononeuritis multiplex/peripheral neuropathy and peripheral eosinophilia

MEDIUM VESSEL PAN

Segmental, non-granulomatous necrotizing inflammation Unknown etiology in most cases, any age (average 40-50s), M>F

Kawasaki disease (see Paediatrics, P98)

Arteritis and mucocutaneous lymph node syndrome

Features of Medium Vessel Vasculitis • Livedo reticularis • Erythema nodosum • Raynaud’s phenomenon • Nodules • Digital infarcts • Ulcers

Small Vessel Non-ANCA-Associated Vasculitis RH19 Rheumatology

Toronto Notes 2023

Table 21. Classification of Vasculitis and Characteristic Features Classification

Characteristic Features

LARGE VESSEL GCA/Temporal arteritis

Inflammation predominantly of the aorta and its branches Ages >50, F>M Temporal headache, jaw claudication, scalp tenderness, vision loss

Takayasu’s

“Pulseless disease,” unequal peripheral pulses, chronic inflammation, most often the aorta and its branches Most common in young adults of Asian descent, ages 10-40, F>M, risk of aortic aneurysm

OTHER VASCULITIDES Buerger’s disease (“Thromboangiitis Obliterans”)

Inflammation and clotting of small and medium-sized arteries and veins of distal extremities, may lead to distal claudication and gangrene, the most important etiologic factor is cigarette smoking. Most common in young Asian males, M>F

Behçet’s disease

Multi-system disorder presenting with ocular involvement (uveitis), recurrent oral and genital ulceration, venous thrombosis, skin and joint involvement Most common in Mediterranean and Asian populations, average age 30 y/o, M>F

Vasculitis mimicry (i.e. pseudovasculitis)

Cholesterol emboli, atrial myxoma, subacute bacterial endocarditis (SBE), APS

Large Vessel Vasculitis

GCA Takayasu’s ateritis

Large artery

Medium Vessel Vasculitis

PAN Kawasaki disease

Medium artery

Small Vessel Vasculitis Small artery

ANCA-Associated Vasculitis GPA MPA EGPA Non-ANCA-Associated Vasculitis Cryoglobulinemic vasculitis IgA vasulitis (IgAV) Hypocomplementemic urticarial vasculitis

Arteriole

Capillary vessel

©Willow Yang 2021

Figure 9. Classification of vasculitides by vessel size J. C. Jennette, R. J. Falk, P. A. Bacon, et al, Arthritis & Rheumatology (65, 1), p. 1, copyright © 2020, Modified by Permission of John Wiley and Sons

Small Vessel Non-ANCA-Associated Vasculitis CUTANEOUS VASCULITIS • subdivided into: ■ drug-induced vasculitis ■ serum sickness reaction ■ vasculitis associated with other underlying primary diseases (CTD, infections, malignancies – hematologic > solid tumours) Etiology and Pathophysiology • cutaneous vasculitis following: ■ drug exposure (allopurinol, gold, sulfonamides, penicillin, phenytoin) ■ viral or bacterial infection ■ idiopathic causes • small vessels involved (post-capillary venules most frequently) • usually causes a leukocytoclastic vasculitis: debris from neutrophils around vessels • sometimes due to cryoglobulins which precipitate in cold temperatures Clinical Presentation • palpable purpura (usually on lower extremities) ± vesicles and ulceration, urticaria, macules, papules, bullae, subcutaneous nodules ■ renal or joint involvement may occur, especially in children Investigations • vascular involvement (both arteriole and venule) established by skin biopsy

Small Vessel ANCA-Associated Vasculitis RH20 Rheumatology

Toronto Notes 2023

Treatment • stop possible oending drug; treat underlying primary disease • NSAIDs, low-dose corticosteroids ■ immunosuppressive agents in resistant cases • usually self-limiting

Small Vessel ANCA-Associated Vasculitis GRANULOMATOSIS WITH POLYANGIITIS (GPA, formerly known as Wegener’s Granulomatosis) Definition • granulomatous inammation of vessels that may aect the upper airways (rhinitis, sinusitis), lungs (pulmonary nodules, inltrates caused by pulmonary hemorrhage), and kidneys (glomerulonephritis, renal failure) • highly associated with c-ANCA by indirect immunouorescence (IIF) and PR3-ANCA by ELISA; however, changes in ANCA levels do not predict remission or relapse • incidence: 2-3 in 100000; more common in Northern latitudes

Classic Features of GPA • Necrotizing granulomatous vasculitis of lower and upper respiratory tract • Focal segmental glomerulonephritis

Table 22. Classification Criteria for GPA* Clinical Criteria

Score

Criteria

Description

Nasal involvement

Crusting, ulcers, epistaxis, congestion, blockage, or septal defect/ perforation

+3

Cartilaginous involvement

Ear/nose cartilage inflammation, hoarseness or stridor, endobronchial involvement, or saddle nose deformity

+2

Hearing loss

Conductive or sensorineural

+1

See Landmark Rheumatology Trials RH34 for more information on the RAVE trial. It examined the ecacy of rituximab for the induction and maintenance of remission in patients with ANCA-associated Vasculitides.

Laboratory, Imaging, and Biopsy Criteria c-ANCA or anti-PR3-positive

+5

Pulmonary nodules, mass, or cavitation on chest imaging

+2

Granuloma, extravascular granulomatous inflammation, or giant cells on biopsy

+2

Inflammation, consolidation, or eusion of nasal/paranasal sinuses, or mastoiditis on imaging

+1

Pauci-immune glomerulonephritis on biopsy

+1

p-ANCA or anti-MPO-positive

-1

Blood eosinophil count >1x109 /L

-4

*Diagnosed if ≥5 American College of Rheumatology, 2022

Etiology and Pathophysiology • pathogenesis depends on genetic susceptibility and environmental triggers (e.g. infection) ■ dysregulated immune response due to loss of B and T cell tolerance ■ acute vascular injury mediated by neutrophils and monocytes Clinical Presentation • systemic ■ malaise, fever, weakness, weight loss • head, eyes, ears, nose, and throat (HEENT) ■ sinusitis or rhinitis, nasal crusting and bloody nasal discharge, nasoseptal perforation, saddle nose deformity ■ proptosis due to: inammation/vasculitis involving extraocular muscles, granulomatous retrobulbar space-occupying lesions or direct extension of masses from the upper respiratory tract ■ hearing loss due to involvement of cranial nerve (CN) VIII • pulmonary ■ cough, hemoptysis, granulomatous upper respiratory tract masses, tracheal and bronchial stenosis • renal ■ hematuria, proteinuria, elevated Cr, glomerulonephritis • other ■ joint, skin, eye complaints-iritis, vasculitic neuropathy Investigations • blood work: anemia (normal mean corpuscular volume (MCV)), increased WBC, increased Cr, increased CRP, elevated platelet count, ANCA (PR3 > MPO) • urinalysis: proteinuria, hematuria, RBC casts • CXR/CT: pneumonitis, lung nodules, inltrations, cavitary lesions • biopsy for conrmation of disease: skin, renal (segmental necrotizing glomerulonephritis), lung (vasculitis, necrosis) • CRP may be used to monitor response to treatment in some patients

See Landmark Rheumatology Trials RH34 for more information on the MAINRITSAN3 trial. It examined the ecacy of extended maintenance rituximab in patients with ANCAassociated Vasculitides

Medium Vessel Vasculitis RH21 Rheumatology

Toronto Notes 2023

Treatment • severe, life or organ-threatening disease ■ induction therapy: IV glucocorticoids + either IV or oral cyclophosphamide OR rituximab ■ glucocorticoid: methylprednisolone 0.5-1.0 g/d IV x1-3 d followed by prednisone 1 mg/kg/d PO x2-4 wk and then gradual taper ■ cyclophosphamide: 2 mg/kg/d (max 200 mg/d) PO for maximum of 3-6 mo OR 15 mg/kg IV (max 1200 mg) every 2 wk for 3 doses, then every 3 wk for 3-6 doses (dose adjust for older age and renal failure) ■ rituximab: 375 mg/m2 x4 weekly infusions ■ maintenance therapy: initiated once remission is achieved, consider corticosteroid-sparing agents such as rituximab for maintenance, azathioprine, MTX, and mycophenolate are reasonable alternatives • plasma exchange can be an adjunct treatment for patients with severe organ involvement (renal failure, pulmonary hemorrhage) not responding to conventional induction treatment • non-organ-threatening disease ■ prednisone 0.5-1 mg/kg/d PO and MTX 15-25 mg PO/SC weekly OR azathioprine 2 mg/kg/d • screening and prophylaxis ■ all patients should receive screening and prophylaxis for corticosteroid-induced osteoporosis, PUD prevention, and Pneumocystis jiroveci prophylaxis (trimethoprim/sulfamethoxazole 160/800 mg PO 3x/wk)

Medium Vessel Vasculitis POLYARTERITIS NODOSA Definition • systemic, necrotizing vasculitis of medium-sized vessels, dened as visceral arteries and their branches • ANCA-negative, classically lung-sparing • 5-10% associated with hepatitis B positivity • incidence: 0.7 in 100000; aects individuals between 40-60 yr; M:F=2:1 Table 23. Classification Criteria for PAN* Criteria

Description

1. Weight loss

≥4 kg, not due to dieting or other factors

2. Myalgias, weakness, or leg tenderness

Diuse myalgias or muscle weakness

3. Livedo reticularis

Mottled, reticular pattern over skin

4. Neuropathy

Mononeuropathy, mononeuropathy multiplex, or polyneuropathy

5. Testicular pain or tenderness

Not due to infection, trauma, or other causes

6. dBP >90 mmHg

Development of HTN with dBP >90 mmHg

7. Elevated Cr or BUN

Cr >130 mol/L (1.5 mg/dL), BUN >14.3 mmol/L (40 mg/dL)

8. Hepatitis B positive

Presence of hepatitis B surface antigen or Ab

9. Arteriographic abnormality

Commonly aneurysms

10. Biopsy of artery

Presence of granulocytes and/or mononuclear leukocytes in the artery wall

*Diagnosed if 3 or more of the above 10 criteria present American College of Rheumatology, 1990

Etiology and Pathophysiology • focal pan-mural necrotizing vasculitis in small and medium-sized arteries • thrombosis, aneurysm, or dilatation at lesion site may occur • healed lesions show proliferation of brous tissue and endothelial cells that may lead to luminal occlusion Clinical Presentation • systemic: fatigue, weight loss, weakness, fever, arthralgias • dermatologic: livedo reticularis, nodules, purpura, eruptions • renal: renal insuciency leading to HTN • neurologic: mononeuropathy multiplex in both motor and sensory nerves • abdominal: abdominal pain, mesenteric arteritis Investigations • blood work: CBC, CRP, Cr, BUN, urinalysis, liver enzymes, p-ANCA, hepatitis B and C serology • imaging: CT or MRI angiography shows beading appearance of blood vessels seen • biopsy of aected organ (e.g. skin, nerve); biopsy of highly vascular tissues (e.g. liver) not recommended due to risk of aneurysm rupture Treatment • PAN with no major organ manifestations ■ glucocorticoids ± azathioprine

Large Vessel Vasculitis RH22 Rheumatology

Toronto Notes 2023

• PAN with major organ manifestations (CNS, cardiac, GI, renal) ■ induction therapy with high-dose glucocorticoids + cyclophosphamide for 3-6 mo followed by maintenance therapy with low-dose prednisone and either azathioprine, MTX, or leunomide ■ treatment should be a minimum of 18 mo • hepatitis B virus-associated vasculitis ■ prednisone 1 mg/kg/d PO x7 d (then taper and withdraw by 14 d) ± methylprednisolone 15 mg/ kg/d IV x1-3 d ■ aer corticosteroid therapy, treat with plasma exchange + antiviral therapy

Large Vessel Vasculitis GIANT CELL ARTERITIS/TEMPORAL ARTERITIS Table 24. Classification Criteria for GCA* Criteria

Description

1. Age at onset ≥50 2. New H/A

Often temporal

3. Temporal artery abnormality

Temporal artery tenderness or decreased pulsations, not due to arteriosclerosis

4. Elevated ESR

ESR ≥50 mm/h

5. Abnormal artery biopsy

Mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells

GCA Criteria Presence of 3 or more criteria yields sensitivity of 94%, specificity of 91%

*Diagnosed if 3 or more of the above 5 criteria present American College of Rheumatology, 1990

Epidemiology • most common vasculitis in North America • patients >50 yr; peak incidence 70-80 yr • F:M=2:1 • north-south gradient (predominance in Northern Europe and US) • aects extracranial arteries Clinical Presentation • new onset temporal H/A ± scalp tenderness overlying temporal artery • sudden, painless loss of vision and/or diplopia due to narrowing of the ophthalmic or posterior ciliary arteries (PCA more common); can aect both eyes • tongue and jaw claudication (pain in muscles of mastication on prolonged chewing) • PMR (proximal pain and stiness, constitutional symptoms, elevated ESR) occurs in 30% of patients • aortic arch syndrome (involvement of subclavian and brachial branches of aorta resulting in pulseless disease), aortic aneurysm ± rupture are late complications • constitutional symptoms (e.g. fever of unknown origin in patients ≥65 yr) and shoulder/pelvic girdle pain and stiness Investigations • diagnosis made by clinical suspicion, increased ESR, increased CRP, colour Doppler U/S of temporal ± axillary arteries (+ halo sign), MRI, consider temporal artery biopsy Treatment • if suspect GCA, immediately start high-dose prednisone 1 mg/kg PO in divided doses for 2-4 wk, and then taper prednisone by 10 mg per 1-2 wk as symptoms resolve; highly eective in treatment and prevention of blindness and other vascular complications • consider low-dose ASA to help decrease visual loss • if presenting with vision loss at diagnosis, methylprednisolone 1000 mg/d IV for 3 d followed by highdose prednisone 1 mg/kg/d PO in divided doses for 4 wk • tocilizumab, an IL-6 receptor monoclonal antibody, has also been used in combination with glucocorticoids to treat GCA (new or relapsing) Prognosis • increased risk of thoracic aortic aneurysm and aortic dissection • yearly CXR ± abdominal U/S as screening

Medical Emergency If untreated, GCA can lead to permanent blindness in 20-25% of patients Treat on clinical suspicion

Seronegative Rheumatic Disease RH23 Rheumatology

Toronto Notes 2023

Seronegative Rheumatic Disease ReA

Table 25. A Comparison of the Spondyloarthropathies Feature

AS

PsA

ReA

EA

M:F

3:1

1:1

8:1

1:1

Age of Onset

20s

35-45

20s

Any

Peripheral Arthritis

25%

96%

90%

Common

Distribution

Axial, large joints

Any

LE*

LE*

Sacroiliitis

100%

40%

80%

20%

Dactylitis

Uncommon

Common

Occasional

Uncommon

Enthesitis

Common

Common

Common

Less Common

Skin Lesions

Rare

100% Eventually psoriasis, 70% at onset of arthritis

Occasional Keratoderma blennorrhagica

Occasional Pyoderma, erythema nodosum

Uveitis

Common

Occasional

20%

Rare

Urethritis

Rare

Uncommon

Common

Rare

HLA-B27

90-95%

40%

80%

30%

*LE = lower extremities

AS PsA

EA U-SpA

Figure 10. Spondyloarthropathy subsets

AS shares some features with the other three types of seronegative spondyloarthropathies such as ReA, EA, PsA, and U-sPA

Ankylosing Spondylitis Definition • chronic inammatory arthritis involving the sacroiliac joints and vertebrae • enthesitis is a major feature (e.g. Achilles tendinitis, plantar fasciitis) • prototypical spondyloarthropathy

Consider AS in the dierential for causes of aortic regurgitation

Table 26. ASAS Classification Criteria for Axial Spondyloarthritis* 1. Back pain of any type for at least 3 mo and age of onset 5 cm at T4), cervical (global decrease, oen extension rst) ■ postural changes: decreased lumbar lordosis + increased thoracic kyphosis + increased cervical exion = increased occiput to wall distance (>5 cm) • peripheral ■ asymmetrical large joint arthritis, most oen involving lower limb ■ enthesitis: tenderness over tibial tuberosity, or Achilles tendon and plantar fascia insertions into the calcaneus ■ dactylitis: toes or ngers • extra-articular manifestations ■ ophthalmic: acute anterior uveitis is common (25-30% patients) ■ renal: amyloidosis (late and rare), IgA nephropathy ■ gastrointestinal: IBD ■ cardiac: aortitis, aortic regurgitation, pericarditis, conduction disturbances, heart failure (rare) ■ respiratory: apical brosis (rare) ■ neurologic: cauda equina syndrome (rare) ■ skin: psoriasis Investigations • x-ray of SI joint: “pseudowidening” of joint due to erosion with joint sclerosis → bony fusion (late), symmetric sacroiliitis • x-ray of spine: “squaring of edges” from erosion and sclerosis on corners of vertebral bodies (shiny corner sign) leading to ossication of outer bres of annulus brosis (bridging syndesmophytes) → “bamboo spine” radiographically • MRI of spine: assess activity in early disease; detection of cartilage changes, bone marrow edema, bone erosions, and subchondral bone changes. Best seen on T2 short tau inversion recovery (STIR) images (suppress fat and see bone edema) • labs: CBC, elevated ESR/CRP, ALP, Ca 2+ , serum protein electrophoresis (SPEP), BMD, HLA-B27 Treatment • non-pharmacological therapy ■ prevent fusion from poor posture and disability through: exercise (e.g. swimming), postural and deep breathing exercises, outpatient PT, and smoking cessation • pharmacological therapy ■ NSAIDs (rst line of treatment for peripheral and axial disease) ■ glucocorticoids (topical eye drops, local injections, occasionally require systemic steroids prior to other eective Rx) ■ DMARDs only for peripheral arthritis (SSZ, MTX) ■ if inadequate response to two NSAIDs (or DMARD for peripheral arthritis only), consider antiTNF agents or anti-IL-17 for axial and peripheral involvement ■ manage extra-articular manifestations • surgical therapy ■ hip replacement and vertebral osteotomy for marked deformity (latter rarely performed) Prognosis • spontaneous remissions and relapses are common and can occur at any age • function may be excellent despite spinal deformity • favourable prognosis if female and age of onset >40 yr • early onset with hip disease may lead to severe disability; may require arthroplasty

Cervical lordosis Thoracic kyphosis Lumbar lordosis Sacral kyphosis ANKYLOSING SPONDYLITIS Increased occiput to wall distance Increased cervical flexion Increased thoracic kyphosis Decreased lumbar lordosis © Cassandra Cetlin

Figure 12. AS postural change

FABER (Flexion, ABduction, and External Rotation) Test Passively flex, abduct, then gently externally rotate the leg. If pain is elicited during this movement, the location of the pain may help determine the location of the patient’s pathology (e.g. hip joint, SI joint). However, it is poorly reproducible and inaccurate in discerning inflammatory vs. mechanical back pain

Modified Schöber Test • Patient must be standing erect with normal posture • Mark an imaginary horizontal line connecting both posterior superior iliac spines (close to the dimples of Venus) • A mark is placed 10 cm above this horizontal line, and another 5 cm below • The patient bends forward maximally: measure the dierence between these two points • Report the increase (in cm to the nearest 0.1 cm) • The better of two tries is recorded

Extra-Articular Manifestations of AS 5 As Anterior uveitis Apical lung fibrosis Aortic incompetence Amyloidosis (kidneys) Autoimmune bowel disease (ulcerative colitis)

Enteropathic Arthritis RH25 Rheumatology

Toronto Notes 2023

Enteropathic Arthritis Definition • see Gastroenterology, Inammatory Bowel Disease, G22 Clinical Presentation • MSK manifestations in the setting of either ulcerative colitis (UC) or Crohn’s disease (CD) include peripheral arthritis (large joint, asymmetrical), spondylitis, and hypertrophic osteoarthropathy • non-arthritic MSK manifestations can occur secondary to steroid treatment of bowel inammation (arthralgia, myalgia, osteoporosis, AVN)

Both AS and EA feature symmetric sacroiliitis

Table 28. Comparing Features of Spondylitis vs. Peripheral Arthritis in EA Parameter

Spondylitis

Peripheral Arthritis

HLA-B27 Association

Yes

No

Gender

M>F

M=F

Onset Before IBD

Yes

No

Parallels IBD Course

No

Yes

Type of IBD

UC=CD

CD

Treatment

NSAIDs (use cautiously, may exacerbate bowel disease); TNF inhibitors if resistant

NSAIDs, DMARDs; TNF inhibitors if resistant

Psoriatic Arthritis Definition • arthritic inammation associated with psoriasis Etiology and Pathophysiology • unclear but many genetic, immunologic, and some environmental factors involved (e.g. bacterial, viral, and trauma) Epidemiology • psoriasis aects 1% of the population • arthropathy in 15% of patients with psoriasis • 15-20% of patients will develop joint disease before skin lesions appear Clinical Presentation • dermatologic ■ psoriasis: well-demarcated erythematous plaques with silvery scale ■ psoriatic nail changes (potential predictor for PsA): pitting, transverse or longitudinal ridging, discolouration, subungual hyperkeratosis, onycholysis, and oil drops • musculoskeletal ■ 5 general patterns ◆ asymmetric oligoarthritis (30 min (50%) • ophthalmic ■ conjunctivitis, iritis (anterior uveitis) • cardiac and respiratory (late ndings) ■ aortic insuciency ■ apical lung brosis • neurologic ■ cauda equina syndrome • radiologic ■ oating syndesmophytes ■ pencil-in-cup appearance at IPs ■ osteolysis, periostitis Treatment • treat skin lesions (e.g. steroid cream, salicylic and/or retinoic acid, tar, UV light) • NSAIDs and/or IA steroids (as an adjuvant), benet should be seen within a few wk, should not be the sole therapy >3 mo • DMARDs to minimize erosive disease (use early in peripheral joint involvement) ■ non-biologic DMARDs (MTX, SSZ, or leunomide) ■ biologic therapies include anti-TNF agents, anti-IL-17 (secukinumab), and anti-IL-12/23 (ustekinumab)

Check “hidden” areas for psoriatic lesions (ears, hairline, umbilicus, gluteal cleft, nails) TNF inhibitors are eective treatments for PsA with no important added risks associated with their short-term use

Reactive Arthritis RH26 Rheumatology

Toronto Notes 2023

Table 29. CASPAR Criteria for PsA* Criterion

Description

1. Evidence of psoriasis

Current, past, or family history

2. Psoriatic nail dystrophy

Onycholysis, pitting, hyperkeratosis

3. Negative results for RF

Preferably by ELISA, nephelometry

4. Dactylitis

Current or past history

5. Radiological evidence

Juxta-articular bone formation on hand or foot x-rays

*To meet the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria, a patient must have inflammatory articular disease (joint, spine, or entheseal) with ≥3 points from the above 5 categories. Arthritis Rheum 2006 Aug;54(8):2665-2673. Classification criteria for PsA development

Reactive Arthritis Definition • one of the seronegative spondyloarthropathies in which patients have a peripheral arthritis (≥1 mo duration) accompanied by one or more extra-articular manifestations that appears shortly aer certain infections of the GI or GU tract • this term should not be confused with rheumatic fever or viral arthritides Etiology • onset following an infectious episode either involving the GI or GU tract ■ GI: Shigella, Salmonella, Campylobacter, Yersinia, C. dicile species ■ GU: Chlamydia (isolated in 16-44% of ReA cases), Mycoplasma species • acute clinical course ■ onset 1-4 wk post-infection ■ lasts wk to mo ■ oen recurring ■ spinal involvement persists Epidemiology • in HLA-B27 patients, axial > peripheral involvement • M>F Clinical Presentation • musculoskeletal ■ asymmetric peripheral arthritis, spondylitis/sacroiliitis, enthesitis (Achilles tendinitis, plantar fasciitis), dactylitis • ophthalmic ■ iritis (anterior uveitis), conjunctivitis • dermatologic ■ keratoderma blennorrhagicum (hyperkeratotic skin lesions on palms and soles) and balanitis circinata (small, shallow, painless ulcers of glans penis and urethral meatus) are diagnostic • gastrointestinal ■ oral ulcers, diarrhea • genitourinary ■ urethritis, prostatitis, cervicitis, cystitis, sterile pyuria; presence not related to site of initiating infection Investigations • diagnosis is clinical plus laboratory • evidence of antecedent or concomitant infection (stool culture, urine, and genital swab testing) • blood work: normocytic, normochromic anemia, and leukocytosis • sterile cultures • serology: HLA-B27 positive, elevated ESR/CRP Treatment • antibiotics for non-articular infections • NSAIDs (naproxen 500 mg BID/TID, diclofenac 50 mg TID, indomethacin 50 mg TID/QID), PT, exercise • local therapy ■ IA steroid injection (triamcinolone acetonide) ■ topical steroid for ocular involvement • systemic therapy ■ corticosteroids (starting dose 20 mg/d) ■ DMARDs (for refractory reactive arthritis with peripheral joint involvement only) (SSZ, MTX) ■ TNF-α inhibitors for spinal inammation (for disease refractory to NSAIDs, DMARDs)

Clinical Triad of Reactive Arthritis • Arthritis • Conjunctivitis/uveitis • Urethritis/cervicitis

“Can’t See, Can’t Pee, Can’t Climb a Tree” T riad of conjunctivitis, urethritis, and arthritis is 99% specific (but 51% sensitive) for ReA

Crystal-Induced Arthropathies RH27 Rheumatology

Toronto Notes 2023

Prognosis • self-limited, typically 3-5 mo, varies based on pathogen and patient’s genetic background • chronic in 15-20% of cases

Crystal-Induced Arthropathies Parameter

Gout

Pseudogout

Gender

M>F

M=F

Age

Middle-aged males Post-menopausal females

Usually elderly

Onset of Disease

Acute Acute Can become chronic if high uric acid untreated, Chondrocalcinosis is asymptomatic but the clinical feature is generally acute people with renal failure, kidney transplant

Crystal Type

Monosodium urate Negative birefringence (yellow when parallel to compensator filter), needle-shaped

CPPD Positive birefringence (blue when parallel), rhomboid-shaped

Distribution

First MTP classically; also midfoot, ankle, knee, or polyarticular

Knee, wrist; monoarticular, or polyarticular if chronic

Radiology (note findings are nonspecific)

Erosions

Chondrocalcinosis OA (knee, wrist, 2nd and 3rd MCP)

Treatment

Acute: NSAIDs, corticosteroids, colchicine Chronic: ± allopurinol, febuxostat

NSAIDs, corticosteroids

• 1st MTP = podagra • Ankle • Knee

© Jerry Won, after Linda Colati

Table 30. Gout vs. Pseudogout

Figure 13. Common sites of involvement of gout (asymmetric joint involvement)

Gout Definition • derangement in purine metabolism resulting in hyperuricemia; monosodium urate crystal deposits in tissues (tophi) and synovium (microtophi) Etiology and Pathophysiology • uric acid can be obtained from the diet or made endogenously by xanthine oxidase, which converts xanthine to uric acid • an excess of uric acid results in hyperuricemia • uric acid can deposit in the skin/subcutaneous tissues (tophi), synovium (microtophi), and kidney, where it can crystalize to form monosodium urate crystals that lead to gout • non-modiable risk factors include: genetic mutations, male gender, and advanced age • modiable risk factors include: diet (alcohol, purine rich foods such as meats and seafoods, fructose/ sugar sweetened foods; see list of precipitants below) • other risk factors: renal failure, metabolic syndrome, dehydration (e.g. diuretics) Clinical Presentation • single episode progressing to recurrent episodes of acute inammatory arthritis • acute gouty arthritis ■ severe pain, erythema, joint swelling, usually involving lower extremities ■ joint mobility may be limited ■ attack will subside spontaneously within d to wk (5-10 d); may recur • tophi ■ urate deposits on cartilage, tendons, bursae, so tissues, and synovial membranes ■ common sites: rst MTP, ear helix, olecranon bursae, tendon insertions (common in Achilles tendon) • kidney ■ gouty nephropathy ■ uric acid nephrolithiasis Investigations • joint aspirate: >90% of joint aspirates show crystals of monosodium urate (negatively birefringent, needle-shaped) if done early in course of presentation • x-rays may show tophi as so tissue swelling, bone/joints - punched-out lesions, erosion with “overhanging” edge ■ U/S shows double-contour sign • correlated with hyperuricemia in the blood Treatment • acute gout ■ NSAIDs: high-dose, then taper as symptoms improve ■ corticosteroids: IA, oral, or IM (if renal, cardiovascular, or GI disease and/or if NSAIDs contraindicated or failed). IV for patients with multiple joints aring, unable to take oral medication, and already have IV line ■ colchicine 1.2 mg at the rst signs of an attack followed by 0.6 mg 1 h later and 0.6 mg BID on subsequent days until the attack has resolved

An acute gout attack may mimic cellulitis; however, joint mobility is usually preserved in cellulitis unless it overlaps a joint

Precipitants of Gout Drugs are FACT Furosemide Aspirin ® (low-dose)/Alcohol Cyclosporine Thiazide diuretics Foods are SALT Seafood Alcohol (beer and spirits) Liver and kidney Turkey (meat)

2020 American College of Rheumatology Guideline for the Management of Gout Arthritis Rheumatol 2020;72:879-95 • Initiate urate lowering therapy (ULT) for patients with: • ≥1 SC tophi • Radiographic damage attributable to gout • Frequent gout flares (≥2/yr) • Allopurinol is preferred over all other ULTs as a firstline agent for all patients (including CKD stage ≥3) • Initiate concomitant anti-inflammatory prophylaxis (e.g. colchicine, NSAIDs, prednisone/prednisolone) for 3-6 mo • Continue ULT to target and maintain serum urate 50 yr, bilateral shoulder aching, and abnormal ESR/CRP Points without U/S (0-6)

Points with Abnormal U/S** (0-8)

Morning stiness duration >45 min

2

2

Hip pain or limited ROM

1

1

Absence of RF or ACPA

2

2

Absence of other joint involvement

1

1

At least one shoulder with subdeltoid and/or biceps tenosynovitis and/or glenohumeral synovitis (either posterior or axillary) and at least one hip with synovitis and/or trochanteric bursitis on U/S

N/A

1

Both shoulders with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis on U/S

N/A

1

*A score of 4 or more is categorized as PMR in the algorithm without U/S and a score of 5 or more is categorized as PMR in the algorithm with U/S **Optional U/S criteria Ann Rheum Dis 2012;71:484-492

Epidemiology • incidence: 50 in 100000 per yr in those >50 yr • age of onset typically >50 yr, F:M=2:1 Clinical Presentation • constitutional symptoms prominent (fever, weight loss, malaise) • pain and stiness of symmetrical proximal muscles (neck, shoulder and hip girdles, thighs) • gel phenomenon (stiness aer prolonged inactivity) • physical exam reveals tender muscles, but no true weakness or atrophy Investigations • blood work: oen shows anemia of chronic disease, elevated platelets, elevated ESR and CRP, and normal CK; up to 5% of PMR reported with normal inammatory markers Treatment • goal of therapy: symptom relief • start with prednisone 12.5-25 mg PO once daily, reconsider diagnosis if no response within several days • taper slowly with improvement over 1 yr period with close monitoring, if in remission taper until discontinued • relapses should be diagnosed and treated on clinical basis; do not treat a rise in ESR as a relapse • treat relapses aggressively (50% relapse rate) • monitor for steroid side eects, glucocorticoid-induced osteoporosis prevention, and follow for symptoms of GCA

Fibromyalgia Definition • chronic (>3 mo), widespread (axial, le- and right-sided, upper and lower segment), non-articular pain with characteristic tender points Diagnosis Table 32. 2010 ACR Preliminary Diagnostic Criteria for Fibromyalgia Criteria

Comments

Widespread Pain Index = number of areas in which the patient had pain A patient satisfies diagnostic criteria for fibromyalgia if the following 3 over the last wk (max score = 19): conditions are met: L and R: shoulder girdle, upper arm, lower arm, hip, upper leg, lower 1. Widespread Pain Index (WPI) ≥7 and SS score ≥5 or WPI 3-6 and leg, jaw SS score ≥9 One Area: chest, abdomen, upper back, lower back, neck 2. Symptoms have been present at a similar level for at least 3 mo 3. The patient does not have a disorder that would otherwise explain Symptom Severity (SS) Score = sum of: the pain a) severity of fatigue b) waking unrefreshed c) cognitive symptoms over the past wk d) extent of somatic symptoms (IBS, H/A, abdominal pain/cramps, dry mouth, fever, hives, ringing in ears, vomiting, heartburn, dry eyes, SOB, loss of appetite, rash, hair loss, easy bruising, etc.) All (a-d) rated on 0-3 scale: 0 = no problem, 1 = mild, 2 = moderate, 3 = severe Arthrit Care and Res 2010;62(5):600-610

RH30 Rheumatology

Toronto Notes 2023

Epidemiology • F:M=3:1 • primarily ages 25-45, some adolescents • prevalence of 2-5% in general population • overlaps with chronic fatigue syndrome and myofascial pain syndrome • strong association with psychiatric illness Clinical Presentation • widespread aching, stiness • easy fatigability • sleep disturbance: non-restorative sleep, diculty falling asleep, and frequent wakening • symptoms aggravated by physical activity, poor sleep, emotional stress • patient feels that joints are diusely swollen although joint examination is normal • neurologic symptoms of hyperalgesia, paresthesias, allodynia • associated with irritable bowel or bladder syndrome, migraines, tension H/As, restless leg syndrome, obesity, depression, and anxiety • physical exam should reveal only tenderness with palpation of so tissues, with no specicity for trigger/tender points Investigations • blood work: includes TSH; all typically normal unless unrelated, underlying illness present • serology: do not order ANA or RF unless there is clinical suspicion for a CTD or inammatory arthritis • laboratory sleep assessment Treatment • non-pharmacological therapy ■ graded exercise programs including aerobic (>20 min/d, 2-3 d/wk) and resistance training (>8 repetitions per exercise, 2-3 d/wk) ■ other therapies with some evidence: acupuncture, CBT, hydrotherapy, meditative movement (yoga, Tai chi) ■ there is no evidence for biofeedback, chiropractics, hypnotherapy, meditation • pharmacological therapy (to help with symptoms, not curative) ■ low-dose tricyclic antidepressant (e.g. amitriptyline) ◆ for sleep restoration ◆ select those with lower anticholinergic side eects ■ SNRI: duloxetine, milnacipran ■ anticonvulsant: pregabalin, gabapentin ■ analgesics may be benecial for pain that interferes with sleep (NSAIDs, not narcotics) Prognosis • variable; usually chronic, waxes and wanes, with some pain and fatigue that usually persists Table 33. Clinical Features of Inflammatory Myopathy vs. Polymyalgia Rheumatica vs. Fibromyalgia Polymyositis

PMR

Epidemiology

F>M, 40-50 yr

F>M, >50 yr

Fibromyalgia F>M, 25-45 yr

Muscle Involvement

Proximal muscle

Proximal muscle

Diuse

Weakness

Yes

No

No

Pain

Painless

Painful

Painful

Stiness

Present

Significant morning and gelling stiness (shoulders, neck, hips)

May have morning stiness

Investigations

Muscle biopsy, CK, EMG, rule out malignancy

ESR/CRP, rule out GCA

Sleep assessment, TSH

ESR/CRP

Usually normal

Markedly elevated

Normal

Treatment

High-dose steroids, immunosuppressants

Low-dose steroids

Exercise, sleep restoration

Common Medications RH31 Rheumatology

Toronto Notes 2023

Common Medications Table 34. Common Medications for Osteoarthritis Class

Generic Drug Trade Name Name

Dosing (PO)

Indications

Contraindications

Adverse Eects

Analgesics

acetaminophen

Tylenol®

1000 mg TID q4 h (3 g daily max)

1st line

Severe liver disease/ impairment

Hepatotoxicity, overdose, potentiates warfarin

NSAIDs

ibuprofen diclofenac diclofenac/ misoprostol naproxen meloxicam

Advil® Voltaren® Arthrotec® Naprosyn® Aleve® Mobicox®

200-600 mg TID 25-50 mg TID 50-75/200 mg TID 125-500 mg BID 7.5-15 mg once daily

2nd line

GI bleed, renal impairment, allergy to ASA, NSAIDs, pregnancy (T3), anticoagulants

Nausea, tinnitus, vertigo, rash, dyspepsia, GI bleed, PUD, hepatitis, renal failure, HTN, nephrotic syndrome

COX-2 Inhibitors

celecoxib

Celebrex®

200 mg once daily Dyspepsia/GERD

Renal impairment, cardiovascular disease, GI Bleed

Same as NSAIDs above

Other Treatments

Comments

Combination analgesics (acetaminophen + codeine, acetaminophen + NSAIDs)

Enhanced short-term eect compared to acetaminophen alone More adverse eects: sedation, constipation, nausea, GI upset

IA corticosteroid injection

Short-term (wk-mo), joint specific treatment Decrease in pain and improvement in function Used for management of an IA inflammatory process when infection has been ruled out

IA hyaluronic acid q6 mo

Used for mild-moderate OA of the knees; however, little supporting evidence and not considered to be eective Precaution with chicken/egg allergy

Topical NSAIDs

Topical diclofenac (Pennsaid®, Voltaren Emulgel®) May use for patients who fail acetaminophen treatment and who wish to avoid systemic therapy, better on small joints

Capsaicin cream

Mild decrease in pain

Glucosamine sulfate ± chondroitin

Limited evidence of benefit in OA knee. No regulation by Health Canada

Table 35. DMARDs Generic Drug Name

Trade Name

Dosing

Contraindications

Adverse Eects

hydroxychloroquine $

Plaquenil®

400 mg PO once daily Retinal disease, G6PD initially deficiency 200-400 mg PO once daily maintenance (5 mg/kg ideal body weight per day to a maximum of 400 mg/d)

GI symptoms, skin rash, macular damage, neuromyopathy Requires annual ophthalmological screening to monitor for retinopathy

sulfasalazine $

Salazopyrim® Azulfidine® (US)

1000 mg PO BID-TID

Sulfa/ASA allergy, kidney disease, G6PD deficiency

GI symptoms, rash, H/A, leukopenia

methotrexate $

Rheumatrex® Folex/Mexate®

7.5-25 mg PO/SC weekly

Bone marrow suppression, liver disease, significant lung disease, immunodeficiency, pregnancy, EtOH use

Oral ulcers, GI symptoms, cirrhosis, myelosuppression, pneumonitis, tubular necrosis

leflunomide $$

Arava®

10-20 mg PO once daily Liver disease, lung disease, Alopecia, GI symptoms, liver pregnancy dysfunction, interstitial pulmonary fibrosis, HTN

cyclosporine $$

Neoral®

2.5-3 mg/kg/d divided Kidney/liver disease, and given in 2 doses PO infection, HTN

HTN, decreased renal function, hair growth, tremors, bleeding

gold (injectable) $

Solganal® Myochrysine®

50 mg IM weekly after gradual introduction

IBD, kidney/liver disease

Rash, mouth soreness/ulcers, proteinuria, marrow suppression

azathioprine $

Imuran®

2 mg/kg/d PO once daily

Kidney/liver disease Rash, pancytopenia (especially ↓ WBC, ↑ AST, ALT), biliary stasis, thiopurine S-methyltransferase (TPMT) vomiting, diarrhea deficiency

cyclophosphamide $

Cytoxan®

1 g/m/mo IV as per protocol

Kidney/liver disease, neutropenia

COMMONLY USED

NOT COMMONLY USED

Cardiotoxicity, GI symptoms, hemorrhagic cystitis, nephrotoxicity, bone marrow suppression, sterility, bladder cancer

Landmark Rheumatology Trials RH32 Rheumatology

Toronto Notes 2023

Table 35. DMARDs Generic Drug Name

Trade Name

Dosing

Contraindications

Adverse Eects

etanercept $$$

Enbrel®

25 mg biweekly or 50 mg weekly SC

Fusion protein of TNF receptor and Fc portion of lgG

infliximab $$$

Remicade®

3-5 mg/kg IV q8 wk

Chimeric mouse/human monoclonal anti-TNF

adalimumab $$$

Humira®

40 mg SC q2 wk

Monoclonal anti-TNF

golimumab $$$

Simponi®

50 mg SC q1 mo or 2 mg/kg q8 wk

Monoclonal anti-TNF

certolizumab $$$

Cimzia®

400 mg SC q2 wk x3 then 200 mg SC q4 wk

PEGylated monoclonal anti-TNF

apremilast $$$

Otezla®

Day 1: 10 mg (AM) PO, titrate up to 30 mg BID by day 6

PDE4 inhibitor which reduces production of TNF-α

abatacept $$$

Orencia®

500-1000 mg IV infusion q1 mo or 125 mg SC q1 wk

Costimulation modulator of T cell activation

rituximab $$$

Rituxan®

1 g x2 IV infusions, 2 wk Causes B cell depletion, binds to CD20 apart q6 mo

tocilizumab $$$

Actemra®

4-8 mg/kg IV q4 wk or 162 mg SC q1-2 wk

IL-6 receptor antagonist

tofacitinib $$

Xeljanz®

5 mg BID

Selective JAK 1/3 inhibitor and thus interferes with JAK-STAT signaling pathway

upadacitinib $$

Rinvoq®

15 mg once daily

Selective JAK1 inhibitor and thus interferes with JAK-STAT signaling pathway

secukinumab $$$

Cosentyx®

150 mg monthly

Blocks IL-17A

NEWER DMARDs (Biologics)

Landmark Rheumatology Trials Trial Name

Reference

Clinical Trial Details

COMET

Lancet 2008;372:375-82

Title: Comparison of Methotrexate Monotherapy with a Combination of Methotrexate and Etanercept in Active, Early, Moderate to Severe Rheumatoid Arthritis (COMET): A Randomised, Double-Blind, Parallel Treatment Trial Purpose: To compare the ecacy of MTX monotherapy or MTX plus etanercept for remission and radiographic non-progression in RA patients. Methods: 542 RA MTX-naive outpatients with moderate-to-severe disease for 3-24 mo were randomly assigned to MTX alone (titrated from 7.5-20 mg/wk) or MTX (same titration) plus etanercept 50 mg/wk. Results: Clinical remission was achieved in 50% of patients on combined treatment vs. 28% taking MTX alone (dierence, 22.05%; P7, or PSA >20 ng/mL) • CT scanning to assess metastases • MRI: being investigated for possible role in detection, staging, MRI-guided biopsy, and active surveillance Table 18. 2018 TNM Classification of Prostate Carcinoma (AJCC 8th edition) T

N

M

TX: primary tumour cannot be assessed

NX: regional lymph nodes were not assessed

M0: no distant metastasis

T0: no evidence of primary tumour

N0: no regional lymph node metastasis

T1: clinically undetectable tumour, normal DRE and TRUS T1a: tumour incidental histologic finding in 5% of tissue resected T1c: tumour identified by needle biopsy (due to elevated PSA level)

N1: spread to regional lymph nodes

cM1: distant metastasis cM1a: nonregional lymph nodes cM1b: bone(s) cM1c: other site(s) with or without bone disease

N Sux (sn): regional lymph node metastasis identified by SLN biopsy only (f): regional lymph node metastasis identified by FNA or core needle biopsy only

T2: palpable, confined to prostate T2a: tumour involving ≤ one half of one lobe T2b: tumour involving > one half of one lobe, but not both lobes T2c: tumour involving both lobes

pM1: distant metastasis, microscopically confirmed pM1a: nonregional lymph nodes, microscopically confirmed pM1b: bone(s) microscopically confirmed pM1c: other site(s) with or without bone disease, microscopically confirmed

T3: tumour extends through prostate capsule T3a: extracapsular extension (unilateral or bilateral) T3b: tumour invading seminal vesicle(s) T4: tumour invades adjacent structures (besides seminal vesicles) T Prefix (c): clinical T (p): pathological T. There is no pathological T1 T Sux (m): synchronous primary tumours are found in single organ

Table 19. Prostate Cancer Mortality Risk Low-Risk (if any of following)

Intermediate-Risk (if any of following)

High-Risk (if any of following)

PSA

20

Gleason Score

0 ■ requires hormonal therapy/palliative radiotherapy for metastases; may consider combined androgen blockade ■ bilateral orchiectomy – decreases testosterone production by 90% ■ GnRH agonists (e.g. leuprolide, goserelin), see Table 28, U47, GnRH antagonist (e.g. degarelix) ■ antiandrogens (e.g. bicalutamide) ■ local irradiation of painful secondaries or half-body irradiation • CRPC ■ ADT should be maintained ■ non-metastatic CRPC: observation vs. apalutamide, enzalutamide, or darolutamide ■ metastatic CRPC: abiraterone, enzalutamide, docetaxel-based chemotherapy ◆ post-docetaxel: second-line chemotherapy cabazitaxel ◆ if symptomatic without visceral metastases: radium-223 ◆ HRR mutation: olaparib ◆ bone metastases: denosumab and/or zoledronic acid is recommended ± palliative radiation Table 20. Treatment Options for Localized Prostate Cancer Modality

Population Considered

Limitations

Watchful Waiting

Short life expectancy ( inguinal ■ surgical correction facilitates testicular monitoring and may reduce malignancy risk • increased risk of testicular torsion (reduced by surgical correction)

Disorders of Sexual Dierentiation Definition • formerly known as intersex disorders: considered social emergency • abnormal genitalia for chromosomal sex due to the undermasculinization of males or the virilization of females Classification 1. 46 XY DSD ■ defect in testicular synthesis of androgens ■ androgen resistance in target tissues ■ palpable gonad 2. 46 XX DSD ■ most due to CAH (21-hydroxylase deciency most common enzymatic defect) → shunt in steroid biosynthetic pathway leading to excess androgens

A phenotypic male newborn with bilateral non-palpable testicles should be considered 46 XX with salt-wasting CAH and must undergo proper evaluation prior to discharge

Enuresis U43 Urology

■ undiagnosed and untreated CAH can be associated with life-threatening electrolyte abnormalities in the newborn (salt-wasting CAH) 3. ovotesticular DSD 4. mixed gonadal dysgenesis (46 XY/45 XO most common karyotype) ■ presence of Y chromosome → partial testis determination to varying degrees Diagnosis • thorough FMHx noting any consanguinity • maternal Hx, especially medication/drug use during pregnancy (maternal hyperandrogenemia) • P/E: palpable gonad (= chromosomal male), hyperpigmentation, evidence of dehydration, HTN, stretched phallus length, position of urethral meatus • laboratory tests ■ plasma 17-OH-progesterone (aer 36 h of life) → increased in CAH ■ plasma 11-deoxycortisol → increased in 11-β-hydroxylase deciency ■ basal adrenal steroid levels ■ serum testosterone and DHT pre- and post-hCG stimulation (2000 IU/d for 4 d) ■ serum electrolytes ■ chromosomal evaluation including sex karyotype • U/S of adrenals, gonads, uterus, and fallopian tubes • endoscopy and genitography of urogenital sinus Treatment • steroid supplementation as indicated (e.g. CAH) • sex assignment aer extensive family consultation ■ must consider capacity for sexually functioning genitalia in adulthood, fertility potential, and psychological impact • reconstruction of external genitalia between 6 and 12 mo • long-term psychological guidance and support for both patient and family

Enuresis • see Paediatrics, P11

Bladder and Bowel Dysfunction Definition • bladder and bowel dysfunction describes voiding and defecation symptoms without a neurogenic or anatomic cause Clinical Features • storage symptoms (urgency, frequency, urge incontinence) • voiding symptoms (hesitancy, slow ow, intermittency) • gastrointestinal symptoms (constipation and encopresis) Treatment • stool soeners (i.e. polyethylene glycol 3350) • urotherapy and bladder retraining • pelvic oor physiotherapy • anticholinergics (solifenacin, propiverine, tolterodine) • neuromodulation via transcutaneous electrical nerve stimulation

Selected Urological Procedures Bladder Catheterization • catheter size measured by the French (Fr) scale – circumference in mm (30 Fr = 1 cm diameter) • each 1 mm increase in diameter = approximately 3 Fr increase (standard size 14-18 Fr) • should be removed as soon as possible to reduce the risk of UTI Continuous Catheterization • indications ■ accurate monitoring of U/O ■ relief of urinary retention due to medication, neurogenic bladder, or intravesical obstruction ■ temporary therapy for urinary incontinence ■ perineal wounds ■ clot prevention (22-24 Fr) for CBI ■ intra- and postoperative ■ comfort for end of life care

Toronto Notes 2023

Circumcision U44 Urology

Toronto Notes 2023

Alternatives to Continuous Catheterization • intermittent catheterization ■ PVR measurement ■ to obtain sterile diagnostic specimens for U/A, urine C&S ■ management of neurogenic bladder or chronic urinary retention • condom catheter • suprapubic catheter

Robinson tip

Coudé tip

Causes of Dicult Catheterizations and Treatment • patient discomfort → use sucient lubrication (± xylocaine) • collapsing catheter → lubrication as above ± rmer or larger catheter (silastic catheter) • meatal/urethral stricture → dilate with progressively larger catheters/balloon catheter • traumatic injury: repeated prior attempts at catheterization have created traumatic false passage • BPH → use Coudé catheter as angled tip can help navigate around enlarged prostate (always angle up/ anteriorly) • urethral disruption/obstruction → liform and followers or suprapubic catheterization • anxious patient → anxiolytic medication

Inflation port

Urine Two-way Foley Inflation port

Contraindications • trauma: blood at the urinary meatus, scrotal hematoma, pelvic fracture, and/or high riding prostate

Circumcision Definition • removal of some or all of the foreskin from the penis Epidemiology • 30% worldwide • frequency varies with geography, religious aliation, socioeconomic status Medical Indications • pathological phimosis and recurrent paraphimosis • recurrent UTIs (particularly in infants and in association with other urinary abnormalities) • balanitis xerotica obliterans or other chronic inammatory conditions Contraindications • unstable or sick infant • congenital genital abnormalities (hypospadias, epispadias, penoscrotal webbing, concealed penis, ventral curvature); may need foreskin to aid in reconstruction • FMHx of bleeding disorders warrants investigation prior to circumcision Complications • early: bleeding, infection, glans injury, amputation, slippage of circumcision device, rarely death • late: redundant foreskin, cosmetic issues, inclusion cysts, adhesions/skin bridges, suture sinus tracts, ventral curvature, secondary buried penis, phimosis, stula, meatal stenosis • 0.6-2% complication rate

Vasectomy Objective • permanent form of contraception with high probability of reversibility • no-scalpel vasectomy has lower risks of early postoperative complications than conventional vasectomy • fascial interposition and cautery of the vas deferens reduce risk of contraceptive failure • post-vasectomy semen analyses at approximately 3 and 4 mo • other contraceptive methods should be used post-vasectomy until one azoospermic ejaculate or two consecutive ejaculates with 75%) ■ ED (5-10% risk increases with increasing use of cautery) ■ incontinence (0) Drug

Class

Mechanism

Adverse Eects

leuprolide, goserelin “androgen deprivation therapy”

GnRH agonist

Initially stimulates LH, increasing testosterone and causing “flare” (initially increases bone pain) Later causes low testosterone

Hot flashes Headache Decreased libido

degarelix

GnRH antagonist

Competitively binds to the pituitary gland GnRH receptors, thereby reducing the release of LH, FSH and consequently testosterone by testes

Back pain Breast enlargement Decreased libido Hot flashes Headache Slow or fast heartbeat

*cyproterone acetate

Steroidal antiandrogen

Competes with DHT for intracellular receptors: Prevent flare produced by GnRH agonist Use for complete androgen blockade May preserve potency

flutamide, bicalutamide

Non-steroidal antiandrogen

As above

Hepatotoxic: AST/ALT monitoring

abiraterone

Non-steroidal antiandrogen

Irreversible cytochrome P450 ( CYP) 17 inhibition, blocking synthesis of androgens in tumour, testis, and adrenal glands

Adrenal insuciency (concurrent treatment with steroids often required) Hypertriglyceridemia Peripheral edema

enzalutamide

Non-steroidal antiandrogen

Androgen receptor signaling inhibitor (full antagonist)

Peripheral edema Fatigue and weakness Hot flashes

*Very rarely used

Table 30. Continence Agents and Overactive Bladder Medications Drug

Class

Mechanism

Indication

Adverse Eects

oxybutynin

Antispasmodic

Inhibits action of acetylcholine on smooth muscle Decreases frequency of uninhibited detrusor contraction Diminishes initial urge to void

Overactive bladder Urge incontinence + urgency + frequency

Dry mouth Blurred vision Constipation Supraventricular tachycardia

oxybutynin tolterodine trospium solifenacin darifenacin fesoterodine propiverine

Anticholinergic

β-sympathetic receptor blocker in the bladder; relaxes bladder during storage phase

Overactive bladder Urge incontinence + urgency + frequency

As above

mirabegron

β 3 agonist

Sympathomimetic eects: Urinary sphincter contraction Anticholinergic eects: Detrusor relaxation

Overactive bladder Urge incontinence + urgency + frequency

Blood pressure should be monitored

imipramine

Tricyclic antidepressant

Prevents the release of neurotransmitters

Stress and urge incontinence

As above Weight gain Orthostatic hypotension Prolonged PR interval

Botulinum toxin A bladder injections

Neurotoxin

Prevents the release of neurotransmitters

Refractory OAB incontinence both neurogenic and non-neurogenic

Urinary retention, UTI

Note: All anticholinergics are equally eective and long-acting formulations are better tolerated. Newer muscarinic M3 receptor specific agents (solifenacin, darifenacin) are equally ecacious as older drugs, however, RCTs based on head-to-head comparison to long acting formulations are lacking

Landmark Urology Trials Trial Name

Reference

Clinical Trial Details

N Engl J Med 2003;349:215-224

Title: The Influence of Finasteride on the Development of Prostate Cancer Purpose: To determine whether the drug Finasteride (5-alpha reductase inhibitor) could prevent prostate cancer in men ages 55 and older. Methods: 18882 men 55 yr or older with a normal digital rectal examination and a (PSA) level equal to or less than 3.0 ng per milliliter were randomly to receive finasteride (5 mg per day) or placebo for 7 yr. Results: There was a 24.8% reduction in prostate cancer prevalence over the 7-yr period among the Finasteride arm compared to the placebo arm (95 % confidence interval, 18.6 to 30.6 percent; P