Text Book of Neonatal Ventilation [1 ed.]

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™

Text Book of Neonatal Ventilation

Chief Scientific Editor

Dr Amitava Sengupta

NEOCON 2017 37th Annual Convention of National Neonatology Forum- India Gurgaon (NCR), Haryana, India

™

Text Book of Neonatal Ventilation

Chief Scientific Editor

Dr Amitava Sengupta

NEOCON 2017 37th Annual Convention of National Neonatology Forum- India Gurgaon (NCR), Haryana, India

NEOCON 2017 37th Annual Convention of National Neonatology Forum- India Gurgaon (NCR), Haryana, India Office Bearers - National Neonatology Forum- India

Dr B D Bhatia President NNF

Dr Ajay Gambhir President NNF 2015 - 2016

Dr Alok Bhandari Hon. Secretary

Dr Lalan K Bharti Treasurer

Organizing and Scientific Committee – NEOCON 2017

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Dr N K Jain Patron

Dr M P Jain Convener

Dr N S Yadav Org. Chairman

Dr Sanjay Wazir Org. Chairman

Dr Amitava Sengupta Chairman, Workshop Committee

Dr Premalatha Krishnan Chairperson, Scientific Committee

Dr Ramesh Goyal Org. Secretary

Dr Ajay Arora Org. Secretary

Message from Team National Neonatology Forum (NNF), India Dear Esteemed Delegates and Friends, Greetings from NNF India ! It is our pleasure to invite you to the Preconference Workshops on Neonatal Ventilation at the 37th Annual Convention of National Neonatology Forum- India (NEOCON 2017) being held at Gurgaon, NCR, Haryana, India on 7th December 2017. In the Ventilation workshops, we have for you an eminent Panel of International & National Faculty, with rich academic and clinical experience in the subject. The workshops aim to give you an overview and as well focus on the advances and salient aspects of Neonatal Ventilation in today’s context. Neonatal respiratory care comprises of a fascinating blend of basic sciences and clinical application, in one of the fastest growing areas in medicine. This has been facilitated by development of microprocessor based technology, which has dramatically changed the way we manage neonatal respiratory failure these days. Gone are the days when all infants placed on ventilators were handled in the same way. Clinicians now have a wide range of tools to customize management in a disease and infant specific manner. This exceptional manual on Neonatal Ventilation has been planned and prepared by our Chairman Workshop Committee, Dr Amitava Sengupta, a well known neonatologist and includes contributions of the highest level from our eminent International & National Faculty. Wishing you all the best for a wonderful and fruitful learning experience. Team NNF - India

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Message from Team NEOCON 2017 Dear Esteemed Delegates and Friends, Greetings from NEOCON 2017 ! It is our pleasure to invite you to the Preconference Workshops on Neonatal Ventilation at the 37th Annual Convention of National Neonatology Forum- India (NEOCON 2017) being held at Gurgaon, NCR, Haryana, India on 7th December, 2017. This year three separate Ventilation Workshops are being conducted in dedicated categories as given below a. Advanced Ventilation (HFO, Nitric Oxide & ECMO) b. Conventional Ventilation - The Art and Science & Lung Protective Strategies c. Non Invasive Ventilation CPAP and HHHFNC (Heated Humidified High Flow Nasal Cannula) Optimal respiratory management is of prime importance in Neonatal Intensive Care and we have now entered the age of evidence based medicine with rapid advances in techniques of respiratory support in newborns. This exceptional book on Neonatal Ventilation reflects changes in practice, equipment and science of respiratory support in neonatal medicine. It has been conceptualized and organized by our Chairman Workshop Committee, Dr Amitava Sengupta, a core neonatologist of repute. Our list of contributors represents a profound group of International and National luminaries in this field, who have given their valuable time for making of this book. Wishing you all the best for a very wonderful and fulfilling learning experience. Team NEOCON 2017 Gurgaon (NCR) India

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Preface The field of neonatology has seen some remarkable progress over the last four decades in care of the newborn. Improvements in outcome have mainly reflected from the major advances in respiratory care of the term and preterm infant. The vast progress in the knowledge and understanding of areas like development of the respiratory system, gas exchange during various phases of lung development, and alterations that can lead to respiratory failure and its complications have culminated in the enormous recent advances of today. This has considerably improved the quality of respiratory and ventilatory support being administered in neonatal intensive care units (NICUs) across the globe. This book aims to give an overview and as well focus on the salient areas and aspects of neonatal ventilation in today’s context. The contents of this book has been developed as a readily available source of information on various key aspects of neonatal respiratory care including principles of mechanical ventilation, diagnostic and therapeutic techniques, strategies for reducing ventilator induced lung injury and advances in care of a ventilated infant. Microprocessor based technology continues to refine equipments and offers us many new methods to manage neonatal respiratory failure. The contributors are a distinguished group of International and National health care professionals who are leaders in this field and it is sincerely hoped that the material contained in this volume will be helpful to all those who come into contact with neonatal intensive care units, including postgraduate students, residents and fellows, nurses, paediatricians and neonatologists. The user of this manual will best serve patients by recognizing that, optimal ventilatory management of infant blends accurate clinical assessment, effective technique, and a touch of the art of respiratory management. I am indebted to our eminent authors for taking the time and effort to provide their valuable insights and knowledge and enhancing the academic standard of the book. Dr Amitava Sengupta, Fellowship Neonatology (Neth) Director: Mother & Child Unit, Neonatology & Pediatrics Paras Hospitals, Gurgaon (NCR), India Chairperson & Executive Director Development and Supportive Care (DSC) Foundation for Newborn & Children (India) Chairman Workshop Committee: 37th Annual Convention of National Neonatology Forum (NEOCON 2017) National Assessor, NICU Accreditation Program (NNF-UNICEF) 2014. National Instructor, FBNC Program (NNF-UNICEF) 2014. National Faculty, NNF-IAP Advanced NRP 2010. Chief Advisor, 49th Annual National Conference of IAP (Pedicon 2012).

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Contributors List Ajay Lal, Fellowship Neonatology (NNF- India)

Naveen Gupta, MD, DNB Neonatology

Consultant, Division of Neonatology, Mother & Child Unit, Paras Hospitals, Gurgaon (NCR), India

Fellowship from BC Children Hospital, Vancouver, Canada Neonatologist and NICU Incharge, Senior Consultant - Neonatology Rainbow Children’s Hospital, New Delhi, India

Amitava Sengupta, Fellowship Neonatology (Neth) Director: Mother & Child Unit, Neonatology & Pediatrics Paras Hospitals, Gurgaon (NCR), India Chairperson & Executive Director Development and Supportive Care (DSC) Foundation for Newborn & Children (India) Chairman Workshop Committee: 37th Annual Convention of National Neonatology Forum (NEOCON 2017)

Anil Gupta, MD, Fellowship Neonatology Consultant, Neonatology, Little Stars Children’s Hospital, Hyderabad, India

N Karthik Nagesh, MD, FRCPCH (UK), FNNF Chairman, Manipal Advanced Children’s Centre (MACC),Manipal Hospital, Bangalore Chairman, Neonatology & NICUs, Manipal Hospitals Professor of Pediatrics (Adjunct), Manipal University

Pankaj B Agrawal, MD, MMSC Assistant Professor of Pediatrics, Harvard Medical School Staff Scientist, Division of Genetics and Genomics Medical Director, Gene Discovery Core, Manton Center for Orphan Disease Research, Boston Children’s Hospital Associate Member, Broad Institute of Harvard & MIT

Ashish Jain, MD, DM (Neonatology) Assistant Professor Department of Neonatology, LNJP & Allied Hospitals Maulana Azad Medical College, New Delhi, India

Ashish Mehta, MD, Fellowship Neonatology (Australia) Director, Arpan Newborn Care Center, Ahmedabad, India

Piyush Shah, MD, Fellowship Neonatology (Australia) Consultant Neonatology, Cloudnine Hospitals, Mumbai, India

Sanjay Wazir, MD, DM (Neonatology) Director: Neonatology, Cloudnine Hospitals, Gurgaon (NCR), India President: IAP Neonatology Chapter 2017 National Faculty: NNF-IAP Advanced NRP 2010

Avneet Kaur, MD, DNB Neonatology Senior Consultant & Incharge NICU Apollo Cradle, Moti Nagar, New Delhi, India

Satish Ghanta, MD

St. Petersburg State Pediatric Medical University, St. Petersburg, Russia

Neonatal Fellowship (Sydney, Aus) Bayley Scales Accredited Developmental Pediatrics (Sydney, Aus) Pediatric & Cardiac Intensive Care Fellowship (Sydney, Aus) Director – Neonatal & Pediatric Intensive Care Services Little Stars Children’s Hospital, Hyderabad, India

Gopal Agrawal, MD, DM (Neonatology)

Srinivas Murki, MD, DM (Neonatology)

Consultant: Neonatology, Cloudnine Hospitals Gurgaon (NCR), India

Director Neonatology, Fernadez Hospital, Hyderabad, India

D V Prometnoy, MD

I V Boronina, MD Voronezh State Medical University named after N.N. Burdenko, Russia Jay Kishore, MD, DNB (Neonatology) NICU In-charge Senior Consultant Neonatology & Pediatrics Max Super Specialty Hospital, Patparganj, New Delhi, India Kedar Sawleshwarkar, MD Fellowship Neonatology Director, Deogiri Children’s Hospital, Aurangabad, India Formerly - Associate Professor, Govt. Medical College, Aurangabad National Faculty NRP India National Instructor FBNC program

Manish Balde, Fellowship Neonatology (IAP) Consultant Neonatology, Cloudnine Hospitals, Gurgaon (NCR), India Megha Consul, MD, DNB, Pediatrics, Fellowship in Neonatal Perinatal Medicine, University of Western Ontario, Canada Consultant-Neonatalogy, Max Hospital, Gurgaon (NCR), India

Monika Kaushal, MD, DM (Neonatology) FRCPCH, UK Consultant -Neonatal -Perinatal Medicine Chief of Neonatology, Emirates Speciality Hospital, Dubai Health Care City Head of Department - Neonatology, Irani Hospital Dubai

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Suman Rao, MD, DM (Neonatology) Professor & Head, Department of Neonatology St. John’s Medical College & Hospital Bangalore, India

Surya Prakash, MD, Fellowship Neonatology Consultant, Neonatology, Little Stars Children’s Hospital, Hyderabad, India

T J Antony, MD, FRCPCH, UK Director & Head: Neonatology Fortis Memorial Research Institute, Gurgaon (NCR), India

Vladimiras Chijenas, MD Consultant Neonatologist, Neonatal Division, Vilnius Maternity Hospital Vilnius, Lithuania UNICEF Consultant team leader 2014-15

YU S Aleksandrovich, MD St. Petersburg State Pediatric Medical University, St. Petersburg, Russia

Chapter 1

An Introduction to Mechanical Ventilation in the Newborn ..........................................................08

Chapter 2

Oxygenation and Oxygen Therapy .........................................................................................................14

Chapter 3

Physiology of respiration and pulmonary mechanics ......................................................................23

Chapter 4

Modes of Ventilation.....................................................................................................................................29

Chapter 5

Pulmonary Graphics .....................................................................................................................................36

Chapter 6

Blood gas analysis..........................................................................................................................................40

Chapter 7

Supportive Care during Mechanical Ventilation ................................................................................50

Chapter 8

Art and science of weaning from Mechanical Ventilation ..............................................................57

Chapter 9

Disease - Specific Ventilation Strategies ................................................................................................64

Chapter 10

Surfactant therapy: Practical aspects .....................................................................................................70

Chapter 11

Less Invasive Surfactant Administration (LISA) / Minimal Invasive Surfactant Therapy (MIST) in Preterm Neonates ................................................................................74

Chapter 12

Practical Application of CPAP ....................................................................................................................80

Chapter 13

Role of HHHFNC in preterm infants- the Evidence ............................................................................83

Chapter 14

Humidified High Flow Nasal Cannula - Clinical application ...........................................................87

Chapter 15

Nasal Intermittent Positive Pressure Ventilation (NIPPV) in the Newborn ................................91

Chapter 16

Noninvasive High Frequency Oscillatory Ventilation .......................................................................97

Chapter 17

Supportive Care and Complications with babies on Non-Invasive Ventilation ................... 104

Chapter 18

Lung Protective Strategies in Newborns ............................................................................................ 108

Chapter 19

Ventilator Induced Lung Injury (VILI) In Neonates ......................................................................... 118

Chapter 20

High Frequency Ventilation .................................................................................................................... 126

Chapter 21

High Frequency Ventilation: Physiology and Machines ............................................................... 131

Chapter 22

Inhaled Nitric Oxide ................................................................................................................................... 136

Chapter 23

Pulmonary Air Leaks in the Newborn .................................................................................................. 140

Chapter 24

Transport of Ventilated Infants .............................................................................................................. 145

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The publisher and the chief scientific editor cannot be held responsible for errors or any consequences arising from the use of information contained in this book, the views and opinions expressed do not necessarily reflect those of the publisher or chief scientific editor.

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An Introduction to Mechanical Ventilation in the Newborn Amitava Sengupta Director, Mother & Child Unit, Neonatology & Pediatrics, Paras Hospitals, Gurgaon (NCR), India

01 CHAPTER

Background The last five decades have seen remarkable advances in the field of Neonatal medicine. Medical Advances Survival of Extremely Low Birth weight Premies Understanding Nutrition of Pulmonary Cellular Biology Function Genetics Respiratory Pharmacologic Support agents devices Micro methods for Parameters in Neonates

Surfactant

This has reflected with dramatic reductions in both neonatal and infant mortality. A variety of progresses have been responsible for this improvement, including better obstetric care, improved nutrition and pharmacologic agents, research and development of newer respiratory support devices, micro methods for measuring a variety of parameters in the neonate, and use of surfactant. The expansions of knowledge and major advances have enabled the neonatal team to save more babies of lower gestational age and extremely low birth weight (ELBW). History of Mechanical Ventilation in Neonates (From Jay P. Goldsmith, Edward Karotkin, Introduction to Assisted Ventilation; Assisted Ventilation of the Neonate, 6th Edition, 2017.) On 7th August 1963, a premature baby boy with a birth weight of 2100 grams was born to Jacqueline Kennedy and President of USA, John F. Kennedy by cesarean section at 34 weeks’ gestation. The neonate had hyaline membrane disease and was transported from Cape Cod, Masachusetts, to Boston. The Kennedy baby was treated with most advanced therapy of that time (Hyperbaric Oxygen), but unfortunately died at 39 hours of age. 08

The New York Times, August 8, 1963 1. Prior to 1971, mortality for RDS was 90% in infants with Birth weight between 750 to 1500 grams. In 1971, Dr. Gregory, an anesthesiologist introduced “Continuous Positive Airway Pressure” (CPAP) and with this modality alone mortality fell to 35%. 2. Early 1970s – ventilators, modifications of adult devices delivered intermittent gas flows (IPPV) 3. The next 25 years saw significant advances and production of a new generation of ventilators specially designed for neonates. 1971 to 1995:- Advances • First generation - BABYbird I; Bournes BP 200 (IMV & CPAP) • Second generation – Sechrist & Bear Cub; Electronic controls, microprocessors, micro circuits & Light emitting diode (LED) • Third generation – Advances in microcircuits & microprocessors (SIMV, assist/control mode , pressure support) • Direct measurement of pulmonary function • Pulmonary graphics. • High- frequency ventilation (HFV) • Extracorporeal membrane oxygenation (ECMO) • Liquid ventilations Surfactant replacement therapy was the most important advance in the treatment of RDS in the last 40 years. 1. 1959 Avery & Mead – Discovered surfactant

deficiency as a critical factor in neonatal RDS 2. 1990 - Licensing of two exogenous surfactant preparations in United States.

When to Intervene? Now we are sensitized to the fact, that there are certain limits to what we can do. Embryonic fetal and postnatal lung developments have been described anatomically and physiologically. We are able to ventilate babies in the saccular phase of lung development (26-36 weeksgestational age) during which there is refinement of gas exchanging acini. Can we, or should we, approach, with the same enthusiasm the canalicular stage (1626 weeks- gestational age) during which there is formation of gas-exchanging acini ? To clearly understand and appreciate the appropriate time for intervening with mechanical ventilation, it is well in place to be acquainted with the various phases of lung development.

Phases of Lung Development Period (phase) Embryonic phase

Gestational age Development 3-6 weeks Development of proximal airway Pseudoglandular 6-16 weeks Development of phase lower conduction airways Canalicular phase 16-26 weeks Formation of gas exchanging acini. Terminal sac phase 26-36 weeks Refinement of acini. Alveolar phase 36 week to 3 Alveolar proliferation years and development Adapted from: Jay P. Goldsmith, Edward Karotkin, Martin Keszler; Physiologic Principles Assisted Ventilation of the Neonate: an evidence – based approach to newborn respiratory care, 6th Edition, 2017.

Over the years, smaller and more immature-gestation infants are being rescued. Often, however, they are unfortunate to lead a life of handicap and hardship. In the early 1990s, one realized and started to indentify the gestational age at which conventional gas exchange could not adequately occur because of the anatomic and physiologic immaturity of the premature infants’s lung. Controversy exists as to where that limit is: 22 to 24 weeks’ gestation, 400 to 600 grams or is a gestational age of 26 weeks a safe limit? Biologic variability allows that the line need not be drawn too sharply, so that each baby can be evaluated individually for viability and suitability for aggressive intervention. In recent years, emphasis has shifted from pushing back the envelope of Gestational age and birth weight viability to improving functional outcomes of those babies who have the potential to be treated effectively.

Thus, the present day theme in neonatal ventilation has shifted from the “why” and “how” of neonatal ventilation to “how best” to support the newborn’s respiratory system to achieve optimal outcomes without sustaining damage from the known sequelae of ventilator devices. If intervention is chosen, initially the “Columbia approach” of respiratory support may be followed in which an attempt to not intubate or mechanically ventilate the infant is made. This is accomplished by early use of nasal continuous positive airway pressure (CPAP), Nasal Intermittent Positive Pressure Ventilation (NIPPV), permissive hypercapnia, and a variety of other strategies which are discussed in subsequent chapters.

Sequelae of our Treatment Regimes With years of research and advancement we have learnt to understand and appreciate the tangible possibilities of Sequelae of our treatment regimes. The primary ones being:1. Chronic Lung disease 2. Central nervous System injury During the study of mechanical ventilation it is essential to know the primary factors which are responsible for “Ventilator Induced Lung Injury (VILI)”. These essentially include the processes mentioned below Volutrauma refers to the damage caused by over distension of the lung by the delivery of too much gas. Barotrauma, or excessive pressure, may damage airway epithelium and disrupt alveoli. Atelectotrauma refers to the damage caused by the continual opening and closing (the cycle of recruitment and subsequent de‐recruitment) of lung units. Biotrauma is a collective term to describe the injurious effects of infection and inflammation (and oxidative stress) on the developing lung. Rheotrauma refers to injury caused by inappropriate airway flow. Adapted from: S M Donn, S K Sinha; Minimising ventilator induced lung injury in preterm infants; Arch Dis Child Fetal Neonatal Ed 2006;91:F226– F230.

Infants Born at Lower Extremes of Viability have the possibilities of the following morbidities:1. Impaired mental development (17%-21%) 2. Cerebral palsy (12% -15%) 3. Blindness & /or Deafness (8%) 4. Long term neurodevelopmental outcome has remained unchanged over the years. In today’s scenario, Ethical considerations focusing on prenatal consultation and resuscitation decisions have become as important as choosing an appropriate ventilator setting. 09

An Introduction to Mechanical Ventilation Mechanical ventilation of the neonate is a complex and highly invasive procedure and must be undertaken with great caution after having obtained adequate knowledge, competence and expertise in it’s art and science. At the outset, it would be interesting to get acquainted with the Five W’s of assisted ventilation Five W’s of assisted ventilation (From Assisted Ventilation of the Neonate, 6th Edition, 2017, Chapter 1; by Jay P. Goldsmith, MD, Edward Karotkin, MD, FAAP) Who: which neonates are candidates for ventilation? Who is an inappropriate candidate? What are the ethical and legal considerations? Where: which hospital should undertake assisted ventilation of the neonate? What equipment and personnel are necessary? What is meant by regionalized perinatal care? When: when is a patient in respiratory failure? What are the causes of inadequate ventilation? Why: what are the neurologic and physical outcomes of babies who are ventilated? What are the financial ramifications? What: what are the types and classifications of ventilators?

Definition Assisted ventilation involves movement of gas into & out of the lung by an external source connected directly to the patient. External Sources include 1. Resuscitation bag 2. Continuous distending pressure device 3. Mechanical ventilator Attachments to Patients comprise of 1. Face Mask 2. Nasal prongs 3. Endrotracheal tube 4. Tracheostomy Purpose of mechanical ventilation 1. Facilitate Alveolar Ventilation with adequate Co2 removal 2. Tissue Oxygenation 3. Reduce work of breathing Goals of Mechanical Ventilation 1. Achieve and maintain adequate gas exchange 2. Adopt lung protective strategies 3. Prevent hemodynamic impairment 4. Adopt strategies to prevent neurologic injury 5. Minimize work of breathing 10

Respiratory support in the sick or preterm neonate is a significant component of the care delivered in the Neonatal Intensive Care Unit (NICU). Neonates admitted for specialized care often require some degree of mechanical ventilation. Before venturing into mechanical ventilation, it must be understood that the process and techniques demand time, resources and experienced professionals. Understanding the principles behind neonatal ventilation is essential so that Neonatal Caregivers in the NICU have the necessary knowledge to understand best practices. An intubated neonate receiving full ventilator support

As earlier mentioned, the primary aim of assisted ventilation is to achieve adequate gaseous exchange and restore adequate patient respiratory efforts without any resultant lung injury or chronic lung disease (CLD). Ventilation may be initiated for immediate care of the depressed or apneic infant and acute conditions with respiratory failure. Respiratory failure results from inadequate  gas exchange by the respiratory system and leads to altered levels of arterial oxygen, carbon dioxide or both. Hypoxemia involves a fall in levels of oxygen carried in blood and Hypercapnia involves a rise in arterial carbon dioxide levels in blood. Respiratory failure is classified as either Type I or Type II, based on whether there is a high carbon dioxide level. The definition of respiratory failure usually includes abnormal blood gases (hypoxemia, hypercapnia, or both), and evidence of increased work of breathing. Type 1 respiratory failure is defined as a low level of oxygen in the blood (hypoxemia) without an increased level of carbon dioxide in the blood (hypercapnia). The PaCO2  may be normal or low. It is typically caused by a ventilation/perfusion (V/Q) mismatch; the volume of air flowing in and out of the lungs is not matched with the flow of blood to the lungs. The basic defect in type 1 respiratory failure is failure of oxygenation. This type of respiratory failure is caused by conditions that affect oxygenation such as: • Low ambient oxygen (e.g. at high altitude) • Ventilation-perfusion mismatch (parts of the lung receive oxygen but not enough blood to absorb it,

e.g. pulmonary embolism) • Alveolar hypoventilation • Diffusion problem (oxygen cannot enter the capillaries due to parenchymal disease, e.g. in pneumonia or RDS • Shunt (oxygenated blood mixes with non-oxygenated blood from the venous system, e.g. right to left shunt) Type 2 respiratory failure  involves inadequate alveolar ventilation with both oxygen and carbon dioxide levels in blood being affected and a fall in pH. It is essentially defined as the buildup of carbon dioxide levels (PaCO2) that have been generated by the body but cannot be eliminated.

IPPV) before other parameters become manifest. Indications (other than respiratory distress) requiring support for breathing include Hemodynamic instability Sepsis, Suspected metabolic disorder, Suspected IEM and renal failure. It has been observed that in case of shock and acidosis, 40 % of energy expenditure goes for breathing alone. So mechanically ventilating these babies will reduce work of breathing (WOB), thereby reducing metabolic demand and improving outcome, Assessment of Respiratory Distress in the Newborn

Hypercapnic respiratory failure is the inability to remove CO2 by spontaneous respiratory efforts and results in an increasing arterial PaCO2 and a decreasing pH. Hypoxemia is usually (but not invariably) present. In many instances arterial oxygen levels are normal.

Clinical Manifestations of Respiratory Failure and Indications for Mechanical Ventilation in the Newborn The decision to start mechanical ventilation in a neonate should be individualized and based on clinical as well as blood gas parameters. Presence of two or more parameters listed will form an indication for mechanical ventilation. 1. Increase or decrease in respiratory efforts (nasal flaring, grunting, retractions) - Respiratory rate greater than 70. 2. Cyanosis with FiO2 greater than 0.4 (40%) 3. Intractable apneic spells 4. Impending or existing shock 5. Worsening hypercapnia and/or hypoxemia a. PaCo2 greater than 60 mmHg in acute respiratory failure b. PaO2 less than 50 mm Hg in FiO2 greater than 1.0 (100%) 6. pH less than 7.25 Note: In case facility for blood gas analysis is not available and infant is in severe respiratory distress, it is prudent to initiate mechanical ventilation on clinical grounds. 1. Severity of intercostal and sub costal retractions is a major indicator of abnormality in lung volume and mechanics. Retractions are the initial signs of respiratory failure in the neonate, as the highly compliant chest, attempts (in vain) to keep the poorly compliant lungs expanded. 2. If severe retractions are evident, a neonate should be started on assisted ventilation (either CPAP/

Adapted from : Jay P. Goldsmith, Edward Karotkin; Introduction to Assisted Ventilation ; Assisted Ventilation of the Neonate, an evidence – based approach to newborn respiratory care, 6th Edition, 2017.

Score Severity of respiratory distress 0 No respiratory distress 7 or >7- Impending respiratory failure (need for mechanical ventilation), 10 Severe respiratory distress Downe’s Scoring System  0 1 2 Cyanosis None In room air In 40% FIO2 Retractions None Mild Mod Severe Grunting None Audible with Audible without stethoscope stethoscope Air entry Good Decreased or delayed Barely audible Respiratory rate 80 or apnea  Score: > 4 = Clinical respiratory distress; monitor arterial blood gases > 8 = Impending respiratory failure Arterial Blood Gases Normal Respiratory Failure pH 7.35-7.45 55-60 mmHg PaO2 Above 60 mmHg 90-95% 60 50-60 7.5L/min through 3mm internal diameter tube and with turbulent flows, resistant increases exponentially.

Breathing requires the expenditure of energy. For gas to be moved into the lungs, force must be exerted to overcome the elastic and resistive forces of the respiratory system. This is mathematically expressed by the following equation: Work of breathing = Pressure (force) × Volume (displacement) where pressure is the force exerted and the volume is the displacement. Work of breathing is the integrated product of the two, or simply the area under the pressure–volume curve. Approximately two-thirds of the work of spontaneous breathing is the effort to overcome the static elastic forces of the lungs and thorax (tissue elasticity and compliance). Approximately one-third of the total work is applied to overcoming the frictional resistance produced by the movement of gas and tissue components(airflow and viscous).The following diagram shows resistive and elastic work of breathing.

Airway or tube length- The shorter the tube, the lower the resistance.

Airway or tube diameter In a single-tube system, the radius of the tube is the most significant determinant of resistance. As previously described, Poiseuille’s law states that resistance is inversely proportional to the fourth power of the radius. Therefore, a reduction in the radius by half results in a 16-fold increase in resistance and thus the pressure drop required to maintain a given flow. It is important to fully appreciate that resistance to flow increases exponentially as ETT diameter decreases. This is one of the reasons extremely low birthweight infants are difficult to wean from mechanical ventilation. In a multiple tube system, like the human lung, resistance depends on the total cross-sectional area of all of the tubes. Although the individual bronchi decrease in diameter as they extend toward the periphery, the total cross-sectional area of the airway increases exponentially. Density of gas is influenced by barometric pressure. Decreasing the density of gas by two thirds (heliox mixture of 80% helium and 20% oxygen) decreases resistance to one third compared to that when room 26

AC, joining points of no flow is showing compliance line, area ABCA is showing work done in overcoming frictional resistance during inspiration. Area ACEA is showing work done in overcoming elastic resistance (ACEA), which incorporates the frictional resistance encountered during expiration (ACDA); ABCEA, or the entire shaded area is displaying total work done. Time constant – It is the time taken for the airway pressure (and volume) changes to equilibrate throughout the lung and is proportional to the compliance and resistance of the respiratory system Time constant = Compliance x Resistance For example, if an infant has lung compliance of 2 mL/ cm H2O (0.002 L/cm H2O) and a resistance of 40 cm

H2O/L/s, time constant is calculated as follows: Time constant = 0.002 L/cm H 2 O × 40 cm H 2 O/L/s = 0.080 s. Patients with a short time constant as in hyaline membrane disease ventilate well with short inspiratory and expiratory times and high ventilatory frequency, whereas patients with a long time constant as in meconium aspiration syndrome and BPD require longer inspiratory and expiratory times and slower rates. It is the percentage change in pressure of alveoli in relation to time as shown in the following diagram.

and increased physiologic dead space. The physiologic dead space results in part from areas of inefficient gas exchange because of low perfusion (wasted ventilation).

CO2 elimination during assisted ventilation CO2 diffuses easily into the alveoli and its elimination depends largely on the total amount of gas that comes into contact with the alveoli (alveolar ventilation). Minute alveolar ventilation is calculated from the product of the frequency (per minute) and the alveolar tidal volume (tidal volume minus dead space). Minute alveolar ventilation = Frequency × (Tidal volume minus dead space) On a pressure-targeted ventilator, the tidal volume depends upon the pressure gradient between the airway opening and the alveoli; this is PIP minus the positive end expiratory pressure (PEEP, also referred to as baseline pressure), or amplitude.

Hypoxemia The pathophysiologic mechanisms responsible for hypoxemia are in order of relative importance in newborns: ventilation–perfusion mismatch, shunt, hypoventilation, and diffusion limitation.

Oxygenation during assisted Ventilation Oxygenation depends upon FiO2 and mean airway pressure. During pressure-targeted ventilation, any of the following will increase mean airway pressure: increasing inspiratory flow, increasing peak inspiratory pressure (PIP), increasing the inspiratory:expiratory (I:E) ratio, or PEEP. Mean airway pressure maybe calculated as follows: K (PIP-PEEP)×Ti/Ti+Te + PEEP where K is a constant that depends upon the shape of the early inspiratory part of the airway pressure curve ( K ranges from approximately 0.8–0.9 during pressure-limited ventilation); Ti is inspiratory time; Te is expiratory time. For the same change in mean airway pressure, increases in PEEP and PIP increase oxygenation more. A very high mean airway pressure transmitted to the intrathoracic structures may impair cardiac output and thus decrease oxygen transport despite an adequate PaO2.

Hypercapnia The pathophysiologic mechanisms responsible for hypercapnia are V/Q mismatch, shunt, hypoventilation,

West’s Zones and Ventilation-Perfusion Relationships Both ventilation and perfusion are greater in the lung bases (in the erect position). Perfusion is relatively better than ventilation in the bases. Ventilation is more uniformly distributed than perfusion and therefore ventilation is relatively better in the apices. Blood that pours in from the pulmonary arteries tends to flow downwards towards the base, and therefore perfusion to the base is relatively better than the apex. Gas is affected by gravity, but less so than liquid; the effect of gravity on air is demonstrated by the “thinning” of the air at altitude (decreased barometric pressure). Consequently, even though air/gas also tends to fall towards the bases of the lungs (in the erect position), its distribution throughout the lungs is more uniform than that of blood/liquid. The result is that both perfusion and ventilation are greater in the bases than at the apices (of the lungs), but perfusion (blood flow) is relatively greater than ventilation in the base (shunt) and ventilation is relatively greater than perfusion in the apices (dead space). West described the ventilation-perfusion relationships at different levels in the lungs, and demonstrated 3 clear zones. In zone 1, in the apices, alveolar pressure is greater than both arterial and venous pressures (in the blood vessels). In zone 2, in the mid zone, arterial pressure > alveolar pressure > venous pressure. In zone 3 arterial pressure > venous pressure > alveolar pressure 27

The practical applications of this are: 1. Application of excessive pressures into the alveoli (i.e. PEEP), can increase dead space ventilation. 2. Likewise dead space is also increased in hypovolemia - the fluid level in the lungs drops - worsening gas exchange. 3. Measurement of pulmonary capillary wedge pressure must be made in zone 3, where alveolar pressure does not influence the readings.

3. Time cycling- inspiration ends when a certain preset time is reached 4. Flow cycling- inspiration ends when flow has a reached a critical low level 5. Mixed cycling- two or more independent cycling mechanisms are present in the same ventilator. 6. High frequency ventilation- ventilators capable of cycling at rates greater than 150 breaths/min.

In terms of ventilation-perfusion (V/Q) matching, dependent regions of the lungs tend to have the best V/Q relationships.

References

Negative Pressure Ventilation It is mainly of historical interest. Assisted ventilation is provided without the need of endotracheal intubation. Thus the trauma to the airway is avoided and risk of infection is reduced.

Positive Pressure Ventilation This type of ventilation is classified on the basis of cycling mode 1. Volume cycling- inspiration ends when a certain volume is reached. 2. Pressure cycling- inspiration ends when a certain preset pressure is reached.

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1. Goldsmith JP, Karotkin EH, Keszler M. Physiologic Principles. Assisted ventilation of the neonate: an evidence-based approach to newborn respiratory care, sixth edition, Elsevier, Inc; 2017. 2. Donn SM, Sinha SK. Pulmonary Mechanics. Manual of Neonatal Respiratory Care: 3rd edition, Springer; 2012. 3. Polgar G, String ST: The viscous resistance of the lung tissues in newborn infants. J Pediatr 69:787, 1966. 4. Bryan AC, Bentivoglio LG, Beerel F, et al: Factors affecting regional distribution of ventilation and perfusion in the lung. J Appl Physiol 19:395, 1964. 5. Bancalari E. Pulmonary function testing and other diagnostic laboratory procedures in neonatal pulmonary care. In: Thibeault DW, Gary GA, editors. Neonatal pulmonary care. 2nd ed. East Norwalk, CT: Appleton-Century Crofts; 1986. p. 195–234. 6. Bhutani VK, Sivieri EM. Physiological principles for bedside assessment of pulmonary graphics. In: Donn SM, editor. Neonatal and pediatric pulmonary graphics. Principles and clinical applications. Armonk, NY: Futura; 1998. p. 57–79.

Modes of Ventilation Monika Kaushal Chief of Neonatology, Emirates Speciality Hospital, Dubai Health Care City, Head, Department of Neonatology, Irani Hospital Dubai

Introduction The standard mode of ventilation used earlier in neonates was intermittent mandatory ventilation (IMV). Recently we have synchronized modes of ventilation available that synchronizes with babies’ spontaneous efforts. There are certain new hybrid modes available.

Intermittent Mandatory Ventilation (IMV) This is pressure controlled/limited, time cycled mode of ventilation. It provides a set number of mandatory mechanical inflations at fixed preset rates. The patient continues to breath spontaneously using fresh gas flow available in the ventilator circuit. This would look like as shown in figure 1 that baby is breathing of his own and ventilator is giving breathes of its own.

Fig 1. IMV

04 CHAPTER

Ingento EP and Drazen J: Mechanical ventilators, in Hall JB, Scmidt GA, and Wood LDH(eds.): Principles of Critical Care. New York, McGraw-Hill, Inc., 1992, p.145

Drawbacks of Intermittent Mandatory Ventilation (IMV) Without synchronization of baby’s spontaneous efforts the irregular respiratory pattern of neonate leads to frequent asynchrony between infant and ventilator leading to ventilator giving inspiration when baby is expiring. This results in • High airway pressure • Pneumothorax • Reduced efficiency of gas exchange • Large fluctuations in blood pressure and intracranial pressure leading to risk of lung injury and intraventricular hemorrhage. To over come this we may increase the ventilator rates, paralyze the baby or use synchronized mode of ventilation. High rate would lead to hypocarbia and reduced ventilator drive. Paralysis would result in greater dependence on respiratory support, edema and inability to assess the baby’s neurological status. Synchronization is one way out to overcome the

Fig 2: pressure volume and flow volume loops during non-synchronized IMV, SIMV and AC in a single patient. Large and random variation with IMV, more consistent loops but with difference in spontaneous and mechanical breaths in SIMV and consistent loops with SAC.

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drawbacks of IMV. The advantages of synchronization are many as seen in figure 2 and table1

Patient Triggered Ventilation Lets see how does the time cycled pressure limited ventilator works.( Figure 2)

Fig 3: Time cycled pressure-limited ventilator (TCPL)

For synchronization, ventilator should detect the spontaneous effort by the infant and respond by initiating a breath in a fraction of a second. Microprocessor technology helps in this. Synchronization needs signal from respiratory efforts that triggers ventilator to deliver ventilator breath.

than inspiration. Benefits of triggering are listed in table 1.The types of trigger devices available and their relative advantages are listed in Table 2. Figure 4 depicts right and wrong trigger. Benefits of synchronization/triggering  Elimination of asynchrony  Greater patient comfort  Improved gas exchange  Decreased need for sedation  Avoidance of muscle paralysis  Reduction of airway pressures  Decreased work of breathing  Decreased risk of barotrauma or volutrauma  Decreased risk of intraventricular hemorrhage  Better respiratory muscle training  Faster weaning from mechanical ventilation Table 2: Trigger Devices

There are four things involved in the synchronized mode of ventilation. They are 1. Trigger: trigger is one that signals the ventilator to begin inspiration based on input. We need a device, which should be: a. Sensitive enough. b. Have rapid response time to match with the short inspiration time and rapid respiratory rate of neonate. c. Should work efficiently despite of leak from side of tube. d. Must not be affected by artifact of motion other

Fig 4: Middle is the ideal trigger , right one has low trigger threshold so auto cycling , left one has too much air leak so long trigger delay and high work of breathing (WOB)

How to set the trigger • Start with best sensitivity • Check for auto triggering /cycling • Reduce the trigger sensitivity till auto cycling is abolished

Table 1: Benefits of synchronization Method/sensor Airway pressure /pressure transducer

Signal Pressure

Airflow/hot wire anemometer or pneumotachograph Thoracic impedance/ECG Leads Abdominal transducer / Graseby capsule

Flow

Esophageal electrode

Electrical activity of the diaphragm /transesophageal electromygraphy

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Thoracic impedance Abdominal motion

Advantage Simple, no dead space

Disadvantage Lacks sensitivity cause long trigger delay, high work of breathing, no tidal volume measurement Good sensitivity, rapid Added dead space, prone to auto response, provides tidal triggering with ETT leak volume measurement No added dead space Affected by placement poor electrode adhesion, no tidal volume measurement Rapid response, no Susceptibility to artifact with incorrect added dead space, position, affected by change in patient position, limited availability, no tidal volume measurement No added dead space, Costly, somewhat invasive, limited very rapid response, availability, no tidal volume measurement not affected by leak , ideal for NIV

• Once baby improves trigger may be increased to ensure that baby is triggering well and is ready for extubation. Problems with trigger • Autotrigger/autocycling: trigger by a signal other than patients efforts. Any flow of gas near the sensor will be detected as an effort by the infant, which can occur if there is water in the circuit and in presence of peritubular leak. • Failure to trigger: if baby has apnea there is failure to trigger • False trigger: may be due to motion artifact espc when graseby capsule • Delaying triggering: poor system response time will have delayed triggering and will increase work of breathing • Ineffective triggering: if very high threshold is kept which baby may not be able to achieve especially in the beginning. • Double triggering: Double triggering occurs during a strong patient effort when inspiratory time of ventilator is shorter than patients. Overcome the problems of trigger • Flow triggering: reduces WOB • Sensitivity set lowest: prevents autocycling • Sensor near the patient: proximal end of ET • Appropriate leak compensation: stability of PEEP • Neural adjusted ventilator assist: ventilator support is determined by diaphragmatic electric activity (EAdi). Theoretically this is best synchrony between infant and ventilator but lack in data. 2. Limit This is the variable set which the ventilator cannot exceed. This can be pressure, volume and flow limited usually neonates are managed by pressure limited ventilators. Now we have hybrid modes with pressure and to some extent volume limits available.

Fig 5: Phase variables trigger, limit and cycle

Fig 6: pressure, flow and volume scalar graphics showing effect of time cycling in right half where we can see the inspiratory hold due to pressure plateau and left side is flow cycled when ventilator starts exhalation once flow drops to 15% of peak flow.

4. Termination sensitivity: measures the decline in inspiratory flow that can be adjusted to end mechanical breath when flow declines to 0-25% of peak flow (figure 7). This prevents air trapping when baby is breathing rapidly and insures adequate inspiratory time when breathing slowly.

3. Cycling This is the method by which the ventilator terminates the inspiratory phase. It may be time cycled where we set a time for inspiration after which it ends. This however results in expiratory asynchrony as baby may be expiring when the ventilator is still inspiring. To overcome this flow cycling is used which makes it more physiological. Figure 5: depicts trigger, limit and cycling. And figure 6 shows how time and flow cycle differ.

Fig 7: flow termination sensitivity

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Synchronized Modes of Ventilation • Synchronized intermittent mandatory ventilation (SIMV) • Assist control (AC)/Patient triggered ventilation (PTV)/synchronized positive pressure ventilation (SIPPV) • Pressure support ventilation (PSV)

Synchronized Intermittent Mandatory Ventilation (SIMV) • SIMV breaths are mechanically delivered at a set rate that is synchronized to the onset of spontaneous infants breaths. (Figure 8) • If the infant breathes faster than the set rates the additional spontaneous breaths are possible because of continuous flow in circuit. • The ventilator does not support however these breaths. • The ventilator waits for the infant to initiate the breath for a period known as assist window and if baby fails to initiate a breath in this period ventilator delivers the mechanical breath. (figure 9) • It is time cycled so there is asynchrony in expiration • We set PIP, PEEP, RR, and Te

Assist control (AC)/Patient triggered ventilation (PTV)/synchronized positive pressure ventilation (SIPPV) • Ventilator assists every single “detectable” respiratory effort of baby • Baby decides ventilator breath rate, however a back up ventilator rate has to be kept • We Set: PIP, PEEP, Ti and RR (apnea / back up rate) • In this complete inspiratory synchrony occur but not expiratory synchrony. • If infants spontaneous respiratory rate is very high, this mode results in hyperventilation which may reduce the time for expiration and thereby result in air trapping Figure 10 shows how AC works and Figure 11 shows difference in SIMV and AC

Fig 10: pressure , Flow and volume scalar waveforms during AC. Purple is spontaneous effort and each breath is supported by ventilator which gives uniform transpulmonary pressure and tidal volume

Fig 8: pressure flow and volume scalar graphics in SIMV. Purple are patients own efforts and green are ventilator inflation. Patients own efforts also contribute to transpulmonary pressure (vertical line) and hence Vt . in small infants with high ETT resistance and weak respiratory effort, Vt barely exceeds anatomic and instrumental dead space, leading to inefficient rapid shallow breathing.

Fig 9: SIMV-Assist window

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Fig 11: Difference in SIMV and AC

Pressure Support Ventilation (PSV) To have synchrony between inspiration and expiration and avoid the inspiratory hold we have pressure support mode. (Figure 12) • Patient triggered, pressure limited and flow cycled (figure 6) • Baby decides RR and duration of breath (Ti), with the help of expiration synchrony • Assist infants breath with a pressure boost

• No apnea back up, good weaning mode • SET : PIP, PEEP, Percentage of peak inspiratory flow *Peak Flow) at which inspiratory phase of a pressure control or TCPL breath is terminated (figure 7) • If pressure is chosen to deliver full tidal volume it is PSmax, if chosen to overcome the imposed work of breathing it is PSmin • Termination sensitivity should be set appropriately usually 15%. if extreme (25%) can reduce Ti and lead to hypoventilation, if other extreme (5%) can result in asynchrony. • Prevention of gas trapping: patient’s safety • Pressure Support with mandatory rate: patient safety • Expiratory synchronization: improved patient’s comfort • Can be used only if baby has reliable respiratory efforts so used in weaning • Can be used as adjunct to SIMV as reduces work of breathing, improves minute ventilation, facilitates early extubation.

to reach more normal value that results in less tachypnea and more efficient breathing pattern

Benefits of SIMV Plus PSV

Figure 14: Effect of Psv with SIMV on Vt. First one is without PS, second with PS of 3 and last is with PS of 6 and we can see improvement of Vt with the support and with increase of support

Hybrid and Newer Modes • • • • • • • •

SIMV/AC/PSV + Volume Guarantee VAPS – Volume assured pressure support PRVC- Pressure regulated volume control PAV-Proportional assist ventilation NAVA Apnea back up ventilation Adaptive support ventilation Volume bracketing

Volume Guarantee (VG) Fig 12: flow and time termination

SIMV Plus PSV • Breaths delivered at breath rate setting are Time Cycled • Patient may breathe spontaneously and receive Pressure Support • Pressure Support breaths are flow cycled • Delivered at same PIP as SIMV breaths • Set: select SIMV mode and then on PSV set up

Fig 13: Pressure, flow and volume scalar waveforms during SIMV with PSV. Addition of PS to spontaneous untriggered breaths increase transpulmonary pressure and Vt allowing VT

Volume Guarantee (VG) is modification of pressure controlled ventilation to deliver a target tidal volume (Vt) by microprocessor –directed adjustments of inflation pressure or inflation time. Some devices regulate Vt delivery on flow measurement during exhalation and some during inhalation. The one measured in exhalation are more near patients Vt. VG can be combined with SIMV, AC or PSV. The operator chooses a target Vt and pressure limit up to which the ventilator operating pressure may be adjusted. The microprocessor compares the exhaled Vt of previous breath and adjusts the working pressure up and down to target the Vt (Figure 15).

Fig 15: device compares the measured Vt to target Vt and

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Table 3: Clinical guidelines for VG ventilation Recommendation Initiation of VTV Start as early as possible Choose basic mode of ventilation SIMV/AC/PSV May add PSV to SIMV, only SIMV inflations are VG Select back up rate, keep 10 breaths less than spontaneous rates (30 for term and 40 preterm ) Select PEEP appropriately according to infants diagnosis, condition and FiO2 Calibrate flow sensor and make sure is working properly Select Vt ml/kg • 4-6 : Preterm with RDS • 5-6: 2 week Set PIP limit 3-5 cm H2O above expected PIP need If Vt not met make sure ET in good position, leak minimal and then only increase PIP if required Confirm adequacy of support by looking at chest rise, adequate breath sounds, monitor SaO2 and ABG When changing from PC to CG mode match with Vt generated in PC mode and then only set PIP 3-5 cn H2O above PIP used Subsequent adjustments Once working PIP is known set PIP LIMIT 25% above upper limit of range If indicated adjust Vt in steps of 0.5 ml/kg Base Vt adjustments on PH and not PaCO2 , do not lower VT target if Ph not alkalosis Lower the PIP limit to just keep it 25% above upper range of PIP required Assess infants RR, comfort, oxygen requirement and working pressure, not just blood gas , increase Vt if necessary to achieve adequate support Verify appropriateness of support by clinical assessment if large support needed regulates the PIP within preset limits to achieve Vt that is set. The measured Vt is exhaled one to decrease error due to ET leak. If VT exceeds 130% of target the inflation gets terminated.

The advantages of VG are that the patient receives required PIP and not more, more stable TV, less hypocapnia, faster recovery from suctioning. It works better with AC then SIMV. Close monitoring of sensor and leak is required. Steps to successful VG ( table 3 )

Proportional Assist Ventilation (PAV) • Servo controlled • Ventilator receives continuous feed back about how much effort is made by patient, and ventilator proportionally provides support • Patient decides rate, volume, timing so synchrony is excellent and work of breathing, PIP, MAP are lower. • Back up ventilation is required for apnea 34

Rationale Compliance and resp efforts change rapidly soon after birth They result in more stable Vt and less WOB PSV pressure is set value not subject to VG They are safety for apnea, but If too low will give more fluctuation in SaO2 and if too high more untriggered inflations VG uses lowest possible PIP, adequate PEEP is required to maintain FRC Accurate Vt measurement is essential for VTV Vt is now the primary control variable • typical Vt for average preterm • impact of instrumental dead space (DS) • increased alveolar DS • increased anatomic and alveolar DS To allow adjustment of working pressure both up and down ETT obstructed in carina would cause high PIP, ETT in Rt bronchus would cause high PIP and volutrauma Recommendations are population derived but individual infant may require high or lower Vt Changing primary control variable does not change the relation of compliance, PIP and Vt. Average PIP will be less than or equal to that on PC Important safety feature to alert provider to change in support This steps leads to meaningful change Ph and not PCO2 is the primary control of respiratory drive, infants compensate for base deficits by hyperventilating As compliance and respiratory effort improves working PIP comes down Tachypnea and retractions indicate increase WOB, if Vt is set below infants physiological need, the ventilator lowers the PIP and infant has to work harder to maintain its MV Machines are fallible, do not blindly trust

Mandatory Minute Ventilation (MMV) • Type of pressure support where target MV is set. • Every 7.5 sec ventilator averages the breaths and decides how many additional SIMV breaths are required to catch up to achieve target MV.

Pressure Regulated Volume Control (PRVC) • Pressure limited • Time cycled o Adaptive pressure ventilation o Autoflow • Automatically adjusts pressure support level to minimum needed to maintain constant set Vt • Limitations of PRVC • As patient demand increase producing higher Vt because of more patient efforts, pressure level drops giving less ventilator support at a time when the patient may be needing more

• As pressure support level drops, mean airway pressure drops, possibly causing hypoxemia Autoflow • Combines volume support and PRVC in a single mode • Switches between pressure support and pressure control, with patient effort determines if breath will be VS/PRVC • If no efforts then gets PRVC , if efforts come back switches to VC Adaptive pressure ventilation • Dual control breath-to-breath mode. Pressure limit of spontaneous breaths is constantly adjusted • Need to enter weight, set PIP alarm, PEEP, FiO2, Flow cycle variable (10-40%)and peak flow (20-200%)

Volume assured pressure support (VAPS) • Allows a feedback loop based on Vt • Switches even with single breath from pressure control to volume control if minimum Vt not achieved • Set: pressure limit, RR, Peak flow rate, PEEP, FiO2, trigger sensitivity, minimum target volume • Once a breath is triggered rapid variable flow pushes pressure to reach set pressure support level • Vt delivered from machine is monitored • If patient efforts are weak or impedance changes it gets converted from pressure support to volume control • If pressure too high, all breaths are pressure limited • If peak flow set too low, switch from pressure to volume late in breath, Ti is too long

Apnea back up ventilation It is pressure support mode with apnea back up

Volume Bracketing The target volume is maintained within a set range

Key Messages • • • •

PTV is beneficial Good trigger key to good PTV Minimize the leak for better triggering Inspiratory and expiratory synchrony has to be achieved • Keep low back up rates in AC to improve ventilator triggering • Try and use VG mode with the PTV • There are many new modes: know your ventilator

References 1. Goldsmith JP, Karotkin EH, Kezler, Suresh, Saunders philadelphia, 6th edition 2017: 180-200 2. Sarkar S, Donn SM, In support pressure support. Clin perinatal 2007; 34: 117-128 3. Claure N, Banclari E, Automated respiratory support in newborn infants. Seminars in fetal and neonatal medicine 2009;14: 35-41 4. Hummler H, Schuze. Newer and alternative modes of mechanical ventilation in neonates 2009; 23(1): CD000456 5. Osorio W et all. Effects of pressure support during an acute reduction of SIMV in preterm infant. J Perinatol. 2005 6. Wheeler KI, Morley CJet al: Lower back up rates improve ventilator triggering during AC ventilation: a RCT. J perinataol 2012

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Pulmonary Graphics Suman Rao Professor & Head, Department of Neonatology, St. John’s Medical College & Hospital, Bangalore, India

05 CHAPTER

Introduction Neonatal ventilation is both a science and an art! The advent of pulmonary graphics has aided fine tuning of neonatal ventilation.. It refers to the direct and online visualization of the three fundamental parameters of the respiratory systems i.e. • Driving pressure P • Air flow V • Tidal Volume V

PEEP and the uppermost point represents PIP. The area under the curve gives the mean airway pressure. The inspiratory time can be measured from the point of upward deflection until PIP is reached and expiratory time begins with PIP and lasts until the next positive deflection. Oxygenation is directly proportional to mean airway pressure (increaseis achieved by increased PIP, increased PEEP, Increased inspiratory time and increased rate)

Of these the pressure and flow are directly measured. Volume is derived from the integration of the flow signal. From these variables other measures of pulmonary mechanics are derived eg: compliance and resistance. The two basic types of pulmonary graphics are: • Scalars – the 3 parameters of pressure, flow and volume are plotted against time on the X axis • Loops – two parameters are plotted against each other. Eg: Pressure volume loop; flow volume loop.

Scalars

1. Pressure Scalar

The pressure waveform has an upward deflection which represents inspiration and downward deflection representing expiration. It begins with 36

1. Represents the Flow . If the flow is high, it results in a square wave and if the flow is low it results in a sine wave. 2. Represents the PIP (that governs both oxygenation and ventilation) 3. Represents the Ti. – Longer the Ti, greater is the MAP (area under the curve) 4. Represents the PEEP – As change in PEEP affects both inspiratory and expiratory parts of the respiratory cycle, we can see why PEEP is the single most contributor to MAP 5. Represents the rate. Change in rate by shortening Te contributes to oxygenation. The pressure scalar is like a shark fin in volume ventilation and a sine/square wave in pressure ventilation:

2. Flow Scalar In the flow scalar, the wave form above baseline zero represents positive flow (into patient i,e. inspiration.) This has 2 parts, the initial accelerating flow at the start of inspiration and decelerating flow as velocity shows as the lung approaches capacity. The highest

point of the positive point of the wave is peak inspiratoryflow.Below zero represents expiration (from patient) and this also has an accelerating and decelerating flow. The lowest negative point of the waveform is peak expiratory flow

the expiratory flows take to reach the baseline, greater is the resistance.

3. Volume Scalar The flow is a decelerating flow in pressure ventilation and a constant flow or square flow in volume ventilation.

The flow scalar helps in 1. Identifying adequacy of inspiratory time Fig 5- Flow waveform showing in the initial period of inappropriately long inspiratory time where there is no flow in the latter part of inspiration(white block arrow). This is called the inspiratory pause or the area of no flow. This suggests that the Ti is very long and unnecessarily adding to barotraumas. By reducing the Ti, ventilation is optimized. The red block arrow shows it to be normalized.

2. Identifying Gas trapping. Expiratory flow does not return to baseline before the next breath starts. Reducing rates and providing adequate expiratory time will prevent this.

3. Aids in identifying increasing resistance: the longer

Similar in appearance to pressure but starts and ends on the baseline. The peak of the volume scalar depicts the tidal volume. It helps in identifying the mode of ventilation. In SIMV mode, the tidal volume of spontaneous breaths are lower than the supported breaths. By evaluating the tidal volume of spontaneous breaths, weaning and extubation can be considered. E.T tube leak can be determined-

Loops Pressure – Volume Loop

The horizontal X axis represents the degree of positive pressure exerted by the ventilator and the vertical Y axis represents the gas volume change in the lung. The loop begins with at PEEP and as the pressure delivered to the lung increases, there is a concomitant increase in the volume of gas delivered to the lung. The inspiratory limb ends at PIP and the expiratory limb begins, whereby pressure and volume fall as the lung empties. The shape the loop is referred as hysteresis. 37

If an imaginary line is drawn to connect the origin of the loop with the PIP, it can estimate the dynamic compliance of the lung – i.e. change in volume/change in pressure which is give by the slope of the loopnormally 450 from the axis. 1. The PV loop helps to evaluate the compliance of the respiratory system. A sleeping loop is typical of low compliance. With surfactant treatment compliance improves and the slope of the loop moves towards the vertical axis

4. PV loop helps in optimizing the PEEP.

to

When PEEP is increased in this situation the loop normalized to an elliptical shape. Trend date: Numerically and chart Help in determining alterations in ventilatory support, changes in disease processes and response to treatment such as surfactant.

The Flow – Volume Loop

2. PV loop helps in identifying overdistenion : Loop flatten at the upper end = “ducks tail” or “penguin beak”. No change in volume in spite of increase in pressure as the lung is already full causing a beaking of the upper part of the loop 3. A figure of 8 is typical of “inadequate flows”.

Normal: Flow –volume loop should be circular or oval in shape (egg on its side). The upper and lower limits representing peak inspiratory and expiratory flow respectively should be equivalent. It is important to know that the flow-volume loop has no convention on the direction of inspiratory and expiratory limb and varies with different manufacturers. It helps in identifying air leak. The expiratory flow reaches the volume axis before the origin.

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The flow volume loop given information on air resistance.

• Respiratory pattern • Readiness to extubate 4. Response to treatment: bronchodilators, diuretics, steroids, surfactant. 5. Understand respiratory mechanics Pressure, volume , flow, loops compliance 6. Disease evaluation: Type: restrictive/obstructive • severity

Trend date: Numerically and chart Help in determining alterations in ventilatory support, changes in disease processes and response to treatment such as surfactant. The role of pulmonary graphics are: 1. Optimise ventilation • PIP • PEEP • Circuit air flow • Ti • Synchrony & rate • Tidal volume 2. Optimize inspiratory time

Graphics offer the clinician: 1. The ability to look at how an individual patient’s pulmonary status is changing over time. 2. The ability to follow basic lung function parameters. Using these findings, the clinician can make ventilator adjustments that will avoid volutrauma or atelectrauma, which may help avoid ventilatorinduced lung injury. It is now recognized that even being on appropriate ventilator support still appears to carry the risk of lung injury. 3. The ability to make ventilator adjustments and assess their usefulness in improving lung function of the patient. 4. The ability to assess how the patient’s lung function is handling weaning, which may help earlier extubation to a less invasive support. 5. The ability to assess the effects of medications such as surfactant, bronchodilators, diuretics, steroids, etc., on lung function. This will allow for more appropriate use of these medications.

Conclusions Online pulmonary graphic analysis is a major technological advance which will improve safety and efficacy of neonatal ventilation. It gives a breath to breath performance of the ventilator and the interaction with the baby. It helps detect complications like air trapping and hyperinflation easily and helps fine tune ventilation on an individual basis.

Suggested Reading

3. Evaluate spontaneous effort: • Tidal volume • Minute ventilation

1. Null DM, Suresh GK. Pulmonary function and graphics. In: Goldsmith JP, Karotkin EH, Keszler M, Suresh GK (eds): Assisted ventilation of the neonate: an evidence based approach to newborn respiratory care. 6th ed, Philadelphia, Elsevier 2017 pg 108-127 2. Mammel MC, Donn SM. Real-time pulmonary graphics. Semin Fetal Neonatal Med. 2015;20(3):181-91 3. Becker MA, Donn SM. Real-time pulmonary graphic monitoring. Clin Perinatol. 2007;34(1):1-17 4. Bhutani VK. Clinical application of pulmonary function and graphics. Semin Neonatol 2002;7:391-9

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Blood Gas Analysis Suman Rao Professor & Head, Department of Neonatology, St. John’s Medical College & Hospital, Bangalore, India

06 CHAPTER

Introduction Arterial blood gas (ABG) measurements are the “gold standard” by which adequacy of oxygenation and ventilation is assessed. The neonate especially the preterm neonate is particularly susceptible to acid base disorders due to lesser blood buffer quantity, immature kidneys, and a fragile cardiovascular status. Blood gas measurement is a reflection of the “milieu interior” of the infant. Goals of ABG in newborn are to characterize the type of disorder, quantify the magnitude and assess the nature and extent of compensation.

Indications for ABG 1. 2. 3. 4. 5. 6. 7.

Severe respiratory or metabolic disorders Clinical features of hypoxia or hypercarbia Shock Sepsis Decreased cardiac output Renal failure Ideally any baby on oxygen therapy / respiratory

support 8. Inborn errors of metabolism

Considerations for Interpretation of Neonatal Blood Gases Pre-analytic • Sample site • Patient status • Technique • Storage time Analytic

• Instrument precision • Clinical requirements Turnaround time

Sample site The most accurate arterial blood gas values are obtained from indwelling arterial catheters. Not only does it allow the accurate measurement of arterial blood gases without disturbing the patient, but it also allows blood pressure monitoring and simplifies collection of other blood samples. ABG samples can also be collected from intermittent peripheral artery punctures, arterialized

Table 1: Blood gas monitoring techniques Technique Indwelling umbilical artery catheterization

Advantages • Steady state gases • Usually easily placed • Easy access once catheter placed • Can be used for fluid and medication infusion • Can be used for continuous blood pressure monitoring Indwelling • Steady state gases peripheral artery • Easy access once catheter placed catheterization • Can be used for continuous blood pressure monitoring Intermittent • Allows access when no catheter in place arterial puncture Arterialized capillary sampling Transcutaneous monitoring Pulse oximetry

End-tidal CO2 monitoring

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• • • • • • • • • • • •

Can be performed easily Low complication rate Good for chronically ill patients Fair estimates of pH, PCO2 Non invasive Continuous record of PO2 and PCO2 or in older BPD patients Noninvasive Continuous record of O2 saturation No burns Non invasive Continuous record of end tidal CO2 Rapid assessment of tracheal intubation

Disadvantages • Potential for major complications • Catheter cannot be placed in 10-15% of patients

• • • • • • • • • • • • •

Potential for major complications Catheter cannot be placed in 25% of patients Cannot be used for medication or blood infusion Potential for major complications although less than with indwelling catheters Patient may not be in a steady state Patient may not be in a steady state Not reliable for PO2 Not reliable when perfusion is poor

Expensive equipment May be unreliable if perfusion is decreased May cause burns at electrode site Works less well in active patients’ May not work in hypotensive or edematous patients • More useful in larger ventilated patients • Adds significant dead space • Only rough estimate of PaCo2 in infants with significant lung disease.

capillary bed samples, central venous blood samples. Continuous monitoring particularly by pulse oximeter, end tidal CO2 monitors and transcutaneous blood gas monitors are adjuncts in care of a sick neonate and cannot totally replace ABG measurements. The relative advantages and disadvantages of these techniques are shown in table 1: Collection of Samples Ideal artery for sampling in newborn is radial or umbilical artery. One must perform “Allen Test” to ensure collateral blood supply by ulnar artery before puncturing radial artery. If sample from umbilical artery catheter (UAC) is being taken, one should assure free flow of blood and remove three to four times dead space volume before sample is taken. Indwelling arterial line may only be put if round the clock facilities for ABG estimation are available considering this as a potent source of infection. Arterialised capillary samples are comparable to arterial blood (Table 2). If capillary sample (100-150 micro L) is being taken from prewarmed heel, let the capillary fill from the tissue site from where blood is oozing out. Avoid squeezing and first drop of blood. Rotate the capillary in palm. to mix anticoagulant with blood. Care should be taken not to include any air bubble in the capillary. Venous blood is good for HCO-3 estimation but bad for pH, PCO2 and PO2. While drawing venous sample make sure that no tourniquet is applied, artery is not compressed and sample is drawn against the flow of blood towards heart. Table 2: Comparison of Blood Gas Analysis at different sites

Arterial PH Same PO2 Higher PCO2 Lower HCO 3 Same Recommendation Good

Capillary

Venous --------------- Lower Lower Higher --------------- Same Fair Bad

Precautions for Collection of Blood Sample 1. Heparin is acidic and lowers pH. Use heparin of lower strength (1000 units per ml instead of 5000 units per ml) or heplock solution. 2. Use small volume of heparinised saline just for lubricating syringe and plunger. If volume is more, dissolved oxygen in heparinised saline may increase PO2. 3. Avoid air bubble and let syringe fill spontaneously. An air bubble may falsely increase PO2 upto 150 mm Hg or if the blood PO2 is high, as the O2 and CO2 diffuse into the air bubble, a false low PO2 and PCO2

may be recorded. 4. It is desirable to use a glass syringe as plastic syringes are permeable to air. 5. Sample may be collected in a heparinised capillary from hub of needle used to puncture artery. 6. If a sample is collected from an indwelling arterial catheter: • Assure free flow • Remove 4 times the dead space and keep aside in a sterile tray • Draw sample slowly • Take sample and inject the blood back slowly 7. The sample should be processed immediately, Blood is a living medium. The cells consume oxygen and produce CO2. Drop in PO2 depends on initial PO2. If the latter is very high, significant drop may be noticed. The changes are as depicted in Table 3. Slush of ice (not cubes) should be used for storing samples till processing. The sample should be shaken, homogenised before putting in machine. Table 3: Changes in ABG every 10 minutes in vitro pH PCO2 PO2

37°C 0.01 0.1 mm Hg 0.1 mm Hg

4°C 0.001 0.01 mm Hg 0.01 mm Hg

• It is obvious that blood sample should be stored at 4°C, if it cannot be processed immediately for minimal error. All samples should be processed within 15 min if kept in room air and within 1 hour if kept in ice. 8. the total turn around time from sampling to report analysis should not take more than 15 min in a level III NICU.

Interpretation of ABG The terminology of arterial blood gas (ABG) is complex and confusing. It is made worse by the printouts generated by recent microprocessors. Basically the machines measure pH, carbon dioxide and oxygen. All other parameters are derived based on software in machine which can be obtained manually if one knows how to use Siggaard Andersen Nomograms (Fig 1). Most ABG machines give a standard print out (Fig 2). Interpretation of blood gas reports is important for management of a sick newborn. However, it should not be interpreted in isolation, without clinical data. Neither a blood gas measurement nor the most sophisticated noninvasive monitors can replace careful clinical observation. Further, the ABG must always be compared with the previous results. 41

Fig 1: Siggard-Andersen nomogram

42

THb A Haemoglobin (Hb) of patient. A few machines measure haemoglobin, others need this information to be fed. If no information is fed, machine may assume any Hb or it may be at mercy of technician. Haemoglobin is required to calculate oxygen content (O2 CT) of blood. Temp Patient temperature has to be fed into machine because the machine measures all values at 37°C. Temperature affects pH, PCO2 and PO2. Hence, it is desirable to have values corrected for patient temperature. BE (ABE); BeEcf (SBE); BB BE refers to actual base excess in variance from (above or below) total buffer base (BB). Normal BB is 48-49 mmol/L. If BB is 40, it means buffer base is reduced by nearly 8 mmol/L, or BE is –8 (also called base deficit). If BB is 60, it means buffer base is increased by nearly 12 mmol/L, or BE is +12.

Fig 2: Print out generated by ABG machine

The interpretation of ABG reports involves two interrelated but separate processes: 1. Acid-base homeostasis 2. Oxygenation Terminology of ABG Acidosis Alkalosis Hypercapnia Hypocapnia Hypoxia Hyperoxia

pH 7.45 PCO2 > 50 mm Hg PCO2 70 mm Hg

Normal Neonatal ABG values pH 7.35 – 7.45 PCO2 35 – 45 mm Hg PO2 50 – 70 mm Hg HCO3 20 – 24 mEq/L BE ±5

Understanding the printout BARO It denotes barometeric pressure at site where machine is installed. It varies from place to place and it is determined by automated barometer in the machine. Barometric pressure is required for calculation of alveolar oxygen pressure.

BB is dependent on haemoglobin, as 25% of BB is constituted by haemoglobin buffer. Fifty percent of BB is contributed by bicarbonate and 25% by other buffers (proteins, phosphate, sulphate). HCO3 (ABC); st HCO3 (SBC); TCO2 TCO2 is sum of HCO-3 and amount of CO2 dissolved in plasma. For each mm Hg PCO2 , 0.03 ml CO2 is dissolved per 100 ml of plasma. As HCO-3 values change with CO2 levels, st HCO-3 is used to denote value of HCO-3, independent of CO2 changes (i.e. at pCO2 of 40 and temperature of 37°C). St. pH It is the pH adjusted for temperature of 37°C and pCO2 of 40 mm of Hg. This would represent pH value purely due to metabolic status. CH+ Concentration of hydrogen ion in nmol/L at 37°C and patients temperature. O2 CT It is the sum of oxygen bound to haemoglobin + oxygen dissolved in plasma. For each gm saturated Hb, 1.34 ml O2 is bound to hemoglobin and for each mm Hg PO2 0.003 ml oxygen is dissolved per 100 ml of plasma. O2 sat Proportion/percentage of hemoglobin which is saturated with oxygen. Aa DO2 Alveolar to arterial oxygen gradient. Normal value is 5 to 15 mm Hg.

43

RQ Amount of CO2 liberated per minute divided by amount of O2 utilised per minute. Normal values are 200 ml/250 ml =0.8.

A primary alteration in the HCO3 implies metabolic acidosis or alkalosis

FiO2 Inspired oxygen fraction concentration. This value has to be fed to machine, it is required for calculation of alveolar oxygen concentration.

Metabolic alkalosis: pH > 7.45 and a primary increase in HCO3 >24 mEq/l

DBE/dTHB It is called hemoglobin indicator. The normal value of this parameter is 0.32. If this value is more than 0.32 then it indicates, the hemoglobin of the patient should be measured accurately in order to calculate exact base excess.

Interpretation of ABG is a step wise process Step 1 Step 2 Step 3 Step 4 Step 5

What is the reported pH? What is the PCO2? What is the HCO3 value? What is the Base Excess (BE)? Is the primary acid-base disturbance uncompensated/partially compensated/well compensated? Step 6 Is the acid base disorder simple or mixed? Step 7 Identify and treat the cause of the underlying acid base disorder Step 1: What is the reported pH? The pH gives an idea of the primary acid-base disturbance. A pH 7.45 indicates alkalosis. Acidemia and alkalemia refer to alteration of pH in blood while acidosis, alkalosis to the processes that cause acid or alkali at tissue level to accumulate. *The pH may be within the normal range yet acidosis / alkolosis may exist, hence assessment of Step 2 & 3 are essential irrespective of pH value in diagnosing acidbase disorder. Step 2: What is the PCO2?

Step 3: What is the HCO3 value? Steps 2 & 3 tells us if the primary problem is metabolic or respiratory? A primary alteration in the PCO2 implies respiratory acidosis or alkalosis Respiratory acidosis: pH 50 mm Hg Respiratory alkalosis: pH > 7.45 and a primary decrease in PCO2 < 35 mm Hg

44

Metabolic acidosis: pH +2 it indicates metabolic alkalosis. If it is < - 4, it indicates metabolic acidosis, BE > +10 or 3g/kg/day while on parentaral nutrition. 7. Renal immaturity – loss of bicarbonate 8. Late metabolic acidosis – immaturity of kidney to handle high solute load especially sulphur containing aminoacids. 9. Metabolic disorder -IEM 10. Decreased cardiac output 11. Acetazolamide (diamox) use 12. Use of excessive PEEP, increase work of breathing Metabolic alkalosis 1. Iatrogenic – bicarbonate therapy 2. Use of diuretics 3. Following blood transfusion – citrate in blood gets converted to bicarbonate 4. Persistent vomiting – Congential adrenal hyperplasia 5. Prolonged gastric aspiration 6. Urea cycle disorder Respiratory Acidosis Due to decreased minute ventilation 1. Tube block 2. Tube dis-lodgement 3. Increased dead space – long endotracheal tube, adapters, and small bore tube 4. Opening of ductus (PDA) 5. Pulmonary interstitial edema 6. Pulmonary air leak 7. Collapse, consolidation Treatment of neonatal metabolic acidosis consists of general supportive care and specific measures directed to treat underlying cause. Treatment of hypothermia, hypovolemia, (anemia, hypoxia and electrolyte disturbances) will usually correct metabolic acidosis secondary to asphyxia or poor tissue perfusion. Antibiotics should be given if sepsis is suspected. Many infants require ventilatory support. Bicarbonate 46

is considered by some to be unnecessary and even harmful, leading to changes in cerebral blood flow and paradoxically to increased cerebrospinal fluid or intracellular acidosis.

Approach to Acid-Base disorders 1. The CO2 – Bicarbonate (Boston) approach To minimize pH changes that occur when an acidbase disorder occurs, buffers in the blood are the first mechanism that come into play. Buffers stabilize pH, hemoglobin, bicarbonate and protein are the principal buffers of blood. Extravascular space does not have hemoglobin and hence the buffering capacity is less than that of blood. Because we have no measure of extra and intracellular buffering capacity, it is difficult to predict how much pH will change when the concentration of acid or CO2 changes. The equation CO2 + H2O = H2CO3 = H+ + HCO-3 shows that any addition or subtraction of H+ or of HCO-3 ions causes a change in CO2 level. By changing ventilation, CO2 concentration can be altered. The Henderson Hasselbach equation can be used to calculate one variable only if the other two are known; for example, we can calculate (HCO-3) if pH and (H2CO3) are known. The equation cannot be used to predict what will happen if only one variable changes and if we know nothing about the other two. Although, we can estimate what might happen in response to an acid-load or ventilatory change, we cannot be accurate. Standard bicarbonate concentration (SBC) (22-26) mEq/L It is the concentration of the HCO-3 in the plasma from blood l which is equilibrated to bring the PCO2 to 40 mm of Hg at 37°C i.e. it overcomes the changes in HCO-3 due to respiratory causes and reflects a non-respiratory acid-base change. Under ideal condition SBC=HCO3 (n) variation = ± 2 mEq/L. If respiratory acidosis is present, HCO3 > SBC (because this blood will have a pCO2 > 40 mm of Hg and therefore when equilibrated to 40 mmHg, some of the CO2 will leave the blood. Hence SBC will be lowered). If respiratory alkalosis is present HCO3 < SBC (because during equilibration to 40 mm some CO2 gets absorbed and therefore SBC increases). Remember following 1. SBC Low – Metabolic acidosis High – Metabolic alkalosis 2. Difference between actual HCO3- and SBC indicates • respiratory acidosis if HCO3 > SBC • Respiratory alkalosis if HCO3 < SBC

3. When HCO3 = SBC then respiratory balance is present - When both are low but equal then compensated metabolic acidosis 4. When SBC is /¯ then HCO3 must also /¯ But /N/¯ HCO3 - may be associated with (n) SBC 2. The Base deficit / Excess (Copenhagen) approach Total buffer base (BB) in a neonate is 48-49 mmol/L. Half of this is due to HCO3-, 25% due to haemoglobin buffer and another 25% due to protein, sulfate, phosphate buffers. A value of BE of ± 5 is considered normal. Abnormal pH with BE> -5 (based deficit 620 for 12 hr on FiO2 100% is an indication for ECMO in West, because risk of mortality is > 80%. An advantage of using arterial PO2 to alveolar PO2 ratio (a/ApO2) instead of AaDO2 is that the ratio does not change with varying inspired oxygen concentration. In healthy adult the ratio a/ApO2 is more than 0.8. In infants with the severe RDS the a/ApO2 ratio could fall to as low as 0.1 to 0.2. In addition, high arterial pCO2 values indicate reduced ventilation. As baby recovers from RDS the a/ApO2 improve gradually from low (0.1 to 0.3) to normal (0.7 to 0.9). A value of < 0.22 of arterial to alveolar oxygen ratio is indication for administering surfactant.

Oxygenation Index MAP x FiO2 x 100 Postductal pO2 40 – mortality risk > 80-90% 25-40 – Moratlity risk 50-60% If oxygenation index >40, it is a indication for use of ECMO

ABG exercises For following ABG (A to F) confirm the values of TCO2’ O2 content, AaDO2 . Are these correctly derived by machine? Baro Pr.

A

B

C

D

E

F

747

737

747

730

747

747

Water vap. pr.

47

47

47

47

47

47

Hb

15

10

12

10

10

10

pH

7.418 6.881 7.322 7.516 7.516 7.531

PCO2 mmHg

28.8

51.1

36.4

21.4

PO2 mmHg

43.8

29.5

96.3

112.1 112.1 139.0

BE (ABE) mmol/L

-3.9

-22.2 -6.7

-2.7

-2.7

+3.5

Beecf (SBE) mmol/1

-5.4

-21.1 -6.8

-4.9

-4.9

+2.2

21.4

29.7

BB mmol/L

44.0

23.4

41.1

45.3

45.3

51.5

HCO3 mmol/L

18.1

9.3

18.3

17.4

17.4

25.0

StHCO3 mmol/L

20.3

8.2

18.8

21.1

21.1

27.5

TCO2 mmol/L

19.0

10.8

19.4

18.0

18.0

25.9

O2 ct vol %

15.1

6.8

16.1

13.7

13.6

13.8

O2 sat %

81.0

50.0

96.6

98.6

98.6

99.2

FiO2

0.50

1.0

0.30

0.30

0.30

0.30

Aa DO2

270.6 619.5 70.0

72.1

72.1

35.3

Suggested Reading 1. Woodruff DW. 6 Easy steps to ABG analysis. E Booklet. www. ED4NURSES.com 2012 2. Quigley R, Baum M. Neonatal acid base balance and disturbances. Seminars Perinatol 2001;28:97-102 3. Sood P, Paul G, Puri S. Interpretaion of arterial blood gas. Indian J Crit Care med 2010;14:57-64 4. Deorari A. Blood Gas Analysis. Workbook AIIMS 2008

49

Supportive Care during Ventilation Satish Ghanta1, Anil Gupta2 1

Director, Neonatal & Pediatric Intensive Care Services, Little Stars Children’s Hospital, Hyderabad, India, Fellowship Neonatology, Consultant, Neonatology, Little Stars Children’s Hospital, Hyderabad, India

2

07 CHAPTER

Neonates needing ventilation require close monitoring to detect subtle changes that can signal either the need for weaning or a deterioration requiring additional intervention. Mechanical ventilation has proved to be essential to the survival of most extremely premature neonates and will continue to play a key role in neonatal intensive care.1 Although lifesaving, neonatal ventilation is associated with acute and chronic lung and airway complications, including but not limited to air leaks, atelectasis, infection, and bronchopulmonary dysplasia.1,2 Antenatal steroids, surfactant treatment, and new strategies for neonatal respiratory care have dramatically changed the presentation, clinical course, and long-term outcomes for neonates with respiratory illness.3Focus has expanded from ensuring survival to reducing the incidence of chronic lung disease and neurodevelopmental impairment.4

monitoring) of the newborn, and they still have an important role. In general, the emphasis on noninvasive monitoring has resulted in the development and availability of new technologies (Transcutaneous monitoring of Po2 and Pco2, Pulse oximetry and Endtidal CO2 monitoring) that allow close monitoring without invasive procedures.

It is not a set of lungs that clinicians are treating, it is a critically ill infant, who is part of a family, and who requires mechanical ventilation for support.Every infant receiving mechanical ventilation in a NICU receives care from a team dedicated to ensuring that the best possible outcome is achieved given the resources that are currently available.

It is important that neonates receiving respiratory support have their oxygen status monitored on a continuous basis. Oxygen is a drug. As such, it should be managed with same diligence as other drugs.6 Excessive oxygen administration is linked with both retinopathy of prematurity and bronchopulmonary dysplasia.7Although several large, multicentre studies have attempted to define best targets for oxygen saturation values in neonates, definitive limits have been elusive. There remains uncertainty as to what oxygen saturation should be targeted. Knowing that neither hyperoxia nor hypoxia are desirable, it seems most prudent to focus care on minimizing saturation fluctuations, while maintaining targets at 90% to 94% in preterm babies.8

Monitoring 1. Clinical Monitoring 2. Non -Invasive – HR, RR, BP, % Saturation, Capnography and Transcutaneous Po2 & Pco2 3. Invasive – IABP, Blood gas 4. Imaging & Investigations – X-ray, USG

Pulse oximetry has become the standard, non-invasive continuous method to estimate arterial oxygen saturation in neonates and to guide oxygen therapy.5 Nearly all of the neonatal mechanical ventilators that are currently available provide airway graphics monitoring. A complete understanding of airway graphics is vital for determining response to different therapies (i.e., surfactant and bronchodilators), clinical improvement and deterioration, equipment malfunction and appropriate setting changes.

Maintaining tight control of oxygen levels presents a significant challenge for clinicians. Among the challenges is the significant lability displayed by ventilated premature infants related to their disease conditions, responses to environmental stimuli and need for ongoing interventions such as suctioning and other invasive procedures.

Suctioning Fig 1: pulse oximetry

Electrocardiography, blood pressure, and serial arterial and/ or capillary blood gases have been the traditional mainstays of bedside monitoring (along with clinical 50

The presence of an ETT causes irritation to tissue and increased secretions. It is necessary to clear this artificial airway periodically to maintain ventilation for the infant. ETT suctioning has been associated with a number of complications in infants including hypoxemia, bradycardia, atelectasis, airway trauma,

and pneumothorax. Systemic adverse effects are also ofconcern, including increased blood pressure, changes in intracranial pressure, and an increased risk of infection.9

suctioning, the need for reintubation, antibiotic exposure, and use of sedation, feeding, or parenteral nutrition with days of mechanical ventilation being the most significant risk.15

Best practice for endotracheal suctioning is to suction only as needed based on clinicalassessment versus performing routine endotracheal suctioning.10 The indications for suctioning include visible or audible secretions in the endotracheal tube, coarse or absent respiratory sounds, bradycardia, desaturation, and increased work of breathing. Ventilators with pulmonary mechanics may show a change in tidal volume, minute ventilation, and flow-volume loops when secretions are present. In neonates a maximum of 100 mm Hg pressure is recommended. for endotracheal suctioning11.Given the potential for adverse effects and a lack of evidence supporting the benefit of routine nasal saline instillation, this practice is not recommended.10,12

Box 1: Some of the empirically based VAP prevention strategies for neonates on assisted ventilation 1. avoiding the use of mechanical ventilation and extubating infants as soon as possible 2. avoiding repeated intubations 3. maintaining separate ETT suctioning tubing and oral suctioning tubing 4. changing the ventilator circuit only when visibly contaminated 5. avoiding saline instillation with ETT suctioning 6. suctioning the ETT only when needed 7. keeping the head of the bed elevated 30 degrees 8. performing mouth care every 4 hours and 9. performing appropriate hand hygiene.

To reduce trauma to the tracheal mucosa, the suction cathetershould be inserted to a premeasured depth that includesthe ETT and the adaptor13. In a 4-handed endotracheal suctioning strategy, person 1 supports the infant’s efforts at self-regulation, such as promoting flexion, allowing finger grasp, or touching the infant gently, while person 2 performs the suctioning procedure. They found that the use of four hands for suctioning resulted in an increase in oxygen saturation during the observation period compared to presuctioning levels and that infants displayed more stress and defensive behaviours after routine one-person suctioning compared to four-handed suctioning9. The research comparing open and closed suctioning practices has not been definitive in determiningwhich system is more advantageous. A Cochrane review found a reduction in the number and severity ofhypoxic events and a decrease in the number and severity of bradycardia with CS. The authors concluded, however, that the evidence was not strong enough to recommend CS as the only acceptable method for suctioning ventilated neonates.14

Prevention of Ventilator associated Pneumonia The most effective means to prevent neonatal VAP is to avoid intubation and the use of mechanical ventilation. However, until the infant is able to be adequately supportedusing non-invasive ventilatory modes, a comprehensive infection prevention approach is necessary. Risk factors for the development of VAP include prematurity, days of mechanical ventilation, ETT

Although these interventions have not yet been rigorously studied, many NICUs are attempting to reduce their VAP rate by bundling similar interventions in the hope of potential benefit.16,17

Airway Security Accidental dislodgment of the ETT can result in serious complications including acute hypoxia, bradycardia, and potential damage to the trachea or larynx. Factors associated with accidental extubation include agitation, ETT suctioning, weighing, turning the patient’s head, loose tape, short ETTs, and retaping the ETT.18 Box 2: Summary of potentially best practices for the prevention of unplanned extubations in neonates 1. A minimum of 2 experienced caregivers should be involved in procedures such as weighing, patient transfer, and securing endotracheal tubes. One person takes responsibility just for safely maintaining the endotracheal tube, whereas the second person performs required tasks. 2. Placement of alert cards at the bedside indicating the depth of placement at the gums along with documentation of endotracheal tube position and securement by both the nurse and respiratory therapist during routine care. 3. The use of a commercially available product to optimally secure the endotracheal tube. 4. Every unplanned extubation is reviewed and analysed for root cause.

An unplanned extubation poses a significant risk of harm to an infant, and should be considered a potentially life-threatening event. Unplanned extubation can cause cardiorespiratory deterioration and other adverse effects, including airway trauma, subglottic stenosis, and ventilator-associated pneumonia (VAP). After the endotracheal tube has 51

been replaced, the infant may experience ventilatorinduced lung injury.in the form of atelectrauma, increased oxygen exposure to bring them back to target oxygenation levels, and prolonged mechanical ventilation days. Unplanned extubation should be a safety concern for all NICUs. As with many quality improvement projects, continuous vigilance, staff training, and benchmarking of events are crucial to maintain standards of care.18 The position of the ETT may be altered with inadequate fixation of the tube, changes in patient position, and flexion and extension of the head. Because the trachea of a term newborn is quiteshort and even shorter in premature infants, small movements of the ETT can result in displacement, causing the tube to move into the right main stem bronchus with flexionor into the neck with extension.19In addition to potentially altering ventilation and blood gas parameters and causing tracheal damage, ETT movement can result in misinterpretationof the ETT position on X-rays.

Humidification Humidification is a natural process of the naso/ oropharynx and the upper airway during natural/ spontaneousbreathing. Optimal warming and humidification of the inspired gasesmaintains the mucus clearing, ciliary function, and the cellular integrity of the respiratory tract. The ETT bypasses the normal humidifying, filtering, and warming systems of the upper airway; therefore, heat and humidity must be provided to prevent hypothermia, inspissation of airway secretions, and necrosis of airway mucosa.

humidifier is necessary to ensure that inspired gases are delivered at or near body temperature (37° C) and that they achieve near-total saturation with water vapor. A modern servo-controlled heated humidifier, with high- and low-temperature alarms and heated wires that prevent accumulationof condensation, should provide adequate humidification with proper operation.

Positioning Positioning an infant who is receiving mechanical ventilation can be a challenging task. Although a comfortable position is essential for rest, an infant’s position can affect chest expansion, patency of the endotracheal tube, and circulation. The Cochrane review comparing various positions for ventilated infants found that prone positioning slightly improved oxygenation, but that there was no evidence of sustained improvement for infants who were positioned prone.22 Benign routine care activities have been linked to changes in cerebral blood flow patterns, possibly contributing to intraventricular hemorrhages.23 Positioning devices and adequate boundaries help provide a stable position for an intubated infant. After reviewing literature and consulting experts in neurophysiology, Malusky and Donze23 recommended midline head positioning for preterm infants to prevent intraventricular haemorrhage but did not reach any conclusion about the duration of midline positioning.

Fig 3: positioning

Skin care Fig 2: Humidifier

Assuming all other forms of infant warming are provided, ventilation with non-humidified gases is a major reason for development of hypothermiain neonates.20 Inadequate humidificationof the respiratory tract may reduce mucociliary clearanceand predispose infants to airway obstruction by secretions, thereby increasing the risk of gas trapping and air leak.21 A heated water 52

Premature infants are more vulnerableto skin injury and stripping of the epidermis. Risk factors forskin injury include gestational age less than 32 weeks, edema,and adhesives applied to the skin to secure tubes, lines, andmonitoring equipment. Emollients are not routinely usedin some NICUs because of concern for infection24 but may beneeded when the infant’s skin is dry and cracking.

Adhesive Application and Removal Medical adhesives comprise an integral part of healthcare delivery in the Neonatal Intensive Care. Premature and full-term infants who require medical interventions and constant monitoring are exposed to adhesives for a wide variety of indications. They secure both critical life support equipment such as endotracheal tubes, intravenous and arterial catheters, and chest tubes, as well as monitoring devices such as electrocardiogram electrodes, pulse oximeter probes and temperature sensors. The traumatic effects of adhesive removal have been documentedon premature infants and include reduced barrierfunction, increased trans epidermal water loss, erythema, andskin stripping. Solvents are not recommended for adhesiveremoval in newborns because these contain hydrocarbon derivativesor petroleum distillates that have potential toxicity whenabsorbed. Skin irritation and injury have been reported relatedto the use of a solvent in a premature infant.25 Pectin-based skin barriers such as HolliHesive and DuoDerm are used betweenskin and adhesive and mold well to curved surfaces while maintainingadherence in moist areas. Although studies initiallydescribed less visible trauma to skin from pectin barriers,26 astudy using direct measurements of skin barrier function foundthat pectin barriers caused a degree of trauma similar to thatof plastic tape.27 Despite this finding, pectin barriers and similarhydrocolloid adhesive products continue to be used in theNICU because they mold well to curved surfaces and adhereeven with moisture. Preventing trauma from adhesives can be accomplished byminimizing use of tape when possible, dabbing cotton on tape toreduce adherence, and using hydrogel adhesives for electrodes. Delaying tape removal maybe helpful, because many adhesives attach less well to skin when in place for over 24 hours. Remove adhesives slowly and carefully,using watersoaked cotton balls and pulling the adhesiveparallel to the skin surface, folding the adhesive onto itself.27

In our practice we have noticed a significant decrease in skin injury after introduction of Duoderm. We use duoderm between skin and adhesives for ET tube, umbilical lines, nasal cannula for oxygen,PICC Line, NG tube fixation etc. we also use duoderm between skin and CPAP interface to reduce mask/prongs injury.

Pressure Ulcers and Skin Breakdown Although the incidence of ischemic injury related to pressureulcers is low in NICU patients. Sites for pressure ulcers in newborns on assisted ventilationinclude the occiput of the head and the ears, because ofthe heavy weight of the infant’s head compared to the body. Inaddition, the circuit connected to the ETT is often secured toavoid displacing the tube, and thus the infant cannot turn ormove the head without assistance.28 Prevention of pressure ulcers to the head and ears involvesusing surfaces that alleviate pressure points. Turning the infant, a minimum of every 4 hours is necessary,along with careful inspection of skin surfaces29. Even when turningside to side is not feasible, lifting the head, shoulders, andhips and supporting these areas with pressure-reducing surfacesis helpful.

Nutrition Attaining adequate growth rates in premature infants ischallenging for a number of reasons. Most fat and energy storesare accrued in the third trimester, leaving preterm infants withlimited caloric reserves at birth. At the same time these infantsoften experience a delay in achieving adequate intake of nutrientsand may have periods of relative undernutrition related tofeeding intolerance or fluid restrictions. Concurrently prematureand sick infants require increased calories for tissue repair,generation of heat, and work of breathing. Early optimal nutritionfor VLBW infants is a key pillar in preventing postnatal growth restriction and the related complications. Strategiesto optimize nutrition include early parenteral nutrition withadequate protein and lipid intake, ensuring adequate proteinintake with parenteral nutrition until oral feeding reaches adequatelevels, minimal enteral feedings introduced on day 1 oflife, use ofmaternal or donor breast milk, and the appropriate fortificationof calories and nutrients.30-32

Pain and Sedation

Fig 4: DuoDerm

There are a variety of interventions that have been shown toreduce pain and agitation in NICU patients. It is important thatstrategies be put in place to prevent and manage infant painand agitation. Repeated exposure to stress and pain in theneonatal period has been shown to have long-term detrimentaleffects 53

including a reduction in brain white matter, decreasedgrowth in the parietal and temporal lobes, and impaired brainorganization.33 The first and most important strategy should be to decrease the number of stressful procedures. Skinto-skincare, facilitated tucking,and swaddling have beenshown to reduce agitation and pain responses to acute painfulprocedures and may be useful as adjunctive strategies for themanagement of ongoing pain.34 Oral sucrose has been shown to reduce crying when offeredto newborns during painful procedures such as heel-stick bloodsampling. Dipping a pacifier in sucrose was also shown to significantlyreduce pain responses in premature infants.35 A systematic review of 13 studies involving more than1500 infants found that there was insufficient evidence to recommendroutine use of opioids in neonates receiving mechanicalventilation because pain scores did not decrease with treatmentand morphine did not reduce adverse effects (death, intraventricularhaemorrhage, and periventricular leukomalacia).36

increased energy consumption,neonatal cold injury (as evidenced by lethargyand oliguria), poor weight gain, and susceptibilityto infection that may jeopardize the condition of a neonate. Therefore, routine neonatal critical care includesmeasures to reduce heat loss by evaporation, conduction,convection, and radiation and use of methods tomaintain normothermia.37Additional thermal support is provided through the use of doublewalled incubators or servo-controlled radiant warmers. Increased humidity is recommended for VLBW infants as a means of reducing trans epidermal evaporative heat loss. To maximize the neutral thermal environment of a VLBW infant, humidity must be added to the incubator air. Many studies have shown an increased survival of infants nursed in higher humidity.38NRP also recommend the use of polyethylene occlusive skin wrapping for infants is less than 32 weeks gestation infants immediately after birth in the delivery room to reduce both evaporative and convective heat losses.39The temperature ofthe humidifier in the ventilator circuit and build-up of condensation in the tubing also must be monitored toensure the temperature of the inspired gases, which inturn affects thermoregulation.

Thermoregulation Thermoregulation is a vital determinant of morbidity, mortality, and optimum health outcome in infants, particularly premature infants. Invasive procedures requiringprolonged access to an infant, such as umbilical catheterization, intravenous access, and radiographicprocedures, may jeopardize thermal stability. Therisk for heat loss and resulting hypothermia is moreprofound in preterm infants than in term infants becauseof the preterm infants limited brown fat and immatureheat-preserving mechanisms. Hypothermia has been independently associated with

Developmentally Supportive Care It involves a broad category of interventions designed to minimize the stress of the NICU environment. These interventions include elements such as control of external stimuli (auditory, visual, tactile, vestibular), positioning or swaddling of the preterm infant, clustering of nursing care activities to avoid disrupting sleep and calming techniques. The goal is to provide a structured care environment which supports, encourages and guides the developmental organization of the premature and/or critically ill infant.40

Best practices in Developmentally Supportive Care (DSC) in the NICU Optimal positioning with Good SelfRegulation (Calming) Infant on Mechanical Ventilation

Position according to Medical Status Infant on Mechanical Ventilation

1. Deep Sleep state 2. Flexion Posture with Mid line orientation 3. Neck in neutral position and aligned with spine 4. Shoulders softly rounded 5. Both hands on upper chest with Mid line orientation 6. Knees flexed with Foot Bracing 7. Hips aligned and softly flexed 8. Nest providing an adequate trough to deliver optimal support 1. Allow for alteration due to positional constraints for medical equipment 2. Caudal Nesting (½ nesting) Full nest not feasible as infant is on ventilation with accessory lines in situ 3. Flexion Posture with Mid line orientation 4. Hands to face (Left) and bilateral Foot Bracing

Adapted from- Amitava Sengupta; Workshops on Developmentally Supportive Care (DSC) in the NICU; Development and Supportive Care (DSC) Foundation for Newborn & Children (India)

54

Skin to Skin Care Mechanical ventilation is not a contraindication to skin-to-skin care. Of course, some infants will be too fragile to move, or some supportive equipment may be unable to be safely managed or secured Kangaroo care can be done with ventilated infants. Practical issues during skin-to-skin holding include transfer techniques from bed/incubator to parent, selecting chairs that support parent and infant comfortably, and monitoring during holding. A prospective study of 53 premature infants with a mean weight of 1253 g (range 631 to 1700 g), including 5 ventilated infants, found that the infants remained clinically stable with more efficient gas exchange, with no risk of hypothermia even for infants weighing less than 1000 g.41 Continuous monitoring of heart rate, oxygenation, and skin temperature is necessary to determine each individual infant’s tolerance during holding. Careful monitoring of all physiologic parameters is necessary during skin-to-skin holding to assess each infant’s response to this valuable experience and to determine when nursing intervention is needed.

Family Centered Care Historically, the role of parents in the NICU was very much that of spectators. However, there has been a major shift in the understanding of the importanceof embedding parental involvement in virtually every moment of the neonate’slife in the NICU. The science surrounding practices such as skin-to-skin care, exclusivehuman milk feedings, and their significant effects on early neurodevelopment is nowadvancing from being considered nice to do to being recognized as making a significantdifference in the short-term and long-term outcome of NICU infants. Parental engagement can begin even before the birth of their infant. Havingan infant fragile/sick enough to require mechanical ventilation is an extremely stressful time for parents and family. Nurses can play a key role in helping the parents to understand how they may be actively involved in their infant’s car.

Summary Care of infants supported with mechanical ventilation is complex, time intensive, and requires constant vigilance by an expertly prepared health care team. Successful management of ventilated neonates requires a comprehensive approach to care, with a focus on the patient as a whole, rather than on a single organ system. Parental involvement in the neonatal intensive care unit is extremely important to patient outcomes, and front-line nurses provide critical

supports to parents during each infant’s stay in the neonatal intensive care unit.

References 1. Keszler M, Sant’Anna G. Mechanical ventilation and bronchopulmonary dysplasia. ClinPerinatol 2015;42(4):781– 96. 2. Miller JD, Carlo WA. Pulmonary complications of mechanical ventilation in neonates. ClinPerinatol 2008;35(1):273–81. 3. Bancalari EH, Jobe AH. The respiratory course of extremely preterm infants: a dilemma for diagnosis and terminology. J Pediatr 2012;161(4):585–8. 4. Keszler M. Update on mechanical ventilatory strategies. Neoreviews 2013;14(5): e237–51. 5. Hay Jr WW, Rodden DJ, Collins SM, Melara DL, Hale KA, Fashaw LM. Reliability of conventional and new pulse oximetry in neonatal patients. J Perinatol 2002; 22:360–366. 6. Hardy W. Managing desaturations in preterm infants. Adv Neonatal Care 2010;10(6):330–31. 7. Bancalari E, Claure N. Control of oxygenation during mechanical ventilation in the premature infant. ClinPerinatol 2012;39(3):563–72. 8. Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology 2017; 111:107-125. 9. Cone S, Pickler R, Grap M, McGrath J, Wiley Pet. Endotracheal suctioning in preterm infants using four-handed versus routine care. J ObstetGynecolNeonatNurs 2013; 42(1):92104. 10. Gardner D, Shirland L. Evidence-based guideline for suctioning the intubated neonate and infant. Neonatal Netw 2009;28(5):281–302. 11. Trevisanuto D, Doglioni N, Zanardo V. The management of endotracheal tubes and nasal cannulae: the role of nurses. Early Hum Dev 2009;85(10): S85–7. 12. Celik SA, Kanan N. A current conflict: use of isotonic sodium chloride solution on endotracheal suctioning in critically ill patients. DimensCrit Care Nurs 2006;25(1):11-14. 13. Soltau TD, Carlo WA: Respiratory system. In Kenner C, Lott J (eds): Comprehensive Neonatal Care: An Interdisciplinary Approach. 5th ed. New York, Springer Publishing, 2014, pp 131-151. 14. Taylor JE, Hawley G, Flenady V, Woodgate PG. Tracheal suctioning without disconnection in intubated ventilated neonates. Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No.: CD003065. 15. Cernadar M, Aguar M, Brugada M. Ventilator-associated pneumonia in newborn infants diagnosed with an invasive bronchoalveolar lavage technique: a prospective observational study. PediatrCrit Care Med 2013; 14(1):55-61. 16. Garland J. Strategies to prevent ventilator-associated pneumonia in neonates. ClinPerinatol 2010;37(3):629-643. 17. Smulders CA, van Gestel JP, Bos AP. Are central line bundles and ventilator bundles effective in critically ill neonates and children? Intensive Care Med2013; 39(8):1352-1358. 18. Merkel L, Beers K, Lewis M, Stauffer J, Mujsce DJ, Kresch MJ. Reducing unplanned extubations in the NICU. Pediatrics 2014;133(5): e1367-e1372.

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19. Kako H, Krishna S, Ramesh A, Merz MN, Elmaraghy C, Grischkan J, et al. The relationship between head and neck position and endotracheal tube intracuff pressure in the pediatric population. PediatrAnesth 2014;24(3):316-321. 20. Meyer MP, Hou D, Ishrar NN. Initial respiratory support with cold, dry gas versus heated humidified gas and admission temperature of preterm infants. J Pediatr 2015;166(2):245250. 21. Tarnow-Mordi WO, Reid E, Griffiths P.Low inspired gas temperature and respiratory complications in very low birth weight infants. J Pediatr 1989; 114:438-442. 22. Rivas-Fernandez M, Figuls M, Diez-Izquierdo A, Escribano J, Balaguer A. Infant position in neonates receiving mechanical ventilation. Cochrane Database Syst Rev. 2016 Nov 7;11:CD003668. 23. Malusky S, Donze A. Neutral head positioning in premature infants for intraventricular hemorrhage prevention: an evidence-based review. Neonatal Netw. 2011;30(6):381-396. 24. Edwards WH, Conner JM, Soll RF. The effect of prophylactic ointment therapy on nosocomial sepsis rates and skin integrity in infants with birth weights of 501 to 1000 g. Pediatrics 2004;113(5):1195-1203. 25. Ness M, Davis D, Carey W.Neonatal skin care: a concise review. Int J Derm 2013;52(1):14-22. 26. O’Neil A, Schumacher B: Application of a pectin barrier for medical adhesive skin injury (epidermal stripping) in a premature infant. J Wound, Ostomy ContNurs 2014;41(3):219-221. 27. Lund C: Medical adhesives in the NICU. Newborn Infant Nurs Rev 2014;14(4):160-165. 28. Murray JS, Noonan C, Quigley S, Curley MA. Medical devicerelated hospital-acquired pressure ulcers in children: an integrative review. J PediatrNurs 2013;28(6):585-595. 29. Scheans P. Neonatal Pressure Ulcer Prevention. Neonatal Netw. 2015;34(2):126-32. 30. Adamkin DH, RadmacherPG.Fortification of human milk in very low birth weight infants (VLBW