Pediatric and Neonatal
`Mechanical Ventilation
`
`Second Edition
`
`Praveen Khilnani MD FAAP FCCM (USA)
`Senior Consultant and lncharge
`Pediatric lniensivist and Pulmonologist
`Max Hospitals, New Delhi, India
`
`Foreword
`
`RN Srivastav
`
`LJBRARY
`TECHNICAL ‘RESOURCES CENTER
`® GREENWLLE TECHNICAL COLLEGE
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`JAYPEE BROTHERS MEDICAL PUBLISHERS {Pi LTD
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`Exhibit 2029
`Praxair Distrib., Inc. et al., v. Mallinckrodt Hosp. Prods. IP Ltd.
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`Ex. 2029-0001
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`

`
`Published by
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`Jaypee Brothers Medical Publishers (P) Ltd
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`Pediatric and Neonatal Mechanical Ventilation
`
`© 2011, Jaypee Brothers Medical Publishers
`
`All rights reserved. No part of this publicalion and DVD-ROM should be reproduced, stored in a
`retrieval system. ortransmiited in any form or by any means: electronic, mechanical, photocopying,
`recording. or otherwise, without the prior written permission of the editor and the publisher.
`
`_This book has been published in good faith that the material provided by contributors is
`original. Every effort is made to ensure accuracy of material, but the publisher, printer and
`editor will not be held responsible for any inadvertent error(s). In case of any dispute, all
`legal matters are to be settled under Delhi jurisdiction only.
`
`First Edition: 2008
`
`Second Edition: 2011
`
`ISBN 978-93-5025-245-1
`
`Typeset atJPBMP typesetting unit
`Printed at Flajkamal Electric Press, Plot No. 2, Phase-lV, Kundli, Haryana.
`
`Ex. 2029-0002
`
`

`
`Dedicated to
`
`my mother
`Late Shrimati Laxmi Devi /fhilnani
`
`who left for heavenly abode on 13th May, 200].
`She always knew I could do it whenever I thought I couldn't.
`She was the one who taught me to be always optimistic and hardworking.
`God will take care of the rest.
`
`Late Smt Laxmi Devi Khilnani
`
`(19th Jan, 1930- 13th May, 200])
`
`Ex. 2029-0003
`
`

`
`Contributors
`
`Jeffrey C Benson
`Pediatric lntensivist
`
`Veena Raghunathan
`PICU Fellow
`
`Children’s Hospital of Wisconsin
`Wisconsin, Michigan, USA
`
`Sir Ganga Ram Hospital
`New Delhi, India
`
`Satish Deopujari
`Consultant Pediatric lntensivist
`
`Child Hospital
`Nagpur, Maharashtra, India
`
`Garima Garg
`PICU Fellow
`
`Max Superspeciality Hospital
`New Delhi, India
`
`Shipra Gulati
`PICU Fellow
`
`Max Superspeciality Hospital
`New Delhi, India
`
`Praveen Khilnani
`
`Senior Consultant and lncharge
`Pediatric Intensivist and
`
`Pulmonologist, Max Hospitals .
`New Delhi, India
`*
`
`Sankaran Krishnan
`
`Pediatric Pulmonologist
`Cornell University
`New York, USA
`
`Aniali A Kulkarni
`Senior Consultant Neonatologist
`IP Apollo Hospitals
`New Delhi, India
`
`Meera Ramakrishnan
`
`Sr Consultant lncharge PICU
`Manipal Hospital
`Bengaluru, Karnataka, India
`
`S Flamesh
`
`Pediatric Anesthesiologist
`KK Child Trust Hospital
`Chennai, Tamil Nadu, India
`
`Suchitra Fianjit
`lncharge PICU
`Apollo Childrens Hospital
`Chennai, Tamil Nadu, India
`
`Reeta Singh
`Consultant Pediatrics
`
`Sydney, Australia
`
`Anil Sachdev
`Senior Consultant PICU
`
`Sir Ganga Ram Hospital
`New Delhi, India
`
`Ramesh Sachdeva
`
`Vice Preside t
`
`Pediatric lntinsivist
`Children’s Hospital of Wisconsin
`Wisconsin, Michigan, USA
`
`Ex. 2029-0004
`
`

`
`Deepika Singhal
`r Consultant Pediatric lntensivist
`Pushpanjali Crc>sslaysHospital
`Ghaziabad, Uttar Praaesh, India
`K
`7
`
`Nitesh Singhal
`Consultant
`Pediatric lntensivist
`Max Superspeciality Hospital
`New Delhi, India
`
`Rajiv Uttam
`Senior Consultant
`Pediatric lntensivist
`Dr BL Kapoor Memorial Hospital
`New Delhi, India
`
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`Ex. 2029-0005
`
`

`
`Foreword
`
`The author of this book, Pediatric and Neonatal Mechanical Ventilation, is an
`
`experienced pediatric intensivist with over 30 years of experience and
`expertise in the field of anesthesia, pediatrics and critical care. He has been
`involved in training and teaching at Various conferences and mechanical
`ventilation workshops in India as well as at an international level. The text
`presented is intended to be a practical resource, helpful to beginners and
`advanced pediatricians who are using mechanical ventilation for newborns
`and older children.
`
`RN Srivastav
`Senior Consultant
`
`Apollo Center for Advanced Pediatrics
`Indraprastha Apollo Hospital
`New Delhi, India
`
`Ex. 2029-0006
`
`

`
`Preface to the
`
`Second Edition
`
`After the first edition came out in 2006, Pediatric and Neonatal Mechanical
`Ventilation became instantly popular with pediatric residents in the
`Pediatric Intensive Care Unit (PICU) due to its small size and simple and
`practice-oriented approach.
`Recently, more advances have come up in the field of mechanical
`ventilation including newer modes such as airway pressure release
`ventilation,lneurally adjusted ventilatory assist (NAVA) and high
`frequency oscillatory ventilation (HFOV).
`Newer ventilators with sophisticated microchip technology are able to
`offer better ventilation with precision with graphics and monitoring of
`dynamic parameters on a real-time basis as well as sophisticated alarm
`systems to check pressures (over distention) and volumes delivered to the
`patient via the breathing circuit (leaks if any). Newer advances such as
`FiO2 weaning by feedback loop with real-time sensing of SpO2 in the patient
`by the microchip built in the ventilator are soon going to be a reality.
`In the second edition, newer chapters on specific scenarios of Ventilation
`in Asthma, ARDS, Extracorporeal Membrane Oxygenation (ECMO),
`Patient ventilator synchrony have been added. Flow charts have also been
`included in most of the chapters for ready reference. Some newer
`ventilators and their information have also been added in chapter on
`commonly available ventilators.
`I sincerely hope that this book will continue to be of practical use to the
`residents and fellows in the pediatric and neonatal intensive care unit.
`'3
`
`Praveen Khilnani
`
`Ex. 2029-0007
`
`

`
`Preface to the
`
`First Edition
`
`As the field of pediatric critical care is growing, the need for a simple and
`focused text of this kind has been felt for past several years in this part of
`the world for pediatric mechanical ventilation. Effort has been made to
`present the method and issues related to mechanical Ventilation of neonate,
`infant and the older child. Basic and some advanced modes of mechanical
`ventilation have been described for advanced readers, topics like high
`frequency ventilation, ventilator graphics and inhaled nitric oxide have
`also been included. Finally, some commonly available ventilators and their
`features and utility in this part of the world have been discussed. I hope
`this book will be helpful to pediatricians, residents and neonatal pediatric
`intensivists who are beginning to work independently in an intensive care
`setting, or have already been involved in care of critically ill neonates and
`children.
`
`Praveen Khilnani
`
`
`
`
`
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`Ex. 2029-0008
`
`

`
`Acknowledgments
`
`Besides a description of available evidence and using my personal
`experience of mechanical ventilation of neonates and children for past
`20 years, I have taken the liberty of using the knowledge and experience
`of my teachers Prof I David Todres (Professor of Anesthesia and Pediatrics,
`Harvard University, Boston, MA), Prof William Keenan (Director of
`Neonatology, Glennon Children Hospital, St Louis University, St Louis,
`MO), Prof Uday Devaskar (Director of Neonatology, UCLA, CA), and
`authorities such as Dr Alan Fields (PICU, Children's National Medical
`Center, Washington DC), and Robert Kacemarek (Director, Respiratory
`Care at Massachusetts General Hospital, Boston, MA).
`I would like to give special acknowledgement to my esteemed
`colleagues such as Dr Shekhar Venkataraman (PICU, Pittsburgh Children's
`Hospital, Pittsburgh, PA), Dr S Ramesh (Anesthesiologist, Chennai),
`Dr Ramesh Sachdeva (PICU, Children's Hospital of Wisconcin, Milwaukie,
`WI), Dr Meera Ramakrishnan (PICU, Manipal Hospital), Dr Sankaran
`Krishnan (Pediatric Pulmonologist, Cornell University, New York),
`Dr Balaramachandran (PICU, KKCT Hospital, Chennai), Dr Krishan Chugh
`and Anil Sachdev (PICU, SGRH, Delhi), Dr Rajesh Chawla (MICU, IP
`Apollo Hospital, Delhi), Dr RK Mani (MICU, Artemis Healthcare Institute,
`Delhi), Dr Rajiv Uttam (PICU, BL Kapoor Memorial Hospital, Delhi),
`Dr S Deopujari (Nagpur), Dr S Ranjit (Chennai), Dr Dinesh Chirla (Rainbow
`Children's Hospital) and Dr VSV Prasad (Lotus Children's Hospital,
`Hyderabad), Dr Deepika Singhal, Pushpanjali Hospital, Ghaziabad,
`.Dr Anjali Kulkami and Dr Vidya Gupta (Neonatology, IP Apollo Hospital,
`} Delhi) and many other dear colleagues for constantly sharing their
`l knowledge and experience in the field of neonatal and pediatric mechanical
`— ventilation and providing their unconditional help with various national
`level pediatric ventilation workshops and CMES.
`Finally, the acknowledgment is due to my family without whose Whole-
`hearted support this task could not have been accomplished.
`
`lMI
`
`Ex. 2029-0009
`
`

`
`- Contents
`
`Structure and Function of Conventional Ventilator
`
`Pr/ween Khilmmi, S Ramesh
`0 Ventilator
`
`Mechanical Ventilation: Basic Physiology
`Przzveen Khilmmi
`
`0 Basic Respiratory Physiology
`- Applied Respiratory Physiology for Mechanical Ventilation
`
`Oxygen Therapy
`Szztish Deopujari, Sztchitra Ranjit
`0 Definition
`
`' Physiology
`Basic Mechanical Ventilation
`
`Praveen Khilmmi, Deepikrz Singhal
`0 Indications of Mechanical Ventilation
`° Basic Fundamentals of Ventilation
`
`Advanced Mechanical Ventilation: Newer Modes
`Pmveen Khilmzni
`
`0 Inverse Ratio Ventilation (IRV)
`° Airway Pressure Release Ventilation (APRV)
`' Pressure Support Ventilation (PSV)
`' Pressure-regulated Volume Control (PRVC)
`Proportional Assist Ventilation (PAV)
`° Nonconventional Techniques
`° Neurally Adjusted Ventilatory Assist (NAVA)
`
`Patient Ventilator Dyssynchrony
`Deepiku Singhal, Przzveen Khilnani
`' Ventilator-related Factors that affect Patient—ventilator
`Interaction
`' Trigger Variable
`° Ineffective Triggering
`
`3
`fl
`
`. Blood Gas and Acid Base Interpretation
`Nitesh Singhal, Praveen Khilmmi
`0 Acidosis
`' Alkalosis
`
`Ex. 2029-0010
`
`

`
`Buffering System
`Homeostasis
`
`Pafliophysgology
`Metabolic rAcidosis
`Treatmen
`Metabolic
`
`alosis
`
`Respiratory Acidosis
`Respiratory Alkalosis
`Mixed Acid-base Disorders
`
`Care of the Ventilated Patient
`
`Meera Rmmzkrishmm, Gnrima Garg
`0 Physiotherapy
`- Appendix: Humidificat-ion andeMechanical Ventilation
`
`Ventilator Graphics and Clinical Applications
`Pmveen Khilmmi
`
`0 Technique of Respiratory Mechanics Monitoring
`° Types of Waveforms
`° Scalars
`
`° Loops
`- Abnormal Waveforms
`
`Ventilation for Acute Respiratory Distress Syndrome
`Shipm Gulati, Prcween Klzilnmii
`Epidemiology of Acute Lung
`Diagnosing Acute Lung Injury
`Management of Pediatric ALI and ARDS
`Respiratory Support in Children with ALI and ARDS
`Endotracheal lntubation and Ventilation
`
`Rescue Therapies for Children with ALI/ARDS
`Potentially Promising Therapies for Children with
`ALI/ARDS
`
`Mechanical Ventilation in Acute Asthma
`
`Am’! Snchdev, Veena Rzzghuimtlmn
`Criteria for Intubation
`
`Intubation Technique
`Sedation during Intubation and Ventilation
`Effects of Intubation
`Ventilation Control
`
`Medical Management of Asthma in the Intubated Patient
`Noninvasive Mechanical Ventilation
`
`Weaning from Mechanical Ventilation
`Snnkarzm Krishmzn, Pmveen Khilmmi
`
`0 Determinants of Weaning Outcome
`- Extubation
`
`Complications of Mechanical Ventilation
`Praveen Khilnani
`
`- Complications Related to Adjunctive Therapies
`
`Ex. 2029-0011
`
`

`
`. Non-Invasive Ventilation
`
`Rajiv Uttam, Praveen Khz'lnani
`0 Mechanism of Improvement with Non—i.nvasive Ventilation
`
`. Neonatal CPAP (Continuous Positive Airway Pressure)
`Praveen Kliilnani
`0 Definition
`
`' Effects of CPAP in the Infant with Respiratory Distress
`0 The CPAP Delivery System
`. Neonatal Ventilation
`
`Anjali A Kulkarni
`
`. High Frequency Ventilation
`Ieffrey C Benson, Ramesh Sachdeva, Praveen Khilnani
`0 Ventilator Induced Lung Injury
`' Protective Strategies of Convenfional Mechanical Ventilation
`- Basic Concepts of HFV (High Frequency Ventilation)
`° Types of High Frequency Ventilation
`' Clinical Application
`° Practical Aspects of High Frequency Ventilation of
`Pediatric and Neonatal Patients
`
`.
`
`Inhaled Nitric Oxide
`
`Rita Singh, Praveen Khilnani
`
`. Extracorporeal Membrane Oxygenation
`Ramesh Sachdeva, Praveen Khilnani
`0 Recent Evidence on Use of ECMO
`
`Commonly Available Ventilators
`Praveen IGn'lnanz'
`
`0 VELA Ventilator: Viasys Health Care (USA)
`- Neonatal Ventilator Model Bearcub 750 PSV—Viasys
`Health Care (USA)
`' Venfilator Model Avea- Viasys Health Care (USA)
`- The SLE 2000 - For Infant Ventilation
`' SLE 5000
`‘
`° The Puritan Bennett® 840"‘ Ventilator
`
`Appendix 1: Literature Review of Pediatric Ventilation
`
`Appendix 2: Adolescent and Adult Ventilation
`
`Index
`
`Ex. 2029-0012
`
`

`
`. .t
`
`n
`Q-
`
`3‘
`
`.T
`3.
`
`D 5
`
`.39,.
`n I
`
`prospective controlled studies using large patient population are needed
`to document any outcome benefits of INO therapy in ARDS.3°
`
`lNO in Cardiology
`
`Pulmonary hypertension with associated right ventricular dysfunction may
`complicate postoperative cardiac patients despite maximal pharmacologic
`and ventilatory support. By reducing mean pulmonary artery pressure,
`INO may protect the right ventricle, while maintaining left ventricular
`filling by increasing pulmonary arterial blood flow.“
`
`Congenital Heart Disease
`
`The use of INO has been shown to be helpful for the assessment of
`pulmonary vascular reactivity in selecting patients for surgery and
`postoperative management.” Post-cardiac surgery pulmonary has been
`successfully treated with INO in patients with significant prospective
`puhnonary hypertension.
`
`Primary Pulmonary Hypertension
`
`INO is used to test pulmonary vascular reactivity. A positive response
`with decrease in pulmonary artery pressure suggests a favorable response
`to long-term vasodilator therapy with prostacyclin or calcium channel
`blockers.
`
`Miscellaneous Llses and Ongoing Trials
`
`1. Lzfe—threatening status asthmaticus: In children with life-threatening
`asthma, hypercapnea increases pulmonary vascular tone, thus
`increasing right ventricular afterload, which is already compromised
`by positive pressure ventilation and air trapping. NO plays an
`important role in regulating bronchial smooth muscle tone. Selective
`vasodilation of ventilated lung units may improve oxygenation and
`carbon dioxide elimination and unload the right ventricle, improving
`cardiac output.”
`I
`2; ~,Cerebral malaria: Some researchers have used it, but prospective
`*
`I multicenter trials and are needed to document beneficial effects.34
`
`3. Heart transplantation: INC is a useful adjunct to the postoperative
`V
`treatment protocol of heart transplant patients with pulmonary
`hypertension. It selectively reduces PVR and enhances right ventricular
`stroke work.35
`
`4. Lung transplantation: Reperfusion injury is a major cause of mortality
`and morbidity among lung transplant recipients. Prop
`lactic lNO does
`not prevent reperfusion injury in human lung transpl
`tation however,
`if started at reperfusion, improves gas exchange and reduces pulmonary
`artery pressure in those patients who develop reperffision injury.36
`5. Acute myocardial infarction (AMI): Given the important role that NO
`plays in regulatory platelet activation, interest has arisen in developing
`technique for increasing NO donors in the setting of AMI.37
`
`Ex. 2029-0013
`
`

`
`6—
`
`Neonatal chronic lung disease: Defined as the continuing need in preterm
`infants for supplemental inspired oxygen at 36 weeks postconceptional
`age. INO imprgves oxygenation in most infants with early chronic lung
`disease, without inducing changes in markers of inflammatory or
`
`oxidative inju.?r.33
`
`Adverse Effects of INO
`
`
`
`
`
`PediatricandNeonatalMechanicalVentilation
`
`1.
`
`Rebound eflects: Abrupt withdrawal of nitric oxide can cause rebound
`pulmonary hypertension, right ventricular failure and severe
`hypoxemia.39
`
`Prolonged bleeding time: INO increases platelet cyclic GMP and by
`inhibiting platelet aggregation can increase bleeding time. Although
`clinically signi-ficant bleeding is foitunately not observed.4°
`. Paradoxical worsening of oxygenation in chronic lung disease.“
`. Elevated pulmonary capillary wedge pressure: In patients with left
`ventricular dysfunction and poor ventricular compliance, an increase
`in pulmonary flow can increase left ventricular filing pressure, leading
`to ventricular failure and pulmonary edema.“
`
`REFERENCES
`
`1.
`
`Palmer RM], Ferrige AG, Moncada S. Nitric Oxide release accounts for the
`biological activity of endothelium derived relaxing factor. Nature
`1987;374:524-6.
`
`. Salzman AL, Denenber AG, Ueta I. Induction and activity of nitric oxide
`synthatase in cultured human intestinal epithelial monolayers. Am] Physio
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`’
`. Frostel CG, Fratacci MD, Wain JC et al. Inhaled nitric oxide: A selective
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`Circulation 1991;83:2038—47.
`
`. Leffer CW, Hessler JR, Green R5. The onset of breathing at birth stimulates
`pulmonary Vascular prostaglandin synthesis. Pediatr Res 1984;18:938-412.
`. Kinsella II’, Abman SH. Inhaled nitric oxide: Current and future uses in
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`. Abman SH, Chatfield BA, Hall SL, Mcmurthy IF. Role of endothelium
`derived relaxing factors during transition of pulmonary circulation at birth.
`Am J Physiol 1990;259:1921-7.
`. UK Collaborative ECMO Trial Group. UK Collaborative randomized trial
`of neonatal extracorporeal membrane oxygenation. Lancet 1996548275-82.
`. Glass P, Bulas DI, Wagner AE, et al. Severity of brain injury following
`neonatal extracorporeal oxygenation and outcome at age 5 years. Dev med
`Child Neurol 1997; 39:441-8.
`. Randermacher P, Santak P, Becker H, Falke KI. Prostaglandin E1 and
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`Anesthesiology 1989;70:601—9.
`. Neonatal inhaled nitric oxide group ( NJNOS). Inhaled nitric oxide in full-
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`
`Ex. 2029-0014
`
`

`
`—
`
`V
`
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`9P!XO3l11!l\IPalellul
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`. Abman SH, Dobyns EL, Kinsella JP. Role of inhaled nitric oxide in the
`treatment of children with severe acute hypoxic respiratory failure. New
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`. Kinsella JP, Troug W, Walsh W, et al. Randomized multicenter trial of
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`. Kinsella JP, Abman SI-I. Recent developments in inhaled nitric oxide therapy
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`. Tworetzky W, Bristow J, Moore P, Brook MM. Inhaled nitric oxide in
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`. Cornfield DN, Maynard RC, ‘O’deregner RA, Guiang SF, et al. Randomized
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`Pediatrics 1999;104(5):1089—94.
`. Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby IL, Perez JA, et
`al. Low dose nitric oxide therapy for persistent pulmonary hypertension of
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`. Davidson D, Barefield ES, Kaltwinkel J, Dudell G, Damask M, Straube R, et
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`V
`. Steinhorn RH, Cox PN, Finernan JR, et al. Inhaled nitric oxide enhances
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`. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born
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`. Elligton M, ‘O’ Reilly D, Allred EN, Mccormick MC, et al. Child health
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`. Kinsella JP. Use of inhaled nitric oxide during interhospital transport of
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`. Mercier JC. Franco-Belgium Neonatal Study Group on inhaled NO.
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`. Bland RD. Inhaled nitric oxide: A premature remedy for chronic lung
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`. Kinsella JP, Walsh WF, Bose CL;’Gerstmann DR, Labelle JJ, Sardesai S, et al.
`Inhaled nitric oxide in premature neonates with severe hypoxemic failure,
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`. Channik RN, Newhart JW, Johnson FW, Williams P], Auger WR, Fedullo
`PF, et al. Pulsed delivery of inhaled nitric oxide to patients with primary
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`tests. Chest 1996;109:1545-9.
`. Rossaint R, Falke KJ, Slaina K, et al. Inhaled NO for the ARDS. N Eng J Med
`1993;328:399.
`A
`. Baxter FJ, Randall J, Miller JD, Higgins DA, Powles C, Choi PT. Rescue
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`. Puybussel L, Stewart T, Rouby ]J, et al. Inhaled NO reverses the increase in
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`Anesthesiology 1994;80:1254-9.
`
`Ex. 2029-0015
`
`

`
`
`
`
`
`PediatricandNeonatalMechanicalVentilation
`
`. Payen DM. Is nitric oxide inhalation a ”cosmetic” therapy in acute
`P
`1'Y
`Y“
`P
`res irato
`distress s
`drome. Am I Res Crit Care Med 1998;157:1361—2.
`. Baldauf M, Silver P, Sagy M. Evaluating the validity of responsiveness to
`inhaled nitricioxide in pediatric patients with ARDS, an analytic tool. Chest
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