Pediatric and Neonatal
`Mechanical Ventilation
`
`Second Edition
`
`Praveen Khilnani MD FAAP FCCM (USA)
`Senior Consultant and lncharge
`Pediatric lntensivist and Pulmonologist
`Max Hospitals, New Delhi, India
`
`Foreword
`
`RN Srivastav
`
`LIBRARY
`TECHNICALRESOURCES CENTER
`® GFIEENWLLE TECHNICAL COLLEGE
`E 0. BOX 5616
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`JAYPEE BROTHERS MEDICAL PUBLISHERS 1P) LTD
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`Mallinckrodt Hosp. Prods. IP Ltd.
`Exhibit 2029
`Praxair Distrib., Inc. et al., v. Mallinckrodt Hosp. Prods. IP Ltd.
`Case lPR2o16-00779
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` '+7a§vm~<wrw-=—v<4—A—as
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`Ex. 2029-0001
`
`

`
`Published by
`
`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 publication and DVD-ROM should be reproduced, stored in a
`retrieval system, ortransmitted 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 oi any dispute, all
`legal matters are to be settled under Delhi jurisdiction only.
`
`First Edition: 2006
`
`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 Khilnani
`
`who left for heavenly abode on 13th May, 2001.
`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 Kh/lnani
`
`(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 Flam Hospital
`New Delhi, India
`
`Satlsh 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 lntensivist and
`
`Pulmonologist, Max Hospitals .
`New Delhi, India
`*
`
`Sankaran Krishnan
`
`Pediatric Pulmonologist
`Cornell University
`New York, USA
`
`Anjali A Kulkarni
`Senior Consultant Neonatologist
`IP Apollo Hospitals
`New Delhi, India
`
`Meera Ramakrishnan
`
`Sr Consultant lncharge PICU
`Manipal Hospital
`Bengaluru, Karnataka, India
`
`3 Ramesh
`
`Pediatric Anesthesiologist
`KK Child Trust Hospital
`Chennai, Tamil Nadu, India
`
`Suchitra Ftanjit
`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
`Pediatric Int nsivist
`Vice President
`
`Chi|dren’s Hpspital of Wisconsin
`Wisconsin, Michigan, USA
`
`Ex. 2029-0004
`
`

`
`Rajiv Uttam
`Senior Consultant
`Pediatric lntensivist
`Dr BL Kapoor Memorial Hospital
`New Delhi, India
`
`vii: Deepika Singhal
`* " a; Consultant Pediatric lntensivist
`I Pushpanjali Crosslay;Hospital
`Ghaziabad, Uttar Pradesh, India
`‘O
`7
`
`Nitesh Singhal
`Consultant
`Pediatric lntensivist
`Max Superspeciality 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
`lndraprastha Apollo Hospital
`New Delhi, India
`
`Ex. 2029-0006
`
`

`
`Preface to the
`
`Second Edition
`
`After the first edition came out in 2006, Pediatric and Neonatal Meclzariiczzl
`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, neurally 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.
`6
`
`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
`
`
`
`
`
`‘:.:....::;::.;3:.~,_;.,_,:.‘._.‘4‘.;74:;4‘§:;:‘-:C;A‘:.;>;:~;;\:;A+~:;.o,;.‘A«a..,___}___
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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 Rarnakrishnan (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 Uttarn (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 Kulkarni and Dr Vidya Gupta (Neonatology, lP Apollo Hospital,
`,5 Delhi) and many other dear colleagues for constantly sharing their
`‘ 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.
`
`'
`
`1uI
`
`Ex. 2029-0009
`
`

`
`Contents
`
`Structure and Function of Conventional Ventilator
`Pruveen Khilnmii, S Ramesh
`0 Ventilator
`
`Mechanical Ventilation: Basic Physiology
`Praveen Khilnrmi
`
`0 Basic Respiratory Physiology
`- Applied Respiratory Physiology for Mechanical Ventilation
`
`Oxygen Therapy
`Satish Deapujari, Suchitra Ranjit
`0 Definition
`
`° Physiology
`Basic Mechanical Ventilation
`
`Praveen Khilnani, Deepiku Singlzul
`0 Indications of Mechanical Ventilation
`' Basic Fundamentals of Ventilation
`
`Advanced Mechanical Ventilation: Newer Modes
`Praveen Khz'lnam'
`
`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, Praveerz Klfilmmi
`° Ventilator-related Factors that affect Patient-Ventilator
`Interaction
`' Trigger Variable
`' Ineffective Triggering
`
`3
`u
`
`. Blood Gas and Acid Base Interpretation
`Nitesh Singhul, Pruveen Khilmmi
`0 Acidosis
`' Alkalosis
`
`Ex. 2029-0010
`
`

`
`
`
`
`
`
`
`A‘PediatricffiandNeonatalMechanicalVentilationAA
`
`
`
`
`
`
`
`Buffering System
`Homeostasis
`
`Pathophysgology
`Metabolic rAcidosis
`Treatmen
`Metabolic
`
`alosis
`
`Respiratory Acidosis
`Respiratory Alkalosis
`Mixed Acid-base Disorders
`
`Care of the Ventilated Patient
`
`Meera Rmmzkrishnan, Grzrimzz Garg
`0 Physiotherapy
`- Appendix: Humidification anclrMechanical Ventilation
`
`Ventilator Graphics and Clinical Applications
`Przzveen K}1ilm2nz'
`
`- Technique of Respiratory Mechanics Monitoring
`Types of Waveforms
`Scalars
`
`Loops
`Abnormal Waveforms
`
`Ventilation for Acute Respiratory Distress Syndrome
`Shipru Gulati, Pmveen Klzilmzni
`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 Chlldren with ALI/ARDS
`Potentially Promising Therapies for Children with
`ALI/ARDS
`
`Mechanical Ventilation in Acute Asthma
`
`Anil Sachdev, Veena Raghmiathan
`Criteria for Intubation
`
`Intubation Technique
`Sedation during Intubation and Ventilation
`Effects of Intubation
`Ventilation Control
`
`Medical Management of Asthma in the lntubated Patient
`Noninvasive Mechanical Ventilation
`
`Weaning from Mechanical Ventilation
`Srmkarcm Krishmm, Pmveen Khilmmi
`- Determinants of Weaning Outcome
`- Extubation
`
`Complications of Mechanical Ventilation
`Praveen Khilmmi
`
`I Complications Related to Adjunctive Therapies
`
`Ex. 2029-0011
`
`

`
`Non-Invasive Ventilation
`
`Rajiv Uttam, Praveen Khilnani
`- Mechanism of Improvement with Non-invasive Ventilation
`
`Neonatal CPAP (Continuous Positive Airway Pressure)
`Praveen Klzilnani
`0 Definition
`
`- Effects of CPAP in the Infant with Respiratory Distress
`' The CPAP Delivery System
`. Neonatal Ventilation
`
`Anjali A Kulkarni
`
`. High Frequency Ventilation
`Iefliey C Benson, Ramesh Sachdeva, Praveen Khilnani
`0 Ventilator Induced Lung Injury
`° Protective Strategies of Conventional Mechanical Ventilation
`' Basic Concepts of I-IFV (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 Khilnani
`
`- VELA Ventilator: Viasys Health Care (USA)
`° Neonatal Ventilator Model Bearcub 750 PSV—Viasys
`Health Care (USA)
`- Ventilator 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
`
`

`
`prospective controlled studies using large patient population are needed
`to document any outcome benefits of INO therapy in ARDS.3°
`
`H10 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
`pulmonary hypertension.
`
`Primary Pulmonary Hypertension
`
`
`
`
`
`apzxoDamnpeleuui
`
`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 Uses and Ongoing Trials
`
`1. Life-threateiiirrg status astlmmticus: 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.”
`v
`2: ;Cerebrul rmzlaria: Some researchers have used it, but prospective
`5 multicenter trials and are needed to document beneficial effects.“
`
`3. Heart transplantation: INO is a useful adjunct to the postoperative
`Y
`treatment protocol of heart transplant patients with pulmonary
`hypertension. It selectively reduces PVR and enhances right ventricular
`stroke worl<.35
`
`. Lung tnmsplantation: 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.“
`. 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 AML37
`
`Ex. 2029-0013
`
`

`
`
`
`jPediatricandNeonatalMechanicalVentilation
`
`
`
`
`
`6. Neonatal chronic lung disease: Defined as the continuingneed in preterm
`infants for supplemental inspired oxygen at 36 weeks postconceptional
`age. INO improves oxygenation in most infants With early chronic lung
`38
`disease, without inducing changes in markers of inflammatory or
`
`oxidative injiuiy
`
`Adverse Effects of INC
`
`1. Rebound efiects: 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 foftunately not observed.“
`. 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
`1996,'270:565—73.
`”
`. Frostel CG, Fratacci MD, Wain IC et al. Inhaled nitric oxide: A selective
`pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.
`Circulation 1991 ;83:2038-47.
`. Leffer CW, Hess1er]R, Green R5. The onset of breathing at birth stimulates
`pulmonary vascular prostaglandin synthesis. Pediatr Res 1984;18:938-42.
`. Kinsella II’, Abman SH. Inhaled nitric oxide: Current and future uses in
`neonates, Semin Perinatol 2000;24(6):387-95.
`. Abman SH, Chatfield BA, Hall SL, Mcmurthy IF. Role of endothelium
`derived relaxing factors during transition of pulmonary circulation at birth.
`Am I Physiol 1990;259:1921-7.
`. UK Collaborative ECMO Trial Group. UK Collaborative randomized trial
`of neonatal extracorporeal membrane oxygenation. Lancet 1996;348:75-82.
`. 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.
`. Randerrnacher P, Santak P, Becker H, Falke KI. Prostaglandin E1 and
`nitroglycerine reduce pulmonary capillary wedge pressure but worsen V/
`Q distribution in patients with adult respiratory distress syndrome.
`Anesthesiology 1989;70:601—9.
`. Neonatal inhaled nitric oxide group ( NINOS). Inhaled nitric oxide in full-
`terrn and nearly full-term infants with hypoxic respiratory failure. N Eng]
`Med 1997;336:597—604.
`
`Ex. 2029-0014
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`

`
`7
`
`~
`
`T3‘
`'3'
`E’.
`(D
`a.
`3.PF
`.1.O
`
`0E
`
`5.9.
`(D
`
`. Abman SH, Dobyns EL, Kinsella JP. Role of inhaled nitric oxide in the
`treatment of children with severe acute hypoxic respiratory failure. New
`Horizons 1999;7(3):386-98.
`. Kinsella ]P, Troug W, Walsh W, et al. Randomized multicenter trial of
`inhaled NO and HFOV in severe PPHN. J Pediatr 1997;131:533-62.
`. Kinsella JP, Abman SH. Recent developments in inhaled nitric oxide therapy
`for the newborn. Pediatr l999;121~5.
`. Tworetzky W, Bristow J, Moore P, Brook MM. Inhaled nitric oxide in
`neonates with persistent pulmonary hypertension. The Lancet 2001:3257:
`118-20.
`. Cornfield DN, Maynard RC, ’O'deregner RA, Guiang SF, et al. Randomized
`controlled trial of low dose inhaled nitric oxide in the treatment of term
`and near term infants with respiratory failure and pulmonary hypertension.
`Pediatrics 1999;104(5):1U89-94..
`. Clark RH, Kueser T], Walker MW, Southgate WM, Huckaby IL, Perez IA, et
`al. Low dose nitric oxide therapy for persistent pulmonary hypertension of
`the newborn. N Eng J Med 2000;342:496-503.
`. Davidson D, Barefield ES, Kaltwinkel J, Dudell G, Damask M, Straube R, et
`al. Safety of withdrawing inhaled nitric oxide therapy in persistent
`pulmonary hypertension. Pediatrics 1999;104:231—6.
`'
`. Steinhorn RH, Cox PN, Fineman JR, et al. Inhaled nitric oxide enhances
`" oxygenation but not survival in infants with alveolar capillary dysplasia.]
`Pediatr 1997;I30:417—22.
`. Finer NN, Barrington K]. Nitric oxide for respiratory failure in infants born
`at or near term (Cochrane Review). Cochrane Database Syst Rev 2001;4:
`201-7.
`. Elligton M, ‘O’ Reilly D, Allred EN, Mccorrnick MC, et al. Child health
`status, neurodevelopmental outcome, parental satisfaction in a randomized,
`controlled trial of nitric oxide for persistent pulmonary hypertension of the
`newborn. Pediatrics 2D0l;107(6):1351—6.
`. Kinsella IP. Use of inhaled nitric oxide during interhospital transport of
`newborns with hypoxemic respiratory failure. Pediatrics 2002;109:158-61.
`. Mercier IC. Franco-Belgium Neonatal Study Group on inhaled NO.
`Uncertainties about the use of inhaled nitric oxide in preterm infants. Acta
`Paediatr 2001 ;90:I5-8.
`. Bland RD. Inhaled nitric oxide: A premature remedy for chronic lung
`disease? Pediatrics 1999;103:667-70.
`. Kinsella JP, Walsh WP, Bose CL,*Gerstmann DR, Labelle J], Sardesai S, et al.
`Inhaled nitric oxide in premature neonates with severe hypoxemic failure,
`a randomized controlled trial. Lancet 1999;354:1061-5.
`. Channik RN, Newhart IW, Johnson FW, Will.iams P], Auger WR, Fedullo
`PF, et al. Pulsed delivery of inhaled nitric oxide to patients with primary
`pulmonary hypertension: An ambulatory delivery system and initial clinical
`tests. Chest 1996;109:1545-9.
`. Rossaint R, Falke K], Slama K, et al. Inhaled NO for the ARDS. N Eng] Med
`1993;328:399.
`A
`. Baxter F], Randall J, Miller ID, Higgins DA, Powles C, Choi PT. Rescue
`therapy with inhaled nitric oxide in critically ill patients with severe
`hypoxemic respiratory failure 2002. Can J Anaesth 2002;49:315-8.
`. Puybussel L, Stewart T, Rouby J], et al. Inhaled NO reverses the increase in
`PVR induced by permissive hypercapnia in patients with ARDS.
`Anesthesiology 1994;230:1254-9.
`
`’
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`Ex. 2029-0015
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`

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`Pediatric1andNeonatalMechanicalVentilation
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`. Payen DM. Is nitric oxide inhalation a ”cosmetic” therapy in acute
`respiratory distress syndrome. Am I Resp Crit Care Med 1998;157:1361-2.
`. Baldauf M, Silver P, Sagy M. Evaluating the Validity of responsiveness to
`inhaled nitricloxide in pediatric patients with ARDS, an analytic tool. Chest
`2001;119:1166-75.
`
`. Maxey TS, S 'th CD, Kern IA, Tribble CG, Jones DR, Kron IL, et al. Beneficial
`effects of inh ed nitric oxide in adult cardiac surgical patients. Ann Thorac
`y Surg 2OD2,'73:529-32.
`. Rimensberger PC, Schopfer IS, Bemer M, Iaggi E, et al. Inhaled nitric oxide
`versus aerosolized iloprost in secondary pulmonary hypertension in
`children with congenital heart disease: Vasodilator capacity and cellular
`mechanisms. Circulation 2001;103:544-8.
`. Nakagua TA, Johnson S}, Falkos SA, Gomez R], Morris A. Life-threatening
`status asthmaticus treated with inhaled nitric oxide. J Pediatr 2000;137:119-
`22.
`,
`. Losert H, Schmid K, Wilfing A, Winkler S, Staudinger T, Kletzmayer J.
`Experiences with severe falciparum malaria in the intensive care unit.
`Intensive Care Med 2000;26:195-201.
`. Ardehali A, Hughes K, Sadeghi A, Esmailian F, Marelli I, et al. Inhaled
`nitric oxide for pulmonary hypertension after heart transplantation.
`Transplantation 200l;72:638-41.
`. Ardehali A, Laks H, Levine M, Shipineir R, Ross D, Watson Lo, et al.
`Aprospecfive trial of inhaled nitric oxide in clinical ltmg transplantation.
`Transplantation 2001;72:112-5.
`. Antman EM, Braunwald E. Acute Myocardial Infarction. In: Heart Disease,
`(6th edn), Braunwald E, Ziper DP, Libby P (Eds). WB Saunders Company
`2OO1;1114-12l9.
`. Clark PL, Ekekezie II, Kaftan HA, Caster CA, Truog WE Safety and efficacy
`of nitric oxide in chronic lung disease. Arch Dis Child Fetal Neonatal
`2002;86:41—5.
`
`. Ivy DD, Kinsella JP, Ziegler W, et al. Dipyridamol attenuates rebound
`hypertension after inhaled NO withdrawl in postoperative congenital heart
`disease. J Thorac Cardiovasc Surg l998;115:875—82.
`. George TN, Johnson K], Bates ]N, et al. The effect of inhaled NO therapy on
`bleeding time and platelet aggregation in neonates. J Pediatr 1998;132:731-
`4.
`
`‘
`
`. Barbera IA, Roger N, Roca J, et al. Worsening of pulmonary gas exchange
`with NO inhalation in COPD. Lancet 1996;347:436—40.
`. Shah AS, Smerling A], Quaegebeur IM, Michler RE. Nitric Oxide treatment
`for pulmonary hypertension after neonatal cardiac operation. Ann Thorac
`Surg 1995;60:1791—3.
`
`Ex. 2029-0016