Intensive Care Chapter ISSN : 2349-6592 Journal of ... july...Dr Rakshay Shetty (Hyderabad), ... Dr...

JOURNAL OF PEDIATRIC CRITICAL CAREaVol. 1 - No.3 July - September 2014

Vol.1 No.3July-Sept. 2014

Journal ofPediatric Critical Care

Offi cial Journal of IAP Intensive Care Chapter

Intensive Care ChapterIndian Acqademy of Pediatrics

ISSN : 2349-6592Website : www.journalofpediatriccriticalcare.com

CONTENTSFrom Editors DeskNCPCC2014 Conference (Nov-6-9 ) HighlightsEvidence Based PracticeCommon Day-to-day Questions in the PICU Regarding Invasive Mechanical Ventilation- Shekhar T Venkataraman

Original Research ArticleIntrapleural Fibrinolytic Therapy with Alteplase in Empyema Thoracis in Children- A prospective pilot studyPradeep Sharma; et al

Symposium: Pediatric Cardiac Intensive Care - 2 Myocarditis in Children -Vinay Joshi; et alCommon congenital Heart Defects -Jesal Sheth; et alPostoperative Care of Common Congenital Heart Defects -Ravi R Thiagarajan Acute Kidney Injury in Children after Cardiac Surgery -Lalitha AV; et alTranscutaneous Closure of ASD and other Cardiac Defects -Vikas Kohli; et al Perioperative Management of total Anomalous Pulmonary Venous Drainage (TAPVD) -Vishal K,Singh; et alPerioperative Management for Transposition of Great Arteries (TGA) -Ajay Kumar Gupta; et alUniventricular Heart Perioperative Management Strategy -Vishal K Singh; et alPediatric Mechanical Circulatory Support -Michael A Maymi; et alHeart Transplantation in Pediatrics -Dipankar Gupta; et al

Best EvidenceJournal Scan -Indira Jayakumar; et al

Critical ThinkingPICU Quiz -Nameet Jerath

JOURNAL OF PEDIATRIC CRITICAL CAREVol. 1 - No.3 July - September 2014 b

PICU Cases and Procedures“Hands on Management”: Simulation Workshop

Date: November 6, 2014 Venue: BLK Superspeciality Hospital, New Delhi

Course Director:Dr Praveen Khilnani (Delhi)International Faculty:Dr Vinay Nadkarni (USA), Dr Utpal Bhalala (USA), Dr Jerry Zimmerman (USA)

National Faculty:Dr Rakshay Shetty (Hyderabad), Dr Jesal Sheth (Mumbai), Dr S Deopujari (Nagpur),Dr Rachna Sharma (Delhi), Dr Jhuma Shankar (Delhi), Dr Urmila Jhamb (Delhi), Dr Shalu Gupta (Delhi)

So what is so Special regarding SIMULATION workshop?• New C oncept: easy learning...Close to reality… you have to see to believe it.• It is a Real life experience in an artifi cially controlled and interactive environment…• Participant will learn from mistakes… under expert faculty guidance….. Without risking patient safety• Limited seats Register early!! www.ncpcc2014.com on line• Delegate will Learn to Manage… Critically ill Child

Real Life Cases of Pediatric Shock (Septic, Dengue, Cardiac), Respiratory Failure, Cardiac Arrest, Arrhythmias, Seizures, Coma

Perform Procedures such as Intubation, CPR, Defi brillation, Mechanical Ventilation, IV Access, Central Line Placement, Fluid Resuscitation, Inotropes, Chest Tubes

It is Completely Hands on Workshop on Live full body computerized mannequins… with features of full display of real time cry, drooling, eye blinking, heart rate, rhythm, pulse, blood pressure, saturations, cyanosis, heart sounds, breath sounds, CPR, Neuro status, pupils size, reaction and a full response to inotropes and various emergency medications………………

JOURNAL OF PEDIATRIC CRITICAL CARE89Vol. 1 - No.3 July - September 2014

Contents

From Editors Desk 91

Editorial Board 92

IAP Intensive Care EB 2014 93

Author Instructions 94

NCPCC 2014 Highlights 99

Evidence Based Practice 101Common Day-to-day Questions in the PICU Regarding Invasive Mechanical VentilationShekhar T. VenkataramanChildren’s Hospital of Pittsburgh, UPMC, Pennsylvania, USA

Original Research ArticleIntrapleural Fibrinolytic Therapy with Alteplase in Empyema Thoracis in Children - A prospective pilot study

108

Sharma PK, Saikia B, Sharma R, Jain P, Hussain Zahid, Khilnani PBLK Super Speciality Hospital, New Delhi, India

Symposium: Pediatric Cardiac Intensive Care - 2Myocarditis in Children 114Vinay Joshi, Preetha JoshiKB Ambani Hospital, Mumbai, India

Common Congenital Heart Defects and Perioperative Issues in Management 121Jesal Sheth*, Praveen Khilnani***Fortis Mulund, **BLK Superspeciality Hospital, New Delhi

Post-operative Care of Common Congenital Heart Defects 127Ravi R. ThiagarajanBoston Children’s Hospital, Harvard Medical School, Boston, MA, USA

Acute Kidney Injury in Children after Cardiac Surgery 133Lalitha AV, Aby Dany Varghese, Anil VasudevanSt John’s Medical College and Hospital, Bangalore, India

Transcatheter Closure of the Atrial Septal Defect and other Cardiac Defects: Current status

143

Vikas KohliDirector, Childrens Heart Institute, BLK Superspeciality Hospital, New Delhi, India

Perioperative Management of Total Anomalous Pulmonary Venous Drainage 151Vishal K Singh, Arun Ramaswamy, Amit Varma, Rajesh SharmaFortis Escorts Heart Institute, Okhla Road, New Delhi, India

Perioperative Management for Transposition of Great Arteries 161Ajay Kumar Gupta, Vishal K Singh, Amit Varma, Rajesh SharmaFortis Escorts Heart Institute, Okhla Road, New Delhi, India

JOURNAL OF PEDIATRIC CRITICAL CAREVol. 1 - No.3 July - September 2014 90

Univentricular Heart – Perioperative management strategy 173Vishal K Singh, Amit Varma, Rajesh SharmaFortis Escorts Heart Institute, Okhla Road, New Delhi, India

Pediatric Mechanical Circulatory Support 186Michael A Maymi, Dipankar Gupta, Wendy E Barras, Joseph Philip, Frederick Jay Fricker,Mark S Bleiweis, Jai P UdassiPediatrics, Cardiology, Intensive Care Unit and Congenital Heart Center, Shands Childrens Hospital, University of Florida College of Medicine, Gainnesville, Florida, USA

Heart Transplantation in Pediatrics 193Dipankar Gupta, Frederick Jay Fricker, Mark S Bleiweis, Jai P UdassiCongenital Heart Center, University of Florida College of Medicine, Gainesville, Florida, USA

Journal Scan 208Indira Jayakumar, Rajeswari Natraj, Sathish Kumar Kandath, Ravi Kumar Thambithurai, Suchitra RanjitDepartment of Pediatric Emergency and Intensive Care, Apollo Childrens Hospital, Chennai, India

Critical Thinking: PICU Quiz 214Nameet JerathIndraprastha Apollo Hospital, New Delhi, India

Printed at: Process & Spot C-112/3, Naraina Industrial Area, Phase-1, New Delhi - 110 028


From Editors Desk

Dear Colleagues It gives me great pleasure in bringing out the July-Sep 2014 issue of Journal of Pediatric Critical care (third quarterly issue of JPCC). There has been a surge of articles to keep our editorial reviewers busy. I wish to thank all the editorial board members for sparing their valuable time and effort in reviewing the articles in a time bound manner.In this issue, in addition to regular features including Journal scan, Quiz, Original research articles; common day to day issues in PICU related to invasive mechanical ventilation are addressed by Dr Shekhar T Venkataraman (Pittsburgh, USA) in light of currently available evidence under Evidence based practice.Many evidence based review articles are published under the symposium Pediatric Cardiac Intensive Care-2 (last JPCC issue had part 1) addressing common issues such as Myocarditis, lesion specifi c care of common congenital heart defects, device closure of heart defects such as ASDs, mechanical circulatory devices and cardiac transplantation by national and international authors from few of the worlds best congenital heart centers.Website is now functional www.journalofpediatriccriticalcare.comAll previous issues of the journal and author instructions can be downloaded from the website .Other websites such as www.PICCIndia.org (IAP intensive care chapter website) and www.NCPCC2014.com (IAP intensive care annual conference website; Conference to be held Nov 6-9, 2014 Hotel LeMeridien, Delhi), are also interlinked with related ISCCM, IAP, IJCCM, Indian Pediatrics, websites. NCPCC2014 organizing and scientifi c committee has put up a great scientifi c program, Advanced pediatric critical care CME, BPICC as well as some new innovative workshops such as Mangement of PICU cases and Procedures (Hands on) on live Mannequins (SIMULATION), Neuro Renal critical care, Advanced ventilation and respiratory ECMO, Ultrasound (Pulse!!), Hemodynamic monitoring and Cardiac ECMO, and Critical care Nursing.Online submission of articles and online time bound review process is in its fi nal stages… soon to be fully functional.Subsequent issues are planned on Neuro, Nephro and Respiratory critical care to keep the reader abreast with the latest in the fi eld of Pediatric critical care.Hoping for a continued support from all the colleagues SincerelyDr Praveen Khilnani MD FAAP FSICCM FCCMEditor in Chief JPCCVice President ISCCMDirector Pediatric Critical Care and Pulmonology ServicesBLK Superspeciality Hospital, New [email protected]


Journal of Pediatric Critical Care (JPCC)Editorial Board

Editor-In-Chief:Dr Praveen Khilnani

Senior Editors and Reviewers:Dr (Prof) Sunit Singhi

Dr K ChughDr S UdaniDr S Ranjit

Sr Rajiv UttamDr Anil Sachdev

Dr Madhu OtivDr S Deopujari

Dr Bala RamachandranDr S Soans

Associate Editors:Dr Nameet JarathDr Kundan MittalDr Rakshay ShettyDr BasavarajDr GnanamDr Sandeep Kanwal

Executive Editor:Dr V S V Prasad

Managing Editor:Dr Dhiren Gupta

Executive Members:Dr Arun BansalDr Banani PoddarDr Ebor JacobDr Lokesh TiwariDr Partha BhattacharyaDr Prabhat MaheshwariDr Dinesh ChirlaDr Deveraj RaichurDr KarunakaraDr Mritunjay PaoDr Deepika GandhiDr Bhaskar SaikiaDr Shipra GulatiDr Vikas TanejaDr Indira JayakumarDr Sanjay BafnaDr Sanjay GhorpadeDr Sagar Lad

Biostatistics:Dr M JayshreeDr Jhuma SankarDr Arun Baranwal

Ethics:Dr Urmila JhambDr Rakesh LodhaDr Meera RamakrishnanDr Vinay Joshi

Website:Dr Maninder DhaliwalDr Vinayak PatkiDr Anjul Dayal

Publication:Dr Rachna SharmaDr Pradeep SharmaDr Sanjeev Kumar

International Advisory Board:Dr Niranjan KissoonDr Jerry ZimmermanDr Joseph CarcilloDr Ashok SarnaikDr Peter CoxDr Shekhar VenkataramanDr Vinay NadkarniDr Mohan MysoreDr Utpal BhalalaDr Suneel PooboniDr Rahul BhatiaDr Ravi Samraj

National Advisors:Dr Y AmdekarDr S C AryaDr R N SrivastavaDr C P BansalDr V YewaleDr M P Jain


IAP Intensive Care ChapterExecutive Board 2014


Manuscript submission will be possible using our online submission system shortly. All submissions should be made by e mail until further announcement regarding the online submission details and the journal website: [email protected]

Journal of Pediatric Critical Care is published quarterly (January, April, July and October) by IAP intensive care chapter. Manuscripts are judged by reviewers solely on the basis of their contribution of original data and ideas, and their presentation. All articles will be critically reviewed within 2 months, but longer delays are sometimes unavoidable. All manuscripts must comply with Instructions to Authors.

COPYRIGHT Submissions considered for publication in JOURNAL OF PEDIATRIC CRITICAL CARE are received on the understanding that they have not been accepted for publication elsewhere and that all of the authors agree to the submission. The journal requires approval of manuscript submission by all authors. A cover letter signed by all authors constitutes submission approval. Manuscripts will not receive a fi nal decision until a completed Copyright Status Form has been received. As soon as the article is published, the author is to have considered transferred his right to the publisher. This transfer will ensure the widest possible dissemination of information. All concepts, ideas, comments, manuscripts, illustrations, and all other materials disclosed or offered to the IAP intensive care chapter on or in connection with this Journal are submitted without any restrictions or expectation of confi dentiality. The IAP intensive care chapter shall have no fi nancial or other obligations to you when you do not submit such information, nor shall you assert any proprietary or moral right of any kind with respect to such submissions. The IAP intensive care chapter shall have the right to use, publish, reproduce, transmit, download, upload post, display or otherwise distribute your submissions in any manner without notice or compensation to you.

ETHICS Investigations on human subjects should conform to accepted ethical standards. Fully informed consent should be obtained and noted in the manuscript. For all manuscripts dealing with experimental work involving human subjects, specify that informed consent was obtained following a full explanation of the procedure (s) undertaken. Patients should be referred to by number; do not use real names or initials. Also the design of special scientifi c research in human diseases or of animal experiments should be approved by the ethical committee of the institution or conform to guidelines on animal care and use currently applied in the country of origin.

STYLE OF MANUSCRIPTS All contributions should be written in English. Spelling should be American English. In general, manuscripts should be prepared according to International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals. JAMA 1997; 269: 927-934. Manuscript should be as concise and clear as possible. Manuscripts not following Instruction to Authors will be returned to the authors.

LANGUAGE Only English articles will be accepted. Prior to submission, manuscripts prepared by authors whose native language is not English should be edited for proper spelling, grammar, and syntax by a professional editor or colleague fl uent in English.

MANUSCRIPTS CATEGORIES Materials reviewed for publication in JOURNAL OF PEDIATRIC INTENSIVE CARE include the following:

EditorialsEditorials will present the opinions of leaders in pediatric intensive care

Author InstructionsFor JPCC (Journal of Pediatric Critical Care) Manuscript Submission


Original articlesOriginal clinical or laboratory investigation of clinical subjects should be reported. The material should be presented as concisely as possible.Review articlesReviews should document and synthesize current information on timely subjects.Case reportsA case report should describe a new disease, or confi rmation of a rare or new disease; a new insight into pathogenesis, etiology, diagnosis, or treatment; or a new fi nding associated with a currently known disease.Rapid communicationsThese should be short papers, brief laboratory investigations and preliminary communications, which report new and exciting results requiring rapid publication.LettersThese should be submitted in response to material published in the journal to make small clinical points or to introduce a point of view. Letters do not carry an abstract.Book reviewsReviews of newly published literature of interest.

MANUSCRIPT Manuscript submission should be made by e mail. Manuscripts should be submitted with text and tables, preferably in a recent Word or Word Perfect for Windows format. If article is submitted electronically, there is no need to send a hard copy. The Copyright Status Form should also be sent by e mail or fax or regular mail.Manuscripts should be clearly in double spacing on one side of good quality A4 paper (30 x 21 cm), using 2.5 cm margins. Pages should be numbered consequently in the top right-hand corner, commencing with the Title Page and including those containing Acknowledgements, References, Tables, and Figures.Conventional Manuscript The manuscript should be arranged as follows, with each section beginning on a separate page, except in the category of Rapid communications.Cover letter A cover letter, in which the authors certify that the work submitted to The JOURNAL OF PEDIATRIC CRITICAL CARE has not been published elsewhere, in any form and that it is not being submitted simultaneously to another journal, should accompany the manuscript. A Copyright Status Form (see next page) signed all authors must accompany each manuscript.Title pageThe category of manuscripts (as listed above) should appear on the title page. The title on the title page should contain no more than 80 letters and spaces. A running title of no more than 40 letters and spaces should be supplied. Each author’s fi rst and last name as well as middle initial, highest academic degree, name of department(s) and institutions to which the work should be attributed, and address should appear. The author to whom communications will be directed should be designated and his or her telephone and FAX number and E-mail addresses (obligatory for submission) provided.AbstractThe abstract should be no longer than 250 words for full-length articles and commensurately shorter for brief communications and case reports. Abstracts should summarize the problem addressed, investigational approach, results, and relevant conclusions.Key wordsNo more than nine key words that will assist indexer in cross-indexing the article should be supplied. It is recommended that authors consult the medical subject heading from Index Medicus.


Main textThe text of observational and experimental articles is usually divided into sections with headings Materials and Methods, Results and Discussion. Long articles may need subheading within some sections. The purpose of the article and the rational for the study or observation should be summarized in an introductory paragraph.Materials and Methods should be described in suffi cient detail to leave the reader in no doubt as to how the results were obtained.Results should be presented in a logical sequence the text.Tables and fi gures should not include material appropriate to the discussion.

DiscussionThe new and important aspects of the study and the conclusions should be emphasized, without repeating data in detail. This section should consider the implications of the fi nding and their limitations. Link the conclusions with the goals of the study, and relate the observations to other relevant studies. New hypotheses and recommendations, when appropriate, may be included. Acknowledgement should be made only to persons who have made genuine contributions and who endorse the data and conclusions.

ReferencesReferences must be double-spaced and cited in text by using Arabic numerals in the order in which they appear in the text. Abbreviate titles of the journals according to Index Medicus. Unpublished data and personal communications should be given in round parentheses in the text and not as references. List all authors or editors, but if the number exceeds six, give six followed by et al.References must be listed in Vancouver style: Standard journal articles: [1] Rose ME, Huerbin MB, Melick J, Marion DW, Palmer AM, Schiding JK, et al. Regulation of interstitial excitatory amino acid concentrations after cortical contusion injury. Brain Res 2002;935(1-2):40-6. Books: [2] Murray PR, Rosenthal KS, Kobayashi GS, Pfaller MA. Medical microbiology. 4th ed. St. Louis: Mosby; 2002.[3] Berkow R, Fletcher AJ, editors. The Merck manual of diagnosis and therapy. 16th ed. Rahway (NJ): Merck Research Laboratories; 1992. Chapter in a book:[4] Meltzer PS, Kallioniemi A, Trent JM. Chromosome alterations in human solid tumors. In: Vogelstein B, Kinzler KW, editors. The genetic basis of human cancer. New York: McGrawHill, 2002; p. 93-113. World Wide Web:[5] Autism Speaks. Transition Tool Kit: A guide for families on the journey from adolescence to adulthood, 2011. Available at: http://www.autismspeaks.org/family-services/tool-kits/transition-tool-kit. Accessed October 6, 2012

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FiguresNumber fi gures as Fig. 1, Fig. 2, etc and refer to all of them in the text.Each fi gure should be provided on a separate sheet. Figures should not be included in the text.

For the fi le formats of the fi gures please take the following into account:• Line art should be have a minimum resolution of 1200 dpi, save as EPS or TIFF- Do not use faint lines and/or lettering and check that all lines and lettering within the fi gures are legible at fi nal size


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Units and AbbreviationsManuscript should be in metric units. Standard abbreviations may be used and should be defi ned in the Abstract and on the fi rst mention in the text. In general, a term should not be abbreviated unless it is used repeatedly and the abbreviation is helpful to the reader.

Review and Selection of PapersAll articles will be critically evaluated by at least three reviewers of the editorial board (or known experts in the fi eld) within 2 months, but longer delays are sometimes unavoidable.

Proofs and ReprintsProofs are sent to the corresponding author, together with a reprint order form approximately 6 weeks prior to the publication. Authors should retain a copy of the original manuscript. Only printer’s errors may be corrected; no changes in, or additions to, the edited manuscript will be allowed at this stage, unless in reply to specifi c editorial queries or requests. Corrected proofs must be returned within 48 hours of receipt, preferably by e mail or fax. If the publisher has not received a reply after 15 days, the assumption will be made that there are no errors to correct, and the article will be published after in-house correction. The reprint order form (with number of reprints requested, invoice and delivery address) should be returned with the corrected proof. Reprints may be ordered prior to publication on the form provided. The designated reviewing author will be responsible for ordering reprints for all authors. Reprints ordered after publication of the journal can be ordered at increased cost by special arrangement.The publisher (IOS press) will provide to authors with a free watermarked PDF fi le of their article.

CHECK LIST FOR AUTHORSLetter to submission Signed Copyright Status Form Three copies of article Title page Category of manuscript Title of article Running title Name (s), academic degrees, and affi liations of author (s) Name, address, telephone and FAX number and e-mail address of corresponding author Abstract including key words (except for Letter to the Editor) Text (double spaced) References (double spaced), on a separate sheet Tables (double spaced), on a separate sheet Figure legends (double spaced), on a separate sheet Figures properly labeled (three sets of glossy prints) Informed consent or certifi cate of ethical committee if indicated.


JPCC Copyright Status Form

Manuscript Number: JPCC________ Received Date: _______________ Manuscript Title : _____________

______________________________________________________________________________________

I/We hereby confi rm the assignment of all right, title and interest in and on the manuscript named above in all versions, forms and media, now or hereafter known, to the IAP intensive care chapter effective if, and when it is accepted for publication. I/We also confi rm that the manuscript contains no material the publication of which violates any copyright or other personal or proprietary right of any person or entity.

I/We shall obtain and include with the manuscript written permission from the respective copyright owners for the use of any textual, illustrative or tabular materials that have been previously published or are otherwise copyrighted and owned by third parties. I/We agree that it is my/our responsibility to pay any frees charged for permissions. I/We affi rm that all authors have participated in the study, have been and approved the manuscript, and accept responsibility for the content of the article and its accuracy; that complied with the “Instructions to authors”.

To be signed by at least all the authors. Please note: Manuscript cannot be processed for publication until the Editor has received this signed form.

Printed Name ______________________ Printed Name ______________________

Signature ______________________ Signature ______________________

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16th National Conference of Pediatric Critical Care 2014Annual Conference of Indian Academy of Pediatric-Intensive Care Chapter

Hosted by:IAP Intensive Care Chapter, Delhi

Indian Academy of Pediatrics - Delhi Branch

Venue:Hotel Le Meridien, Janpath, New Delhi

6th to 9th November 2014

CME -7th November, 2014• Advanced Pediatric Critical Care

BPICC -6th to 7th November, 2014• Basic Pediatric Intensive Care Course

Workshop -6th November, 2014• Advanced Mechanical Ventilation• Advanced Hemodynamic Monitoring• Neuro-Renal Critical Care Skills NEW• Bedside Ultrasound & Echocardiography• PICU Case Scenarios and Procedures:

Simulation NEW• Critical Care Nursing Course

• International Faculty:Dr Jerry Zimmerman (Seatle, USA)Dr Joseph Carcillo (Pittsburgh USA)Dr Ravi Thigarajan (Boston Childrens USA)Dr Shekhar Venkataraman (Pittsburgh USA)Dr Mohan Mysore (Omaha USA)Dr Utpal Bhalala (John Hopkins, USA)and more..

• Eminent National Faculty

ConferenceDr Anil SachdevMs Manju Syal / Mr Satender NegiDepartment of PediatricsInstitute of Child HealthSir Ganga Ram HospitalRajinder NagarNew Delhi-110 060Tel: 011-42251855M. + 919990851191Fax: 011-42251856

Workshop/CMEDr Krishan ChughMs Aparna SharmaSecretaryDepartment of PediatricsFortis Memorial Research InstituteSector - 44, Gurgaon Haryana - 122 002Tel: +911244386666Fax: +911244962222Mobile: +919810324302

For delegates registration and general enquiries please contact:

Mr Jatin BatraDreamz Conference Management Pvt. Ltd. 218, Ansal Magestic Tower, Vikas PuriNew Delhi - 110 018Mobile: 9810558569Email: [email protected]

Registration Fee

Category Till 31.04.2014

Till 30.06.2014

Till 30.10.2014 Spot

Delegates ` 4000 ` 5000 ` 6000 ` 7000

PG Student ` 3000 ` 3000 ` 4500 ` 6000

Certifi cate from HOD is Mandatory

Additional ` 3000 ` 4500 ` 5500 ` 7000

Foreign Delegate US$ 200 US$ 200 US$ 200 US$ 200

CME: ` 2000 Workshop: ` 2500 BPICC: ` 3500

• Kindly send DD/Cheque in favor of “IAP Intensive Care Chapter Delhi” payable at NEW DELHI. For outstation cheque, please add ` 100/-.

• Website www.ncpcc2014.com and Online Registration Available.


Workshops at NCPCC 2014

Two days workshop November 6-7, 2014Basic Pediatric Intensive Care CourseDr Anita Bakshi, Dr Nameet Jerath, Indraprastha, Apollo Hospital, New DelhiThe two days course does a comprehensive cover of the basics of dealing with and managing sick children. On the work stations the emphasis is on the practical issues with airway management, central line placement and RRT forming central points. Stations will also deal with the basics of hemodynamic monitoring, commonly encountered case scenarios in the PICU.

One day workshops: November 6, 2014Advanced Hemodynamic MonitoringDr Vishal Singh Dr Parvati Iyer, Escorts Heart Institute, New DelhiThe aim of the workshop is to strengthen knowledge of the basic principles of hemodynamic monitoring and streamline clinical translation of the data to manage the patient optimally.

Advanced Mechanical VentilationDr Vikas Taneja, Dr Krishan Chugh, Fortis Hospital, GurgaonThis workshop on advanced mechanical ventilation has been designed keeping in view the interests of the practicing intensivists across the country. Being an advanced workshop, the focus of this workshop would be entirely on newer techniques and advances in the fi eld of mechanical ventilation e.g. HFO, NIV.

Bedside Ultrasound & EchocardiographyDr Maninder S Dhaliwal, Dr Veena, Medanta Medicity, GurgaonThe use of bedside ultrasound is rapidly increasing in pediatric critical care settings & is changing our clinical practice to new horizons, where some have even called it as the future stethoscope. The course is designed to maximize time spent engaged in practical skills like scanning or practicing image interpretation. The issues you face each day in PICU where USG can help will be addressed in this comprehensive one day course.

Case Scenarios and PICU Procedures: SimulationDr Vinay Nadkarni, Dr Praveen Khilnani, BLK Superspeciality Hospital, New DelhiOne day “Hands on Only” workshop where in delegates will learn to manage… Real life Cases of Pediatric Shock (Septic, Dengue, Cardiac), Respiratory Failure, Cardiac Arrest, Arrhythmias, Seizures, Coma and Perform PICU Procedures Such as Central Line, Intubation and Airway Management, Defi brillators on Full Body Computerized Mannequins with Features of full Display of Real Time Events: S Imulation

Critical Care Nursing CourseDr Ravi Shankar Dr Rajiv Uttam, Max Superspeciality Hospital, Saket, New DelhiThrough a combination of interactive lectures and hands-on training sessions, course attendees will learn various nursing care practices like assessment of a sick child in PICU, handling a patient on ventilator, preparation for procedures, disease specifi c nursing care etc.

Neuro-Renal Critical Care SkillsDr Prabhat Maheshwari, Dr Rajiv Chabra, Artemis Helth Care Institute, GurgaonFor pediatricians and pediatric intensivists interested in neuro and renal critical care, this workshop would provide a lot of interaction and discussions along with hands on experiences on various neuro and renal critical care issues.


Evidence Based PracticeCommon Day-to-day Questions in the PICU Regarding Invasive

Mechanical VentilationShekhar T. Venkataraman MD

Professor and Medical Director, Respiratory Care Services, Children’s Hospital of Pittsburgh, Pennsylvania, USA

Key words: Pediatric, mechanical ventilation, extubation, readiness to extubate.

IntroductionInvasive mechanical ventilation of infants and children is an important component of the practiceof Pediatric Intensive Care. Many aspects of mechanical ventilation are passed on as gospel truth even when there is evidence to the contrary. Some issues are more related to local practice which may be different depending on the particular Pediatric Intensive Care unit. If we, as practitioners of Pediatric Intensive Care were to be asked to defend out practice, we need to be able to provide either evidence-based explanations or at least acknowledge that the practice while appears to be sound lacks the evidence behind it. The questions posed in this article all relate to invasive mechanical ventilation in infants and children, from intubation to weaning and extubation. Each question may have additional subordinate questions within them. The questions are as follows:1. Are cuffed endotracheal tubes to be avoided in

infants and children?2. What is an optimal weaning technique in infants

and children?3. Are “Readiness to Extubate” trials necessary and

if so, what is an optimal trial?4. What is the utility of a “leak test” before

extubation?Question 1. Are cuffed endotracheal tubes to be avoided in infants and children?The traditional teaching for many years in pediatric

Correspondence:Shekhar T. Venkataraman MDProfessor, Departments of Critical Care Medicine and Pediatrics, University of Pittsburgh School of MedicineMedical Director, Respiratory Care ServicesChildren’s Hospital of Pittsburgh, Pennsylvania, USA

anesthesia and intensive care was that only uncuffed tubes should be used in children below the age of 8 years1-5. The rationale for this teaching is as follows:1. The narrowest part of the airway is the cricoid.

• An endotracheal tube should be large enough to seal the cricoid ring, yet small enough to allow an air leak at low pressures.

• An uncuffed tube that just fi ts and seals at the cricoid level makes a cuffed endotracheal tube unnecessary.

• A cuffed tube may increase the incidence and severity of subglottic stenosis due to compression and ischemic injury to the mucosa.

• Support for this rationale is provided by early reports of no subglottic stenosis with the use of uncuffed ETT tubes (Battersby et al6 reported that prolonged nasoendotracheal intubation with uncuffed ETTs did not lead to subglottic stenosis, and Black et al7 reported no evidence of subglottic stenosis in almost 3000 children managed long term with uncuffed ETTs, although they allowed an air leak of at least 25 cm H2O.

2. Decreased work of breathing• An uncuffed ETT allows an ETT of larger

internal diameter to be used• The larger the diameter of the tube, the lower its

resistance to airfl ow and the less it increases the work of breathing (WOB) in the patient who is breathing spontaneously (whether an appropriately sized endotracheal tube increases the inspiratory work of breathing will be discussed later).

Such reports have supported the widespread clinical acceptance of uncuffed ETTs as the standard of care for children, whether for short- or long-term intubation. However, sizing an uncuffed tube for each patient is imperfect even with the development of several formulae. An undersized tube may result in an unacceptable amount of leak around the endotracheal tube leading to unreliable ventilation and oxygenation.


This may necessitate a tube exchange exposing the patient to the risk of reintubation and airway injury8,9. On the other hand, an oversized tracheal tube may cause laryngeal injury10.First, let us examine whether the anatomic rationale is based on accurate data. Most often cited article by Eckenhoff et al in 195111 reported that the laryngeal anatomy in infants and children was funnel shaped with the narrowest point being the laryngeal exit, the cricoid ring. It was also assumed that as the child matured, the larynx assumed a more cylindrical shape of the adult larynx (as shown in Figure below). The source of his information was an article published in 1897 by Bayeux et al12 who based his description on plaster castings of cadaveric larynxes from 15 children (ages 4 months to 14 years). Recently, 2 studies have demonstrated using two different techniques that, in children, the shape of the larynx is conical in the transverse dimension (with the narrowest portion or the apex of the cone at the level of the vocal cords) and cylindrical in the anteroposterior dimension, and does not change throughout development14,15.

Figure : Anatomy of the adult and infant airway. An infant’s airway is conical with the apex of the cone at the level of the cricoid ring, the exit of the larynx while the adult larynx is cylindrical (adapted from Coté CJ, Todres ID13)

The second rationale is the belief that cuffed endotracheal tubes are associated with a greater incidence of airway trauma compared to uncuffed endotracheal tubes. Published data suggests that the risk of subglottic stenosis is related to and parallels the duration of intubation for uncuffed as well as cuffed endotracheal tubes16-18. Khine et al19 reported that 2.4% and 2.9% of patients developed post-extubation stridor with cuffed tubes and uncuffed

tubes, respectively.Newth et al20, in 2004, reported on 597 patients in the fi rst 5 years of life, with 210 having cuffed endotracheal tubes that there were no signifi cant differences in the use of racemic epinephrine for postextubation subglottic edema, the rate of successful extubation or the need for tracheotomy between those with cuffed and uncuffed endotracheal tube in any age group. Weiss et al21, in a randomized controlled trial of 2246 children (1119/1127 cuffed/uncuffed), aged between birth and 5 years, observed that post-extubation stridor occurred in 4.4% of patients with cuffed and in 4.7% with uncuffed endotracheal tubes. The need for exchanging the endotracheal tube was 30.8% with uncuffed tubes compared to 2.1% for cuffed tubes.Mhanna et al22 showed that in young patients <7 yrs of age, the incidence of postextubation stridor was 43% with a cuffed tube compared to 54% with an uncuffed tube.When using cuffed ETTs, care must be taken not to infl ate the cuff to a pressure of greater than 25 cm H2O, even when newer low pressure, high-volume ETTs are used.Question 2: What is an optimal weaning technique in infants and children?First, let us defi ne weaning. Simplistically, weaning from mechanical ventilation is defi ned as the liberation from mechanical ventilation. Weaning is not any of the following: 1) a reduction in PEEP and/or FiO2 in response to improvement in oxygenation, 2) a reduction in the ventilator rate in response to improvement in ventilation, 3) extubation to noninvasive mechanical. Weaning requires the patient to be breathing spontaneously and for the spontaneous efforts to be able to sustain gas exchange as ventilator support is withdrawn. Weaning is defi ned as being successful when a patient can maintain effective gas exchange, with complete spontaneous breathing and without any mechanical assistance. Weaning is defi ned as being a failure when spontaneous efforts are incapable of sustaining effective gas exchange without mechanical ventilator support. Extubation is simply the removal of an endotracheal tube.Weaning should start:1. When the underlying disease process is improving2. When gas exchange is adequate3. When no conditions exist that impose an undue

burden on the respiratory muscles, such as cardiac insuffi ciency, severe hyperinfl ation, severe

EVIDENCE BASED PRACTICE Common Day-to-day Questions in the PICU Regarding Invasive Mechanical Ventilation


malnutrition, and multiple organ system failure4. When the patient is capable of sustaining

spontaneous ventilation as ventilator support is decreased

There are currently two approaches to weaning. One is the method of slowly reducing the ventilator support, including inspired oxygen concentration, to a minimal acceptable level and then assessing the patient’s readiness to extubate. The second is to assess the patient’s readiness to extubate as soon as the patient meets criteria to initiate weaning. The premise underlying the modern method is that not all patients require a prolonged weaning process. Esteban et al23 showed that 76.2% of patients successfully underwent a 2-hour trial of spontaneous breathing, and 89.4% of them immediately underwent extubation. In a recently completed randomized, controlled trial of weaning modes in children, 42% of the patients initially tested with a minimal pressure-support trial passed the test and underwent extubation24. The second approach requires a more coordinated and disciplined approach to managing patients on mechanical ventilation. Paying attention to nutrition, weaning sedation in a timely fashion, and allowing spontaneous breathing to maintain muscle tone and strength are key to successful weaning using the second method. One of the factors that affected weaning in Randolph’s study was sedation24.Question 3: Are “Readiness to Extubate” trials necessary and if so, what is an optimal trial?The fi rst question is the necessity of a “Readiness to Extubate Trial” (RET). These trials are commonly referred to as “Spontaneous Breathing Trials” but as will be described later, they do not fully assess the patient’s ability to breathe spontaneously without any assistance. In the early years of mechanical ventilation of infants and children, it was common to extubate the patient from a low level of ventilator support, usually a ventilator rate of 4-6 breaths/min. Khan et al25 measured the fraction of the total minute ventilation that was provided just before extubation and found that when the ventilator was providing more than 30% of the minute ventilation just before extubation, there was a 27.5% risk of reintubation compared to 8.5% when the ventilator was providing less than 20% of the total minute ventilation. All the patients who were extubated looked comfortable before extubation. The implication

of this fi nding is that when patients are receiving a high level of ventilator support, they may look comfortable but that does not mean that they are ready to be weaned and extubated. Therefore, an RET is essential as a tool to evaluate whether the patient can be extubated.Currently, there are three methods of RETs. These are (1) T-piece trials, (2) CPAP trials, and (3) minimal pressure-support trials. In T-piece trials, the patient is removed from the ventilator but does not undergo extubation. Humidifi ed supplemental oxygen is provided without any positive pressure support. CPAP trials are conducted without removing the patient from the ventilator with a low level (e.g., 5 cm H2O) of CPAP. Minimal pressure support trials are performed with a low level of pressure support ventilation with or without PEEP. The duration of the trial can range from 30 minutes to 2 hours. There are two types of weaning failure: trial failure and extubation failure26-28. Trial failure is defi ned as a failure to sustain effective gas exchange and breathing during a trial of spontaneous breathing while the patient is still intubated. Criteria for failing an RET are given in the Table below. Extubation failure is defi ned as the requirement for reintubation within 48 hours after extubation.

Table: Criteria for Terminating a Spontaneous Breathing Trial1 Inability to maintain gas exchange

Pulse oximeter saturations less than 95% with 40% inspired oxygenNeeding more than 50% inspired oxygen to maintain oxygen saturations >95%

2 Inability to maintain effective ventilationMeasured exhaled tidal volume less than 5 ml/kgAn increase in PaCO2 greater than 50 mmHg or an increase of more than 10 mmHgRespiratory acidosis with pH less than 7.3

3 Increased work of breathingRespiratory rate outside of the acceptable range for their age for age<6 months 20-60/min6 months-2 years 15-45/min2-5 years 15-40/min>5 years 10-35/minUse of accessory respiratory musclesIntercostals/suprasternal/supraclavicular retractionsA paradoxical breathing pattern

4 Other signs of distressDiaphoresisAnxietyHeart rate higher than the 90th percentile for a given ageChange in mental status (agitation or somnolence)Systolic blood pressure lower than the 3rd percentile for a given age



If a patient has any of these signs at any time during the breathing trial, the trial should be terminated and mechanical ventilation should be reinstituted. PaCO2, partial pressure of carbon dioxide. (Adapted from references 25-28).The most common method of RET seems to be the “minimal pressure support”. In children, minimal pressure support is always provided with PEEP. Randolph et al24 described a minimal pressure support technique in which the level of pressure support was adjusted for the endotracheal tube size. On the other hand, in a study comparing minimal pressure support with T-piece trials, Farias et al used a pressure support of 10 cm H2O for all patients26-28. Why is the most common method of an RET the “minimal pressure support” technique?It has been taught for years that the endotracheal tube increases the inspiratory work of breathing. Several studies have shown that the smaller or longer the endotracheal tube, the greater the resistance to inspiratory fl ow. There is a common belief that infants and children are “breathing through a straw”. Physicians are, therefore, reluctant to subject infants and young children to a trial of complete spontaneous breathing with either CPAP or a T-piece circuit because of concern about the work of breathing imposed by the endotracheal tube and the breathing circuit. Proponents of this paradigm routinely extubate patients after a “minimal pressure support” RET. The proponents of a “minimal pressure support” approach to the RET speculate that this overcomes the resistance to breathing through the artifi cial airway.Let us examine this concern critically. First, it is important to understand that the endotracheal tube replaces the natural airway from the nose to the tip of the endotracheal tube. It is not adding to the resistance of the natural airway but replacing it with its resistance. So, is the resistance to breathing spontaneously greater with the endotracheal tube than without it? Newth et al29 have elegantly explained this in a recent review of weaning and exutbation. As explained by them, the subglottic area of the infant is 20 times greater in proportion to body size than that of an adult. The main determinants of endotracheal tube resistance are internal diameter and length. Inspiratory resistance imposed by the endotracheal tube must be understood in the context of the physiologically relevant inspiratory fl ow.

Peak inspiratory fl ow in humans is about 0.5-1 L/kg/min. When we examine the published data and convert the relevant resistace to the pressure drop across the endotracheal tube, it amounts to about 1-2 cms, a trivial amount30-32. When we consider that the endotracheal tube supplants but does not add to the inspiratory resistance, this supposed resistance to breathing is either nonexistent or very trivial. In adults, it has been repeatedly shown recently that the work of breathing was not increased due to the presence of an endotracheal tube33,34. Willis et al35 showed, very elegantly, that the work of breathing associated with T-piece breathing was similar to that with complete spontaneous breathing after extubation in infants and children.In fact, this study showed that the work of breathing with all the support modes including minimal pressure support mode was considerably less than that after extubation. Taken together, these studies suggest that with support modes the patient is receiving a substantial amount of assisted ventilation. Therefore, an RET performed with a support mode may not truly represent complete spontaneous breathing and any evaluation made may overestimation of the ability of children to breathe spontaneously when they are extubated.There is a concern that T-piece trials may not be tolerated by children. The studies by Farias et al26-28

have shown that RETs with a T-piece circuit are well tolerated by children. Despite these theoretical concerns, Farias et al26-28 showed that patients extubated using either T-piece or pressure-support trials had similar rates of reintubation. These should serve to dispel the myth that infants and children cannot be subjected to a T-piece trial before extubation.Question 4. What is the utility of a “leak test” before extubation?It is very common to perform an endotracheal “leak “test” before extubation. So, the obvious questions are:• What is a leak test?• How is it performed?• What are the factors that affect a leak?• What is the interobserver reliability?• Does the leak test predict postextubation stridor?• Does the leak test predict need for reintubation?• What to do if a leak is absent or heard only at high

pressures?Leaking of air around the endotracheal tube



during positive pressure ventilation was used by anesthesiologists to select the appropriate-sized endotracheal tube. Management of croup and epiglottitis initially involved performing a tracheostomy for airway obstruction. Starting from late 1960s, endotracheal intubation, mainly nasotracheal, was employed in epiglottitis and croup. Extubating a patient with epiglottits required vocalization around the endotracheal tube and direct laryngoscopy showing a reduction in infl ammation of the supraglottic structures. In the 1970s, the leak test was used to determine safety of extubation in croup36,37,38. Adderley and Mullins39 were the fi rst to report on their experience with using the leak test to decide to extubate patients with croup. They defi ned leak as one of: vocalization around the tube, an air leak heard with the child coughing, or an airleak demonstrated with a positive pressure insuffl ation of 40cm H20 using a modifi ed Jackson-Rees “T” piece set. Three out of 23 (13%) planned extubations with a leak and 3 out of 8 (37.5%) without a leak failed extubation and were reintubated. These fi ndings were then extrapolated to using the leak test before extubation for all intubated patients. It is important to remember that patients with croup who were intubated usually had an endotracheal tube that was smaller than would have been used in patient without upper airway obstruction. Therefore the signifi cance of a leak test in patients with upper airway obstruction may be different from those without upper airway obstruction. For a leak test to be reliable, it has to have the following characteristics:1. It must be reproducible2. It must not be variable3. It must have good predictive capacity for

important outcomesFirst, it is important to understand the factors that might affect a leak test. Finholt et al40 conducted an elegant study in the operating room where the children were anesthetized. The technique of measuring a leak was that described by Addreley and Mullins39 using a self-infl ating bag with gas fl ow to increase the airway pressure to 40 cms and listening for an audible airleak with a stethoscope over the larynx. They fi rst measured the leak with the head in neutral position with the patient paralyzed with neuromuscular blockade. Following this, measurements were made with partial (fade with

tetanic stimulation) and full (no fade with tetanic stimulation) return of neuromuscular function, with the head turned to the side and when returned to a neutral position (control), with the tube tip just past the vocal cords (high), with the tip just above the point where breath sounds became unequal (low), and with the tube midway between these locations. The “leak” pressure increased progressively with recovery of neuromuscular blockade from 16.9 mmHg to 23.7mmHg (40% increase) with partial return of neuromuscular function and to 30.6 mmHg with full recovery of neuromuscular function (81% increase). With the patient, fully paralyzed, turning the head to one side signifi cantly increased “leak” pressure by 68%. Changing the depth of insertion did not affect the leak pressure. So, the obvious question would be “What are the proper conditions to perform a leak test?”. It seems unreasonable to paralyze the patient just for the leak test. Most of the published studies examining the utility of a leak test in children have been with uncuffed tubes. There are no studies comparing the leak test between cuffed and uncuffed tubes.Second issue is reproducibility and variability. Schwartz et al41 reported that the interobserver difference between 2 anesthetists increased as the value of leak test increased. There was considerable variability in the measurements between the two observers. On the other hand, Pettignano et al42 reported very good agreement between different performers, albeit in a very small sample of 13 children.Third issue is predictability. Most of the studies show at least an increase in the incidence of postextubation stridor in patients with no leak. All the studies that have reported an increased incidence of stridor with no leak extubated their patients irrespective of the leak. At Children’s Hospital of Pittsburgh, currently there are 3 approaches to a patient with no leak at 40 cms:1. Postpone extubation until a leak is present.

Usually treated with steroids for at least 24 hours.2. Postpone extubation but extubate even if no leak

is present but after steroids are administered for 24 hours.

3. Extubate and treat with steroids4. Extubate and only treat patient if patient becomes

symptomatic.



The fi rst 2 choices are based on the fear that they are at higher risk of reintubation and therefore, it is prudent to postpone extubation. A closer examination of the published literature suggests that we need to revise our thinking about not extubating or postponing extubation when there is no leak. The following studies are from patients who were not intubated for upper airway obstruction. Lee et al43 reported that 1/47 (2.1%) children with a leak pressure >40 and 5/100 (5%) with a leak pressure <40 developed post-extubation stridor. When they were analyzed using 10 cm ranges, there was no increase in the incidence of stridor as the leak pressure increased. Mhanna et al22 reported that the occurrence of post-extubation stridor was age-dependent with the older children (>7yrs) having a higher incidence. A closer look at their study reveals the following: 1) In patients <7 yrs, almost half the patients developed stridor whether they had a leak or not at 30 cms with no difference in the rates of reintubation, 2) In patients >7 yrs, 4/42 had a leak at >30 cms; all had stridor and three required treatment with racemic epinephrine, and most importantly, 3) Out of the 4 patients who were reintubated, 3 had a leak at <20cms.A more recent study by Wratney et al showed that in 59 children (48 had uncuffed tubes), a leak pressure >30 cm H2O was common and did not predict an increased risk for extubation failure44. Therefore, children who have otherwise met the criteria for extubation but do not have an endotracheal tube air leak may successfully tolerate extubation provided the reason for intubation was not upper airway obstruction.In conclusion, I have attempted to answer day-to-day questions regarding important issues related to invasive mechanical ventilation with evidence supporting or refuting our current accepted notions.

References1. Zuckerberg AL, Nichols DG. Airway management in pediatric

critical care. In: Rogers MC, Nichols DG, editors. Textbook of Pediatric Intensive Care. 3rd edition. Philadelphia (PA): Williams & Wilkins; 1996. p. 63

2. Zucker HA. The airway and mechanical ventilation. In: Chang AC, Hanley FL, Wernovsky G, Wessel DL, editors. Pediatric Cardiac Intensive Care. Philadelphia (PA): Williams & Wilkins; 1998. p. 95

3. Kovarik WD, O’Rourke P. Pediatric and neonatal intensive care. In: Miller R, editor. Anesthesia. 5th edition. Oxford (UK): Churchill Livingstone; 2000; 2103-2460

4. Fisher DM. Anesthesia equipment for pediatrics. In: Gregory

GA, ed. Pediatric Anesthesia, 4th edn. New York: Churchill Livingstone, 2001; 214–216

5. Gilligan BP, Luten RC. Pediatric resuscitation. In: Rosen’s Emergency Medicine: Concepts and Clinical Practice. 5th edition. St Louis (MO): Mosby; 2002. p. 91

6. Battersby EF, Hatch DJ, Towey RM. The effects of prolonged naso-endotracheal intubation in children. A study in infants and young children after cardiopulmonary bypass. Anaesthesia. 1977; 32(2): 154-7

7. Black A. E., Hatch D. J., Nauth-Misir N. Complications of nasotracheal intubation in neonates, infants and children: a review of 4 years’ experience in a children’s hospital. Br J Anaesth. 1990; 65((4)):461–467

8. Mostafa SM. Variation in subglottic size in children. Proc R Soc Med 1976; 69: 793-5

9. Khine HH, Corddry DH, Kettrick RG et al. Comparison of cuffed and uncuffedendotracheal tubes in young children during general anesthesia. Anesthesiology 1997; 86: 627-31

10. Holzki J. Laryngeal damage from tracheal intubation. Paediatr Anaesth 1997; 7: 435-7

11. Eckenhoff JE. Some anatomic considerations of the infant larynx infl uencing endotracheal anesthesia. Anesthesiology 1951; 12: 401-10

12. Bayeux. Tubage de larynx dans le Croup. Presse Med 1897; 20:1

13. Coté CJ, Todres ID: The pediatric airway. In Coté CJ, Ryan JF, Todres ID et al (eds): A Practice of Anesthesia for Infants and Children. Philadelphia, WB Saunders, 1992, p 55

14. Litman RS, Weissend EE, Shibata D, Westesson P-L. Developmentalchanges of laryngeal dimensions in unparalyzed, sedated children. AnesthAnalg 2003; 98: 41-5

15. Dalal PG, Murray D, Messner AH, Feng A, McAllister J, MolterD. Pediatric laryngeal dimensions: an age-based analysis.AnesthAnalg 2009;108: 1475–9

16. Joshi VV, Mandavia SG, Stern L et al. Acute lesions induced byendotracheal intubation. Am J Dis Child 1972; 124: 646-649

17. McDonald IH, Stocks JG. Prolonged nasotracheal intubation: areview of its development in a paediatric hospital. Br J Anaesth1965; 37: 161-172

18. Allen TH, Steven IM. Prolonged endotracheal intubation ininfants and children.Br J Anaesth 1972; 44: 834-840

19. Khine HH, Corddry DH, Kettrick RG, et al. Comparison of cuffed and uncuffed endotracheal tubes in young children during general anesthesia. Anesthesiology 1997; 86: 627-31

20. Newth CJL, Rachman B, Patel N, Hammer J. The Use of Cuffed versus Uncuffed Endotracheal tubes in Pediatric Intensive Care. J Pediatr 2004;144:333-7

21. Weiss M, Dullenkopf A, Fischer JE, Keller C, Gerber AC. and the European Paediatric Endotracheal Intubation Study Group. British Journal of Anaesthesia 2009; 103: 867-73

22. Mhanna MJ, Zamel YB, Tichy CM, Super DM. The “air leak” test around the endotracheal tube, as a predictor of postextubation stridor, is age dependent in children. Crit Care Med. 2002; 30(12): 2639-43

23. Esteban A, Frutos F, Tobin MJ, et al: A comparison of four methods of weaning patients from mechanical ventilation, N Engl J Med, 1995; 332: 345-350

24. Randolph AG, Wypij D, Venkataraman ST, et al; Pediatric



Acute Lung Injury and Sepsis Investigators (PALISI) Network: Effect of mechanical ventilator weaning protocols on respiratory outcomes in infants and children: a randomized controlled trial, JAMA 2002; 288: 2561-2568

25. Khan N, Brown A, Venkataraman ST: Predictors of extubation success and failure in mechanically ventilated infants and children, Crit Care Med 1996; 24: 1568-1579

26. Farias JA, Alia I, Esteban A, et al: Weaning from mechanical ventilation in pediatric intensive care patients, Intensive Care Med 1998; 24: 1070-1075

27. Farias JA, Retta A, Alia I, et al: A comparison of two methods to perform a breathing trial before extubation in pediatric intensive care patients, Intensive Care Med 2001; 27: 1649-1654

28. Farias JA, Alia I, Retta A, et al: An evaluation of extubation failure predictors in mechanically ventilated infants and children, Intensive Care Med 2002; 28: 752-757

29. Newth CJL, Venkataraman S,Willson DF et al. Weaning and extubation readiness in pediatric patients.PediatrCrit Care Med. Jan 2009; 10(1): 1-11

30. Manczur T, Greenough A, Nicholson GP, et al. Resistance of pediatric and neonatal endotracheal tubes: infl uence of fl ow rate, size, and shape. Crit Care Med. 2000; 28(5):1595–1598

31. Jarreau PH, Louis B, Dassieu G, et al. Estimation of inspiratory pressure drop in neonatal and pediatric endotracheal tubes. J Appl Physiol. 1999; 87(1): 36-46

32. Hammer J, Newth CJ. Infl uence of endotracheal tube diameter on forced defl ation fl ow-volume curves in rhesus monkeys. EurRespir J. 1997; 10: 1870–1873

33. Ishaaya AM, Nathan SD, Belman MJ: Work of breathing after extubation, Chest 1995; 107: 204-209,

34. Straus C, Louis B, Isabey D, et al: Contribution of the endotracheal tube and the upper airway to breathing workload, Am J RespirCrit Care Med 1998; 157, 23-30

35. Willis BC, Graham AS, Yoon E, Wetzel RC, Newth CJL. Pressure-rate products and phase angles in children on minimal support ventilation and after extubation Intensive Care Med 2005; 31:1700-1705

36. Geraci RP: Acute epiglottitis-Management with prolonged nasotracheal intubation. Peds 1968; 41: 143-145

37. Tos M: Nasotracheal intubation in acute epiglottitis. ArchOtolaryngol 1973; 97: 373-375

38. Schuller DE, Birck HG: The safety of intubation in croup and epiglottitis. Laryngoscope 1975; 55:33-39

39. Adderley RJ, Mullins GC. When to extubatecroup patient: the”leak” test. Can J Anaesth 1987; 34: 304-6

40. Finholt DA, Henry DB, Raphaely RC. Factors affectingleak around trachealtubesin children. Can AnaesthSoc J 1985; 32: 326-329

41. Schwartz RE, Stayer SA, Pasquariello CA. Tracheal tube leak test: isthere interobserver agreement? Can J Anaesth 1993; 40: 1049-52

42. Pettignano R1, Holloway SE, Hyman D, LaBuz M.Is the leak test reproducible? South Med J. 2000; 93(7): 683-5

43. Lee KW, Templeton JJ, Dougal RM. tracheal tube size and post-intubation croup in children. Anesthesiology 1980; 53: S325

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Original Research ArticleIntrapleural Fibrinolytic Th erapy with Alteplase in Empyema Th oracis

in Children – A prospective pilot studySharma PK* MD, Saikia B* MD, Sharma R* MD, Jain P** MCH, Hussain Z*** MD, Khilnani P**** MD

*Consultant, Pediatrics Critical Care , **Consultant, Pediatrics Surgery, ***Fellow, Pediatrics Critical Care, ****HOD, Pediatrics Critical Care and Pulmonology. BLK Super Speciality Hospital, New Delhi, India

Correspondence:Dr Pradeep Kumar SharmaFlat no 48, Pocket 7, Sector 21, RohiniNew Delhi 110086Tel: +919868797049Email: [email protected]

IntroductionTube thoracostomy, fi brinolytics, open decortication, and video-assisted thoracoscopic surgery (VATS) are the various modalities of treatment for empyema thoracis in children.1 Tube thoracostomy alone is widely practiced in developing countries and

AbstractObjective: Outcome of children treated with Intrapleural alteplase therapy in empyema thoracisDesign: Prospective interventional pilot studySetting: Pediatric Critical care and Pulmonology unit at Tertiary care HospitalSubjects: All patients of empyema thoracis from 1 month to 18 years of age admitted from May 2012 to April 2014.Method and intervention:Children were selected for intrapleural alteplase therapy and treated under an IRB (Institutional Review Board) approved protocol.Alteplase (4 mg) was diluted with 50 ml NS and instilled through Intercostal drain(ICD). Chest tube was kept clamped for 1 hour and then opened. The primary outcomes measured were: clinical improvement, lung expansion, ICD days and hospital stay. Secondary outcomes were 24 hour ICD output and adverse effects.Results:A total of 13 patients were given intrapleural alteplase. Median age was 3 years and ranged from 11 month to 14 years. Clinical and radiological improvement was seen in 84.6% (11/13) cases. Fever subsided within 5 days in 54% with median of 4 days (2-8days). Respiratory distress settled in median 5 days (2-7 days). ICD days were 6.63±1.8 (mean±SD) days. ICD days after starting alteplase were 3.45±1.03 (mean±SD) days. Mean hospital stay was11.27±4.14 (mean±SD) days in successful cases. Mean hospital stay including failure case was 13±5.75 (mean±SD) days.Average fl ow per day before alteplase was 64.5±65 ml/day which increased to 194.8±146.3 ml/day with intrapleural alteplase. (P value 0.006). Persistent fever, distress and lung collapse were seen in 15.4% (2/13) cases and both required surgical intervention.Conclusion: Intrapleural alteplase therapy in empyema is benefi cial in reducing effusion volume, clinical symptoms, hospital stay, and the need for surgical intervention.Further large trials are needed for optimum dose, duration of therapy and clamp timing for intarpleural fi bniolytic therapy as well as to defi ne relative contraindications to use of alteplase therapy.Key words: Empyema thoracis; intrapleural fi brinolysis; alteplase; Pediatric

carries signifi cant morbidity.2-4 Use of intrapleural enzymatic agents for dissolution of empyema thoracis was fi rst described over fi ve decades ago; it has still not come into routine use.5 Intrapleural alteplase has been shown to be cost effective with minimum morbidity.6-8 VATS has comparable results to fi brinolysis, however, is invasive and costly.7,8 We undertook the study of intrapleural alteplase therapy in pediatric empyema thoracis in Indian children.

Material and MethodsThis was a prospective interventional pilot study,


conducted in the Department of Pediatric critical care and Pulmonology unit at our institution from May 2012 to April 2014. The diagnostic criteria for empyema thoracis were: Presence of pleural effusion on clinical, radiological examination, and aspiration of purulent pleural fl uid from the thoracic cavity. After IRB approval for the pilot study, all children diagnosed with empyema thoracis as per above criteria from the age of 1 month to 18 years were included in the study after informed consent. Children who showed clinical improvement and lung expansion within 24-48 hours of ICD placement, children with signifi cant pleural thickening with organized collections (stage III empyema) on ultrasound chest, were not given alteplase therapy and were excluded from the study.Complete blood count, prothrombin time (PT)/ International normalized ratio (INR), C-reactive protein, erythrocyte sedimentation rate (ESR) and blood culture were sent on all patients. Pleural fl uid cytology, biochemistry, gram stain, acid fast bacillus stain, and cultures were sent. Chest radiograph and ultrasound were done. Intercostal tube (ICD) was placed in cases of empyema, loculated effusion and exudative collection based on pleural fl uid examination.Chest radiograph and ultrasound were repeated after 24-48 hour of placement of ICD. Intrapleural alteplase therapy was given to patients with persistent symptoms with septated, loculated collections evident on ultrasound chest or aspiration of intrapleural pus. All children were managed with intravenous ceftriaxone and cloxacillin as initial therapy along with other supportive therapy as indicated. However in 6 cases, due to non-availability of cloxacillin, intravenous vancomycin was used. Methods (Intrapleural alteplase instillation therapy protocol) and outcomes measured are listed in table 1 and 2.

Table 1: Intrapleural alteplase instillation therapy protocolPrerequisite: INR < 1.5 and platelet count > 50000/ mm3

Procedure

1. Injection alteplase 4 mg was diluted with 50 ml NS and instilled through ICD. Chest tube was kept clamped for 1 hour and then opened.

2. Intrapleural alteplase was given once daily for maximum of 3 days.

3. Children were monitored for fever and respiratory distress.

4. Chest radiograph was done 24 hours after 2nd or 3rd dose as indicated by clinical improvement or deterioration.

Table 2: Outcomes measuredS No. Primary Secondary1 Clinical Improvement Average per day ICD output

2 Lung ExpansionAny side effects (bleeding, pain, allergic reaction, respiratory distress)

3 Duration of ICD (Days)

4 Length of Hospital stay (Days)

ICD - Intercostal tube

Tube removal and dischargeIntravenous antibiotics were continued till 48 hours of afebrile period. The ICD was removed when there was no drainage or minimal drainage from ICD (<20 ml/day) along with clinical improvement and lung expansion on chest radiograph. The criteria for discharge included: absence of fever for at least 48 hours, stable clinical condition and good lung expansion. Oral antibiotic therapy were completed for further 10-14days after discharge.

Failure of therapy Failure of therapy was defi ned if there was no improvement in clinical condition or persistence of intrapleural collection or persistent lung collapse. No improvement in clinical condition was defi ned as persistence of fever spikes (≥100.4*F) and poor oral intake. In case of failure of therapy surgical intervention (VATS/Open thoracotomy) was performed by pediatric surgeon.

ResultsA total of 17 children were admitted with empyema thoracis. Two cases showed clinical improvement with lung expansion after ICD alone and 2 had stage III empyema, all 4 cases were excluded from the study. A total of 13 patients were given intrapleural alteplase based on selection criteria. Median age was 3years and ranged from 11 month to 14 years. Male to Female ratio was 1:1.16. Right and left sided empyema was seen in 6 cases each while one case had bilateral involvement. All children presented with fever ranging from 2 -22 days with median of 10 days. Cough and respiratory distress (RD) were seen in 92% (11/13) of cases. Duration

ORIGINAL RESEARCH ARTICLE Intrapleural Fibrinolytic Therapy with Alteplase in Empyema Thoracis in Children


of RD ranged from 1-20 days with median 5 days. Chest pain and abdominal pain were seen in 15.4 % (2/15) cases. Mean Hemoglobin (Hb) at presentation was 9±1gm/dl and 85% of cases had Hb<10gm/dl. High total leucocyte count was seen in 77% (10/13) of patients and one patient had leucopenia. Neutrophilic leucocytosis (Neutrophils >65%) was seen in 77% of cases. Pleural fl uid revealed frank pus in 70% of cases and pleural fl uid sugar was < 40mg in 92% of cases. Pleural fl uid revealed bacterial growth in 38.4% of cases (5/13), out of which 3 were Staphylococcus aureus and 1 each Burkholderia cepacia and Acenitobacter Baumanii. All blood cultures were negative except one child who had positive blood culture growing Burkholderia cepacia. INR was >1.5 in 2 cases at presentation which was corrected over next 48hours.. Platelet count was above 50000/cmm in all cases. Chest radiograph revealed pleural effusion and parenchymal opacities in all cases (Table 3). Mediastinal shift was seen 61.5% (8/13) and pyopneumothorax was seen in 15.4% (2/15). Ultrasound of chest revealed collapsed lung in all cases. Sepations/Loculated collections were seen in 77% (10/13) cases. Pericardial effusion was seen in 15.4% (2/15) and one case had multiple liver abscesses. Contrast enhanced computed tomography (CECT) chest was done in total of 7 cases out of which 4 were done at outlying hospitals with CECT fi lms and reports brought by parents on day of admission to our hospital.

Clinical improvement and Lung expansionClinical and radiological improvement was seen in 84.6% (11/13) cases. Fever subsided within 5 days in 54% patients with median of 4 days (ranging 2-8days). Respiratory distress settled in median of 5 days (ranging 2-7 days).

ICD days and Hospital stay ICD days were 6.63±1.8 (Mean ± SD) days. ICD days after starting alteplase were 3.45 ± 1.03 (Mean ± SD). ICD manipulation was not required in any case. Mean hospital stay was11.27 ± 4.14 (Mean ± SD) days in successful cases. Mean hospital stay in all patients

including failure case was 13±5.75 (Mean ± SD) days.

Average Flow (ml/day) from ICDAverage fl ow per day before alteplase was 64.5 ± 65 ml/day which increased to 194.8 ± 146.3 ml/day with intrapleuralalteplase. (P value 0.006)

Adverse effectsNo major adverse effects were noted. Although all cases had some pain, in most cases manageable by oral analgesics. Only 3(23%) children had severe pain requiring intravenous analgesics. Most cases (77%) had minor bleeding in the form of blood tinged discharge without causing hemodynamic compromise or need for transfusion.

Failure of therapyPersistent fever, distress and lung collapse was seen in 15.4% (2/13) cases. Both underwent CECT (Contrast Enhanced computerized tomogram) chest which revealed thick enhancing pleural thickening apart from collapse-consolidation of lung. VATS was done in one and another case required open decortication.

Antibiotics and supportive therapyAll children received intravenous antibiotics. Intravenous ceftriaxone and cloxacillin, or ceftriaxone and vancomycin were started in 46% (6/13) cases and one case was continued on Meropenem/vancomycin. Antibiotics were changed in only 2 cases: one changed as per culture sensitivity report and in one case was upgraded due to clinical deterioration. All cases received oxygen and mechanical ventilation was required in 23% (3/13) cases.

DischargeAll children were discharged after clinical and radiological improvement. None of the cases had chest deformity at the time of discharge. Chest radiographs at discharge showed resolution of effusion with complete lung expansion in all cases. None of the cases had mediastinal shift, rib crowding or scoliosis on chest radiograph at the time of

ORIGINAL RESEARCH ARTICLE Intrapleuralfi brinolytic Therapy with Alteplase in Empyema Thoracis in Children


discharge. Figures 1-3 show examples of serial X rays from 3 randomly selected patients who recieved therapy with aleteplase. Chest radiographs showed parenchymal opacities and pleural thickening in 27% (3/11) of children treated with alteplase therapy alone and was seen in 38.4% (5/13) in all cases including the failed cases (Table 3). Follow up Chest radiographs after 2 weeks in these patients revealed complete resolution (Figure 1-3 shows serial chest radiographs of 3 randomly selected patients who received alteplase therapy).

Table 3: Radiological Findings upon Admission and Discharge, No. (%)

X-ray fi ndings At admission At Discharge At DischargeWith failure

casesPleural effusion 13(100%) 0 0Parenchymal opacities

13(100%) 3/11(27%) 5/13(38.4%)

Pyopneumothorax 2/13(15.4%) 0 0Mediastinal shift 8/13(61.5%) 0 0Pleural thickening 0 3/11(27%) 5/13(38.4%)Rib crowding/ Scoliosis

0 0 0


Figure 3: Serial chest x ray3a: AT admission: Left Pleural effusion; 3b: 48 hours after ICD: Persistent Left collection with underlying lung collapse; 3c: Post 3rd dose Alteplase: Fully Expanded left lung; 3d: At discharge-Day 9: Complete Resolution

Figure 1: Serial chest x ray1a: AT admission: Left side white out; 1b: 48 hours after ICD: Collapsed left Lung with persistent collection; 1c: Post 3rd dose Alteplase: Expanded left lung with residual collection; 1d: At discharge-Day 9: Expanded left Lung with pleural thickening; 1e: After 2 weeks follow up: Complete resolution

Figure 2: Serial chest x ray2a: AT admission: Left Pyopneurnothorax; 2b: 24 hours after ICD: Persistent Pyopneurnothorax; 2c: Post 2nd dose Alteplase: Expanded left lung with residual Pyopneurnothorax; 2d: At discharge-Day 9: Fully Expanded left Lung; 2e: After 2 weeks follow up: Complete resolution


Standard Approach to Pediatric Para-pneumonic Effusion (PPE) at Author’s Institution

Para-pneumonic Effusion (PPE)

Chest radiograph,Ultrasound chest

Small/non-drainable PPE

Clinical Improvement

Clinical and Radiological Improvement after 24-48 hours

Complicated PPE (Thick pus/ Loculation)

Antibiotics, ICD and intrapleural alteplase

Continue antibiotic and investigate for the cause

Persistent pleural space disease

VATS/Surgical intervention

Moderate/Large PPE

Uncomplicated PPE

Antibiotics with ICD

Antibiotics alonePleural Tap

Continue Same

Clinical improvement

USG/CECT Chest

No pleural space disease

No

No

Yes

Yes Yes

No

Yes

DiscussionThis prospective interventonal pilot study in pediatric empyema thoracis has shown good clinical and pulmonary outcome with intrapleuralalteplasetherapy.In developing countries most frequently used treatment modality is ICD alone. Lung re-expansion

at 1 week was seen in 6% cases and 64% did not achieve full lung re-expansion even after 3 weeks of ICD in a study comprising of 31 children2. Open drainage was required in 71% of cases. Mean hospital stay was 33 days and 52% patients were hospitalized for at least 5 weeks.2In another study with 265 cases



surgical intervention was required in 21.5%.Mean hospital days varied from 17-23±7 days in successful cases and increases signifi cantly in patients requiring surgical interventions.3 A recent study comprising of 25 children managed with ICD alone has shown chest deformity at 6 weeks follow up in 20% cases and radiological deformities in 32%.4

Thomson et al demonstrated signifi cantly shorter hospital stay (7.4 versus 9.5 days) in children treated with urokinase as compared to ICD alone.9 British thoracic society guidelines for pediatric empyema statethat fi brinolytictherapy increases pleuraldrainage with overall successful outcome without surgery in 90%.1A cohort study comparing alteplase with ICD alone showed increased drainage and decreased hospital stay in alteplase group6. One randomized control trial (RCT) comparing VATS with urokinase and another with alteplase did not show any difference in clinical outcome in both arms.Failure rates for fi brinolysis were 16.6% in both series7,8.

Both concluded that fi brinolysis offers non-operative management with decreased resource utilization and costs compared to VATS and should be primary treatment of choice in managing pediatric empyema.Clinical improvement, hospital stay and failure rate(15.4%) of our study is comparable to other studies with fi brinolytic therapy. The study showed excellent pleural recovery and there was no residual clinical chest deformity or overcrowding of rib or scoliosis on chest radiograph at discharge. Although our study is small in size, the strength of study is its prospective nature and use of a standard protocol on all patients. The present study is also the fi rst systematically planned study in India to best of our knowledge to use intrapleural alteplase for fi brinolysis in pediatric population with diagnosis of Empyema thoracis. We observed signifi cant increase in fl ow through ICD even in the failed cases. As suggested by our fi ndings the duration of symptoms prior to alteplase may not be precisely predictive of response or failure. In conclusion intrapleural alteplase therapy in empyema is benefi cial in reducing effusion volumes, clinical symptoms, hospital stay, and the need for surgical intervention. However in author’s experience most important factor is patient selection. Small or

non-drainable parapneumonic effusions (PPEs)can be managed with antibiotics alone. Moderate PPE with clinical and radiological improvement after 24-48 hours of ICD do not need fi brinolysis. As suggested by our study, complicated PPEs (Thick pus, presence of loculation and non responders) should be given intrapleural fi brinolysis as primary therapy. Further larger trials are needed for optimum dose, duration of therapy and clamp timing for intarpleural fi bniolytic therapy to learn the best outcome modalities for this commonly encountered condition.

References1. Balfour-Lynn IM, Abrahamson E, Cohen G, Hartley J,

King S, Parikh D, Spencer D, Thomson AH, Urquhart D, on behalf of the Paediatric Pleural Diseases Subcommittee of the BTS Standards of Care Committee. BTS guidelines for the management of pleural infection in Children. Thorax 2005; 60 (Suppl I): i1–i21

2. Corazon ML, Rodriguez V, Catalan GT. Outcome of Pediatric Empyema Thoracis Managed by Tube Thoracostomy. Asian CardiovascThorac Ann 2006; 14: 98-101

3. Baranwal AK, Singh M, Marwaha RK, Kumar L. Empyema thoracis: a 10-year comparative review of hospitalised children from south Asia.Arch Dis Child 2003; 88: 1009-1014

4. Kumar A, Sethi GR, Mantan M, Aggarwal SK, Garg A. Empyema Thoracis in Children: A Short Term Outcome Study. Indian Pediatr. 2013; 50: 879-882

5. Tillet W, Sherry S. Effect in patients of streptococcal fi brinolysin (streptokinase) and streptococcal deoxyribonuclease on fi brinous purulent and sanguineous exudations. J Clin Invest 1949; 28: 173-86.

6. Weinstein M, Restrepo R, Chait PG, Connolly B, Temple M, Macarthur C. Effectiveness and safety of tissue plasminogen activator in the management of complicated parapneumonic effusions Pediatrics. 2004; 113: e182-185

7. St Peter SD, Tsao K, Spilde TL, et al. Thoracoscopic decortications vs tube thoracostomy with fi brinolysis for empyema in children: A prospective, randomized trial. J Pediatr Surg. 2009; 44(1): 106-111.

8. Sonnappa S, Cohen G, Owens CM, et al. Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema. Am J RespirCrit Care Med 2006; 174: 221-7.

9. Thomson AH, Hull J, Kumar MR, Wallis C, Balfour-Lynn IM, on behalf of the British Paediatric Respiratory Society Empyema Study Group. Randomised trial of intrapleuralurokinase in the treatment of childhood empyema. Thorax 2002; 57: 343-347

ORIGINAL RESEARCH ARTICLE Intrapleuralfi brinolytic Therapy with Alteplase in Empyema Thoracis in Children


Introduction and Defi nitionMyocarditis is a non-infectious myocardial infl ammation from various infectious, immune and non-immune insults. It is the common indication for listing for cardiac transplants and signifi cant cause of sudden cardiac death in the young. However there is a lot of controversy regarding classifi cation, diagnosis and treatment of myocarditis.The standardized and widely accepted Dallas criteria for diagnosing myocarditis were published in 19871. By Dallas criteria, active myocarditis is defi ned as infl ammation of myocardium with necrosis and/or degeneration of adjacent myocytes and borderline myocarditis is defi ned as an infl ammation of myocardium without evidence of myocyte injury. It is also classifi ed according to severity of clinical manifestation (mild, moderate and severe) and myocardial involvement (focal, confl uent and diffuse)

IncidenceMyocarditis is the most common cause of heart failure in children with a structurally normal heart admitted to Pediatric Intensive Care Unit (PICU). The exact incidence and prevalence of myocarditis in children remains unknown because of its insidious onset, wide spectrum of clinical presentation, requirement of biopsy for diagnosis, limitations of biopsy itself and limitations of Dallas criteria in defi ning myocarditis. The reported incidence from a population based from Finland, is 1.59 per 100,000 person-years in children aged <1year, 0.24 per 100,000 person-years in children 1-4 years and 0.12 per 100,000 person-years in children 5-14 years2. In a recent autopsy series published from Great Ormond Street Hospital,

Pediatric Cardiac Intensive Care - 2Myocarditis in Children

Vinay Joshi MD, Preetha Joshi MDConsultaint Pediatric Intensivists, KB Ambani Hospital, Mumbai

London, UK3, histologically proven myocarditis was present in 28 out of 1516 children (1.8%, age range 10 days to 16 years, median age 10 months). Of the 28 cases, 15 (54%) infants were under 1 year of age, 5 (18%) were children 1-4 years, 4 (14%) were children 5-9 years, 2 (7%) were children aged 10-14 years and 2 (7%) were children aged > 15 years.

EtiologyThe cause of myocarditis remains unknown quiet often, but many infectious and non-infectious etiologies have been implicated in its causation. Though viral infections predominate amongst the infectious etiologies of myocarditis, various bacteria, protozoa and even worms have been responsible for myocarditis in children. Data from North America and Europe, during 1970s and 1980s show enteroviruses particularly Coxsackie B virus as the most common causative agent4,5,6,7, but by 1990s adenovirus was identifi ed more commonly as compared to enteroviruses as a causative agent of myocarditis in children8,9,10. However recent reports suggest that parvovirus B has been the most common virus isolated in children with myocarditis11. The non-infectious causes of myocarditis in children include immune mediated diseases, collagen vascular diseases and toxins (Table 1).

PathogenesisThe pathogenesis of myocarditis involves both direct and immune mediated myocyte injury. The invasion of myocyte by a cardiotrophic virus is followed by its replication and activation of immune response. The replicated virus enters the interstitium, activates B cells leading to local infl ammation and further activation of immune response and production of antibodies against cardiomyocytes12. The natural killer (NK) cells play a major role in the pathogenesis of myocarditis as they limit the extent of myocardial

Correspondence:Dr Vinay Joshi MDKB Ambani Hospital, Mumbai, IndiaTel: 09320608666Email: [email protected]


Table 1. Known causes of MyocarditisBacterial Fungal, Protozoal &

Parasitic Viral Immune Mediated Toxin or Drugs

C diptheriae, C burnetti, H infl uenza, M pneumoniae, N meningitides, Leptospira, Rickettsia, streptococcus pneumoniae, T palladium, V cholera

Ascaris sp, Aspergillus, Cryptococcus, E granulosus, Histoplasma, Nocardia, Schistosoma, Toxoplasma, Trypanosoma cruzi, Trichinella spiralis

Adenovirus, Coxsackie B,Cytomegalovirus, Dengue, Echovirus, EBV, Hepatitis A, Hepatitis C, HIV-6, HIV, Infl uenza A, Infl uenza A & B, HSV-1, Parvovirus B 19, RSV, Varicella zoster, Yellow fever

Kawasaki’s disease, Systemic Lupus Erythematosus, Sarcoidosis, Scleroderma, Giant Cell Myocarditis, Wegener’s granulomatosis, Polymyositis

Amitriptyline, Ethanol, Arsenic, Carbon monoxide, Colchicine, Electric shock, Iron, Copper, INH, Lead, Snake bite, Scorpion sting, Tetanus toxin, Tetracycline

injury by destroying the virus infected macrophages and thereby reducing the neo antigen load presented by macrophages to cytotoxic T lymphocytes13. T cells produce injury by direct cytotoxic injury, through macrophages, by production of antibodies, cell mediated cytotoxicity and direct lysis by antibody and complement13 (Table 2).

Table 2. Mechanisms of Myocardial Injury in MyocarditisDirect myocardial invasionImmunological activationFormation of anti-heart antibodies

Clinical presentationClinical manifestations of the disease range from non-specifi c clinical symptoms like fever, myalgia, palpitations, breathlessness or asymptomatic ECG abnormality to cardiogenic shock. Myocarditis is the commonest cause of new onset congestive cardiac failure in an otherwise healthy child with structurally normal heart. Myocarditis has distinct clinical modes of presentations; acute, subacute and fulminant14. Acute and sub-acute myocarditis presents with mild hemodynamic instability requiring nil or minimal inotropic support. The patients with fulminant myocarditis usually present with fever, signs of cardiac failure in the form of fatigue, breathlessness and edema. They have severe hemodynamic instability requiring high dose inotropic support and/or mechanical support. Another form, described by McCarthy et al, is fulminant necrotic myocarditis which presents as fulminant myocarditis as severe heart failure along with signs of myocardial infarction with characteristic ECG changes.

Mode of presentation also varies with the age of a child. Myocarditis can be a cause of sudden infant death in the newborn infants. In older children and adolescents, 10-14 days prior history of preceding viral illness can be obtained in upto 70-90% cases of proven myocarditis15,16. In the later stages they will have resting tachycardia, dyspnea and signs of frank congestive heart failure (Table 3).

Table 3. Clinical manifestations of MyocarditisNewborns and infants:Irritability, lethargy, pallor, poor intake, diffi culty in feeding (suck-rest-suck cycle) and diaphoresis.TachycardiaWeak pulse Cool extremitiesDecreased capillary refi llPale or mottled skinMuffl ed heart sound (pericarditis)S3 may be heard- gallop rhythmHeart murmur caused by AV regurgitation ArrhythmiasBasal crepitationsHepatomegaly

Additional manifestations in older children:Failure to thriveAbdominal painPersistent vomitingJugular venous distension and edema of lower extremities

Natural history of myocarditisClinical course of the disease is variable. Myocarditis which presents with signs and symptoms similar to acute myocardial infarction (Coronary syndrome) usualy results in full recovery. However, children who present with heart failure and cardiogenic shock, have severe left ventricular dysfunction which takes weeks to months for recovery of LV function.

PEDIATRIC CARDIAC INTENSIVE CARE - 2 Myocarditis in Children


Figure 2. LV Dilatation in a 2 yr old child with suspected myocarditis; 2D ECHO- dilated LV and four chamber view.

This group carries a high mortality with 50% patients dying by the age of 5 years17,18 (Myocarditis Treatment Trial, Mayo Clinics Trial).

DiagnosisA new onset cardiac failure in a child with a structurally normal heart should always give rise to suspicion of myocarditis. A 10-14 days prior history of viral illness supports the diagnosis of myocarditis. Evidence of cardiomegaly on the chest radiograph is an important clue to the diagnosis of myocarditis. However, the degree of cardiac enlargement depends upon the stage of myocarditis. In acute and fulminant myocarditis, cardiomegaly may not be signifi cant but radiographic evidence of pulmonary congestion with/without frank pulmonary edema will be evident (Figure 1).

Figure 1: Chest X-ray in a child with myocarditis: showing increased cardiothoracic ratio due to cardiomegaly and hazy lung fi elds due to pulmonary edema.

An electrocardiogram (ECG) in myocarditis may have non-specifi c fi ndings like low voltage QRS complexes, non-specifi c ST–T wave changes, prolonged QTc, conduction abnormalities and occasionally changes consistent with myocardial infarction.Echocardiography19 will show chamber enlargement, decreased contractility, wall motion abnormalities and occasionally valvular enlargement. Left ventricular function would generally be more severely affected compared to right ventricular function (Figure 2).In spite of its limited sensitivity, endomyocardial biopsy is still been considered as a gold standard for the diagnosis of myocardtis20, especially in cases of Fulminant giant cell myocarditis or allergic myocarditis (Table 4).

Table 4. Proposed Indications for Endomyocardial Biopsy17,18

1. Exclusion of potential common etiologies of dilated cardiomyopathy (familial, ischemic, cardiotoxic exposures)

2. Subacute or acute symptoms of heart failure refractory to standard management

3. Substantial worsening of ejection fraction despite optimised pharmacological therapy

4. Development of hemodynamically signifi cant arrhythmias, particularly progressive heart block and ventricular tachycardia

5. Heart failure with concurrent rash, fever or peripheral eosinophilia

6. History of collagen vascular disease such as SLE, scleroderma or PAN

7. Suspicion for giant cell myocarditis (young age, new subacute heart failure, or progressive arrhythmia without apparent etiology)

Other newer modalities like cardiac magnetic resonance imaging (CMR)21 and late gadolinium



enhancement on CMR have been used and are being validated. Various laboratory parameters like polymerase chain reaction (PCR) for diagnosis of viral myocarditis, biochemical tests like Troponin T22 and creatinine kinase (MB fraction) as an evidence of myocardial injury, elevated acute phase reactants (ECR, C- reactive protein), antibody titers for specifi c viral infections and elevated white blood cell count will aid in the diagnosis of myocarditis (Table 5,6).

Table 5. Diagnosis of MyocarditisA. Signs of Cardiogenic shock +Laboratory investigations1. CBC- Hb, Lymphocytosis / neutropenia 2. CPK-MB 3. LDH isoenzyme 1- elevated in idiopathic myocarditis4. Troponin I5. Viral cultures- Nasopharyngeal and rectal swabs6. Viral PCR- rapid, sensitive and defi nitive test7. ESR and CRP8. Blood culture-for bacterial infectionChest X-rayECGEchocardiographyCardiac MRIMyocardial biopsy

Table 6. Differential diagnosis for myocarditisAortic Stenosis, coarctation of aortaEndocardial fi broelastosis Viral pericarditisCarnitine defi ciencyDilated cardiomyopathy- metabolicCardiac tumorsCoronary artery anomalies- ALCAPAStorage disease- GSD I & IIMedial necrosis of coronary arteries Shock

ManagementAs most of the children present in some stage of cardiac failure, they need initial care in the pediatric intensive care unit. The management strategy is planned according to the severity of the clinical presentation. The management is aimed at support of cardiac function by using inotropic support and afterload reduction to improve tissue perfusion and not at the causative organism or factor. Rhythm disturbances causing hemodynamic instability need urgent attention as they could be life threatening. The child may require mechanical respiratory assistance

in the form of invasive or non-invasive positive pressure ventilation. The patient requires meticulous fl uid management to avoid fl uid overload but also to maintain adequate preload and thereby cardiac output.

Hemodynamic monitoringClinical monitoring of hemodynamics is as important as invasive monitoring in myocarditis with shock. This included insertion of arterial lines and central lines which help in monitoring blood pressure, central venous pressure (CVP) as a surrogate for volume assessment and laboratory estimation of lactate and mixed/ central venous oxygen saturation. Bedside ultrasound is a major technological, noninvasive and easy method to assess volume status and cardiac function on a continuous basis.

Inotropic supportInotropic agents are to be chosen and administered with great caution as the myocardium is irritable and use of inotropic agents can instigate and/or worsen arrhythmias.The rapidly acting inotrope, usually preferred in cardiogenic shock with “acceptable hypotension” (maintaining organ perfusion: skin perfusion, urine output, mentation) or normal blood pressure secondary to myocarditis is dobutamine. However, in cases of severe shock with signifi cant hypotension, epinephrine may be used initially to improve the organ perfusion pressure. It is important to remember that epinephrine is very arrhythmogenic and also increases myocardial oxygen consumption and workload signifi cantly. Dobutamine improves contractility and decreases systemic vascular resistance, providing afterload reduction in addition to improving cardiac output. A mild increase in heart rate can occur, although signifi cant tachycardia is unusual.Milrinone, a phosphodiesterase inhibitor, improves myocardial relaxation and therefore fi lling time and thus improving cardiac output. The PRIMACORP study23, a large, randomized, placebo controlled trial, proved the effectiveness of high-dose milrinone for preventing low cardiac output syndrome in children



after cardiac surgery. Although dysfunction related to viral myocarditis is different, this trial remains the only study which looked at milrinone and improvement in cardiac function after myocardial injury; thus, we could extrapolate that its results may be relevant to cardiac dysfunction in myocarditis as well24. Milrinone is also less arrhythmogenic which further enhances it’s role in cardiogenic shock. Newer drugs such as Levosimendan have also been used, however large clinical trials are lacking.25

Other supportive measures to improving oxygen delivery and decrease oxygen consumptionEarly elective intubation and ventilation, adequate sedation and analgesia and maintaining hemoglobin and adequate intravascular volume are some of the important measures. Mechanical ventilation helps by taking away work of breathing as well as by reducing left ventricular afterload by favourably affecting the ventricular transmural gradient by reducing aortic and vascular resistance

Arrhythmia managementThe common clinically signifi cant arrhythmias in myocarditis are ventricular ectopics, ventricular tachycardia and heart block. All tachyarrhythmias need to be treated urgently as they would further impair cardiac function and output. Arrhythmias are managed according to the standard AHA protocol26. Hyperkalemia and ionized hypocalcemia can aggravate ventricular tachyarrhythmias, therefore, should be closely monitored and corrected.

ImmunosuppressionVarious immune suppressive therapies like intravenous immunoglobulin and high dose corticosteroids have been used and studied but adequate benefi cial effects have not been proven by studies17,27,28.

Extracorporeal supportIn children with refractory low cardiac output syndrome, use of ventricular assist device (VAD) or extracorporeal membrane oxygenation (ECMO) can be used as a rescue therapy or as a bridge to a cardiac transplant.

Table 7. Management of Myocarditis/Cardiogenic shockI. Ventilation II. Maintaining tissue perfusionIII. Fluid restrictionIV. Drugs-

1. Inotropic agents2. Diuretics:3. Direct vasodilators:4. Immunomodulators a. IVIG- may be useful; 2g/kg in 2 divided doses b. Steroids- may be useful in autoimmune myocarditis

V. Ventricular Assist Device (VAD)VI. ECMO

Ventricular assist devices are discussed elsewhere in this symposium.

PrognosisThe prognosis of acute myocarditis in newborns is poor with mortality rates as high as 75%. In older infants and children, mortality rates are between 10% - 25%. Most deaths occur in the fi rst week of presentation28. Almost 25% patients continue to have abnormal X-ray and ECG for weeks to months. However in myocarditis, survival to discharge does not imply full recovery and myocarditis can progress to dilated cardiomyopathy29.Viral persistence in the myocardium has been thought to be associated with progressive impairment of left ventricular function and is therefore predictive of adverse outcomes. Survival in children with dilated cardiomyopathy ranges from 60% to 70% at 1 year to 34% to 56% at 5 years. The fi rst 2 years after diagnosis of dilated cardiomyopathy are the most crucial30. The outcomes can vary from nearly complete recovery to worse outcomes like death or need for cardiac transplant. For children with residual myocardial dysfunction at discharge, diuretics and afterload reducers are considered as fi rst-line agents. Transplantation may, however, be considered an option for a child who requires ECMO for more than 10 days and has no clinical signs of improvement31. Cardiac transplantation is discussed else where in this symposium.

Conclusions and future directionsMyocarditis is the end result of both myocardial infection and autoimmunity that results in active infl ammatory destruction of cardiac myocytes. The varied clinical presentation and limited unequivocal methods of diagnosis make this disease a challenging



diagnosis. An x-ray, ECG, ECHO and where warranted, a cardiac MRI, are now the initial standards of evaluation. Hemodynamic monitoring and supportive management of cardiogenic shock form the basis of treatment of myocarditis. Pharmacological therapy like immunoglobulins, steroids and interferons has not been found to be effective.Spontaneous recovery in older children is encouraging, however, patients who progress to chronic dilated Cardiomyopathy experience 5-year survival rates < 50%. Studies looking at further immune modulating therapies are underway and may improve prognosis.

References1. Aretz HT, Billingham ME, Edwards WD, Parker MM, Factor

SM, Fallon JT, Fenoglio JJ. Myocarditis: a histopathologic defi nition and classifi cation. Am J Cardiovasc Pathol. 1987; 1:3-14

2. Kyto V, Saraste A, Voipio-Pulkki LM, et al. Incidence of fatal myocarditis: a populationbased study in Finland. Am J Epidemiol 2007; 165: 570-4

3. Weber et al, 2008 Weber M.A., Ashworth M.T., Risdon R.A., et al: Clinicopathological features of pediatric deaths due to myocarditis: an autopsy series. Arch Dis Child 2008; 93: 594-598

4. Levi D, Alejos J. Diagnosis and treatment of pediatric viral myocarditis. Curr Opin Cardiol 2001; 16:77-83

5. Friedman RA. Myocarditis. In: Garson A, Bricher JT, McNamara DG eds. The science and practice of Pediatric cardiology, Philadelphia, PA: Lea and Febiger; 1990: 1577-1589

6. Park MK. Pediatric Cardiology for practitioners, 4th ed. St. Louis, MO:Mosby; 2002: 289-290

7. Martin AB. Congenital cardiovascular disease/diabetes: acute myocarditis:rapid diagnosis by PCR in children, Circulation 1994; 90(1): 330-339

8. Calabrese F, Rigo E, Milanesi O, et al. Molecular diagnosis of myocarditis and dilated cardiomyopathy in children: clinicopathologic features and prognostic implications. Diagn Mol Pathol 2002; 11(4):212-221

9. Baboonian CJ. Eradication of viral myocarditis: : Is there hope? Am Coll Cardiol 2003; 42(3):473-476

10. Bowles NE, Towbin JA. Molecular aspects in myocarditis. Curr Infect Dis Rep 2000; 2(4): 308-314

11. Bock CT, Kingel K, Aberle S. Human Parvovirus B19: A new emerging pathogen of infl ammatory cardiomyopathy. J Vet Med B Infect Dis Vet Public Health 2005; 52(7-8):340-3

12. Liu PP. Advances in understanding of myocarditis Circulation 2001; 104(9):1076-82

13. Godeny EK. Murine natural killer cells limit coxackievirus B3 replication. J Immunol 1987; 139 (3): 913-18

14. McCarthy RE. Long-term outcome of fulminant myocarditis as compared to acute (non-fulminant myocarditis. N Eng J Med 2000; 342 (10): 690-95

15. English RF. Outcomes of children with acute myocarditis. Cardiol Young 2004; 14: 488-93

16. Martin AB. Acute myocarditis: Rapid diagnosis by PCR in children. Circulation1994, 90:330-39

17. Mason JW, O’Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, Moon TE, for the Myocarditis Treatment Trial Investigators. A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med. 1995; 333: 269 –275

18. Wu LA, Lapeyre AC, Cooper LT. Current role of endomyocardial biopsy in the management of dilated cardiomyopathy and myocarditis. Mayo Clin Proc 2001; 76(10):1030-8

19. Lieback E, Hardouin I, Meyer R, Bellach J, Hetzer R. Clinical value of echocardiographic tissue characterization in the diagnosis of myocarditis. Eur Heart J. 1996; 17:135-142

20. Richardson P, McKenna W, Bristow M, et al. Report of the 1995 world health organization/international society and federation of cardiology task force on the defi nition and classifi cation of cardiomyopathies. Circulation. 1996; 93: 841-842

21. Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: A JACC white paper. J Am Coll Cardiol. 2009; 53: 1475–1487

22. Lauer et al, Niederau C, Kuhl U, et al. Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol 1997; 30 (5): 1354-59

23. Hoffman TM, Wernovsky G, Atz AM, et al. Effi cacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 2003; 107(7): 996-1002

24. Schwartz SM, Wessel DM. Medical cardiovascular support in acute viral myocarditis in children. Pediatr Crit Care Med 2006; 7(6)(suppl): S12-S16

25. Ercan S, Davutoglu V, Cakici M, Kus E, Alici H, Sari I. Rapid recovery from acute myocarditis under levosimendan treatment: report of two eases. J. clin pharm ther. 2013; 38(2): 179-80

26. http://www.americanheart.org/ downloadable/ heart/ 1279224109481 Methodology_Manual% 206. 2010.pdf

27. Parillo JE, Cunnion RE, Epstein SE, Parker MM, Saffredini AF, Brenner M, Schear GL, Palmeri ST, Cannon RO, Alling D. A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med. 1989; 321: 1061– 0168

28. Wojnicz R, Nowalany-Kozielska E, Wojciechowska C,



Glanowska G, Wilczewski P, Niklewski T, Zembala M, Polonski L, Wodniecki J, Rozek MM. Randomized, placebo-controlled study for immunosuppressive treatment of infl ammatory dilated cardiomyopathy: two-year follow-up results. Circulation. 2001; 104: 39-45

29. Lee KJ, McCrindle BW, Bohn DJ, et al. Clinical outcomes of acute myocarditis in childhood. Heart.1999; 82(2):226-233

30. Gagliardi MG, Bevilacqua M, Bassano C, et al. Long-term follow-up of children with myocarditis treated by immunosupression and of children with dilated cardiomyopathy. Heart. 2004; 90(10): 1167-1171

31. Batra AS, Lewis AB. Acute myocarditis. Curr Opin Pediatr. 2001; 13(3): 234-239



Common Congenital Heart Defects and Perioperative Issues in ManagementJesal Sheth MD*, Praveen Khilnani MD**

*Consultant Pediatric and Neonatal Intensivist, Fortis Hospital, Mulund, Mumbai, **Director Pediatric Critical Care and Pulmonology, BLK Superspeciality Hospital, Pusa Road, New Delhi

Keywords: Pediatric, congenital heart defects, acyanotic, perioperative, correction

IntroductionIncidence of congenital heart disease (CHD) is approximately one in every 1,000 live births however variation in incidence from 1- 4 in every 1000 live births exists in reported literature1,2. Acyanotic congenital heart defects account for 70% of all congenital heart disease3. One third have critical CHD and require intervention within the fi rst year of life4.Ventricular septal defect (VSD), Atrial septal defect (ASD) and Patent ductus arteriosus (PDA) account for a majority percentage of all congenital heart defects5. In these defects there is an abnormal communication between the high-pressure left side of the heart and the low-pressure right side of the heart allowing blood to shunt from left to right (Table 1).

Table-1 Acyanotic congenital heart defects:Intracardiac Extracardiac

Atrial septal defect (ASD) Patent ductus arteriosus (PDA)Ventricular septal defect (VSD) Coarctation of the aorta

Blood fl ow through the shunt depends on the size of the shunt and the relative resistances on either side of the shunt. If the defect is large enough not to impede blood fl ow (i.e. non-restrictive defect), then the main determinant of the degree of shunting across this defect depends on the resistance on both sides of the shunt. If the defect opening is small (i.e. restrictive defect), then the degree of shunting will depend more on the size of the defect and less on the resistance across the defect. The drop in pulmonary vascular resistance (PVR) occurring shortly after birth creates

the driving force for the left-to-right shunting of blood across the defect.The pressure difference resulting in left-to-right shunting of blood through the defect consequently leads to turbulence of abnormal blood fl ow producing a heart murmur in systole and sometimes in diastole, excessive blood fl ow into the lungs causing pulmonary vascular congestion leading to shortness of breath, increased volume overload of the myocardium resulting in hypertrophy and chamber dilation, and eventual congestive heart failure (CHF). Development of CHF is the main concern in acyanotic shunt lesions, as opposed to cyanotic CHD in which hypoxia is the main concern. CHF presents as sweating, feeding diffi culties, poor growth or failure to thrive (FTT), S3 gallop, and if left-sided, also tachypnea, subcostal retractions, and/or pulmonary rales. Chest radiographs in CHF may demonstrate cardiomegaly and increased pulmonary vascular congestion and edema. Echocardiograms are the primary diagnostic modality, but magnetic resonance imaging provides excellent anatomic evaluation and often yields even more information than angiography.Untreated defects with large shunts will eventually result in injury to the pulmonary arterioles, vascular obstruction, and pulmonary hypertension. The development of permanent injury to the pulmonary vessels is a function of the duration of exposure to this excessive blood fl ow, and occurs more rapidly in VSD and PDA than in ASD. If this process is not reversed, eventually the Eisenmenger’s complex of right to left shunting may occur as the elevated right-sided pressures (pulmonary hypertension) exceed left-sided pressures. Following is a critical review and discussion of specifi c lesion characteristics and perioperative issues6-9. A detailed lesion specifi c postoperative management is described in various subsequent sections of part 2 of Pediatric cardiac intensive care symposium in this issue.

Correspondence:Dr Jesal Sheth MDIncharge: Neonatal and Pediatric Intensive Care UnitFortis Hospital, Mulund, MumbaiE mail:[email protected]


Ventricular Septal Defect VSD is the most common form of CHD at 15-20% of all cases of isolated CHD. Small defects account for about 85% of all VSDs.They are typed as per location in septum: 1. Perimembranous2. Infundibular3. Muscular4. InletSymptoms depend on the size of the defect. Symptoms can be related to mild to severe congestive heart failure.Smaller defects (2-4 mm) are usually asymptomatic and more likely to spontaneously close (50% by 2 years). About 30-40% of small perimembranous and muscular defects spontaneously close within the fi rst six months of life. Small defects usually do not require surgery or activity restrictions and patients are monitored with periodic follow-up. Larger non restrictive VSDs are more likely to be symptomatic and less likely to spontaneously close. CHF can manifest around six to eight weeks of age. Early surgical repair may be indicated. The physiology of the shunting results in volume overload of the right ventricle(RV), right atrium (RA) and the pulmonary circulation that is transmitted to the left side of the heart as well. Initially, the increased blood volume returning to the left ventricle (LV) increases the stroke volume (Frank-Starling mechanism), however with time the volume overload can lead to LV dilatation, systolic dysfunction and symptoms of left-sided heart failure as early as 2-3 months of age (failure to thrive, tachypnea, lower respiratory tract infections)6. The volume overload of the pulmonary vasculature leads to increased pulmonary artery pressure (PAP) and pulmonary arteriolar hypertrophy with time with pulmonary hypertension setting in as early as the age of 2-3 months. If Qp: Qs (pulmonary to systemic blood fl ow) ratio is greater than 2, accompanied by symptoms of right ventricular volume overload, tachypnea, poor feeding, failure to thrive, then surgery for VSD closure is indicated.On cardiac auscultation one may hear grade II-VI harsh holosystolic murmur along the lower left sternal border and a prominent P2 as the pulmonic valve closes later than the aortic valve. A VSD murmur is

not heard at birth till pulmonary vascular resistance (PVR) and pulmonary pressures are high. Once PVR falls, the left-to-right shunt increases resulting in a new emergence of increased severity of murmur on day 2 or day 3 of life. Subacute bacterial endocarditis prophylaxis are recommnaded to children with VSD. In large defects with near systemic pressures in the right ventricle and pulmonary artery, surgical closure should be performed prior to 18 to 24 months of age even if heart failure control and adequate weight gain are present. Total surgical correction is currently recommended. If the congestive heart failure is diffi cult to control with the usual anticongestive measures or if failure to thrive is present, surgical closure should be undertaken earlier. At the present, transcatheter VSD occlusion is considered experimental.Typically VSD closure involves a patch closure and common postoperative issues are related to post cardiopulmonary bypass status, low cardiac output syndrome, residual signifi cant muscular VSD, rarely ventricular outfl ow tract obstruction caused by patch and aortic insuffi ciency if VSD is Subaortic. Usual post operative vascular lines include central and arterial line. Some units use left atrial lines. Pacing wires are kept for temporary pacing for conduction defects, such as AV conduction abnormalities and transient right bundle branch block. Conduction issues usually resolve in 2-3 days. In the event of an AV block persisting for longer than 7-10 days, a permanent pacemaker may be required. Pulmonary hypertension needs special attention as right ventriculat failure and tricuspid reguirgitation may need to be monitored closely. Chest and mediastinal drain output is monitored closely. Most patients can be successfully extubated in 48 hours after surgery. Close monitoring of fl uid therapy, inotropy as required directed to prevent pulmonary hypertension and optimal RV volume are the key issues in post operative period. Detailed lesion specifi c management issues are addressed in another review in this issue (page 127).

Atrial Septal Defect ASD accounts for 10% of all CHD. It is more common in females.Types based on different locations are:

Common Congenital Heart Defects and Perioperative Issues in ManagementPEDIATRIC CARDIAC INTENSIVE CARE - 2


1. Sinus venosus: Sinus venosus defects are located near the opening of the SVC.

2. Secundum: Most common is secundum defects are which occur through the fossa ovalis.

3. Primum : Primum defects are a form of endocardial cushion defects involving the lowest part of the atrial septum between the atrioventricular valves. These are almost always associated with abnormal development of atrioventricular valves, most commonly a cleft mitral valve. Primum defects can be associated with Downs syndrome, Ellis-Van Creveld syndrome, and Holt-Oram syndrome.

Endocardial cushion separates the atrioventricular valves and forms the lower portion of the atrial septum and the upper portion of the interventricular septum. If ASD presents in infancy,then increased left atrial pressure, mitral valve stenosis,left ventricular dysfunction or left ventricular outfl ow obstruction should be suspected and investigated.Most patients remain asymptomatic, but some children can develop right atrial and ventricular dilation, leading to atrial arrhythmias and ventricular dysfunction. Patients may have a hyperactive precordium, right ventricular heave, fi xed wide split S2, systolic ejection murmur at the second left intercostal space (increased fl ow across the pulmonic valve), or a mid-diastolic murmur at the lower right sternal border (increased fl ow across the tricuspid valve). Flow across the ASD is low velocity and not turbulent, so there is no audible murmur from the ASD itself. Similar to VSDs, smaller defects are expected to spontaneously close while larger ones usually require surgical intervention with patch closure. Despite lack of symptoms at presentation, elective closure of the ASD is recommended around 4 to 5 years of age and is recommended so as to (i) prevent development of pulmonary vascular obstructive disease later in life, (ii) reduce probability for development of supraventricular arrhythmias and (iii) prevent symptoms during adolescence and adulthood.. Closure during infancy is not undertaken unless the infant is symptomatic. Right ventricular volume overloading by echocardiogram and a Qp:Qs >1.5 (if the child had cardiac catheterization) are indications for early closure.Device closure of ASD is discussed else where in this

issue (refer to page 143)The Amplatzer Septal Occluder is rapidly becoming the device of choice by percutaneous right heart catheterization. Both immediate and mid-term follow-up results of Amplatzer Septal Occluder appear excellent with immediate complete closure rates varying from 62% to 96% which improved to 83% to 99% at six to 12 month follow-up.Peoblems in the immediate postoperative period includea. Low cardiac output b. Atrioventircular valve regurgitation [rapid fl uid boluses may lead to annular dilatation and aggravate regurgitation, so rapid boluses should be avoided]

c. Pulmonary hypertension d. AV block or supraventricular arrhythmias need to

be monitored.e. Cardiac dysrhythmias and mitral valve prolapse

may be late sequelae of a treated or untreated ASD. Atrial fl utter or fi brillation may also occur in adults with a history of atrial septal defect, regardless of the treatment.

Patent Ductus Arteriosus PDA results from retention of the fetal ductus arteriosus, which normally closes at about one to two weeks of age. This defect accounts for 5-10% of CHD and is more common in females. PDA can co exist with prematurity, VSD, coarctation of the aorta and rubella exposure during the fi rst trimaster of pregnancy. As pulmonary vascular resistance decreases after birth, blood shunts from the aorta into the pulmonary artery, resulting in increased pulmonary artery blood fl ow and left atrial and ventricular overload. A large PDA results in large left to right shunt leading to pulmonary over circulation and low aortic diastolic pressure, leading to extensive aortic runoff and systemic end-organ hypoperfusion. Pulmonary vascular obstructive disease may occur as early as one year of age. On clinical exam one fi nds bounding arterial pulses, a widened pulse pressure, an enlarged heart, a prominent apical impulse, a classic continuous machine-like murmur at the base and a mid-diastolic murmur at the apex. Small defects are usually asymptomatic, while large



PDAs present with recurrent pulmonary infections, CHF, and failure to thrive. Closure may occur spontaneously.It is generally believed that the presence of an isolated ductus is an indication for closure, mainly to prevent bacterial endocarditis. Waiting until 6 to 12 months of age is generally recommended unless child is symptomatic with heart failure or pulmonary compromise. Indomethacin can be used for medical closure. Some require surgical closure with placement of an embolic device, such as an intravascular coil or PDA occluder, ligation, or division. PDA is the only CHD that is considered surgically “cured” without long-term sequelae. Post operative complications are rare but well known including opening of sutures (If no division performed after ligation), recurrent laryngeal nerve palsy (hoarseness and stridor), phrenic nerve injury(elevation of dome of diaphragm) and very rarely ligation of descending aorta (lower extremity pulses feeble or none along with upper extremity hypertension), left pulmonary arterial ligation(left lung gets oligemic)Subacute bacterial endocarditis prophylaxis is recommended for all PDAs. There may not be any need for this prophylaxis three months following surgical or transcatheter closure, provided there is no residual shunt.Aortic Stenosis (AS) AS is the obstruction of the left ventricle outfl ow tract. AS accounts for 7% of CHD and is described by location: 1) valvular (most common);2) subvalvular or subaortic; or 3) supravalvular (least common, associated with

Williams Syndrome). As a word of caution critical aortic stenosis may present in newborn period as the ductus closes , in a similar way as the entire spectrum of left sided obstructive lesions such as aortic arch abnormalities, aortic atresia, hypoplastic left heart syndrome (Acidotic, Low perfusion, new born in shock at day5-7. Prostaglandin E1 therapy may be life saving temporizing measure to keep the ductus arteriosus patent to achieve systemic perfusion.When the child grows, the cardiac output increases resulting in an increased pressure gradient across the stenosis. Obstructed fl ow from the left ventricle results in increased pressure and hypertrophy. Mild AS is usually asymptomatic with some exercise

intolerance and easy fatigability. Moderate AS may present with chest pain, dyspnea on exertion, dizziness, and syncope. Severe AS presents with weak pulses, left-sided heart failure, and chest pain and could lead to sudden death. Clinical exam may reveal a left ventricular thrust at the apex, systolic thrill at the right base or suprasternal notch, ejection click, or III-IV/VI systolic murmur at sternal border with radiation to carotids. AS can be treated by percutaneous balloon valvuloplasty. Surgical intervention with valvulotomy or valve replacement is indicated for symptomatic patients with high pressure gradients across the narrowed valve. There is no activity restriction in mild AS, but no competitive sports are allowed for moderate to severe AS. Lifelong anticoagulation therapy is required if a prosthetic valve replacement is performed. Postoperative complications may include management of hypertrophic non compliant LV, signifi cant residual stenosis and or regurgitation, coronary ischemia.

Coarctation of aorta Coarctation of the aorta accounts for 6-8% of CHD. It is a narrowing of the aorta that may occur anywhere along its length, but 98% of cases occur distal to the left subclavian artery, where the PDA inserts into the descending aorta. Varying degrees of aortic arch hypoplasia may coexist with coarctaion of aorta, males are more commonly affected than females. Children with Turner syndrome are at increased risk compared to the general population. Other associated anomalies include a bicuspid aortic valve (85%) or an aberrant origin of the right subclavian artery distal to the coarctation (1%). Clinical presentation depends on the severity of constriction and associated cardiac lesions.The classic clinical sign is a higher blood pressure and bounding pulses in the upper extremity, especially the right as most defects are distal to the right subclavian artery, compared to decreased blood pressure and diminished pulses in the legs. At birth, during the fi rst new born detailed examination all upper and lower extremity pulses must be examined carefully. In the few defects occurring proximal to the right subclavian artery, the BP and pulses of the right arm



may be equal to the legs. It is useful to measure blood pressure in both arms and at least one leg to detect blood pressure differential. Older children may develop shortness of breath with exertion, leg pain with exercise, and chest pain with exercise.Obstruction of outfl ow from the left ventricle leads to left ventricular hypertrophy. In newborns, the ductus arteriosus usually allows for adequate lower body perfusion until it closes at its normal time. Severe obstruction leads to hypoperfusion, acidosis, heart failure, and shock. In severe cases, a ductus arteriosus patency should be maintained with a prostaglandin E1 infusion. A severe coarctation in association with a VSD causes increased left-to-right shunting across the VSD, leading to CHF within the fi rst few months of life. In that case coarctation repair is recommended fi rst followed by VSD repair.On examination, cardiac auscultation reveals a systolic murmur at the left sternal border, and especially on the back between the scapulae. Chest radiography may demonstrate cardiomegaly due to left ventricular hypertrophy, inferior rib notching due to erosion by collateral arterial circulation to bypass the obstruction, and a “reverse 3 sign” indicating the indentation of the aorta. The echocardiogram demonstrates narrowing of the distal aortic arch. The MRI produces a clearer picture than the echocardiogram of the anatomy of the coarctation. An angiogram is sometimes necessary to clarify the presence of associated cardiac lesions. Urgent surgical repair is performed in infants with circulatory shock, cardiomegaly, blood pressure extremes or severe CHF. Otherwise surgical repair is usually performed between the ages of one to two years. Post-operative complications may include, rebound systemic hypertension, due to catecholamine release and renin or residual coarctation due to narrow transverse arch,Rebound systemic hypertension usually resolves in fi rst 24 hours. Persistent CHF may be seen if there is associated AS, mitral valve or left ventricular disease.Syndrome of mesenteric arteritis can occur. This is usually caused by refl ex spasm of mesenteric arteries that are suddenly exposed to higher pressures after the coarctation is removed. The spasm can be severe enough to result in bowel ischemia. These patients are at risk for necrotizing enterocolitis. Typically a

fever, leukocytosis, abdominal distension, vomiting or blood in stool 4-8 days post coarctation repair should make one suspect gut ischemia.Spinal cord ischemia due to anterior spinal artery syndrome(related to poor perfusion during clamping of aorta is another known complication.Other complications related to thoracotomy and surgical fi eld include injury to recurrent laryngeal nerve and phrenic nerve.

Some common issues in preoperative care:Special health maintenance is indicated in patients with acyanotic CHD. Growth impairment is directly proportional to the severity of hemodynamic disturbance. Patient with acyanotic CHD tend to have more weight than height growth delay (versus both weight and height delay in cyanotic CHD). Contributing factors are caloric deprivation and reduced adipose stores, lower birth weight, increased caloric requirements, coexisting musculoskeletal, neurologic, renal, or gastrointestinal malformations, mild steatorrhea, and excess protein loss. Up 10% of children with CHD may have genetic syndromes. Poor nutrition results from anorexia, fatigability, vomiting, fl uid restriction, and frequent respiratory infections. Cardiac drugs (i.e., diuretics) may exacerbate anorexia and cause early satiety. Systemic and respiratory illnesses can increase the body temperature and raise the metabolic rate by up to 13% for each degree centigrade above normal. Hypertrophic cardiac muscle can account for up to 30% of total oxygen consumption compared to the usual 10%. The caloric intake for catch-up growth is estimated at 140 to 200 calories per kg per day. In infants unable to gain suffi cient weight with breastfeeding, supplementation can be achieved with a higher caloric density formula or tube feedings. In most patients, catch-up growth is largely complete within six to 12 months of surgery. As per American Heart Association (AHA) [2007], guideline on infective endocarditis prophylaxis includes: 1) prosthetic cardiac valve or prosthetic material

used for valve repair, 2) previous infective endocarditis, 3) unrepaired cyanotic CHD (including palliative

shunts and conduits),



4) completely repaired CHD with prosthetic material or device, whether placed by surgery or by catheter intervention, during the fi rst six months after the procedure as endothelization of prosthetic material usually occurs during that time period,

5) repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibits endothelialization) and

6) cardiac transplant recipients who develop cardiac valvulopathy.

Antibiotic prophylaxis is no longer recommended for any other form of CHD other than those listed above (11-12).The CDC (Centers for Disease Control) recommends that the routine immunization schedule should be followed with some exceptions: 1) Varicella and MMR (measles, mumps, and rubella) vaccines are indicated at 12 months of age rather than at 15 months; 2) Polyvalent pneumococcal vaccine (the pneumococcal vaccine usually used in adults) is recommended at two years of age (this is in addition to pneumococcal conjugate vaccine given at 2, 4, 6, and 12 to 15 months); and 3) Infl uenza vaccine should be given yearly beginning at age six months in this higher-risk population(13)

References 1. Hoffman JI and Kaplan S. The incidence of congenital heart

disease. Journal of the American College of Cardiology. 2002; 39: 1890-1900

2. Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW; et al Congenital heart disease: prevalence at livebirth. The Baltimore-Washington Infant Study. American journal of epidemiology.1985;121:31-6

3. Miyague NI, Cardoso SM, Meyer F, et al. Epidemiological study of congenital heart defects in children and adolescents. Analysis of 4,538 cases. Arq Bras Cardiol 2003; 80:274-278

4. Marino BS, Bird GL and Wernovsky G. Diagnosis and management of the newborn with suspected congenital heart disease. Clinics in perinatology. 2001; 28:91-136

5. Bernstein Daniel. Congenital heart disease page1499 in Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics, 17th ed. 2004, Saunders.

6. Silberbach M, Hannon D. Presentation of Congenital Heart Disease in the Neonate and Young Infant. Pediatr Rev 2007; 28:123-131

7. Lara Shekerdemian. Perioperative manipulation of the circulation in children with congenital heart disease. Heart 2009 95: 1286-1296

8. Bronicki RA, Chang AC. Management of the postoperative pediatric cardiac surgical patient. Crit Care Med 2011 ;39 :1974-84

9. Rae-Ellen W. Kavey.Optimal Management Strategies for Patients With Complex Congenital Heart Disease. Circulation. 2006;113:2569-71

10. Suarez VR, Thompson LL, Jain V, et al. The effect of in utero exposure to Indomethacin on the need for surgical closure of a patent ductus arteriosus in the neonate. Am J Obstet Gynecol 2002;187:886-888

11. Wilson W, Taubert KA, Gewitz M, et al. Prevention of Infective Endocarditis: Guidelines From the American Heart Association: A Guideline From the AHA Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. Circulation 2007;116:1736-54

12. Warnes C A, Walsh EP, Gary D; et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease. Circulation AHA.108.190690

13. Centers for Disease Control and Prevention. Birth-18 Years and Catch-up Immunization Schedules. http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html. US 2013



Key words: Congenital Heart Defects, Post-operative Care, Low Cardiac Output Syndrome

IntroductionChildren with acquired and congenital heart disease amount to 30 – 40% of all admissions to Pediatric Intensive Care Units (PICU)1. Children with heart disease may require care in PICUs for many reasons including management of cardiac failure, management of rhythm issues, and recovery following surgery for congenital heart disease. Thus knowledge of assessment and management of children with cardiac disease is essential to the practice of Pediatric Intensive Care MedicineCongenital heart discase (CHD) occurs in 4/1000 live births and is the leading cause of birth defect associated mortality in children2,3. One third have critical CHD and require intervention within the fi rst year of life4. Successful repair of CHD requires accurate anatomical diagnosis, skilled surgical and perfusion teams, excellent post-operative care, and long-term follow-up and care.

Post-operative care of children undergoing congenital surgeryPost-operative care of children undergoing surgery for CHD requires the coordinated effort of a team of caregivers including medical, surgical, nursing, allied health care professionals, and family members. The post-operative care requires knowledge of pre-operative condition, anatomy and physiology of the CHD. At the time of ICU admission a detailed sign-

Post-operative Care of Common Congenital Heart DefectsRavi R. Th iagarajan MBBS, MPH

Consultant, Cardiac Intensive Care Unit, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

Correspondence:Ravi Thiagarajan MBBS, MPHDepartment of Cardiology, Cardiac Intensive Care Unit, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USATel: (617) 355 7866; Fax: (617) 713 3808Email: [email protected]

out of information from the operating room team to the ICU providers is of paramount importance. Intra-operative course and information from intra-operative imaging at the end of the operation should be obtained from the operating room team. Post-operative assessment should include physical examination, review of hemodynamic data, laboratory data, ECG, and CXR. Evaluation of the post-operative patient should be focused on diagnosing residual heart defects, assessing cardiac output (CO), surgical bleeding, and end-organ function. A plan for management of the post-operative patient, type of frequency of laboratory assessment, and expected time course to extubation from mechanical ventilation should be made with the time of admission to the PICU.Post-operative management should aim to optimize CO and tissue oxygen delivery by ensuring adequate preload, myocardial contractility, and afterload, ensuring sinus rhythm, and reducing oxygen consumption (Table 1)1. Low Cardiac output syndrome (LCOS) resulting in a Cardiac Index (CI) of < 2L/min/m2 occurs in about 25% of infants undergoing cardiac surgery5. LCOS increases risk of mortality, morbidity, and resource utilization and should be promptly diagnosed and managed. Post-operative LCOS resolves over the fi rst 24-48 hours in most cases. Hoffman et al showed that prophylactic use of milrinone infusion reduced the incidence of post-operative LCOS and improved clinical outcomes in children undergoing cardiac surgery6. Persistent LCOS or a post-operative course deviating from the expected course for type and physiology of CHD should promptly trigger investigation for residual heart defects that may impair recovery1. Other post-operative considerations include adequate pain control, nutrition, and care of the patient’s family. Weaning from mechanical ventilation and extubation should be considered once hemodynamic stability and good hemostasis has been achieved.


Specifi c issues pertinent to the post-operative management of 3 common forms of CHD following surgical repair are discussed below.

Ventricular Septal Defect (VSD)Defects in the inter-ventricular septum are the commonest form of congenital heart defects (20% of all defects) with an incidence of 0.38 - 2.3/1000 live births3. Ventricular Septal Defects (VSD) can be single or multiple and can occur in the outlet (conoventricular), membranous, inlet, or the muscular portions of the inter-ventricular septum7. VSD cause a left-to-right shunt at the ventricular level and symptoms depend on the size of the defect. Large defects (approximately

the size of the aortic valve) cause increased pulmonary blood fl ow and equalize pressures in the left (LV) and right ventricles (RV). Small defects may be asymptomatic and present with murmurs, however large defects present with symptoms of congestive heart failure (CHF) due to excessive pulmonary blood fl ow. Diagnosis and location of VSDs can be confi rmed using an echocardiography (ECHO). Cardiac catheterization can be used to quantitate the magnitude of left-to-right shunt.Indications for surgical intervention in patients depend on the size of VSD, presence of CHF, and response to CHF therapies. Because some defects can close spontaneously, patients with small - moderate sized VSD responding to CHF therapy could be followed for spontaneous closure up to 5 years of age.Simple and single VSD can be successfully closed in the operating room. Post-operative recovery following simple VSD closure should be generally uneventful. Post-operative assessment following surgical closure of VSD should focus on the presence of residual VSD, and conduction abnormalities including heart block from injury to the conduction system. Post-operative low cardiac output syndrome (LCOS) should be anticipated and managed appropriately. Most patients undergoing VSD closure should only require a brief period of mechanical ventilation and Intensive Care Unit admission and should recover without complications.

Tetralogy of FallotTetralogy of Fallot is a common form of cyanotic congenital heart disease with an incidence of 0.21 – 0.37/1000 live births3, 8. The characteristics features of TOF include 1.VSD (conoventricular type), 2.Right Ventricular Outfl ow Tract (RVOT) obstruction (consisting of a combination of obstruction at, below, or above the level of the pulmonary valve), 3. Dextroposed Aorta that overrides the ventricular septum, and 4. Right Ventricular Hypertrophy (RVH)9. Van Praagh et al have proposed that the fundamental problem underlying the development of TOF is hypoplasia of the sub-pulmonary infundibulum10. The physiology of TOF is determined the severity of obstruction of the RVOT9. When obstruction to the RVOT is minimal the predominant physiology is one

Table 1: Post-operative Management following Surgical Repair of Congenital Heart Defects1. Receive Information from Cardiac Surgical Team: “Sign-

out” and Assess patient Review operative course Review information post-operative hemodynamic assessment in

OR2. Post-operative Assessment and Post-Operative Management

Plan Physical Exam and Review of Laboratory Data Post-operative management plan3. Ensure Adequate Pre-Load Use CVP or atrial fi lling pressure to titrate preload4. Support Myocardial Contractility E.g. Dopamine or Epinephrine5. Reduce Afterload Vasodilators or Inodilators Positive pressure ventilation6. Manage Rhythm Treat Arrhythmia Temporary Pacing7. Provide Mechanical ventilation Maintain Functional Residual Capacity to lower PVR Using minimal Mean Airway Pressure8. Reduce Oxygen Consumption Mild Hypothermia Mechanical ventilation Pain management, sedation, and neuromuscular blockade9. Monitor for Recovery Follow heart rate, urine output, mixed venous oxygen saturation,

or serum lactate levels10. Rule out Residual Heart Defects Physical exam, Echocardiography, or Cardiac Catheterization11. Mechanical Circulatory Support Consider ECMO for failure of conventional medical therapies

CVP: Central Venous Pressure; PVR: Pulmonary Vascular Resistance; ECMO: extracorporeal Membrane Oxygenation

Post-operative Care of Common Congenital Heart DefectsPEDIATRIC CARDIAC INTENSIVE CARE - 2


of a left-to-right shunt across the VSD. When RVOT obstruction is severe, then RV pressure rises and a right-to-left shunt across the VSD ensues causing cyanosis and pulmonary blood fl ow is reduced. The obstruction to the RVOT may be “dynamic” or increase under circumstances such as crying or agitation resulting in marked worsening of cyanosis resulting in “hypercyanotic” or “Tet Spells”11.As previously stated the clinical manifestation of TOF vary based on the degree of RVOT9. Cyanosis, RVOT ejection systolic murmur, RVH on Electrocardiogram (EKG), and a boot shaped heart indicating RV enlargement on CXR may be present and indicate a diagnosis TOF. ECHO can be used to demonstrate the anatomical details of VSD, degree and site of RVOT obstruction. Other anatomical details may be important for surgical planning include presence or absence of additional VSDs, size of the proximal and branch pulmonary arteries, presence or absence of Aorto-Pulmonary collateral vessels, coronary anatomy, and presence of atrial communication. TOF may be associated with other chromosomal (DiGeorge Syndrome) and non-chromosomal (VATER) syndromes. These issues should be evaluated as they can complicate the post-operative course and management.“TET Spells” can be caused both by increased RVOT obstruction brought on by catecholamine induced spasm of the pulmonary infundibulum or as result of a decrease in systemic vascular resistance encouraging increased right-to-left shunting at the VSD9, 11. Management includes calming an agitated child, supplemental oxygen administration and placing the infant in knee chest position. If a spell cannot be terminated, then intravenous access should be obtained, narcotics should be administered, and preload to the RV should be increased by volume expansion should be used. Bolus doses of Phenylephrine to increase systemic vascular resistance and decrease right-to-left shunting may be needed. Some children may not respond to these measures and may require endotracheal intubation, mechanical circulatory support, or emergency surgical intervention.All patients with TOF require surgical intervention to correct the underlying anomalies9. Timing of

intervention for patients with TOF is somewhat controversial with some groups pursing a full TOF repair by 3 -4 months of age and other delaying repair to later age (6 months – 1 year) using a Systemic to Pulmonary Artery (Blalock-Taussig Shunt) to provide pulmonary blood fl ow which awaiting full repair. Severe RVOT obstruction or “TET Spells”is an indication for early surgical interventionincluding in the neonatal period. Full repair of TOF includes relief of RVOT obstruction and VSD closure. Most children undergoing TOF repair make an uneventful post-operative recovery. Clinical assessment following admission to the ICU after TOF repair should focus on detection of residual anatomical abnormalities including the presence of a residual VSD or signifi cant RVOT obstruction. LCOS due to diastolic dysfunction of the right ventricle also called “restrictive RV physiology” is common in patients undergoing repair of TOF12, 13. Myocardial injury and edema resulting from incision of the RVOT, RV hypertrophy, and post-operative pulmonary regurgitation are thought to contribute to development of restrictive RV physiology. These patients have a non-compliant RV thus need increased venous pressure for RV fi lling in diastole. LCOS in these patients can arise from decreased RV output and adverse inter-ventricular interaction due to RV diastolic dysfunction both resulting in decreased LV output and CO. Patients with “restrictive RV physiology” present with signs of LCOS, poor perfusion, elevated central venous pressures, metabolic acidosis, oliguria, hepatomegaly, ascites, and pleural effusion. A decompressing atrial communication (e.g. Patent Foramen Ovale) can help maintain LV preload and CO by allowing a right to left atrial shunt, and offset the high RA pressure by allowing decompression into the LA via the communication. Although an atrial communication can make post-operative management of patients with RV physiology easier, it comes at the expense of lower oxygen saturation because of the right-to-left shunt. The right-to-left shunt will decrease and oxygen saturation will increase as RV compliance improves over time in the post-operative period. The diagnostic features of restrictive RV physiology were described by Cullen et al using Doppler



Echocardiography in patients with Tetralogy of Fallot and includes demonstration of antegrade fl ow into the pulmonary artery in atrial systole12. Antegrade fl ow into the pulmonary artery during atrial systole contributes to cardiac output and can be decreased by the use of positive pressure mechanical ventilation often used during recovery following cardiac surgery13, 14. Thus mechanical ventilation in patients recovering from TOF should be provided with the lowest mean airway pressure possible. Early extubation from mechanical ventilation in the post-operative may be benefi cial in the patients15, 16.A number of cardiac arrhythmias requiring intervention have been described following TOF repair17. Junctional ectopic tachycardia (JET) s a common (4n – 22%) rapid, automatic, and catecholamine sensitive tachycardia seen following TOF repair. Early detection and aggressive management of JET is essential because JET often results in loss of atrio-ventricular (a-v) synchrony and can decrease cardiac output. Management of JET includes, use of sedation and neuromuscular blockade, decreasing vasoactive support where possible, induced hypothermia (usually 34 - 35oC), use of antiarrhythmic agents (procainamide, amiodarone) and temporary atrial pacing to provide a-v synchrony18,19. Recently administration of intravenous magnesium following weaning from cardiopulmonary Bypass has been shown to reduce the incidence of JET and use of Intravenous Dexmedetomidine have been shown to be effective in the management of JET20, 21.

D-Transposition of Great Arteries (also see p161)The estimated incidence of D-Transposition of the Great Arteries (D-TGA) is 0.21 – 0.38/1000 live births and accounts for 7 – 8% of all congenital cardiac malformations3, 22. D-TGA is thought to arise from abnormal rotation and septation of the arterial truncus however the exact embryological origin of the defect has not been clearly defi ned. In D-TGA the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. This results in a parallel systemic and venous circulation where desaturated venous blood returning to the heart is ejected to the systemic circulation resulting in profound cyanosis and saturated pulmonary venous return is ejected

back into the pulmonary circulation. Survival and oxygenation depends on mixing of desaturated systemic venous and saturated pulmonary venous return via a Patent Ductus Arteriosus (PDA), Atrium (Patent Foramen Ovale or Atrial Septal Defect) or Ventricle (Ventricular Septal Defect).The diagnosis of D-TGA in any cyanotic newborn is madeusing 2-dimensional echocardiography (ECHO) because physical exam, chest radiography, and electrocardiography may not be contributory to making the diagnosis. In addition to confi rming the diagnosis of D-TGA, ECHO should survey the presence of other cardiac abnormalities as these issues may have implications surgical planning. These include VSD (present in 20% of cases), Aortic arch obstruction, coronary anatomy, and the presence left ventricular outfl ow tract obstruction. Pre-operative management includes maintaining adequate oxygen saturation and cardiac output. Patient with profound cyanosis require resuscitation with use of prostaglandin E1 (PGE1) infusion, mechanical ventilation, and an emergent Balloon Atrial Septostomy(BAS) to ensure adequate mixing and oxygen saturation.The Arterial Switch Operation (ASO) is the procedure of choice in patients with D-TGA. The procedure is performed via median sternotomy and cardiopulmonary bypass and includes transection of the great vessels and restoring their connection to the appropriate ventricle, translocation of coronary arteries to the neo-aorta and closure of atrial communications (and VSD when present). The optimal timing of ASO is though around 5– 10 days of age, however a recent study showed increased morbidity and cost for when ASO is undertaken after 3 days of age22, 23. Because the myocardium of left ventricle in D-TGA pumping to a low resistance pulmonary circulation can involute over time, infants presenting late (> 8 weeks) with DTGA are at risk of LV failure after ASO and require special consideration with regards to LV training or post-operative support of the LV prior to ASO. Strategies for management of children presenting late with D-TGA and LV involution include a 2-staged procedure where a pulmonary artery band and Blalock-Taussig shunt are used to train the LV prior to ASO or recovery of



the LV function with ECMO support24-27.All general principles of Intensive Care monitoring and management for children undergoing cardiac surgery apply to patients recovering following ASO1. Special considerations include managing Post-Operative Low Cardiac Output Syndrome (LCOS) and recognition and management of coronary ischemia. Wernovsky et al in a cohort of 170 neonates (122 had cardiac index measurements) undergoing ASO demonstrated that a decrease in cardiac index (CI) occurred during the 9 to12 post-operative hours following cardiac surgery and approximately 24% of patients in this had a CI< 2.0 L/min/m2

during the fi rst 24 post-operative hours5, 6. Thus LCOS is common following ASO and management strategies should include ensuring adequate pre-load, enhancing myocardial performance using inotropes and inodilators, afterload reduction, ensuring sinus rhythm, mechanical ventilation, and therapies aimed at reducing oxygen demand/consumption (hypothermia, sedation, and neuromuscular paralysis). Careful monitoring of heart rate, systolic blood pressure, peripheral perfusion, urine output and serum lactate can help assess cardiovascular function. Progressive deterioration should prompt further evaluation with ECHO and consideration of mechanical circulatory support. Myocardial ischemia may be suggested by LCOS, hypotension, increasing Left Atrial (LA) pressure, ST-T abnormalities on ECG, and regional LV wall motion abnormalities on ECHO should prompt investigation of coronary anastomosis and possible revision. Survival to hospital discharge and long-term outcomes appear to be good for neonates undergoing ASO.

SummarySuccessful management of children undergoing surgery for CHD requires detailed understanding of anatomy and physiology of the CHD both in pre and post-operative periods, and coordination of a multidisciplinary team of experts and anticipation and management of complications that arise in the post-operative period.

References1. Wessel DL. Managing low cardiac output syndrome after

congenital heart surgery. Critical care medicine. 2001; 29: S220-30

2. Hoffman JI and Kaplan S. The incidence of congenital heart disease. Journal of the American College of Cardiology. 2002; 39: 1890-900

3. Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW, Hepner SI and Downing JW. Congenital heart disease: prevalence at livebirth. The Baltimore-Washington Infant Study. American journal of epidemiology. 1985; 121:31-6

4. Marino BS, Bird GL and Wernovsky G. Diagnosis and management of the newborn with suspected congenital heart disease. Clinics in perinatology. 2001; 28: 91-136

5. Wernovsky G, Wypij D, Jonas RA, Mayer JE, Jr., Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW and Wessel DL. Postoperative course and hemodynamic profi le after the arterial switch operation in neonates and infants. A comparison of low-fl ow cardiopulmonary bypass and circulatory arrest. Circulation. 1995; 92: 2226-35

6. Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, Bailey JM, Akbary A, Kocsis JF, Kaczmarek R, Spray TL and Wessel DL. Effi cacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation. 2003; 107: 996-1002

7. Redmond JR and Lodge AJ. Atrial Septal Defects and Ventricular Septal Defects. In: D. G. Nichols, R. M. Ungerleider, P. J. Spevak, W. J. Greeley, D. E. Cameron, D. G. Lappe and R. C. Wetzel, eds. Critical Heart Disease in Infants and Children. Second ed. Philadelphia, PA: Elsevier; 2005: 579 - 592

8. Davis S. Tetralogy of Fallot With or Without Pulmonary Atresia. In: D. G. Nichols, R. M. Ungerleider, P. J. Spevak, W. J. Greeley, D. E. Cameron, D. G. Lappe and R. C. Wetzel, eds. Critical Heart Disease in Infants and Children. Second ed. Philadelphia, PA: Elsevier; 2005: 755 - 766

9. Rajagopal SK and Thiagarajan RR. Perioperative care of children with tetralogy of fallot. Current treatment options in cardiovascular medicine. 2011; 13:464-74

10. Van Praagh R, Van Praagh S, Nebesar RA, Muster AJ, Sinha SN and Paul MH. Tetralogy of Fallot: underdevelopment of the pulmonary infundibulum and its sequelae. The American journal of cardiology. 1970; 26: 25-33

11. Kothari SS. Mechanism of cyanotic spells in tetralogy of Fallot--the missing link? International journal of cardiology. 1992; 37:1-5

12. Cullen S, Shore D and Redington A. Characterization of right ventricular diastolic performance after complete repair of tetralogy of Fallot. Restrictive physiology predicts slow postoperative recovery. Circulation. 1995; 91:1782-9

13. Shekerdemian LS, Schulze-Neick I, Redington AN, Bush A and Penny DJ. Negative pressure ventilation as haemodynamic rescue following surgery for congenital heart disease. Intensive care medicine. 2000; 26: 93-6

14. Shekerdemian LS, Bush A, Shore DF, Lincoln C and Redington AN. Cardiorespiratory responses to negative pressure ventilation after tetralogy of fallot repair: a hemodynamic tool for patients with a low-output state. Journal of the American College of Cardiology. 1999; 33: 549-55



15. Shekerdemian LS, Penny DJ and Novick W. Early extubation after surgical repair of tetralogy of Fallot. Cardiology in the young. 2000; 10: 636-7

16. Heinle JS, Diaz LK and Fox LS. Early extubation after cardiac operations in neonates and young infants. The Journal of thoracic and cardiovascular surgery. 1997; 114: 413-8

17. Hoffman TM, Bush DM, Wernovsky G, Cohen MI, Wieand TS, Gaynor JW, Spray TL and Rhodes LA. Postoperative junctional ectopic tachycardia in children: incidence, risk factors, and treatment. The Annals of thoracic surgery. 2002; 74: 1607-11

18. Walsh EP, Saul JP, Sholler GF, Triedman JK, Jonas RA, Mayer JE and Wessel DL. Evaluation of a staged treatment protocol for rapid automatic junctional tachycardia after operation for congenital heart disease. Journal of the American College of Cardiology. 1997; 29: 1046-53

19. Perry JC, Fenrich AL, Hulse JE, Triedman JK, Friedman RA and Lamberti JJ. Pediatric use of intravenous amiodarone: effi cacy and safety in critically ill patients from a multicenter protocol. Journal of the American College of Cardiology. 1996; 27: 1246-50

20. Manrique AM, Arroyo M, Lin Y, El Khoudary SR, Colvin E, Lichtenstein S, Chrysostomou C, Orr R, Jooste E, Davis P, Wearden P, Morell V and Munoz R. Magnesium supplementation during cardiopulmonary bypass to prevent junctional ectopic tachycardia after pediatric cardiac surgery: a randomized controlled study. The Journal of thoracic and cardiovascular surgery. 2010; 139: 162-169 e2

21. Chrysostomou C, Beerman L, Shiderly D, Berry D, Morell VO and Munoz R. Dexmedetomidine: a novel drug for the treatment of atrial and junctional tachyarrhythmias during the perioperative period for congenital cardiac surgery: a preliminary study. Anesthesia and analgesia. 2008; 107: 1514-22

22. Karl TR and Kirshbom PM. Transposition of the Great Arteries and the Arterial Switch Operation. In: D. G. Nichols, R. M. Ungerleider, P. J. Spevak, W. J. Greeley, D. E. Cameron, D. G. Lappe and R. C. Wetzel, eds. Critical Heart Disease in Infants and Children. Second ed. Philadelphia, PA: Elsevier; 2005: 715 - 730

23. Anderson BR, Ciarleglio AJ, Hayes DA, Quaegebeur JM, Vincent JA and Bacha EA. Earlier arterial switch operation improves outcomes and reduces costs for neonates with transposition of the great arteries. Journal of the American College of Cardiology. 2014; 63: 481-7

24. Bisoi AK, Malankar D, Chauhan S, Das S, Ray R and Das P. An electron microscopic study of left ventricular regression in children with transposition of great arteries. Interactive cardiovascular and thoracic surgery. 2010; 11:768-72

25. Bisoi AK, Sharma P, Chauhan S, Reddy SM, Das S, Saxena A and Kothari SS. Primary arterial switch operation in children presenting late with d-transposition of great arteries and intact ventricular septum. When is it too late for a primary arterial switch operation? European journal of cardio-thoracic surgery : offi cial journal of the European Association for Cardio-thoracic Surgery. 2010; 38:707-13

26. Bisoi AK, Ahmed T, Malankar DP, Chauhan S, Das S, Sharma P, Saxena A and Boopathy NS. Midterm outcome of primary arterial switch operation beyond six weeks of life in children with transposition of great arteries and intact ventricular septum. World journal for pediatric & congenital heart surgery. 2014; 5:219-25

27. Wernovsky G, Giglia TM, Jonas RA, Mone SM, Colan SD and Wessel DL. Course in the intensive care unit after ‘preparatory’ pulmonary artery banding and aortopulmonary shunt placement for transposition of the great arteries with low left ventricular pressure. Circulation. 1992; 86: II133-9



Acute Kidney Injury in Children aft er Cardiac SurgeryLalitha AV*, MD, Aby Dany Varghese, MD**, Anil Vasudevan, MD***

*Associate Professor in Paediatrics and PICU In Charge, **Senior Resident PICU, ***Associate Professor,Department of Pediatrics, St John’s Medical College and Hospital, Bangalore

Key words: AKI, Cardiac surgery, Peritoneal Dialysis, Continuous renal replacement therapy

IntroductionAcute kidney injury (AKI) occurs in up to 30% of patients who undergo cardiac surgery (CS), while 1% of patients have AKI severe enough to require some form of renal replacement therapy.1,2

The mechanism of AKI is probably multifactorial (hemodynamic insult, infl ammatory mediators, cardiopulmonary bypass and nephrotoxins). AKI after CS is associated with adverse outcomes, including prolonged intensive care and hospital stays, diminished quality of life and increased long-term mortality.3 Even mild degrees of post-operative AKI can cause a significant increase in mortality and morbidity.3-5 Mortality in children developing AKI after CS remains high, inspite of advances in surgical techniques, intensive care management and increased use of renal replacement therapies.6

Factors leading to AKI-associated mortality include fl uid overload, acidosis, hyperkalemia and abnormal cross-talk between organs resulting in decreased end organ function. Patients who survive have an increased rate of chronic renal disease secondary to the AKI sustained in post-operative period. Early diagnosis of AKI as well as appropriate management in the peri-operative period should help to decrease the mortality, morbidity and chronic residual renal damage.

CorrespondenceDr Lalitha AV, MD DNB, FNB (Pediatric Critical Care)Associate Professor in Pediatrics and PICU In Charge Department of Pediatrics, St John’s Medical College and Hospital, Sarjapur Road, Bangalore-560 034Email ID : [email protected] : 09448461673

Incidence The incidence of AKI following CS has been diffi cult to determine. AKI was found to be more common children undergoing complex CS for congenital heart disease. Depending on the patient’s age, RACHS (Risk Adjusted classifi cation for Congenital Heart Surgery) score, time on cardiopulmonary bypass (CPB), need for extracorporeal life support (ECLS) and defi nition of AKI, the incidence of AKI can be as high as 42%, 1-17% needing dialysis and with a 20%-100% mortality rate.7-10

Risk factors of AKI in Post op CSThe kidneys receive 20% of cardiac output and are very sensitive to hypo perfusion and hypo perfusion related injuries.11 The etiology of AKI after CPB is multifactorial and incompletely understood. CS incurs risk for AKI through hypotension, inflammation and the use of nephrotoxic medications. Prematurity, single ventricle physiology, longer cardiopulmonary bypass time, peak postoperative lactic acid concentration, higher postoperative lactate levels and a history of heart surgery are few of the predictors of AKI development in post-operative period.12,13

Pathophysiology of AKI following CSThe clinical phases of AKI after cardiopulmonary bypass (CPB) are characterized by pathologic changes occurring in the clinical course and are determined by preoperative, intraoperative, and postoperative events.14 (Figure 1) The characteristics of the neonatal-infant kidney represent an additional risk factor for the development of AKI under these conditions.


PATHOPHYSIOLOGIC FACTORSPreoperativ Intraoperative Postoperative• Hypovolemia • CPB-SIRS Response • Ongoing hemodynamic instability• Hypotension • Emboli generated by CPB • High vasopressor requirements• Drugs affecting • Hemodynamic alterations • Hemodynamic alterations Renal function • Pigment nephropathy • Mechanical circulatory support (Eg ARB’s, Dinretics) devices (Eg IABP, VAD)

Figure 1 Acute kidney injury after cardiopulmonary bypass (CPB): an overview of the pathophysiologic features and management strategies. ANP - atrial natriuretic peptide; ARB-_ angiotensin receptor blocker; CH- congestive heart failure; IABP -intraaortic balloon pump; MAP- mean arterial pressure; SIRS- systemic infl ammatory response syndrome; VAD - ventricular assist device.15

DiagnosisAcute kidney injury (AKI), formerly known as acute renal failure is characterized by an abrupt (<48 hours) and sustained decline in glomerular fi ltration rate and an inability of kidneys to appropriately regulate fl uid, electrolytes and acid-base homeostasis. The pRIFLE and AKIN criteria (Table1) were developed by panels of experts to provide a uniform defi nition of AKI and facilitate recommendations for patients suffering from renal failure.16,17

These defi nitions rely upon serum creatinine levels and urine output to defi ne and categorize the severity of kidney injury. Although new concepts such as

RIFLE and AKIN have helped standardize the defi nition of AKI, the criteria involved in making the diagnosis can take hours to days, leading to delayed recognition of renal dysfunction.

Creatinine Serum creatinine, the traditional marker of renal function, only rises appreciably after a 50% loss in GFR. In addition, it does not peak till 1 to 3 days after CS, has a low sensitivity and specifi city and is affected by several non renal factors such as age, gender, muscle mass, vigorous exercise, andmedications.18,19

Urine outputThe most readily available surrogate marker of renal function is urine output. Compared to creatinine, it is more sensitive to changes in renal hemodynamics. Unfortunately, variations in urine output are considerably less specifi c, except when severely diminished or absent. Oliguria is defi ned as urine output of less than 0.5mg/kg/hour. The presence of an oliguric state gives physicians a sign that kidney function is at risk or already perturbed, however, the presence of normal urine output cannot provide assurance that renal function is unperturbed.

UrinalysisIn patients with decreased urine output or suspected acute kidney injury, urinalysis is an important tool that can differentiate prerenal from renal failure.

Table 1: pRIFLE, AKIN, KDIGO Criteria pRIFLE Criteria AKIN Criteria KDIGO CriteriaStage SCr- Based Urine output Stage SCr- Based Urine output Stage SCr- Based Urine outputRisk >25%eCCI ↓ <0.5 ml/kg/h

for 8hI SCr ↑ ≥0.3mg/dl

OR 150-200% in <48hrs

<0.5ml/kg/h for 8h

I 1.5–1.9 times baseline OR >0.3 mg/dl increase in 48h

<0.5ml/kg/h for 8h

Injury >50%eCCI ↓ <0.5 ml/kg/h for 16h

II SCr ↑ 200%-300%

<0.5ml/kg/h for 16h

II 2.0–2.9 times baseline <0.5ml/kg/h for 16h

Failure >75%eCCI ↓OReCCl 35mL/min/1.73m2

<0.5 ml/kg/h for 24h OR<0.3ml/kg/h for 12h

III SCr ↑ 200%-300%ORSCr >4.0mg/dl

<0.5ml/kg/h for 24h OR<0.3ml/kg/h for 12h

III 3.0 times baselineOR ↑ in serum creatinine to>4.0 mg/dl OR In patients <18 years, ↓ in eGFR to <35 ml/min per 1.73 m2

<0.5ml/kg/h for 24hOR<0.3ml/kg/h for 12h

AKIN, Acute Kidney Injury Network; eCCl, estimated creatinine clearance; KDIGO, Kidney Disease Improving Global Outcomes; pRIFLE, pediatric version of the RIFLE criteria (Risk, Injury, Failure, and 2 outcome criteria, Loss and End-Stage Kidney Disease); SCr, serum creatinine

Acute Kidney Injury in Children after Cardiac SurgeryPEDIATRIC CARDIAC INTENSIVE CARE - 2


Consequently, it can be very useful in guiding treatment. Table 2 describes select variables and their association with the aetiology of acute kidney injury.

Table 2: Lab investigations to differentiate Pre renal and renal injury.Indices Prerenal RenalUrine osmolality(mosmol/kg H2O) >500 <350Urine Specifi c gravity >1.020 <1.020Urinary Sodium(Na) <20 >20Fractional excretion of fi ltered Na (%) FENa <1 >1

Early detection of AKI: The emerging role of biomarkers in following CSAt present, there are no specifi c markers of AKI which can be used in the early post-operative period. Research to develop such a biomarker is of utmost importance as AKI develops early after CS, mostly within 72hrs. Non-availability of such a reliable test is partly responsible for the limited progress that has been made in preventing and treating post-operative renal failure.20 Plasma biomarkers that have been recently found to be useful in early diagnosis and prognostication are neutrophil gelatinase-associated lipocalin and cystatin C, while useful urinary biomarkers include neutrophil gelatinase-associated lipocalin, interleukin 18 (IL-18), and kidney injury molecule.21-23 Currently, these biomarkers are being evaluated and are not available for routine bedside use.

General measures to prevent AKI after CSAs a general rule, hemodynamics and cardiac function optimization are a priority in patients with a congenital heart defect. Low cardiac output state (LCOS) consists of an inadequate systemic oxygen delivery to meet the metabolic demands of the organ systems associated with low cardiac output.23 LCOS plays an important role after pediatric open-heart surgery, affecting up to 25% of infants between 6 and 18 hours after surgery, and results in longer intensive care unit stay and increased mortality.24 Features of LCOS include tachycardia, poor systemic perfusion, decreased urine output, increased lactate, and reduced mixed venous oxygen saturation.

Infants suffering from LCOS with decreased kidney perfusion usually benefi t from inotropes (dopamine, milrinone), vasopressors (high-dose dopamine, epinephrine), vasodilators (milrinone, fenoldopam), and diuretics (furosemide) that must be optimized to achieve the best equilibrium between cardiac function (contractility), blood oxygenation (pulmonary fl ow), and systemic perfusion (kidney, hepatic, gastrointestinal function). Strict clinical observation and constant modifi cation of drug infusion when signs of pulmonary overfl ow/systemic hypoperfusion occur are the main determinants for successful management of these patients.

Medical interventions to prevent AKI after CSPharmacologic interventions have been attempted with inconsistent results, and at this time, there are no known drugs that have conclusively demonstrated renal protection.

HydrationThere is little argument that adequate hydration is a prerequisite to maintaining healthy kidney function. A randomized trial compared a regimen of pre-operative intravenous hydration to standard pre-operative fl uid restriction in patients with known renal dysfunction, defi ned as glomerular fi ltration rate <45mL/min.25

Patients in the hydration group were signifi cantly less likely to develop postoperative renal failure and no patients required renal replacement therapy (RRT), compared to 27% of patients in the control group. Much effort has been put into identifying the ideal fl uid, or ideal combination of fl uids, to maintain perioperative circulating volume. A recent randomized pilot study by Magder et al compared the use of colloids to crystalloids in a postoperative CS population.26 The colloid based resuscitation protocol was associated with less catecholamine use, a lower incidence of pneumonia and mediastinal infection, and less need for cardiac pacing. There was no difference in the daily creatinine, development of RIFLE risk criteria during hospital stay, packed red blood cells transfusion or new dialysis between the 2 groups. It is likely that either colloids or crystalloids are suitable solutions for fl uid resuscitation and that a balanced resuscitation



avoiding high doses of colloids or crystalloids alone would lead to optimal patient outcome.

Glycemic controlIn 2001, van den Berghe published a seminal randomized trial establishing the benefi t of intensive insulin therapy to maintain tight glycemic control (maintenance of blood glucose at a level between 80 and 110 mg per decilitre in postoperative critically ill patients. 27 More than 60% of patients studied had undergone CS. In addition to a signifi cant mortality benefi t, intensive insulin therapy was associated with a 41% reduction in patients requiring dialysis or hemofi ltration.

DopamineDopamine is the commonly used agent in infants after CS, at doses ranging from less than 5 mcg/kg/min (stimulation of DA1 receptors), 5 to 10 mcg/kg/min (stimulation of β1 receptors), up to 20 mcg/kg/min (stimulation of α receptors). Dopamine is titrated after the surgical procedure to achieve adequate mean arterial pressure and systemic perfusion. Dopaminergic receptors (DA1 and DA2) are present in the renal, mesenteric, and coronary vascular beds, but their clinical relevance has been the object of a long-lasting debate. DA receptors appear gradually after birth.28,29 Natriuresis in response to DA agonists also is markedly impaired in the newborn.30 While dopamine increases cardiac output on one hand, on the other hand it increases myocardial oxygen demand by disproportionately increasing inotropy and chronotropy.31 In addition, at higher doses it can increase systemic vascular resistance thereby increasing the after load on the failing heart. The neonatal heart is characterized by the presence of immature adrenergic receptors,and has a relatively limited response to catecholamine administration. This is owing to the presence of low receptor density and affi nity, an increase in β2/β1 receptor ratio, different coupling with intracellular second messengers, and receptor down-regulation after a few hours of catecholamine administration.32 For this reason, high doses of dopamine infusion often are required during postoperative LCOS and the potential

for peripheral and splanchnic vasoconstriction exists. Nevertheless, in clinical practice the priority usually is given to maintenance of adequate mean arterial pressure to achieve kidney perfusion and possibly preserve renal function.

EpinephrineWhen high doses of dopamine fail to restore adequate perfusion pressure, epinephrine infusion often is required in LCOS. Epinephrine has strong α and β-adrenergic–receptor activation. At lower doses (< 0.05 mcg/kg/min), epinephrine increases ventricular contraction, reduces systemic vascular resistance, and increases renal blood fl ow. As the dose is increased, more prominent vasoconstriction occurs and decrease in renal blood fl ow is seen. Controversial debate is ongoing about the role of vasopressors in AKI pathophysiology. The respective roles of epinephrine on kidney function under these conditions are unclear. On one hand, vasopressors improve organ perfusion; on the other hand, they have been considered potentially harmful to renal microcirculation.32

MilrinoneMilrinone is a phosphodiesterase inhibitor that has been shown to increase cardiac output in selected children with LCOS after open heart surgery, most likely as a result of direct myocardial inotropic effect as well as pulmonary and systemic vasodilatory properties.24 A recent multicenter study showed that milrinone, when administered prophylactically to infants after cardiac surgery, is effective in preventing LCOS. 28

DiureticsLoop diuretics such as furosemide are the most used diuretics in the infant undergoing CS.33 Dosage and administration modality vary from boluses (1 mg/kg every 8 or 12 h) to continuous infusion (0.1 to 0.3 mg/kg/h). The administration strategy has been re-evaluated in light of the results obtained in infants treated with continuous versus intermittent furosemide after heart surgery. Furosemide continuous infusions may be preferred to bolus administration because it yields comparable urinary output with a much lower



dose, fewer hourly fl uctuations, and less urinary sodium and chloride wasting. 34, 35 A 3-day trial of 13 post–heart surgery infants and children noted that a mean starting dose of 0.093 was insuffi cient, and required a signifi cant increase to 0.175 mg/kg/h in 10 of 13 patients. These investigators suggest a starting dose of 0.2 mg/kg/hour and eventual tapering.36

Recently, a great amount of interest in the use of dopamine-receptor agonists in post–heart surgery infants has been raised. In a retrospective series of 25 post-CPB neonates, a signifi cant improvement of diuresis was observed with fenoldopam, a selective DA1-receptor agonist, compared with chlorothiazide and furosemide.37

Natriuretic peptidesNatriuretic peptides are known to oppose the renin-angiotensin-aldosterone and arginine vasopressin systems through multiple mechanisms.38 They can induce natriuresis and vasodilatation to prevent hypervolemia and oppose the vasoconstrictive response induced by hypovolemia. Synthetic analogues of these proteins have been suggested as therapies to prevent renal failure following CS. Anaritide, the human recombinant form of atrial natriuretic peptide (ANP), is administered intravenously to induce arterial and venous dilatation, thus decreasing cardiac preload and afterload. Nesiritide, a human recombinant form of Brain-type natriuretic peptide (BNP) is used in the treatment of decompensated heart failure. In a randomized controlled trial of heart failure patients, nesiritide improved diuresis and decreased pulmonary congestion and edema.39 RCTs regarding use of these drugs in children are not available at present.

Treatment of complications DyselectrolytemiaIn children with AKI, serum potassium should be measured at least daily since hyperkalemia is a life threatening complication of AKI. When potassium levels become high or ECG changes develop, emergency treatment may include intravenous infusion of calcium, sodium bicarbonate, glucose and

insulin, or an inhaled beta agonist.40 Administration of loop diuretics can be useful to eliminate potassium, however, varied responses to this medication render the effect unreliable. A sodium potassium exchange resin, such as sodium polystyrene sulfonate (Kayexalate), can be effective in removing potassium, although the maximal effect occurs only after 4-6 hours. Other electrolyte disturbances (hypokalemia, hyponatremia, hypochloremia) can be seen secondary to diuretic therapy and should be monitored closely.

Metabolic acidosisAcidosis occurs frequently in acute renal failure, often complicating treatment in the critically ill patient due to altered homeostasis, decreased cardiac contractility, and attenuated responses to catecholamines. Management of metabolic acidosis should focus on correction of the underlying cause and concomitant morbidity. If acidosis remains after optimal therapy, hemodialysis is the most effective and proven method of correction. There is signifi cant controversy regarding the use of bicarbonate in management of acidosis in the critically ill patient. Observational and randomized studies have failed to show a mortality or morbidity benefi t when sodium bicarbonate is administered to correct acidosis.41

The proposed rationale for the lack of benefi t is that, while bicarbonate may increase extracellular pH, it exacerbates intracellular acidosis by the generation of carbon dioxide. Consequently, the practice of many critical care physicians is to administer sodium bicarbonate only in the presence of profound acidosis (pH <7.1) and associated hemodynamic instability.

RRT of post–heart surgery AKI in infantsThe optimal time to initiate RRT in CSA-AKI remains uncertain. There is no consensus on indications for initiating CRRT. As claimed in the majority of previous studies, accepted indications of RRT include: fl uid overload, overt uremia, hyperkalemia, and severe metabolic acidosis. Furthermore, the presence of any other organ failure accompanied by



AKI may be a valid criterion for RRT. In 2012, the KDIGO guideline on renal support for AKI suggests initiating RRT emergently when life-threatening changes in fl uid, electrolyte, and acid-base balance exist (not graded).42

The indication for RRT in these patients has changed through the years and the present tendency is that of a wider application of this kind of treatment. Although no clear recommendation is made for the application of RRT in patients without acute renal failure, it is widely accepted that RRT can positively affect the clinical course of multiple organ disease syndrome. Up to 20% of all cases of pediatric multiple organ disease syndrome are represented by children who underwent CS. In addition, prevention of fl uid accumulation has been associated recently with an improved survival rate in critically ill children. In post-CPB children with AKI, the application of preventive dialysis proposed years ago, recently has been associated with very low mortality. Depending on the institution’s preference, need for dialysis effi ciency, and availability of access, the 2 dialysis modalities most frequently used in infants with post– heart surgery AKI are peritoneal dialysis and CRRT. Intermittent haemodialysis is not a desirable modality in children after CS due to its impact on systemic hemodynamics.

Peritoneal dialysis (PD)With regard to complications, PD is generally a safe method. Even though cardiothoracic surgery may constitute a relative contraindication to PD due to the risk of peritoneo-pleural diaphragmatic communication, the technique is widely used with a low rate of complications. In this setting, PD has long been advocated as the preferred technique because of better hemodynamic stability, no requirement for vascular access or heparin, simplicity, and low cost.43,44 One of the main disadvantages of PD is a relative lack of effi ciency in water removal with direct consequences on fl uid balance and frequent limitation of parenteral nutrition. Nonetheless, the early application of PD as a therapy for fl uid overload prevention is presently accepted.45 In particular, infants with specifi c risk factors for AKI should be considered for the preventive use of PD. In children undergoing surgery with the Fontan procedure, postoperative

unfavorable hemodynamic conditions (high venous pressure) may lead to a high incidence of renal failure.46 An extraordinarily high survival rate was observed (80%) in a group of infants with post heart surgery AKI in which PD was started much earlier than in other studies (time to PD application after surgery, 5-40 h).47 Although a very limited experience, this study suggests that prevention of renal failure and/or fl uid accumulation may affect survival. PD offers limited fl uid removal compared to extracorporeal techniques. Moreover, in post– heart surgery infants, high dialysate volumes to increase PD clearance lead to modifi cations of atrial, mean pulmonary artery, and systemic pressure.48 For this reason, a PD prescription of 10 mL/kg dwell volume, with continuous 1-hour cycles (5 minute fi ll, 45-minute dwell, and 10-minute drain), is prescribed commonly.49,50

CRRT (Continuous renal replacement therapy)CRRT is a slower form of hemodialysis that allows for faster removal of fl uid and solutes when desired. However, it requires a double lumen vascular access of at least 7 French size, which can sometimes be a limitation in small infants. Its complications include bleeding, hypothermia, thrombocytopenia, electrolytes and acid base imbalance, immune activation, altered drug delivery, nutritional loss, and blood loss as a result of circuit clotting. In small infants, initiation of CRRT can pose a risk of hypotension due to a relatively large circuit volume. PD may not be the optimal modality for patients with severe volume overload who require rapid ultrafi ltration, or for patients with severe life-threatening hyperkalemia who require rapid reduction of serum potassium. Moreover, the amount of ultrafi ltration often is unpredictable because of the impaired peritoneal perfusion in hemodynamically unstable patients such as post– heart surgery infants. These limitations of PD explain the increased use of extracorporeal dialysis in critically ill pediatric patients51 and in post– heart surgery infants.52 These children generally are treated with CRRT, which provides both fl uid and solute re-equilibration and proinfl ammatory mediator removal. Commercially available circuits with reduced priming volume together with monitors providing an extremely



accurate fl uid balance have rendered CRRT feasible in infants.53,54 Infants undergoing CPB show 2 unique features with respect to exposure to a proinfl ammatory state. First, post CS infants are most exposed to the risk of water accumulation, AKI, and infl ammation owing to the nature of hemodilutional, hypothermic CPB and to the massive exposure of blood to the artifi cial surface of CPB.54-57

Second, the exact moment of the renal-infl ammatory injury (ie, CPB initiation) is known. CS patients receive ultrafi ltration during CPB preventively with the fi lter placed in parallel with the CPB circuit to remove infl ammatory mediators from the beginning of their generation. This strategy may exert benefi cial effects on hemodynamics, metabolism, and infl ammation in the postoperative period. A highly specialized patient with respect to this general description is the infant with AKI and an extracorporeal membrane oxygenation treatment (ECMO). In this case, the CRRT circuit is placed in parallel and counter current to the ECMO circuit(Figure2). The blood into the CRRT circuit runs in the opposite direction with the one in the ECMO circuit, with its arterial side connected to the circuit after the pump. The venous side is connected to the bladder, which collects patient venous return. With this set-up the CRRT circuit receives the blood after the ECMO pump, a positive pressure segment, and it returns it to the ECMO bladder where the pressure is close to zero. Although this confi guration may cause minimal recirculation, it results in the safest provision in an ECMO circuit.58 Recent

data detail experience with 2 different subgroups of children: one group that required hemofi ltration alone and a second group that required hemofi ltration and ECMO.59 Not surprisingly, the investigators identifi ed a higher mortality rate in those patients requiring continuous venovenous hemofi ltration and ECMO compared with those patients requiring hemofi ltration alone. The investigators promoted the concept that certain therapies should be reserved for experienced teams.

ConclusionAKI is reported with a high incidence in critically ill children and the incidence is even higher in infants after CS secondary to multiple factors. AKI in this patient population is associated with high mortality and morbidity. Early diagnosis of AKI is imperative in management but no defi nite test is available. Clinicans should have a high index of suspicion and surveillance for AKI in the immediate post-operative period. Development of new biomarkers offers hope in this regard. Management is largely supportive and should focus on pre-operative stabilisation, early diagnosis of AKI, close monitoring of hemodynamic status and renal function, utmost diligence in fl uid management, avoidance of nephrotoxins, correction of metabolic disturbances & dyselectrolytemia and early initiation of renal replacement therapies as indicated. Further research in pediatric congenital heart surgery population is required to better delineate the specifi c population at risk, validate the experimental biomarkers in clinical studies and prospectively study renal replacement therapies in large randomized trials. Large multicentric international trials and registries would be a step ahead in this regard.

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Figure 2 : CRRT circuit connected to ECMO


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18. Park M, Coca SG, Nigwekar SU, Garg AX, Garwood S, Parikh CR.: Prevention and treatment of acute kidney injury in patients undergoing CS: A systematic review. Am J Nephrol 2010; 31: 408–418

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C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P.: Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after CS. Lancet 2005; 365: 1231-1238

20. Siegel NJ, Shah SV.: Acute renal failure: Directions for the next decade. J Am Soc Nephrol 2003; 14: 2176–2177

21. Bagshaw SM, Bellomo R.Cystatin C in acute kidney injury. Curr Opin Crit Care. 2010 : Aug 21

22. Al-Ismaili Z, Palijan A, Zappitelli M. Biomarkers of acute kidney injury in children: discovery, evaluation, and clinical application. Pediatr Nephrol. 2011; 26: 29-40

23. Washburn KK, Zappitelli M, Arikan AA, Loftis L, Yalavarthy R, Parikh CR, et al. Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children. Nephrol Dial Transplant. 2008; 23:566-72

24. Stocker CF, Shekerdemian LS. Recent developments in the perioperative management of the paediatric cardiac patient. Curr Opin Anaesthesiol. 2006; 19: 375-81

25. Marathias, K. P., M. Vassili, et a.Preoperative intravenous hydration confers renoprotection in patients with chronic kidney disease undergoing cardiac surgery. Artif Organs 2006; 30(8): 615-621

26. Magder,S.,B.J.Potter et al .Fluids after cardiac surgery: a pilot study of the use of colloids versus crystalloids. Critical Care Medicine 2010; 38(11): 2117-2124

27. Van Den Berghe, G., P. Wouters, et al .Intensive insulin therapy in the critically ill patients.N Engl J Med 2001; 345(19): 1359-1367

28. Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, et al. Effi cacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation. 2003; 107: 996-1002

29. Cheung PY, Barrington KJ. Renal dopamine receptors: mechanisms of action and developmental aspects.Cardiovasc Res. 1996; 31:2-6. Jose PA, Felder RA, Holloway RR, Eisner GM. Dopamine receptors modulate sodium excretion in denervated kidney. Am J Physiol. 1986; 250:F1033-8

30. Mahajan A, Marijic J. Hemodynamic management. Anesthesia for congenital heart disease. Malden: Blackwell; 2005; p. 225-40

31. Andropolous D, Ogletree ML. Physiology and molecular biology of the developing circulation. Anesthesia for congenital heart disease. Malden: Blackwell; 2005. p. 30-48

32. Bellomo R, Giantomasso DD. Noradrenaline and the kidney: friends or foes? Crit Care. 2001; 5:294-8

33. Dickerson HA, Chang AC. Heart failure in children and young adults. Philadelphia: Saunders; 2006. p. 453-67

34. Luciani GB, Nichani S, Chang AC, Wells WJ, Newth CJ, Starnes VA. Continuous versus intermittent furosemide infusion in critically ill infants after open heart operations. Ann Thorac Surg. 1997; 64:1133-9

35. Singh NC, Kissoon N, al Mofada S, Bennett M, Bohn DJ. Comparison of continuous versus intermittent furosemide administration in postoperative pediatric cardiac patients. Crit Care Med. 1992; 20:17-21

36. Van der Vorst MM, Ruys-Dudok van Heel I, Kist-van



Holthe JE, den Hartigh J, Schoemaker RC, Cohen AF, et al. Continuous intravenous furosemide in haemodynamically unstable children after CS. Intensive Care Med. 2001;27:711-5

37. Costello JM, Thiagarajan RR, Dionne RE, Allan CK, Booth KL, Burmester M, et al. Initial experience with fenoldopam after CS in neonates with an insuffi cient response to conventional diuretics. Pediatr Crit Care Med. 2006; 7:28-33

38. Nakao, K., H.Itoh, et al. A family of natriuretic peptides (ANP.BNP). Nippon Rinsho 1989 47(9): 1987-1995

39. Mills, R. M., T. H. LeJemtel, et al .Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group.Journal of the American College of Cardiology. 1999; 34(1): 155-162

40. Kim, H.-J and S-W Han.Therapeutic approach to hyperkalemia.Nephron 2002; 92 Suppl 1: 33-40

41. Kraut, J. A. and N. E. Madias. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol 2010; 6(5): 274-285

42. Lameire N, Kellum JA; KDIGO AKI Guideline Work Group: Contrast-induced acute kidney injury and renal support for acute kidney injury: a KDIGO summary (part 2). Crit Care 2013; 17: 205

43. Pederson KR, Hjortdal VE, Christensen S, Pederson J, Hjortholm, Larsen S, et al. Clinical outcome in children with acute renal failure treated with peritoneal dialysis after surgery for congenital heart disease. Kidney Int Suppl 2008; (108):S81-6

44. Alkan T, Akcevin A, Turkoglu H, Paker T, Sasmazel A, Bayer V, et al. Postoperative prophylactic peritoneal dialysis in neonates and infants after complex congenital CS. ASAIO J. 2006; 52:693-7

45. Sorof JM, Stromberg D, Brewer ED, Feltes TF, Fraser CD Jr. Early initiation of peritoneal dialysis after surgical repair of congenital heart disease. Pediatr Nephrol.1999; 13:641-5

46. Cetta F, Feldt RH, O’Leary PW, Mair DD, Warnes CA, Driscoll DJ, et al. Improved early morbidity and mortality after Fontan operation: the Mayo Clinic experience, 1987 to 1992. J Am Coll Cardiol. 1996; 28:480-6

47. Fleming F, Bohn D, Edwards H, Cox P, Geary D, McCrindle BW, et al. Renal replacement therapy after repair of congenital heart disease in children. A comparison of hemofi ltration and peritoneal dialysis. J Thorac Cardiovasc Surg. 1995; 109:322-31

48. Dittrich S, Vogel M, Dahnert I, Haas NA, Alexi- Meskishvili V, Lange PE. Acute hemodynamic effects of post cardiotomy peritoneal dialysis in neonates and infants. Intensive Care Med. 2000; 26:101-4

49. McNiece KL, Ellis EE, Drummond-Webb JJ, Fontenot EE, O’Grady CM, Blaszak RT. Adequacy of peritoneal dialysis in children following cardiopulmonary bypass surgery. Pediatr Nephrol. 2005; 20:972-6

50. Golej J, Kitzmueller E, Hermon M, Boigner H, Burda G, Trittenwein G. Low-volume peritoneal dialysis in116 neonatal and paediatric critical care patients. Eur J Pediatr. 2002; 161:385-9

51. Warady BA, Bunchman T. Dialysis therapy for children with acute renal failure: survey results. Pediatr Nephrol. 2000; 15:11-3

52. Jander A, Tkaczyk M, Pagowska-Klimek I, Pietrzykowski W, Moll J, Krajewski W, et al. Continuous veno-venous hemodiafi ltration in children after CS. Eur J Cardiothorac Surg. 2007;31:1022-8

53. Goldstein SL, Hackbarth R, Bunchman TE, Blowey D, Brophy PD.Evaluation of the PRISMA M10 circuit in critically ill infants with acute kidney injury: a report from the Prospective Pediatric CRRT Registry Group. Int J Artif Organs. 2006; 29:1105-8

54. Ricci Z, Morelli S, Vitale V, Di Chiara L, Cruz D, Picardo S. Management of fl uid balance in continuous renal replacement therapy: technical evaluation in the pediatric setting. Int J Artif Organs. 2007; 30: 896-901

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56. Davies MJ, Nguyen K, Gaynor JW, Elliott MJ. Modifi ed ultrafi ltration improves left ventricular systolic function in infants after cardiopulmonary bypass. J ThoracCardiovasc Surg. 1998; 115:361-70

57. Berdat PA, Eichenberger E, Ebell J, Pfammatter JP, Pavlovic M, Zobrist C, et al. Elimination of proinfl ammatory cytokines in pediatric CS: analysis of ultrafi ltration method and fi lter type. J Thorac Cardiovasc Surg. 2004; 127:1688-96

58. Ricci Z, Polito A, Giorni C, Di Chiara L, Ronco C, Picardo S. Continuous hemofi ltration dose calculation in a newborn patient with congenital heart disease and preoperative renal failure. Int J Artif Organs. 2007; 30: 258-61

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Frequently asked questions: FAQs regarding SIMULATIONWhat is Simulation? Real life experience in an artifi cially controlled and interactive environment.

This training methodology has been popular for pilots, space travel training program. It is rapidly becoming popular in teaching medical procedures and ICU treatment modalities in close to real life situations. It is shown on high tech mannequins which depict eye blinking, pupillary reaction, airway, breath sounds, crepts, wheeze, stridor, hypotension, cyanosis, bradycardia, various arrhythmias and cardiac arrest.these mannequins can be intubated and ventilated and IV access with inotropic therapy can be administered.

How do I benefi t from Simulation workshop?

1. Learn intensive care without risking patient safety

2. Learn from mistakes without causing harm to the patient

3. Practice central line placement, intubation, CPR and defi brillation, as well as manage case with shock, respiratory failure and neurological issues(status epilepticus, COMA) without fear.

4. Manage ventilator settings in stress free environment

5. Manage inotropic and vasopressor therapy

How is this methodology better than lectures and skill stations of workshops such as PALS, BPICC, GEM courses ?It is futuristic, easier and hands on workshop on cases managed on live mannequins only. Therefore one remembers and retains what is taught by practice.

All interventions performed by the delegate are followed by a real response (good or bad) on live mannequins and a supervisor experienced faculty can teach on live mannequins and give rationale or disadvantage related to a particular treatment or intervention.

Are the treatment protocols any different from whats given in the Manuals?No. Treatment protocols remain same as per PALS 2010 guidelines and standard PICU evidence based protocols, but once you have practiced it yourself you don’t forget as you Learn from the experts present throughout the process !!


Transcatheter Closure of the Atrial Septal Defect and other Cardiac Defects: Current status

Vikas Kohli MD, FAAP, FAACDirector Childrens Heart Institute, BLK Superspeciality Hospital, Delhi

Correspondence:Dr Vikas Kohli MD FAAP FACCAmerican Board Certifi ed, Fetal, Neonatal, Pediatric CardiologistDirector & HOD, BLK Children’s Heart Institute & Delhi Child Heart Center, 130, Uday Park, New DelhiEmail: [email protected]

Key words: ASD, device closure, pulmonary hypertension, pediatric, infant

IntroductionEver since device closure of congenital cardiac defects has become available, more patients are undergoing device implantation and its acceptability has increased. Since ASD device closure is not only the most common procedure, but also the most representative of intracardiac device use, it is being discussed in detail here. It is not out of place to critically review the current literature of device closure for (ASD’s) from the viewpoint of the pediatrician. Though it is likely that given a choice, majority of parents will opt for device closure, but, an informed decision-making is imperative.

Surgical ASD closureSurgical outcomes will always be considered the gold standard with which the cardiologists will have to compare their results with. The outcomes of surgical ASD are well known and well described. This was the fi rst congenital open heart surgery undetaken in early 1951. With the 50 year follow up available, it now well known that currently the surgical risk of ASD closure by surgery is less than 1%; though the morbidity is much higher. Apart from the scar on the chest, there is no longterm implication if the ASD is repaired at the right time, without preceeding arrhythmia, pulmonary hypertension or any associated defects.

It cannot be forgone though, that there is an atrial scar involved in the treatment for closure of the atriotomy through which the ASD is visualized and closed. There is no such atrial scar in device closure.It must be emphasized it is not truly appropriate to compare the two procedures since not all ASD’s can be closed by devices while all ASD’s can be closed by surgery. The scope of the two procedures is different.

History of device closureEver since the pioneering transcatheter device closure of a secundum atrial septal defect by King1 in 1974 and the subsequent work of Rashkind2, cardiologists have been trying for this to be the preferred mode of treatment. The major technological problem has been delivery of a device up to several centimeters in diameter via a catheter only a few millimeters in diameter. The fi rst device used by king required a 23f sheath. Subsequently the clamshell device, a modifi cation of the Rashkind device was delivered through an 11f sheath. The sideris button device can be delivered through an 8f or 9f sheath. The other devices i.e. cardioseal (11f), angelwings (11f) and the ASD occluder system device (10f) also require large delivery sheaths. The major development of the amplatzer device was its delivery through a 7f & 8f sheath making it possible to close ASD’s in younger children also. This technological advancement took place only due to the use of Nitinol material for cardiac devices.After initial trials, the amplatzer device was approved for clinical use in the united states by the FDA in 2001.

The Amplatzer ASD device Though there are several devices in use currently, most notably being the Starfl ex, Cardioseal, Sideris and the Helex, it is the Amplatzer devices for ASD


closure, which has maximum clinical use (Table 1). There are several reasons for this, it is best described as a self-centering, self-expanding, repositionable device. The design of the device constructed with 0.004-0.005 inch Nitinol is superior to the Sideris button device. The 2 discs are connected to each other via a waist. The waist equals the stretched diameter of the ASD. For devices in the range of 11-26 mm, the left atrial disc measures 14 mm more than the waist and the right atrial disc 10 mm more than the waist. This is the only device dependent on endothelial covering over the device for closure of the ASD. The profi le of this device is probably the highest amongst the available devices, though newer designs of the device with lower profi le are available especially for ventricular septal defects.

Table 1: Characteristics of Amplatzer device1. Retreiveable

2. Repositionable

3. Self-expanding & self-centering

4. Fast learning curve

5. Simple loading and detachment technique

The other advantages include the ability to reposition the device without damaging it and its ease of implantation, which signifi cantly decreases the learning curve for new operators. Retrieval of the device prior to release is much simpler as also is repositioning.the indicators used to evaluate device closure i.e. percent implantation compared to intent of closure; successful implantation, effective occlusion rates and requirement of “urgent” surgery are better in comparison to the other devices. Of the devices available presently, the early closure rates at 3 months for this device (>98%) are the highest3. Incidence of severe complication for amplatzer device has been amongst the least (0.3 %). Modes of retrieval of embolized device remain diffi cult though not impossible. The device can be retrieved while still attached to the delivery cable, a feature present only in the clamshell septal occluder. The rounded disk design of the device may also be an advantage in potentially causing less injury to the atrioventricular valves or perforation of intracardiac structures.

Outline of procedureAs is routine in any cardiac cath, the patient is pre-sedated, taken to the cath lab and general anesthesia initiated. There is a need for general anesthesia in ASD device closure mainly for purposes of the prolonged Trans-esophageal Echo (TEE) which needs to be performed during the length of the procedure. In cases where intracardiac echo is performed, the patient may not need general anesthesia; the proceure may be performed under concious sedation.After the femoral venous access is obtained through which the device will be delivered and the femoral arterial access is also obtained to monitor the blood gases and the blood pressure.After sizing via TEE and the sizing balloon, the appropriate sized device is chosen. The device size refl ects the “central waist” part of the device, the “discs” on either side being much larger than the atrial septal defect itself.After this, the device is attached to a delivery cable, loaded and taken into the delivery sheath, which should already be in place across the ASD. The device is then extruded from the sheath and confi rmation is made of the right atrial disc being in the right atrium and the left atrial disc being in the left atrium only. This confi rmation is done by echocardiography and fl uoroscopy projections, if required. At the same time, confi rmation is made of the A-V valves being unaffected by the presence of the device; the IVC, SVC and the right upper pulmonary vein also not being affected by the device.Then fi nally the device is released and takes it predestined orientation, shape and position in relation to the device.One of the critical steps of the procedure involves assessment of the size of the defect. The stretched diameter is usually more than the diameter of the ASD measured on the transesophageal echo. Presently the methods of evaluating the stretched diameter include measurement of the balloon waist at the defect site. The measurements may be made on cine, on transesophageal echo images or outside the body with the balloon fi lled with the same volume. Further advancement towards evaluation of the ASD anatomy by 3-D Echo or MRI prior to the procedure is presently being investigated4.

Transcatheter Closure of the Atrial Septal Defect and other Cardiac DefectsPEDIATRIC CARDIAC INTENSIVE CARE - 2


None of the present devices currently undergoing clinical trial are able to close ASD’s with small rims. Only small and medium sized defects with adequate rims can be closed by these methods. All patients with large ASD’s, ASD’s with small rim and sinus venosus and primum ASD’s have to undergo surgical closure. Anticoagulation has to be made immaculately during the procedure. The patients can usually be discharged by 24-36 hours of the procedure.There has been a recent trend towards use of intracardiac echocardiography for better anatomy delineation during the procedure5. This is done via a catheter and is a replacement for the tee; it requires at least a 9f sheath and this maybe the limiting factor for its use in the pediatric age group.

Indications for closureSymptomatic children prior to school going age and preferably after 2 yrs of age need to have their ASD closed, if feasible, by transcatheter means. The indications for transcatheter closure are the same as of surgical closure in addition to the Echocardiographic evidence of feasibility of closure. The Echocardiographic indications of closure of an ASD include right atrium dilatation, right ventricular dilatation and paradoxical septal motion. All of these together would indicate volume overload of the right heart.Rarely a child may be so symptomatic prior to the school going age that closure will have to be contemplated prior to that period. There maybe several reasons for this to happen. The patient may have severe pulmonary hypertension or any other associated cardiac or non-cardiac illness.All ASD’s more than 8 mm, which are causing right atrial and right ventricular volume overload and paradoxical interventricular septal motion, require closure. The chances of an ASD closing spontaneously after 2-3 years are miniscule; the spontaneous closure rate of ASD are any way far less than that of a VSD.

Selection of cases The evaluation of the atrial septal defect involves a

detailed transthoracic echocardiography focusing on the atrial septal anatomy. There has been discussion on the use of the transesophageal echo and use of 3-D Echocardiographic evaluation. The intracardiac echocardiography may actually provide the most clear resolution of the anatomy. The transthoracic echo provides the preliminary information, which requires detailed discussion. The sinus venosus and the primum atrial septal defects are out rightly rejected for the closure of the defect.For the secundum atrial septal defects, the defects more than 25mm in diameter have been described as the more challenging to close and the cases need careful selection. When evaluating the child with ASD for device closure, traditionally 8 rims have been described which need evaluation. The rims towards the IVC, the SVC, pulmonary veins, A-V valves, coronary sinus and the aorta are the most important ones to focus on. The assessment may best be performed by TEE in majority of the subjects unless the TEE is specifi c of the acceptability of device closure.A study undertaken in 1983 by Cockerham et al showed that 14/54 patients had closed their ASD’s as assessed by catheterization. Statistical analysis of hemodynamic data revealed no difference (except a smaller shunt size) between ASD’s that closed and those that did not in patients who were less than 4 years at initial catheterization.The 14% incidence reported here may underestimate the true incidence of spontaneous closure. An atrial septal fl ap, found in all four patients who closed spontaneously but only in 4 of the 16 patients who did not close spontaneously, may contribute in some way to spontaneous closure6.It seems that defects smaller than 6 mm in diameter are very likely to close spontaneously although follow-up is necessary. Defects larger than 8 mm have a high probability requiring operative closure.Two thirds of secundum ASD’s may enlarge with time and the potential for secundum ASD’s to outgrow the possibility of transcatheter closure with devices.

Outcomes-immediate, intermediate and lateThe early concern of the interventionalists at the outset of the procedure was the immediate safety



of the procedure, which was easily proven to be so. Closure rates were also shown to be very high with majority studies showing complete closure of the ASD by 3 months. The summary of worldwide results are summarized in Table 2.Minor complications have been reported in relation to the device or the procedure. Major complication reported mainly includes device embolization, which is of signifi cant concern since it requires surgical, or transcatheter retrieval. Surgical retrieval is accompanied by surgical closure of the ASD also. As more and more studies have shown better outcomes, the focus is shifting to late and long-term effects of non-surgical closure. Recent reports of neurodevelopment assessment of children who have had surgical closure of ASD compared to device closure have shown interesting results17. The patients with surgical closure of ASD showed signifi cantly lower visual-spatial/visual-motor skills. In previous studies of neuropsychological sequelae of cardiovascular surgery in children, defi cits in visual-spatial and visual-motor functions have been among the most consistent fi ndings. This may be related to the cardiopulmonary bypass.

ComplicationsThe atrial septum is closely related to the atrio-ventricular valves, veins draining the systemic circulation and the pulmonary; aorta and the conduction system of the heart. Complications in relation to these structures can potential happen (table 3). Though it has been reported that the device may need to be retrieved due to obstruction of the

veins, but, A-V valve problems are incidentally less common. The proximity of the ascending aorta to the atrial septum is of signifi cant concern to the interventional cardiologists in the long-term since in specifi c categories of the secundum atrial septal defects (those with a defi cient margin towards the aorta) the majority of the device directly sits on the aorta. There has been a single case report of aortic perforation following the use of atrial septal defect and a case of aorto-right atrial fi stula following implantation18.Similarly, there have been reports of cardiac perforation following implant of the patent foramen device19. Though that device is structurally different from the ASD device (allowing more mobility of the atrial discs over the central connecting part) there does remain a concern about the same after the ASD device.Late device embolization has been reported with the Amplatzer device, as it has been so with the Helex device20. Myocardial damage, albeit minor maybe happening with the device delivery itself21. Total cardiac troponin-i increased signifi cantly at the end of the intervention. No signifi cant increase could be detected in patients with diagnostic balloon sizing only. This may indicate some transient, reversible myocardial membrane instability due to the device. Anomalous course of coronary artery via the atrial septum may get compressed by the device and mimic myocardial infarction22.Procedure related complication might result as in any major cardiac procedure and specifi cally in the study of Fischer et al it occurred in two cases (retroperitoneal bleeding, air embolism) out of 236 device closures15.

Table 2: Summary of published representative worldwide literature of asd device closureSsr no Year Author Ref No Country pts Comments1 1997 Masura 7 Slovak 30 No complications; 6 mo: 100% complete closure2 1998 Thanopoulos 8 Greece 16 No complications; 3 mo: 1/16 trace residual shunt3 1998 Wilkinson 9 Australia 26 1 Embolized device; 3 mo: 92% complete closure4 2001 Omeish 10 Worldwide 3,535 75 not suitable for device; serious complication 0.3%; minor complic

2.8%; 1005 complete closure at 3 yrs5 2002 Oho 11 Japan 35 34/35 successful; 12 mo: 97% complete closure; no complications6 2002 Bjornstad 12 Norway 46 87% successful implantation; no complications7 2002 Kong 13 China 30 No complications; 3.3% trace shunt at 3 mo8 2003 Kannan 14 India 45 Asd’s > 25 mm; 2/45 embolization9 2003 Fischer 15 Germany 236 84% successfully closed; 2.3 yr: 94% complete closure10 2003 Butera 16 Italy 48 No complications; 100% complete closure at 12 mo



In a large analysis of 417 patients, Chessa et al noted 7 patients had device embolization requiring surgical closure of the ASD23. Thirty-four patients experienced 36 complications during the hospitalization (8.6%). Ten patients underwent elective surgical repair because of device malposition (three patients) or device embolization (seven patients). Twenty-four patients experienced 25 minor complications: unsatisfactory device position or embolization; 11 patients experienced arrhythmic problems. Other complications were: pericardial effusion, thrombus formation on the left atrial disc, right iliac vein dissection, groin hematoma, hemorrhage in the retroperitonium and sizing balloon rupture. Two patients had late complications: peripheral embolization in the left leg one year after implantation of an amplatzer device and sudden death 1.5 year later.Hessling at el conducted a detailed study of the cardiac dysrhythmias pre and post device implantation and noted rare and benign problems on holter monitoring24. Others have also reported ST elevation, AV block, late endocarditis and possible transient ischemic attack with device occlusion25. Recent

report of thrombosis over the device on the right or the left atrial disc have been reported26. Potential complications as atrial perforation, atrioventricular valve damage, metal fatigue and fracture need to be watched for in the long term.

Other device related proceduresPatent ductus arteriosusThis is a relatively safe and an easier procedure to perform than the ASD device closure which excellent longterm outcome27. One of the primary differences is that pda is truly not an intra-cardiac structure. The longterm implications of the ASD device are much more due to the movement and difference in the atrial systole and diastole as also the difference in the atrial septum formed by a non-contracting vs. The normally contracting septum. In this respect pda device closure seems to be an easier procedure with lesser longterm implications. The other issues related to pda device closer is that this procedure is usually required in a much younger and smaller patient than the ASD patient. This aybe the challenging part of the procedure.Finally, one has to bear in mind that coils which have been used for about 2 decades now for closure of the pda, have provided good results; but the essential difference between the coils and the devices is that if the device is oversized, which it has been reported to be, then it may exert a radial force on the wall of the pda. The effects of this in the longterm need to be seen. Recent report of 2 such devices requiring sugical retrieval late post deployment in large pdas is of concern (personal communication, Maheshwari s, 2003).

Ventricular septal defectThe closure of muscular ventricular septal defects by devices is currently recommended28. These cannot be performed easily in children under 5 kg of weight. Muscular VSD’s maybe more amenable to such procedure because they are relatively away from the conducting system, from the A-V valves and the semilunar valves. The approach is radically different as compared to the ASD closure, with the device delivery best sought from the neck rather from the groin.Perimembranous VSD’s are closer to the semilunar

Table 3: Complications related to device closureA. Procedure related

1. Air embolism2. Access related • Retroperitoneal hematoma • Leg vein thrombosis • Arterial thrombosis3. Cardiac perforation

B. Device related1. Malposition2. Embolization3. Cobra deformity4. Entrapment (eustacian valve or chiari malformation)5. Inability to retreive6. Allergy (nickel)

C. Cardiac complications1. Structural • Svc obstruction • Pulmonary venous obstruction • Coronary sinus obstruction • Cardiac perforation • Aortic perforation2. Electrical • St elevation (transient) • Non-sinus rhythm (transient) • Premature atrial/ventricular ectopics • Atrial tachyarrhythmias (transient)3. Hematological • Thrombus formation 1. Left atrium 2. Right atrium

D. Unknown: sudden death, late



and A-V valves and defi nitely have an inherent diffi culty in placing devices so close to the valves and the conduction system. Several approaches have been assessed for this and novel devices being brought out with an eccentric disc to allow for non-interference with the valve (Aortic)29. There has been a recent report of such a closure in 10 such patients with success though longterm effect on the aortic valve needs to be watched carefully.

Recent advances in techniques of device closure & surgeryComputer (Robotic) enhancement had emerged as a facilitator of minimally invasive cardiac surgery, and has been used to perform portions of intracardiac procedures via thoracotomy incisions. Argenziano et al describe the fi rst application of robotic technology for totally endoscopic open-heart surgery. Seventeen patients underwent repair of an atrial septal defect by a totally endoscopic approach. In one patient, a residual shunt was identifi ed and repaired on postoperative day 5. Median length of hospital stay was 4 days30.The technical ease of ASD closure has triggered interest in minimally invasive closure (MIC) to obviate the morbidity associated with sternotomy. Ryan et al assessed the safety and effi cacy of minimally invasive ASD closure and compared it to conventional sternotomy approach. The authors found MIC to be an excellent alternative to conventional sternotomy approach in ASD closure. MIC resulted in equivalent success rates in ASD closures, with similar morbidity, no mortality, and a signifi cant difference in postoperative length of stay (3.93 +/- 1.6 days versus 5.36 +/- 2.51 days, p = 0.006)31.Secundum ASD closure by right lateral minithoracotomy has become as standard and safe an operation as the conventional technique and achieves good perioperative results and satisfactory long-term outcomes in the adults. Its role in the pediatric patients needs to be evaluated and may turn out to be an attractive option for patients who are not suitable for closure using catheter-based devices32.With the advent of ultra fast MRI and the development of MRI-compatible catheters and guide wires, the

goal of achieving real-time guidance by MRI for interventions in congenital heart diseases has proven feasible. Such advancement of ASD closure with the help of MRI compatible devices has been described by Rickers et al33.For device closure of ASD, the critical step is evaluation of the defect size and anatomy. The use of transthoracic three-dimensional echocardiography to assess the morphology of atrial septal defects in children prior to closure has been recently described by acar et al. This non-invasive method has been found to be valuable in selecting children for transcatheter or surgical closure of such defects34. Recent reports of closing ASD’s without the use of fl uoroscopy have advanced this procedure to new fronts. It is likely that fl uoroscopy time for this procedure would decrease further, though it remains to be seen whether device deployment without fl uoroscopy would become more acceptable35.

ConclusionIn view of the high success rate of complete closure, safety of device closure and growing experience in use of this device, it seems likely that device closure of ASD is becoming the preferred mode for closure of ASD’s with suitable anatomy. In addition, late and long-term follow up needs to be watched for complications. As technology and experience increases, larger ASD’s are being closed in the cath lab. Further studies to truly delineate the neurodevelopmental issues related to on pump ASD closure vis-à-vis device closure. Focussed research towards the late effects of a device (non-complaint part of inter-atrial septum) in position need to be looked at also. Parents need to be informed of what we know and don’t know prior to undertaking the device closure procedure.

References1. King TD, Mills NL. Nonoperative closure of atrial septal

defects. Surgery 1974; 75(3): 383-82. Rashkind WJ, Cuaso CE. Transcatheter closure of atrial septal

defects in children. Eur j cardiol. 1977; 8:119-203. Omeish A, Hijazi ZM. Transcatheter closure of atrial septal

defects in children & adults using the amplatzer septal occluder. J interv cardiol. 2001 feb; 14(1): 37-44

4. Beerbaum P, Korperich H, Esdorn H, Blanz U, Barth P,



Hartmann J, Gieseke J, Meyer H. Atrial septal defects in pediatric patients: noninvasive sizing with cardiovascular mr imaging. Radiology. 2003 aug; 228(2): 361-9

5. Bartel T, Konorza T, Arjumand J, Ebradlidze T, Eggebrecht H, Caspari G, Neudorf U, Erbel R. Intracardiac echocardiography is superior to conventional monitoring for guiding device closure of interatrial communications. Circulation. 2003 feb 18; 107(6): 795-7

6. Cockerham JT, Martin TC, Gutierrez FR, Hartmann AF JR, Goldring D, Strauss AW. Spontaneous closure of secundum atrial septal defect in infants and young children. Am j cardiol. 1983 dec 1; 52(10): 1267-71

7. Masura J, Gavora P, Formanek A, Hijazi ZM. Transcatheter closure of secundum atrial septal defects using the new self-centering amplatzer septal occluder: initial human experience. Cathet cardiovasc diagn. 1997 dec; 42(4): 388-93

8. Thanopoulos BD, laskari CV, tsaousis GS, Zarayelyan A, Vekiou A, Papadopoulos GS. Closure of atrial septal defects with the amplatzer occlusion device: preliminary results. J am coll cardiol. 1998 apr; 31(5): 1110-6

9. Wilkinson JL, Goh TH. Early clinical experience with use of the ‘amplatzer septal occluder’ device for atrial septal defect. Cardiol young. 1998 jul; 8(3): 295-302

10. Omeish A, Hijazi ZM. Transcatheter closure of atrial septal defects in children & adults using the amplatzer septal occluder. J interv cardiol. 2001 feb; 14(1): 37-44

11. Oho S, Ishizawa A, Akagi T, Dodo H, Kato H. Transcatheter closure of atrial septal defects with the amplatzer septal occluder--a japanese clinical trial. Circ j. 2002 sep; 66(9): 791-4

12. Bjornstad PG, Holmstrom H, Smevik B, Tonnessen TI, Fosse E. Transcatheter closure of atrial septal defects in the oval fossa: is the method applicable in small children? Cardiol young. 2002 jul; 12(4): 352-6

13. Kong X, Cao K, Yang R, XU D, Sheng Y, Huang J, Ma W. Transcatheter closure of secundum atrial septal defect using an amplatzer septal occluder. Chin med j (engl). 2002 jan; 115(1):126-8

14. Kannan BR, Francis E, Sivakumar K, Anil SR, Kumar RK. Transcatheter closure of very large (>or= 25 mm) atrial septal defects using the amplatzer septal occluder. Catheter cardiovasc interv. 2003 aug; 59(4): 522-7

15. Fischer G, Stieh J, Uebing A, Hoffmann U, Morf G, Kramer HH. Experience with transcatheter closure of secundum atrial septal defects using the amplatzer septal occluder: a single centre study in 236 consecutive patients. Heart. 2003 feb; 89(2): 199-204

16. Butera G, De Rosa G, Chessa M, Rosti L, Negura DG, Luciane P, Giamberti A, Bossone E, Carminati M. Transcatheter closure of atrial septal defect in young children: results and follow-up. J am coll cardiol. 2003 jul 16; 42(2): 241-5

17. Visconti KJ, Bichell DP, Jonas RA, Newburger JW, Bellinger DC. Developmental outcome after surgical versus interventional closure of secundum atrial septal defect in children. Circulation. 1999 Nov 9; 100 (19 suppl): ii145-50

18. Chun DS, Turrentine MW, Moustapha A, Hoyer MH. Development of aorta-to-right atrial fi stula following closure of secundum atrial septal defect using the amplatzer septal occluder. Catheter cardiovasc interv. 2003 Feb; 58(2): 246-51

19. Trepels T, Zeplin H, Sievert H, Billinger K, Krumsdorf U, Zadan E, Horvath K. Cardiac perforation following transcatheter pfo closure. Catheter cardiovasc interv. 2003 jan; 58(1): 111-3

20. Peuster M, Reckers J, Fink C. Secondary embolization of a helex occluder implanted into a secundum atrial septal defect.catheter cardiovasc interv. 2003 may; 59(1): 77-82

21. Pees C, Haas NA, Von Der Beek J, Ewert P, Berger F, Lange PE. Cardiac troponin i is increased after interventional closure of atrial septal efects.cathetercardiovasc interv. 2003 jan;58(1):124-9.

22. Casolo G, Gensini GF, Santoro G, Rega L. Anomalous origin of the circumfl ex artery and patent foramen ovale: a rare cause of myocardial ischaemia after percutaneous closure of the defect. Heart. 2003 aug; 89(8): e23

23. Chessa M, Carminati M, Butera G, Bini Rm, Drago M, Rosti L, Giamberti A, Pome G, Bossone E, Frigiola A. Early and late complications associated with transcatheter occlusion of secundum atrial septal defect. J am coll cardiol. 2002 mar 20; 39(6): 1061-5

24. Hessling G, Hyca S, Brockmeier K, Ulmer HE. Cardiac dysrhythmias in pediatric patients before and 1 year after transcatheter closure of atrial septal defects using the amplatzer septal occluder. Pediatr cardiol. 2003 may-jun; 24(3): 259-62

25. Bullock AM, Menahem S, Wilkinson JL. Infective endocarditis on an occluder closing an atrial septal defect. Cardiol young.1999 jan; 9(1): 65-7

26. Yilmaz M, Gurlertop Y, Erdogan F. Right atrial thrombus following closure of an atrial septal defect. Heart. 2003 jul; 89(7): 726

27. Ebeid MR, Masura J, Hijazi ZM. Early experience with the amplatzer ductal occluder for closure of the persistently patent ductus arteriosus. J interv cardiol. 2001 feb; 14(1): 33-6

28. Thanopoulos BD, Karanassios E, Tsaousis G, Papadopoulos GS, Stefanadis C. Catheter closure of congenital/acquired muscular vsds and perimembranous vsds using the amplatzer devices. J interv cardiol. 2003 oct; 16(5): 399-407

29. Thanopoulos BD, Tsaousis GS, Karanasios E, Eleftherakis NG, Paphitis C. Transcatheter closure of perimembranous ventricular septal defects with the amplatzer asymmetric ventricular septal defect occluder: preliminary experience in children. Heart. 2003 aug; 89(8):918-22

30. Argenziano M, OZ MC, Kohmoto T, Morgan J, Dimitui J, Mongero L, Beck J, Smith Cr. Totally endoscopic atrial septal defect repair with robotic assistance. Circulation. 2003 sep 9; 108 suppl 1: ii191-4

31. Ryan WH, Cheirif J, Dewey TM, Prince SL, Mack MJ. Safety and effi cacy of minimally invasive atrial septal defect closure. Ann thorac surg. 2003 may; 75(5): 1532-4



32. Doll N, Walther T, Falk V, Binner C, Bucerius J, Borger MA, Gummert JF, Mohr FW, Kostelka M. Secundum ASD closure using a right lateral minithoracotomy: fi ve-year experience in 122 patients. Ann thorac surg. 2003 may; 75(5): 1527-30

33. Rickers C, Seethamraju RT, Jerosch-Herold M, Wilke NM. Magnetic resonance imaging guided cardiovascular interventions in congenital heart diseases. J interv cardiol. 2003 apr;16(2):143-7

34. Acar P, Roux D, Dulac Y, Rouge P, Aggoun Y. Transthoracic three-dimensional echocardiography prior to closure of atrial septal defects in children. Cardiol young. 2003 feb; 13(1): 58-63

35. Ewert P, Berger F, Daehnert I, Van Wees J, Gittermann M, Abdul-Khaliq H, Lange PE. Transcatheter closure of atrial septal defects without fl uoroscopy: feasibility of a new method. Circulation. 2000 feb 29; 101(8): 847-9

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Perioperative Management of Total Anomalous Pulmonary Venous Drainage

*Vishal K Singh DCH, MD, DNB (Pediatrics), **Arun Ramaswamy BSc, ***Amit Varma, MBBS, AB Internal Medicine (Critical Care Medicine Perinatal and Neonatal), ****Dr. Rajesh Sharma, MS, MCH (Cardiothoracic Surgery)

*Senior Consultant, **Pediatric Cardiac Care (Physician Assistant )MMM-ICVD-Chennai.BITS PILANI ***Director Critical Care, ****Director & Head Pediatric Cardiac Surgery, Fortis Escorts Heart Institute, Okhla Road, New Delhi

Correspondence:Dr. Vishal K SinghSenior Consultant Pediatric Critical Care MedicineFortis Escorts Heart Institute, Okhla Road, New Delhi-110 025.Mb: +919971000328; Fax: +911126825048Email: [email protected]

IntroductionTotal anomalous pulmonary venous drainage (TAPVD) consists of an abnormality of blood fl ow in which all 4 pulmonary veins drain into systemic veins or the right atrium with or without pulmonary venous obstruction1.

The presence of an interatrial communication is necessary to sustain life, and therefore an atrial septal defect (ASD) or patent foramen ovale (PFO) is considered part of the complex. Also, the young age of the patients makes the presence of a Patent Ductus Arteriosus (PDA) usual, and this is not considered a complicating defect. Rarely Ventricular septal defects (VSD) are associated with the anomaly2.

Types of total anomalous pulmonary venous drainageDarling proposed the most commonly used classifi cation system for total anomalous pulmonary venous connection based on the site of pulmonary venous drainage3. In type I (i.e. supracardiac connection), the 4 pulmonary veins drain via a common vein into the right superior vena cava, left superior vena cava, or their tributaries.

Figure 1: Supra Cardiac TAPVC

AbstractTotal anomalous pulmonary venous drainage (TAPVD) is a congenital heart disease involving abnormal drainage of all the four pulmonary veins in to systemic venous drainage or right atrium. TAPVD can occur in isolation or as an additional component of complex congenital heart disease with univentricular or biventricular physiology. If corrected at the right time it allows the baby to have essentially normal growth and development with good quality of life but delay in diagnosis and referral can result in grave consequences like severe pulmonary hypertension, cardiogenic shock and mortality. It can present in the neonatal period or infancy depending upon obstruction to the abnormal pulmonary venous drainage. Obstructed TAPVD when presenting in the neonatal period constitutes a signifi cant pre operative challenge and the outcome is often determined by the positive synergy in the transport and referral hospital team. The current review is targeted to stream line perioperative management strategy based on the currently available evidence in literature.Key words: Total anomalous pulmonary venous drainage (TAPVD): Supracardiac; Infracardiac; Cardiac; Pulmonary hypertension.


In type II (i.e. cardiac connection), the pulmonary veins connect directly to the right heart (e.g. coronary sinus or directly to the right atrium). In type III (i.e. infra diaphragmatic connection), the common pulmonary vein travels down anterior to the esophagus through the diaphragm to connect to the portal venous system. In type IV (i.e. mixed connections), the right and left pulmonary veins drain to different sites (e.g. left pulmonary veins into the left vertical vein to the left innominate, right pulmonary veins directly into the right atrium or coronary sinus.4

Figure 2 A: Coronary Sinus TAPVC

Figure 2 B: Cardiac TAPVC

Smith et al.5 provided an alternative classifi cation for TAPVD: Supra cardiac (without pulmonary venous obstruction) and infra diaphragmatic (with pulmonary venous obstruction). All the pulmonary veins drain into the systemic venous circulation and hence right atrial and right ventricular enlargement occur along with dilation of the pulmonary artery. In case of signifi cant pulmonary venous obstruction, right ventricular hypertrophy occurs.

The left ventricle is of normal size, and left ventricular volume measured in life is usually within the normal limits. Left atrial size usually is diminished because it lacks the contribution of the common pulmonary vein. Total anomalous pulmonary venous connection occurs in isolation in two thirds of patients or manifests as part of a group of heart defects (e.g. heterotaxy syndromes) in approximately one third of patients.1

In infra diaphragmatic connection, severe obstruction almost inhibits pulmonary venous fl ow with obstruction of the common pulmonary vein. This obstruction manifests either as it courses through the diaphragm, at its junction with the portal vein system, or as an obstruction of pulmonary venous fl ow as the ductus venosus closes and pulmonary vein fl ow is forced to cross the liver portal sinusoid system. Finally, in all types, obstruction may occur because of restrictive atrial septal defect size and because of small left atrial size.

Figure 3: Infra Cardiac TAPVC

PresentationPatients with pulmonary vein obstructionPulmonary venous obstruction occurs in virtually all patients with subdiaphragmatic drainage and in approximately 50% of patients with supracardiac drainage6. Patients with obstruction develop symptoms early, usually in the fi rst 24-36 hours of life, including tachypnea, tachycardia, and cyanosis with or without cardiogenic shock. Signs of pulmonary hypertension progress with decreasing pulmonary blood fl ow and worsening cyanosis. Natural history is that of progressive clinical deterioration and early death in the fi rst week or month of life, depending on the degree of pulmonary venous obstruction.6

Perioperative Management of Total Anomalous Pulmonary Venous DrainagePEDIATRIC CARDIAC INTENSIVE CARE - 2


Physical examination fi ndings include severe cyanosis with signifi cant respiratory distress. Cardiac impulse is prominent anteriorly, but, usually, the heart is not clinically enlarged. The pulmonary component of the second heart sound is accentuated, and occasionally a gallop rhythm may be present. A murmur usually is not detectable, yet a systolic murmur over the pulmonary area or a tricuspid insuffi ciency murmur at the mid and lower left sternal border may be present. Peripheral pulses are usually normal after birth but may deteriorate rapidly as heart failure progresses. Liver enlargement commonly occurs, especially in total anomalous pulmonary venous connection (TAPVD) type III with sub diaphragmatic drainage.7

Patients without pulmonary venous obstructionPatients with unobstructed pulmonary venous fl ow present with symptoms more similar to a very large atrial septal defect. Mild failure to thrive with increased respiratory effort than normal with activity or recurrent respiratory infections may be present.Physical examination fi ndings include right ventricular volume loading with increase in right ventricular impulse, a wide split-second sound (usually with normal-intensity pulmonary closure), and pulmonary outfl ow murmur with or without a tricuspid diastolic murmur. Cyanosis infrequently occurs in the fi rst year of life.Reverse difference cyanosis has been reported in the newborn period in total anomalous pulmonary venous connection to the superior vena cava (SVC). In this setting highly saturated blood in the SVC streams preferentially from right ventricle across ductus arteriosus to descending aorta; lower saturated blood in inferior vena cava streams across the foramen ovale to the left heart and aorta, resulting in higher saturation in the foot than in the right hand.8

If a restriction develops in the foramen ovale, some degree of pulmonary hypertension is more likely, with earlier onset of tachypnea, louder pulmonary closure sound, more prominent right ventricular impulse, and a greater likelihood of systemic and pulmonary venous congestion.

ECGA tall peaked P wave in lead II or the right precordial leads characteristic of right atrial enlargement is a

constant fi nding. Right-axis deviation is usual. Right ventricular hypertrophy is invariably present, usually manifested by high voltage in the right precordial leads, occasionally as an incomplete right-bundle-branch block pattern.1,9

Chest radiographyThe lung fi elds refl ect increased pulmonary blood fl ow. The right atrium and right ventricle are enlarged, and the pulmonary artery segment is prominent. The left-sided chambers are not enlarged.A fi gure-of-8 or a snowman appearance of the cardiac show is seen in patients with TAPVD to the left innominate vein. The upper portion of the fi gure-of-8 is composed of the anomalous vertical vein on the left, the left innominate vein superiorly, and the SVC on the right. This diagnostic sign is not usually present in the fi rst few months of life but is often present in the older child and adult. When the anomalous connection is to the right SVC, dilation of this structure results in a prominence at the upper right cardiac border.1

Echocardiography• Apical and subcostal 4-chamber views usually

best identify individual pulmonary veins and their confl uence in patients with total anomalous pulmonary venous connection.

• The common pulmonary vein can be visualized to its point of entry to the systemic venous system or to the coronary sinus using multiple views.

• Right ventricular and pulmonary artery volume loading with fl attened or paradoxic septal motion may be observed on M-mode imaging.

• Subcostal long - and short-axis views help in evaluating the size and fl ow patterns across the foramen ovale or atrial septal defect.1

Computed Tomography with contrast (CT scan) and Magnetic Resonance Imaging (MRI): CT scan and MRI provide a wide-fi eld imaging of the pulmonary veins and blood fl ow within them as well as adjacent cardiovascular structures. Non cardiac structures, such as airways, lungs, spine, and abdominal organs, also are visualized. MRI performed across various planes demonstrates



dynamic nature of blood fl ow, cardiac chambers, and AV and semilunar valves. Imaging techniques such as the CT MRI are particularly useful in complex conditions such as the heterotaxy syndromes, hypoplastic aortic arch and aortic arch interruption, when full delineation of anatomy has not been possible by echo10.Usually, these techniques are not necessary in the initial evaluation of newborns and in the infant with TAPVD as echocardiography is accurate, portable, and readily available.11

TreatmentCorrective surgery is necessary for all patients with this condition. No palliative procedure exists. All infants with pulmonary venous obstruction should be operated on soon after diagnosis, in the newborn period. Infants who do not have pulmonary venous obstruction but do have heart failure with recurrent lower respiratory tract infection and failure to thrive are usually operated on between 4 and 6 months of age. Optimal stabilization the patient prior to surgery from a cardiovascular and metabolic standpoint is important.9

Pre operative Management 1. Intensive anti congestive measures with digitalis

and diuretics should be provided for infants without pulmonary venous obstruction

2. Metabolic acidosis should be corrected if present after establishing mechanical/positive pressure ventilation

3. Infants with severe pulmonary edema (resulting from the infra cardiac type and from other types with obstruction) should be intubated and supported with positive pressure ventilation.

4. If the size of the interatrial communication appears small and immediate surgery is not indicated, balloon atrial septostomy or blade atrial septostomy may be performed to enlarge the communication9

Surgery 1. The goal of surgery is to redirect pulmonary vein fl ow entirely to the left atrium. In patients with a supracardiac or infracardiac connection, the

common pulmonary vein is opened wide and connected side to side to the left atrium. The foramen ovale is closed, and the ascending or descending vein is usually ligated. In a cardiac connection (to right atrium or coronary sinus), the atrial septum is resected partially and a new septum is surgically created, directing pulmonary veins to the left atrium. A coronary sinus may be separately tunneled to the right atrium or left to drain with the pulmonary veins to the left atrium. In selected cases with severe pulmonary hypertension or right ventricular dysfunction, the vertical vein may be left open.[9]

Complications1. In the early post operative period, pulmonary

hypertension due to a small and poorly compliant left heart leading to cardiac failure and pulmonary edema is common and may require prolonged respiratory and medication support postoperatively.

2. In patients with obstructed total anomalous pulmonary venous connection, the pulmonary arteries may be hypoplastic and respond poorly to the vasodilators.

3. Postoperative arrhythmias are usually atrial. [9]

4. The complication of pulmonary venous obstruction occurs later in 5-10% of patients and is usually evident in the fi rst 6 months following surgery. This obstruction is more easily treated surgically if it involves only the pulmonary venous confl uence and anastomosis area. Sutureless marsupialization with pericardium has seemed to help improve surgical results.12

5. If the pulmonary venous obstruction involves intimal fi brotic hyperplasia of individual pulmonary veins extending deeper back into the veins then surgery may not be successful.

6. Surgical mortality remains higher in repair of mixed form of total anomalous pulmonary venous connection, especially in patients with more complex patterns of pulmonary venous connection, which have persistently small or thickened individual pulmonary veins.13



Post operative careFollowing surgery, the child is transferred to the PICU team with detailed information on various parameters listed below (Table 1)

Table 1: Information to be given to the Critical Care team during transfer of child into PICU

Surgery • Type of lesion• Procedure-correction/palliation• CPB time, Aortic cross clamp time

History • Previous medical illness• Medications• Allergies• Previous surgeries / medical history

Anesthesia • Intra operatrive problems - surgical, anesthetic, CPB

• Respiratory parameters• Airway (diffi culties, ET tube size, fi xed, leak)• Ventilator settings and parameters

Haemodynamics • Cardiac rate and rhythm• Filling pressures (central venous pressure-

CVP)• Vaso active agents• Most recent vital signs• Most recent laboratory data - Hct, K+, ABG,

temperature• Mixed venous oxygen saturation (MVO2)

Initial assessment in the PICUA rapid initial assessment of the child is made soon after transfer into the PICU. This includes a detailed physical examination (Table 2) and laboratory studies (Table 3).

Table 2: Physical ExaminationRespiratory • Breath sounds

• ET tube size, fi xed, leak• Chest excursion

Cardiovascular • Heart rate and rhythm• Blood pressure - waveform• Filling pressures - LA/RA• Pulse volume• Heart sounds and cardiac murmurs• Temporary Pacemaker/settings

Skin • Cyanosis turgorCentral nervous system

• Awake status, pupils

Per Abdomen • Addominal Distention, liver size, spleen• Ascites

Table 3: Laboratory studies

Complete blood count

• Hematocrit• platelets

Electrolytes • Sodium• Potassium• Calcium• Magnesium

Arterial Blood gas

• Acidosis (Metabolic/Respiratory)• pH, PCO2, PO2, anion gap, MVO2, Lactate

Coagulation • PT, APTT, ACTPT: Proth Rombin Time, APTT: Activated Partial Thromboplastin Time, ACT: Activated Clotting Time

A chest radiography (AP view) is performed to determine the following1. Position of the tip of the endo tracheal tube2. Location of the central vascular catheters and

other monitoring lines3. Position of the chest tubes4. Heart size5. Lung vascularity, presence of atelectasis,

pneumothorax or pleural effusion6. Pulmonary vascular markings

Principles of post operative managementContinuous monitoring and surveillance of the clinical data are mandatory to direct further treatment following cardiac surgery. Following the repair of TAPVD, medical therapy is directed towards augmenting cardiac output and minimizing pulmonary vascular resistance (PVR) using β adrenergic agonists and pulmonary vasodilators such as dobutamine, isoproterenol, and milrinone.

Hemodynamic managementCardiac output depends on the heart rate and stroke volume. Stroke volume in turn depends on adequate preload, minimizing afterload, contractility, adequate heart rate and optimal cardiac rhythm. Warm peripheral extremities, brisk capillary refi ll and a urine output of atleast 0.5 mL/kg/hr are good indicators of adequate cardiac output.If the heart rate is slow enough to compromise the cardiac output, temporary atrial pacing at higher rate. A few centres still consider isoproterenol in such scenarios. Sinus tachycardia may be due to pain, awakening or hypovolemia and will respond to specifi c



treatment. Junctional tachycardia and junctional ectopic tachycardia are commonly observed in the immediate post operative period. Atrial overdrive pacing usually helps in inducing systematic conduction. Amiodarone, β blocade and IV Magnesium sulphate may help in controlling the heart rate by reducing the excessive conduction rate or by inducing arterio venous block, thereby slowing the ventricular rate. In case of hemodynamic instability cardioversion has to be attempted. Conservative measures such as aggressive sedation, avoiding higher doses of sympathomimetics, digitalization and avoiding pyrexia along with inducing hypothermia may help in controlling the heart rate. Atrio ventricular sequential pacing may be necessary when the conduction is disrupted in conditions like A-V dissociation.Myocardial contractility is impaired after open heart surgery due to ischemia, hypoxia and Cardio pulmonary bypass (CPB) induced myocardial dysfunction. Usage of following drugs may improve the contractility and thus cardiac output.14

InotropesDopamine – 5 – 10 μg/kg/minDobutamine – 5 – 10 μg/kg/minEpinephrine – helps in improving the blood pressure with its α and β adrenergic effects, particularly when the diastolic BP remains low. (Dose 0.03 - 0.1 μg/kg/min)

InodilatorsIsoproterenol – 0.03 – 0.07 μg/kg/minMilrinone – a phosphodiesterase III inhibitor provides inotropy along with peripheral vasodilatation (Dose - 0.3 – 0.7 μg/kg/min). As a result, ventricular fi lling pressures decrease while stroke volume and CO increase.15

VasodilatorsSodium Nitroprusside (SNP) and Nitroglycerin (NTG) - may help in afterload reduction (0.1 - 2 μg/kg/min).16 Vasopressin - produces a non-catecholamine-mediated elevation in systemic vascular resistance and mean arterial pressure without depressing cardiac output and with little effect on pulmonary vascular tone. Vasopressin is benefi cial in patients

with catecholamine refractory vasodilatory shock as well.17,18 This scenario is particularly witnessed if the child is operated in an emergency with latent or evolving sepsis.

Vasodilators

Inhaled Nitric Oxide (NO) Nitric oxide stimulates Guanylate Cyclase to form cyclic GMP, which causes relaxation of vascular smooth muscle. It can be delivered by inhalation directly to alveolar units and is rapidly inactivated by hemoglobin making it the most selective of currently available selective pulmonary vascular dilators (except for oxygen). NO has a half life ranging from 0.1 - 5 seconds in physiologic systems. In case of severe pulmonary hypertension as in obstructed TAPVD, NO is very useful and leads to clinical improvement in majority of neonates and infants.19,20

Sildenafi lA phosphodiesterase V inhibitor increases the concentration of cGMP leading to smooth muscle relaxation and dilatation of pulmonary arteries. A dose of 0.5mg/kg/Q6H was found to be effi cacious in lowering the pulmonary vascular resistance in children with pulmonary hypertension.The drug has minimal systemic effects. Sildenafi l should be avoided in acute pulmonary hemorrhage or in acute respiratory distress syndrome (ARDS) with gross V- Q mismatch.

BosentanAn oral endothelin receptor antagonist that binds with both ETA and ETB receptors. Though limited studies are available, it was found to improve hemodynamics and relieve symptoms of pulmonary hypertension.1

Phenoxy benzamineA non specifi c alpha receptor antagonist, causes vasodilatation. Intravenous phenoxy benzamine has proven to reduce the afterload on the right ventricle in the post operative period. A dose of 0.5 - 2 mg/kg/day is used. In the current era, it is sparingly used though available as a part of standard formulary in most countries.



Respiratory ManagementThe oxygen consumption of the children may be increased following surgery secondary to hyperthermia, increased respiratory and circulatory system activity, muscle system activity and endogenenous secretions of catecholamines. Hence it is important to improve the oxygen delivery while decreasing the oxygen consumption. This may be achieved by using sedatives, analgesics and muscle relaxants.Various respiratory complications such as stridor, mucous plugging, diaphragmatic paralysis, and pulmonary edema can occur as a result of mechanical ventilation and endo tracheal tube. Adequate care can reduce the incidence and risks of these complications. When uncuffed ET tubes are used, a leak of 15 -20 cm H2O is recommended. When cuffed ET tube is used, the cuff is infl ated until the leak just disappears. Warming and humidifi cation of inspired gases will avoid heat loss and thickening of secretions. The temperature of these gases should be kept below 37̊ C. The children who have undergone TAPVD rerouting are usually hyperventilated in view of pulmonary hypertension where in the pH is maintained on the alkalotic side (>7.45) with a low pCO2 (25-30 mmHg). Reasonable physiological positive end expiratory pressure (PEEP) improves oxygenation and decreases atelectasis.

Fluids and electrolytesThe optimal fi lling pressure varies from time to time depending on the myocardial function. Post CPB, patients are total body fl uid overloaded with capillary leak and depleted intravascularly. Although acute volume expansions are often required, patients should be administered only one half to two thirds of the normal maintenance. Factors such as infant bed warmer, rewarming, post operative fever will increase insensible losses by 10 -20% and need to be compensated. Thus, a fl uid requirement of about 1 -1.5 mL/kg/hr with an additional compensation for insensible water loss needs to be administered to maintain adequate fi lling pressures.Hyperkalemia usually occurs as a consequence of decreased cardiac output, poor perfusion, blood transfusion and altered renal function. Care is taken to maintain the serum potassium levels in the range of 3.5 -4.0 mmol/dL. Hyperkalemia is treated with

Glucose Insulin (0.1IU/kg), 10% Calcium chloride solution (0.2 – 0.5 mL/kg), sodium bicarbonate (1-2 mEq/kg). Potassium is supplemented if the serum potassium is less than 3.0 mmol/dL.Hypomagnesemia is commonly reported post cardiac surgery and may lead to ventricular arrhythmias.

Hematologic managementChildren have high incidence of intra operative and post operative bleeding as a result of platelet dysfunction and abnormalities of platelets release. Coagulation cascade factors are inhibited by heparin administered during surgery. Though the heparin effects are reversed by Protamine, “Heparin rebound” occurs several minutes later characterized by bleeding and prolonged activated clotting time. Administration of platelets and fresh frozen plasma or cryoprecipitate may help in achieving hemostasis.

Neurologic complicationsNon specifi c neurologic complications such as involuntary movements, choreoethytosis may result following cardiopulmonary bypass and total circulatory arrest (TCA). Hence close observation and time to time assessment for gross abnormalities, abnormal movements and seizures are necessary.

Gastro intestinal complicationsInitial evaluation includes the presence or absence of bowel sounds and measurement of abdominal girth. The liver and spleen should be percussed for position and span to assess the degree of right ventricular failure. Necrotizing Enterocolitis (NEC) may be seen in infants within 24 hours of surgery characterized by abdominal distention, absence of bowel sounds, and radiographic evidence of bowel distention.

NutritionFeeding may be started after extubation. In case the child requires mechanical ventilation for more than 48 hours and hemodynamically stable, then minimal enteral feeds may be started on the fi rst post operative day after gastro intestinal complications are ruled out. In children with low output state and unstable hemodynamics, the feeding may be delayed till stability is achieved.



InfectionLow grade fever post CPB is common, but persistent high grade fever or other features of sepsis like leucocytosis or leucopenia, thrombocytopenia, persistent hypoglycemia, hypothermia and warm shock should be worked up with appropriate cultures (blood, urine, ET secretion/sputum).14

Guidelines to post op managementUnobstructed TAPVD1. Routine examination on receival from OR2. CXR, ACT and ABG3. Crystalloids 1.5 - 2ml//kg/hr (maximum). Volume

may be restricted to less than 2ml/kg/hr4. Minimal transfusion of blood products; avoid

unless needed5. Elective ventilation (TV - 10 ml/kg, PEEP - 4-6

cm H2O; To maintain a pH >7.4, pCO2 <40; a lower FiO2 < 0.4 in new born and neonates)

6. Inotropes and Inodilators support for myocardial dysfunction

7. ABP to be maintained at minimum optimal level for initial few hours

8. Sedation maintenance IV with Fentanyl / Dexmetedomedine

9. Deep sedation, muscle relaxants may be used in specifi c cases

10. IV Vasodilators (SNP/NTG/Phenoxy benzamine to control systemic / pulmonary pressures)

11. Keep Serum Potassium less than 4 mmol / L12. Initiate Peritoneal dialysis if hyperkalemia / low

urine output / ascites13. Routine echocardiography for biventricular

function, TR (tricuspid regurgitation), PR (pulmonary regurgitation) and TAPVD confl uence.

14. Lasix infusion at the earliest (once peripheries warm, no acidosis, consistently stable hemodynamics)

15. Temporary pacing as required. (A-V sequential pacing in case of A-V dissociation, atrial pacing for sinus bradycardia and nodal rhythm.

16. Heart rate control (Digitalis/hypothermia for sinus tachycardia/nodal tachycardia)

17. IV Metaprolol or Amiodarone for junctional ectopic tachycardia and A-V dissociation.

18. Watch for drainage, urine output and acidosis

along with vital parameters19. Watch for Endo tracheal bleeding during ET

suctioning20. NG feeds from POD 1 (if ventilation planned for

more than 24 hours).21. Vasodilators – Bosentan /Sildenafi l with a

gradual increment in the dosage based on PA pressures in children older than 3 months of age

22. Fluid balance – Target output atleast 15 – 25% more than intake

Obstructed TAPVDUsually neonates and infants with obstructed TAPVD have severe pulmonary hypertension and are likely to have high risk of post operative complications such as pulmonary hypertensive crisis and low cardiac output state. It is a common practice to have a delayed sternal closure in such children1. Routine examination on receival from OR2. CXR, ACT and ABG3. Crystalloids 1 – 1.5ml//kg/hr (maximum).

Volume may be restricted to less than 2ml/kg/hr4. Minimal transfusion of blood products; avoid

unless needed5. Elective ventilation for 24 hours (TV – 10 ml/kg,

PEEP – 4-6 cm H2O; To maintain a pH >7.45, pCO2 <40, a FiO2 of 0.5 – 0.7 except in case of new borns)

6. Inotopes and Inodilators support for myocardial dysfunction

7. ABP to be maintained at minimum optimal level for initial few hours

8. Sedation maintenance IV with Fentanyl / Dexmetedomedine and intermittent boluses of sedation along with muscle relaxants may be used.

9. IV Vasodilators (SNP/NTG/Phenoxy benzamine to control systemic / pulmonary pressures)

10. Keep Serum Potassium less than 4 mmol / L11. Initiate Peritoneal dialysis if hyperkalemia / low

urine output / ascites12. Routine echocardiography for biventricular

function, TR, PR and TAPVD confl uence, rule out pulmonary venous obstruction.

13. Lasix infusion at the earliest (once peripheries warm, no acidosis)

14. Temporary pacing as required. (A-V sequential pacing in case of A-V dissociation, atrial pacing



for sinus bradycardia and nodal rhythm.15. Heart rate control (Digitalis/hypothermia for

sinus tachycardia/nodal tachycardia)16. IV Metaprolol or Amiodarone for junctional

ectopic tachycardia and A-V dissociation.17. Watch for drainage, urine output and acidosis

along with vital parameters18. Watch for Endo tracheal bleeding during ET

suctioning19. NG feeds from POD 1 (if ventilation planned for

more than 24 hours).20. Vasodilators-Bosentan /Sildenafi l with a gradual

increment in the dosage21. Inhaled Nitric oxide if required due to recurrent

PAH crisis.22. Fluid balance-Target output atleast 25-50 %

more than intake

Weaning criteriaThe following indicators of hemodynamic stability should be considered when planning to wean from ventilator support.1. PAP/SAP <0.75 (on invasive monitoring or echo)2. Mean BP > related age normal3. Adequate Peripheral perfusion 4. No increase in inotropic requirements 5. No signifi cant metabolic acidosis6. Urine output > 1 ml/kg/hour7. Absence of pulmonary hypertensive episodes

while weaning the ventilation.8. No neuromuscular blockade, no or minimal IV

sedation9. Tolerate PS/CPAP ventilation without any

adverse events for a considerable period 10. Normal neurologic status11. Normal movement of diaphragmPAP: Pulmonary artery pressure, SAP: Systemic arterial pressure

Management of pulmonary hypertensive crisisPulmonary arterial hypertensive crisis (PAH) is defi ned as pulmonary artery pressures rising to atleast 2/3 rd of the systemic arterial pressure. It is usually characterized by desaturation and systemic hypotension. The presence of a decompressing channel in the form of a patent foramen ovale or an atrial septal defect or an unligated vertical vein or a ventricular septal defect may prevent acute RV failure and low cardiac output. The presence

of a pulmonary artery pressure monitoring catheter can help to establish the diagnosis of pulmonary hyptertensive crisis. In the absence of a decompressing channel, an acute raise in the right atrial pressure may be indicative of pulmonary arterial hypertension. Clinical manifestations include tachycardia, a sudden desaturation with or without bronchospasm. Most commonly, systemic hypotension is seen. Cyanosis may be witnessed if the shunting through the decompressing channel is signifi cant. The most effective strategy to manage PAH (Pulmonary artery hypertension) is prevention. The following measures are to be followed for prevention and management of pulmonary hypertension.• Maintenance of adequate sedation and analgesia,

particularly during ET suctioning• Muscle relaxant and deep sedation if

hemodynamics are stable• Maintaining a pH of 7.45 -7.5, i.e. respiratory

alkalosis in acute pulmonary hypertensive crisis situation, by hyperventilation.

• Bosentan/Sildenfi l in the absence of inhaled nitric oxide

• Inotropes to maintain cardiac output• Extra corporeal Membrane oxygenation if

recurrent crisis and hemodynamically unstable.[14]

Extra corporeal membrane oxygenation (ECMO) Extracorporeal membrane oxygenation (ECMO) has become the most widely used mode of mechanical cardiopulmonary support for children after cardiac surgery21,22. Children with cardiac dysfunction and pulmonary hypertensive crisis unresponsive to conventional pharmacologic therapy may be supported with ECMO in the immediate post op period. The hospital survival rates in children receiving ECMO after heart surgery have ranged between 35% and 60%.23-29

ConclusionManagement of a neonate or infant with TAPVD involves a major perioperative connect between the referring physician and the pediatric cardiologist, pediatric cardiac surgeon and intensivist. The outcome in major centre is entirely dependent upon early detection rapid perioperative stabilization and timely surgical interventions. An intervention at the



right time ensures a essentially normal cardiac status after recuperation, but it is desirable to have a long term growth and neuro developmental follow up.

References1. Allen DH, Driscoll DJ, Shaddy RE, Feltes TF. Moss and

Adams Heart disease in infants , children and adolescents, Edition 7; Vol. II; 776-786

2. Delisle G, Ando M, Calder AL, et al. Total anomalous pulmonary venous connection: Report of 93 autopsied cases with emphasis on diagnostic and surgical considerations. Am Heart J 1976; 91:99-122

3. Darling RC, Rothney WB, Craig JM. Total pulmonary venous drainage into the right side of the heart: Report of 17 autopsied cases not associated with other major cardiovascular anomalies. Lab Invest 1957; 6: 44-64

4. J.C. Hirsch and E. L. Bove. Multimedia Manual of Cardiothoracic Surgery, doi:10.1510/mmcts. 2006.002253

5. Smith B, Frye TR, Newton WA Jr. Total anomalous pulmonary venous return: Diagnostic criteria and a new classifi cation. Am J Dis Child 1961; 101: 41“51

6. Norwood WI, Hougen TJ, Castaneda AR. Total anomalous pulmonary venous connection: Surgical considerations. Cardiovasc Clin 1981; 11: 353“364

7. Nichols: Critical Care Heart Disease in Infants and Children, 2nd edition

8. Yap SH, Anania N, Alboliras ET, Lilien LD. Reversed differential cyanosis in the newborn: a clinical fi nding in the supracardiac total anomalous pulmonary venous connection. Pediatr Cardiol. Apr 2009; 30(3): 359-62

9. Pediatric Cardiology for Practitioners, Myung Park, 5th edition10. Wang JK, Li YW, Chiu I, et al: Usefulness of magnetic

resonance imaging in the assessment of venoatrial connections, atrial morphology, bronchial situs, and other anomalies of right atrial isomerism. Am J Cardiol 1994; 74: 701-704

11. Bando K, Turrentine MW, Ensing GJ, et al. Surgical management of total anomalous pulmonary venous connection. Circulation 1996; 94(suppl): II12-16

12. Devaney EJ, Chang AC, Ohye RG, Bove EL. Management of congenital and acquired pulmonary vein stenosis. Ann Thorac Surg. Mar 2006; 81(3): 992-5; discussion 995-6

13. Behrendt DM, Aberdeen E, Waterson DJ, Bonham-Carter RE. Total anomalous pulmonary venous drainage in infants. I. Clinical and hemodynamic fi ndings, methods, and results of operation in 37 cases. Circulation. Aug 1972; 46(2): 347-56

14. Helfaer MA, Nichols DG. Rogers’Handbook of Pediatric intensive Care, 3rd edition; 238 - 287

15. Chang AC, Atz AM, Wernovsky G, et al: Milrinone: Systemic and pulmonary hemodynamic effects in neonates after cardiac surgery. Crit Care Med 1995; 23:1907–1914

16. Nichols DG, Rogers MC. Textbook of Pediatric Intensive Care, Fourth Edition, 1159-1184

17. Dunser MW, Mayr AJ, Ulmer H, et al: Arginine vasopressin in advanced vasodilatory shock. A prospective, randomized, controlled study. Circulation 2003; 107: 2313–2319 88

18. Rosenzweig EB, Stare TJ, Chen JM, et al: Intravenous arginine–vasopressin in children with vasodilatory shock after cardiac surgery. Circulation 1999; 100 (Suppl II): II- 182–II-186

19. Wessel Dl, Adatia I, Giglia TM, et al: Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass. Circulation 1993; 88: 2128-2138

20. Ronald A. Bronicki et al: Management of the postoperative pediatric cardiac surgical patient. Crit Care Med 2011; 39: 1974-1984

21. Nido PJ. Extracorporeal membrane oxygenation for cardiac support in children. Ann Thorac Surg 1996; 61: 336-339.

22. Duncan BW, Hraska V, Jonas RA, et al. Mechanical circulatory support in children with cardiac disease. J Thorac Cardiovasc Surg 1999; 117: 529-542.

23. Spray T. Extracorporeal membrane oxygenation for pediatric cardiac support. Cardiac Surg State Art Rev 1993; 7:177-188.

24. Duncan BW, Bohn DJ, Atz AM, et al. Mechanical circulatory support for the treatment of children with acute fulminant myocarditis. J Thorac Cardiovasc Surg 2001; 122: 440-448.

25. Duncan BW. Mechanical circulatory support for infants and children with cardiac disease. Ann Thorac Surg 2002; 73: 1670-1677.

26. Kolovos NS, Bratton SL, Moler FW, et al. Outcome of pediatric patients treated with extracorporeal life support after cardiac surgery. Ann Thorac Surg 2003; 76: 1435-1442.

27. Morris MC, Ittenbach RF, Godinez RI, et al. Risk factors for mortality in 137 pediatric cardiac intensive care unit patients managed with extracorporeal membrane oxygenation. Crit Care Med 2004; 32: 1061-1069.

28. Hintz SR, Benitz WE, Colby CE, et al. Utilization and outcomes of neonatal cardiac extracorporeal life support: 1996-2000. Pediatr Crit Care Med 2005; 6: 33-38.

29. Hoskote A, Bohn D, Gruenwald C, et al. Extracorporeal life support after staged palliation of a functional single ventricle: Subsequent morbidity and survival. J Thorac Cardiovasc Surg 2006; 131(5): 1114-1121.



Perioperative Management for Transposition of Great Arteries*Ajay Kumar Gupta, MD Pediatrics **Vishal K Singh, DCH, MD, DNB (Pediatrics), ***Amit Varma, MBBS, AB Internal

Medicine (Critical Care Medicine Perinatal and Neonatal), ****Rajesh Sharma, MS, MCH (Cardiothoracic Surgery)*Associate Consultant **Senior Consultant,Pediatric Critical care Care ***Director Critical Care, ****Director & Head

Pediatric Cardiac Surgery, Fortis Escorts Heart Institute, Okhla Road, New Delhi

Correspondence:Dr. Ajay Kumar GuptaAssociate Consultant, Fortis Escorts Heart InstituteOkhla Road, New Delhi-110 025.Mb: +919250925437; Fax: +911126825048Email: [email protected]

IntroductionTransposition of the great arteries (TGA) is a congenital cardiac malformation in which the normal anatomic positions of the aorta and pulmonary artery are transposed (i.e., the aorta originates from the right ventricle and the pulmonary artery arises from the left ventricle). It is a lethal and relatively frequent malformation, accounting for 5% to 7% of all congenital cardiac malformations1. Without intervention, about 30% of these infants die in the fi rst week of life, 50% within the fi rst month, 70% within 6 months, and 90% within the fi rst year2.

Incidence and epidemiologyThe incidence is reported to range from 20 to 30 per

100 000 live births. There is a male predominance with a male/female sex ratio that varies, in the literature, from 1.5:1 to 3.2:13,4. In 10% of the cases, this cardiac lesion is associated with other noncardiac malformations5. Although earlier epidemiologic and genetic surveys suggested some other associations, e.g., increased prevalence in infants of diabetic mothers or prenatal exposure to sex hormone therapy, these have not been confi rmed.

Defi nition and anatomic featuresThe term transposition was applied in 1814, by Farre, meaning that aorta and pulmonary trunk were placed (positio) across (trans) the ventricular septum6. This congenital cardiac malformation is characterised by atrioventricular concordance and ventriculoarterial discordance. In other words, the morphological right atrium is connected to the morphological right ventricle which gives rise entirely to or most of the aorta; the morphological left atrium is connected to the morphological left ventricle from where the

AbstractTransposition of the great arteries (TGA) is a congenital heart defect in which the normal anatomic positions of the aorta and pulmonary artery are transposed (ie, the aorta originates from the right ventricle and the pulmonary artery arises from the left ventricle). The association with other cardiac malformations such as ventricular septal defect and left ventricular outfl ow tract obstruction is frequent and dictates timing and clinical presentation, which consists of cyanosis with or without congestive heart failure. Newborns with TGA/ intact ventricular septum frequently need preoperative stabilization with PGE1, mechanical ventilation and/ or Balloon Atrial Septostomy(BAS). The arterial switch operation is the procedure of choice that restores the aorta and pulmonary artery to their normal anatomic positions. Intensive support is required to support the left ventricle which faces high resistance systemic circulation postoperatively. The outcome for most of the patients after surgery is good with low incidence of residual defects. Long term follow up is required for concerns regarding neurologic outcome and coronary abnormalities. This review focuses on current standard of care for patients with TGA.Keywords: Transposition, great arteries, preoperative, postoperative, stabilization


pulmonary trunk emerges. A right-sided subaortic infundibulum usually separates the tricuspid from the aortic valve, and fi brous continuity is present between the mitral and the pulmonary valve. Coronary arteries’ anatomy may assume diverse patterns of epicardial distribution, but they invariably originate in the aortic sinuses facing the pulmonary trunk. This fact is constant and independent of the two great vessels’ spatial relation.The term congenitally corrected transposition of the great arteries describes a different entity that conjugates atrioventricular and ventriculoarterial discordance. The prefi xes a-, d- and l- transposition describe the spatial relationship between the aorta and the pulmonary trunk, and should not be used to defi ne this anomaly7.Nearly half of the hearts with TGA have no other anomaly except a persistent patent foramen ovale or a Patent Ductus Arteriosus (PDA). Ventricular Septal defect (VSD) is common and present in about 40% to 45% (however, one third of the defects are small and with trivial hemodynamic signifi cance); and a combination of VSD and signifi cant left ventricle outfl ow tract obstruction (LVOTO) occurs in about 10%. Isolated LVOTO with intact ventricular septum is uncommon: about 5%. LVOTO can be caused by a wide spectrum of lesions, either at valvar or subvalvar level. Aortic arch obstruction is rare in TGA/ intact ventricular septum (TGA/IVS) but is present in 7% to 10% of cases of TGA/VSD8. In the Taussig-Bing (T-B) anomaly, preferential “streaming” of oxygenated blood from the LV through the VSD to the PA mimics TGA physiology. T-B is a double outlet right ventricle (DORV) with subpulmonary VSD, applying the “50% rule” to the pulmonary artery (PA) rather than to the aorta, which has a uniquely right ventricle (RV) origin.

PathophysiologyThe dominant physiologic abnormality in TGA is defi ciency of oxygen delivery to the tissues. The pulmonary and systemic circulations in TGA are parallel rather than in series. Hence, the greatest portion of the output of each ventricle is recirculated to that ventricle. Survival depends on the presence of one or more crossover or mixing points [atrial septal defect (ASD), VSD, or PDA] between these two circulations to achieve an arterial oxygen saturation

that is compatible with life. When the interatrial or interventricular shunting sites are of adequate size, the level of arterial oxygen saturation is infl uenced primarily by the pulmonary-to-systemic blood fl ow ratio, with a high pulmonary blood fl ow resulting in relatively high arterial oxygen saturation.

Clinical manifestationsCyanosis or heart failure with early death summarizes the usual clinical course in the untreated infant with TGA. Its onset and severity depend on anatomical and functional variants that infl uence the degree of mixing between the two circulations. Prominent cyanosis, sometimes with acidosis and cardiovascular collapse, is an early and almost universal fi nding in the neonate with TGA who has inadequate intercirculatory mixing. For this subgroup, it must be recognized that beyond cyanosis the clinical examination is often unrewarding with regard to relevant diagnostic physical fi ndings. Associated LVOTO or pulmonary obstructive disease can reduce the blood fl ow to the pulmonary vascular bed, thus contributing to a marked cyanotic state. If no obstructive lesions are present, and there is a large VSD that allows for satisfactory mixing between the two circulations, cyanosis may go undetected and only be perceived during episodes of crying or agitation. In these cases, signs of congestive heart failure prevail due to excessive ventricular workload. Tachypnoea, tachycardia, diaphoresis, poor weight gain, a gallop rhythm, and eventually hepatomegaly can be then detected later on during infancy.

DiagnosisThe diagnosis of TGA should be suspected in any cyanotic infant, especially if a poor response to hyperoxia test is detected. No characteristic features on clinical examination, chest radiography, or electrocardiography (ECG) reliably allow differentiation of TGA from other causes of neonatal cyanosis. A narrowed superior mediastinum gives to the cardiac silhouette a characteristic egg-shaped appearance on chest radiography. Heart murmurs, cardiomegaly, and pulmonary plethora are more likely

Perioperative Management for Transposition of Great ArteriesPEDIATRIC CARDIAC INTENSIVE CARE - 2


if a high pulmonary blood fl ow is present. Absence of femoral pulses suggests aortic arch obstruction.The “gold standard” for rapid noninvasive diagnosis is two-dimensional echocardiography, which usually provides accurate morphological and functional assessment of the heart, being able to delineate the specifi c features of the transposition of the great arteries. The evaluation of the coronary artery pattern and exclusion of other malformations are two important aspects that need to be addressed prior to surgery. Echocardiography has been refi ned to the point that coronary anatomy can be demonstrated noninvasively in the majority of cases9,10. As echocardiography in experienced hands is a reliable diagnostic tool providing high sensitivity and specifi city, the need for catheterisation is limited. Older infants with more complex forms of TGA may require catheterization to provide specifi c hemodynamic data.Prenatal diagnosis by foetal echocardiography is possible and desirable, as it may improve early neonatal management, thus reducing related morbidity and mortality11,12.

ManagementPreoperative critical care management The initial aim in the management of the affected newborn with TGA with severe hypoxemia is (a) to assure acceptable intercirculatory mixing and (b) maximizing the mixed venous oxygen saturation. The presence of unrestrictive ASD or VSD that provides satisfactory mixing, permits corrective surgery at a later stage without the prior need for palliative procedures.In TGA/ IVS, intravenous prostaglandin E1 (PGE1) infusion is used to maintain PDA patency leading to an increment in pulmonary blood fl ow, which increases pulmonary venous return and left atrial (LA) pressure, thus promoting left to right fl ow at atrial level13. Fever, vasodilation, edema, apnea, and hypertonicity have been observed in infants receiving PGE1, but these complications occur infrequently at doses of 0.01 to 0.02 mcg/kg/minute. Some neonates will not improve following the institution of PGE1, suggesting inadequate mixing because of a restrictive foramen ovale. With an inadequate interatrial opening, the markedly increased pulmonary blood

fl ow resulting from the prostaglandin infusion can lead to deleterious increased pulmonary congestion, and balloon atrial septostomy (BAS) may be required on an urgent basis in this subgroup14.BAS remains an elective procedure in patients who respond favourably to prostaglandin infusion. An adequately performed septostomy usually allows discontinuation of the prostaglandin infusion, thus minimizing the complications from this medication and the repair can be performed on a more semielective (i.e., within 7 to 10 days) rather than urgent basis. Also, surgical inspection of the ductus in patients who are receiving PGE1 has included observations of increased tissue friability and edema in some patients8. Percutaneous needle and catheter sheath placement is used to gain access to the femoral vein. The catheter is advanced to right atrium and across the foramen ovale into the left atrium. The balloon is infl ated with diluted angiographic contrast medium to a 12 to 15 mm diameter and then rapidly withdrawn across the atrial septum abruptly. Following successful septostomy, clinical stabilization and decreased hypoxia must occur. Cardiac complications of the procedure are rare, but atrial wall, pulmonary vein, or inferior vena caval perforation or tears or AV valve damage have been reported. Intracardiac rupture of the balloon occurs infrequently, but it is important to avoid introducing air bubbles during infl ation with the contrast medium to prevent air embolization. There have been reports of BAS associated with preoperative brain injury, but more recent studies suggest the probable casual factor is extent and duration of hypoxemia preoperatively15.Despite above manouvers, some patients remain hypoxemic even with an open ductus arteriosus and an adequate sized atrial communication. In such cases ventilator manouvers should be employed to decrease pulmonary vascular resistance and increase pulmonary blood fl ow, which should concomitantly improve pulmonary venous saturation. Also, increasing the fraction of inspired oxygen serves to lower pulmonary vascular resistance and increase total pulmonary blood fl ow.Also it is important to note that in TGA/IVS most systemic blood fl ow is the recirculated systemic



venous return. In the presence of poor mixing, signifi cant improvements in oxygen delivery can be made by increasing the mixed venous oxygen saturation, which is the major determinant of systemic arterial oxygen saturation. Manouvers include decreasing oxygen consumption (muscle relaxants, sedation, and mechanical ventilation) and improving oxygen delivery (increasing cardiac output with ionotropic agents or increasing oxygen carrying capacity by treating anemia). Coexisting causes of pulmonary venous desaturation (e.g. pneumothorax) should be sought and treated. Nevertheless, it should be emphasised that these measures are not universally benefi cial to these patients. For example, oxygen therapy may promote ductal closure, compromising intercirculatory mixing. Futhermore, aggressive ventilator settings (Positive Inspiratory Pressure and Positive End Expiratory Pressure) leading to excessive alveolar distension should be avoided so that intercirculatory shunts are not disturbed.

Corrective surgeryAlthough medical management and interventional procedures play an important role in the initial care of the neonate with TGA, surgical correction remains the ultimate goal; initial medical management is geared toward making the infant optimal for surgical correction. Arterial switch operation (ASO), which is anatomic correction, is currently the procedure of choice for most of these patients (Figure 1). In this procedure, the great arteries are transected in a manner that allows eventual reanastomosis of the distal aortic segment to the proximal pulmonary artery (neoaortic root). Transfer of the coronary arteries to this pulmonary segment is facilitated by their excision from the aortic sinus with a cuff of adjacent aortic wall. The proximal aortic segment (neopulmonary root) is connected to the distal pulmonary artery segment by an end-to-end anastomosis using the innovative maneuver of Lecompte et al., which passes the anterior aorta posterior to the bifurcation of the pulmonary artery8.

Figure 1: Arterial switch operationA. The location of aortic transaction using the traditional approach (red) and our modifi ed technique (blue).B. The coronary arteries removed as “O”-shaped buttons.C. Patch repair from coronary excision and reconstruction of the neopulmonic root.D. Traditional repair from coronary excision and reconstruction of the neopulmonic root.

In cases with defects in addition to TGA/ IVS, the arterial switch procedure should be tailored towards the individual morphological aspects and complementary interventions may be necessary to repair concomitant malformations. For example, an associated atrial defect, or more commonly the septostomy defect, can usually be closed by direct suture. Closure of the VSD may require the use of a patch to close the communication or, if very small, may just be left open. An obstruction within the aortic arch is best repaired concomitantly, if necessary using a pulmonary homograft to enlarge the aorta16. Some lesions causing LVOTO may be effectively ressected, re-establishing an adequate patency. Complex coronary patterns may require individualized techniques for coronary transfer, adapted to the ostial anatomy and coronary course.Two morphologic features may preclude ASO: an outfl ow tract obstruction lesion that cannot be satisfactory relieved by resection and certain coronary artery patterns that may pose diffi culties during coronary transfer. Whenever the arterial switch is not feasible, alternative approaches are required. A switch at atrial level, either by a Mustard or a Senning procedure, is particularly suitable for hearts with an IVS. The systemic venous return is redirected at atrial level to the



LV. Likewise, pulmonary venous blood is diverted to the RV. In the presence of a VSD with obstruction at the left ventricular outfl ow tract which is not ressectable, the most used options are the REV procedure or the Rastelli operation. In both, an intraventricular tunnel passing through the septal defect is created to connect the LV to the aorta. In Rastelli operation, an extracardiac conduit is placed between the RV and the pulmonary trunk17.

Timing of surgeryOptimal timing of ASO depends on associated anatomic features. After ASO, the LV which preoperatively supports the pulmonary circulation must be able to eject against systemic afterload postoperatively. In patients with TGA/ IVS, closure of ductus arteriosus and normal postnatal fall in the pulmonary vascular resistance result in a low pulmonary artery pressure shortly after birth. However, PA pressure (and hence LV pressure) can be maintained in presence of a non-restrictive ductus arteriosus. The exact time frame in which LV becomes unprepared to support the systemic circulation is unknown, but usually LV remains adequately prepared for at least 2 to 4 weeks after closure of the ductus14. Patients with large VSDs also have systemic pressure in LV and surgery can be electively taken up when the infant is a couple of weeks of age. Adequate LV muscle mass for successful systemic function may also be preserved in older patients with TGA and associated anatomic abnormalities including (a) surgically remediable or dynamic left ventricular outfl ow obstruction, or, (b) a delayed decrease in pulmonary vascular resistance and persistent pulmonary hypertension.In patients with TGA/ IVS presenting immediately after birth, treatment approach is guided by the extent of hypoxemia, hemodynamic and metabolic compromise. There is currently a trend towards early ASO, with BAS being reserved for cases with profound hypoxemia and metabolic compromise; or in cases where corrective surgery must be delayed due to prematurity, sepsis or other perinatal complications. In patients with severe hypoxemia and hemodynamic compromise usual practice is to stabilize the patient with PGE1, BAS and/ or mechanical ventilation and perform ASO at about 7-10 days. Nevvazhay et

al reported repair by ASO in the fi rst hours of life, without undergoing prior BAS for stabilization, in 8 newborns with severe hemodynamic compromise and metabolic disorders18. This needs to be verifi ed in prospective trials. Also, there are reports that earlier the repair in TGA/IVS within fi rst few days of life is associated with decreased resource utilization and no detriment to clinical outcomes. But, further analysis based on a larger cohort of patients is required to verify these results that have important implications for improving the value of care19,20.

Regressed left ventricleIn TGA/ IVS patients presenting late, assessment of LV is paramount to surgical decision making. At what time, the LV has defi nitely lost its ability to sustain a systemic function is an unanswered question. Empiric criteria to determine adequate LV preparation may include (a) an absolute LV systolic pressure that is appropriate for age, (b) a LV pressure at cardiac catheterization that is > 70% systemic levels (left to right ventricular ratio >0.7), (c) left ventricular muscle mass that is within the normal range for body surface area (> 35G/m2), (d) LV posterior wall thickness ≥ 4 mm8. The interventricular septum bulging right to left, with a ‘banana shape’ ventricle indicates that the LV pressure is quite low and that the LV preparation is questionable24. There are varying approaches in managing TGA/IVS with regressed LV from institution to institution. A primary arterial switch with extracorporeal membrane oxygenation (ECMO) in the postoperative period, if required, has been successfully used with good results21. Another less commonly used approach is pulmonary artery banding to retrain the left ventricle, with or without a simultaneous systemic-to-pulmonary shunt, with an interval period before band removal and anatomic correction22. Pulmonary artery banding can produce adequate muscle retraining within days so that the preparatory procedure and the arterial switch operation can be done during the same hospitalization (rapid two-stage arterial switch). Higher incidence of late sequalae (LV dysfunction, right ventricle outfl ow tract obstruction, neoaortic regurgitation) than primary arterial switch23,24 and increased use of resources make two-stage arterial switch less appealing.



In terms of early survival and postoperative primary LV failure, there is suffi cient level 2 evidence indicating that the primary ASO may be performed in infants three to eight weeks of age with comparable outcomes to neonates. The duration of postoperative ventilation and length of postoperative hospital stay is, however, prolonged. For infants between the ages of 2 to 6 months, the strength of the evidence favouring this management approach is limited by the small sample size of reported series and the increased requirement for mechanical support for LV failure25.Approach to an infant with TGA/ IVS is summarised in Figure 2.

Postoperative critical care managementThe aim of postoperative care is to establish a safe homeostatic environment for the infant at minimal metabolic cost. ASO for TGA/IVS is unique in that a ventricle pumping against low pulmonary resistance is placed abruptly in a high-resistance circuit and required to support systemic cardiac output. The ability of the neonatal LV in TGA to adapt to the systemic workload is remarkable, but optimal adaptation may take days to weeks, depending on the age of the child, preoperative LV pressure, and other factors. In older infants with unrestrictive VSD and in other patients with high LV pressure, the LV is

already “prepared” and can be expected to function well against systemic vascular resistance.A basic management strategy emphasizes a low-pressure, high-fl ow circulation to allow gradual hypertrophy of the LV. This requires careful control of temperature, fl uid and electrolyte balance, vascular resistance, and other factors. It is not uncommon for the patient to be shifted from operating room with open sternum in cases with borderline hemodynamics and with concerns of postoperative bleeding. All infants remain sedated by continuous morphine or fentanyl infusion and paralysis may be required, more so for cases with unprepared LV, with intermittent or continuous pancuronium for initial postoperative hours. If tachycardia develops, vecuronium is substituted after verifying the adequacy of sedation. After hemodynamic stabilization and cessation of muscle relaxants, gradual weaning from the ventilator is attempted.

HemodynamicsThe postoperative course following arterial switch surgery can be variable. Myocardial dysfunction is sometimes encountered and may require moderate dose inotropic support. Patients, who present late following regression of neonatal pulmonary vascular resistance, are more likely to encounter left ventricular dysfunction [26]. Invasive monitors utilized

Yes No

Age upto 3 weeks Age 3 weeks to 2-6 months

Severe Hypoxemia and Hemodynamic compromise

Stabilized

PGE1

LV prepared LV regressed

Early ASO

ASO

Not stabilized

PGE1, BAS and/ or Mechanical ventilation

Semielective ASO at 7-10 days

Urgent ASO

Rule out Pulmonary venous desaturation

ASO +/- ECMO

Rapid 2 stage ASO

Atrial switch

Figure 2: Approach to infant with TGA/ IVS



following surgery include arterial, central venous, and LA catheters. The adequacy of the circulation can be assessed by the gradient between core and toe temperature, mixed venous oxygen saturation, acid-base status and serum lactate levels. The critical hemodynamic dictum in postoperative monitoring of ASO patients is LA pressure, which should be titrated between 5 and 8 mm Hg with mean arterial pressure 35 to 45 mm Hg. Systolic arterial pressure should usually be 50 to 60 mm Hg on the fi rst day, with a progressive increase (for a given LA pressure) over the next 72-hour period. Intravenous fl uids are limited to 50% of maintenance. Fluid challenges to increase LA pressure above 8 to 10 mm Hg should be avoided, as the unprepared LV can be forced onto the downslope of the Starling contractility curve, precipitating hemodynamic deterioration. Moderate hypotension (mean arterial pressure, 35 mm Hg) in a well-perfused baby with normal serum lactate and mixed venous oxygen saturation is preferable. ASO patients usually receive milrinone (0.25-0.75 mcg/kg/min) and low-dose dobutamine till hemodynamics are stabilized and patient is successfully weaned from ventilator. Epinephrine for ionotropic support may be required in some cases. Phenoxybenzamine, sodium nitroprusside and/ or nitroglycerine are titrated for afterload reduction. Progressive improvement of LV function is followed with 2D echocardiography and hemodynamic monitoring. If mean arterial pressure decreases signifi cantly in the setting of adequate left atrial pressure, low dose vasopressin, may be used for short duration to improve hemodynamics27,28. Mean PA pressure after newborn ASO is usually one third of systemic mean arterial pressure. Higher PA pressure suggests a residual intracardiac shunt, which should be investigated with Doppler echocardiography. Inadequate sedation, hypoxia, and hypercapnea are other causes of pulmonary hypertension. Persistence of elevated fetal vascular resistance is rare in newborns after ASO. Similarly, postoperative pulmonary hypertensive crisis per se is unusual in newborns but may occasionally complicate the postoperative course in older infants with complex TGA29.After ASO for TGA/IVS, the postoperative chest fi lm usually shows a small heart and nonplethoric lungs. In

contrast, patients with a preoperative volume load, such as those with TGA/VSD or T-B anomaly, may have persistent cardiomegaly for weeks. Echocardiography typically demonstrates mild global impairment of LV function and paradoxical septal motion. Both improve over the fi rst postoperative week.Postoperative complications and sequalae following ASO are discussed next (Table 1).

Table 1: Complications and sequalae after arterial switch operationImmediate

Low Cardiac output• ‘Unprepared’ left ventricle• Prolonged CPB, crossclamp time• Coronary insuffi ciency

BleedingArrhythmiasHigh Pulmonary artery pressure

• Residual intracardiac shunt• Inadequate sedation• Hypoxia, hypercapnea• Late presentation• PPHN

Acute Kidney Injury• CPB related• Hemodynamic instability• Sepsis• Hemolysis

Capillary leak syndromeShort term

Supravalvular pulmonary stenosisNeoaortic regurgitationSupravalvular aortic stenosis

LateMyocardial perfusion abnormalitiesNeurodevelopment impairments

Low cardiac output Persistent systemic hypotension, increasing LA pressure, poor peripheral perfusion, and signs of LV dysfunction suggest coronary arterial insuffi ciency or an unprepared LV. Both precipitate an extremely unstable situation. In the case of coronary insuffi ciency, ST-segment changes may be evident on ECG and regional wall-motion abnormalities observed on echocardiography30. Transient coronary spasm after ASO is a real entity, but this has been diffi cult to prove, due to spontaneous reversibility. Nitroglycerine, 1 mcg/kg/min for 24 to 48 postoperative hours, is believed to be useful if spasm is suspected. Normalization of ST-segment abnormalities has been observed after initiation of this therapy29. Technical problems with



coronary anastomoses are treatable by exploration and revision if recognized early. If revision is unsuccessful or impossible, an internal thoracic artery–to– coronary artery graft can be applied31. Failure of an unprepared LV is more likely to occur in older infants with low preoperative LV pressure. Additional pharmacologic support is indicated, and delayed closure of the sternum with a synthetic membrane skin closure can be helpful32,33. Institution of mechanical circulatory support with ECMO may be lifesaving and help buy added time for ventricular recovery or retraining32.

Hemostasis The extensive anatomic dissection, long suture lines, and prolonged cardiopulmonary bypass (CPB) time for ASO predispose to signifi cant bleeding. The use of fresh heparinized blood for the CPB prime, as well as platelets and fresh frozen plasma after CPB, minimize the resultant coagulopathy. Most important are patience and perseverance on the part of the surgical team before chest closure. Even mild cardiac tamponade is tolerated poorly by newborns after open-heart surgical procedures. The criterion for re-exploration for bleeding is chest drainage exceeding 5 mL/kg/hr in the fi rst hour, 4 mL/kg/hr in the second, and so forth29. In practice, the need for re-exploration after ASO has been rare.

ArrhythmiasCardiac arrhythmias following ASO are infrequent34. The technically most challenging part of the operation is coronary transfer. Arrhythmias (predominantly ventricular), especially on weaning from CPB, frequently indicate coronary insuffi ciency; the coronary anastamosis should be promptly investigated before chest closure, as well as transesophageal assessment of left ventricular wall motion. Serial 12 lead ECGs are valuable in following postoperative ischemic changes.

Acute kidney injury and fl uid overloadIn general, children with congenital heart disease are at increased risk of acute kidney injury (AKI) after cardiac surgery. Several conditions increase vulnerability to this complication, including the acute infl ammatory response to cardiopulmonary bypass

and postoperative hemodynamic instability, ischemia or reperfusion injury, circulating endotoxins, postoperative hemolysis, sepsis complications and baseline renal disease35. General considerations about the treatment of postoperative AKI include correction or removal of the precipitating factor and management of volume status. However, when volume overload and oliguria or anuria supervenes, renal replacement therapy should be considered. In this setting, usually with positive fl uid balance more than 10% body weight, peritoneal dialysis (PD) has been advocated as the preferred technique because of preserved hemodynamic stability, no requirement for vascular access, simplicity, and low cost.Evidence suggests that proinfl ammatory cytokines such as interleukin (IL)-6 and IL-8 are concentrated in the peritoneal fl uid that commonly accumulates after CPB in newborns36. PD catheter drains this abdominal fl uid. Because even moderate hyperkalemia is a myocardial depressant in newborns, early institution of PD is advocated, which is greatly facilitated by intraoperative placement of a Tenckhoff catheter. Low-volume PD provides excellent metabolic support without the diuretic-related complications of metabolic alkalosis, hypokalemia, and nephrotoxicity. Volumes of 10 mL/kg in 2-4 hourly cycles are given to avoid the ventilatory complications of higher-volume dialysis. Isotonic (1.5%) or hypertonic (4.25%) dialysate is used, according to the patient’s fl uid status, serum potassium level, and temperature. Cold dialysate provides effi cient core cooling for postoperative fever.

Capillary leak syndrome Occasionally, CPB in newborns and small infants is associated with a profound capillary leak, massive edema, and increased IV fl uid requirements. These problems are exacerbated with higher bypass and crossclamp time, use of deep hypothermic circulatory arrest (DHCA), and in a patient with sepsis. Abdominal fl uid losses via the PD catheter (if it is used) are replaced with fresh frozen plasma or 5% albumin37. The capillary leak usually stabilizes after 24 to 36 hours, and the excess fl uid can be removed gradually titrating a loop diuretic (e.g. furosemide, metolazone) with 20% albumin and/ or by using hypertonic peritoneal dialysate37. Vasopressors like vasopressin



may be required to maintain adequate systemic arterial pressure in face of restricted volume that can be used29.

MiscellaneousPostoperative infections following surgery for congenital heart disease are fairly common, with incidence reported as 3.7% to 16% in different populations38,39. The rate of NI (nosocomial infections) is higher in patients under 1 year of age, after urgent surgery and urgent reoperation, long CPB and aortic cross-clamp time, also in patients with prolonged mechanical ventilation, massive haemotransfusion, and with delayed sternal closure. Low birth weight and malnutrition exacerbates the problem in developing countries. Adequate screening and treatment of preoperative sepsis is essential for reducing the incidence of postoperative sepsis. As the patients are in extreme stress in immediate postoperative period, high calorie and protein dense feeds are recommended, if patient can be fed enterally. In cases with aortic arch repair, enteral feeds must be delayed for atleast 48-72 hours as there is high incidence of mesenteric ischemia and necrotizing enterocolitis.Once the patient is hemodynamically stable with good urine output (2-4 ml/ kg/ hour) weaning from mechanical ventilation is attempted. Non invasive ventilation is often used following extubation especially in cases with LV dysfunction and those with pulmonary artery hypertension.

Results and sequelae of the arterial switch operationIn the Society of Thoracic Surgeons Congenital Heart Surgery Database, average discharge mortality from 2005–09 for ASO without VSD was 2.9%, and ASO with VSD was 7.0%40. Anatomic variants that may impact operative mortality include (a) an intramural course of a coronary artery, (b) a retropulmonary course of the left coronary artery, (c) multiple VSDs, (d) coexisting abnormalities of the aortic arch, and (e) straddling AV valves. Prolonged duration of global myocardial ischemic (cross-clamp) and circulatory arrest times are risk factors for operative mortality and prolonged hospital length of stay, as is the number of procedures done at a given institution8.

Supravalvular pulmonary stenosis is widely recognized as the most frequent short-term complication of arterial switch. The need for reintervention for supravalvular pulmonary stenosis ranges between 5% and 30%; most institutions report a decreasing incidence of this complication with increasing experience with the operation41,42,43. Supravalvular aortic stenosis is signifi cantly less common than supravalvular pulmonary stenosis. The status of the neoaortic (anatomic pulmonary) root and valve remains a subject of long-term concern. Multiple follow-up studies have described an enlarged neoaortic root and annulus following anatomic correction44,45. There is a surprisingly high incidence of neoaortic regurgitation (neoAR) following the arterial switch operation; however, in the overwhelming majority of cases, the degree of regurgitation is trivial to mild. This high prevalence of neoAR raises the important question of the adequacy of the anatomic pulmonary valve, normally with thin leafl ets and little collagen and elastic tissue when present in the low-pressure pulmonary circulation to support the high-pressure systemic circulation over a patient’s lifetime.The topic of late evaluation of myocardial perfusion has been extensively studied with several different modalities. Stenosis or occlusion of coronaries may occur in 3% to 7% of cases,occasionally asymptomatic, and the problem is more likely with specifi c coronary patterns46. The entire coronary tree may be abnormally small. Late sudden death can occur in patients with coronary abnormalities, but such events have fortunately been rare. Continued surveillance is in order for all TGA patients, at least noninvasively.Perhaps the most important measure of long-term outcome is the neurodevelopment of children after ASO. It has been evident that even with excellent surgical results and uncomplicated postoperative course, a signifi cant proportion of patient exhibit neurodevelopmental delays after ASO. In the Boston follow-up study, 65% of 16 year olds required special education services, and prevalence of low reading and mathematics achievement scores was 3-4 times greater than the general population47,48. Perioperative events associated with adverse longer term neurodevelopmental outcomes in the Boston cohort included prolonged deep hypothermic circulatory arrest



(DHCA) and clinical seizures. In more recent studies, intraoperative factors such as hemodilution on bypass to a hematocrit less than 24%, and low intraoperative regional cerebral oxygen saturation in the fi rst hour after separation from CPB are also associated with worse neurodevelopmental outcomes49,50. Brain immaturity and severe preoperative cyanosis have also been associated with neurological injury in the perioperative period for ASO patients51,52.

ConclusionsASO transforms a complex anomaly into a near-normal heart very early in life. Optimal perioperative critical care support is essential for good immediate and long term outcome. With declining mortality, the stress is now on improving the perioperative care of the cases with delayed presentation, undergoing arterial switch. Also a holistic postoperative follow up with periodic growth and neurodevelopment assessment, is imperative in ensuring early detection and management of concerns which could hamper quality of life.

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36. Bokesch PM, Kapural MB, Mossad EB, Cavaglia M, Appachi E, Drummond-Webb JJ, et al: Do peritoneal catheters remove proinfl ammatory cytokines after cardiopulmonary bypass in neonates? Ann Thorac Surg 2000; 70:639-643

37. Blendis L, Wong F. Intravenous albumin with diuretics:

protean lessons to be learnt? J Hepatol. 1999; 30:727-3038. Lomtadze M, Chkhaidze M, Mgeladze E, Metreveli I, Tsintsadze

A. Incidence and risk factors of nosocomial infections after cardiac surgery in Georgian population with congenital heart diseases. Georgian Med News. 2010; 178:7-11

39. Pasquali SK, He X, Jacobs ML, Hall M, Gaynor JW, Shah SS, et al. Hospital variation in postoperative infection and outcome after congenital heart surgery. Ann Thorac Surg. 2013; 96:657-63

40. Jacobs JP, O’Brien SM, Pasquali SK, Jacobs ML, Lacour-Gayet FG, Tchervenkov CI, et al. Variation in outcomes for benchmark operations: an analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. Ann Thorac Surg. 2011; 92: 2184-91

41. Turon-Viñas A, Riverola-de Veciana A, Moreno-Hernando J, Bartrons-Casas J, Prada-Martínez FH, Mayol-Gómez J, et al. Characteristics and outcomes of transposition of great arteries in the neonatal period. Rev Esp Cardiol (Engl Ed). 2014; 67:114-9

42. Scott WA, Fixler DE. Effect of center volume on outcome of ventricular septal defect closure and arterial switch operation. Am J Cardiol 2001; 88:1259-63

43. Losay J, Touchot A, Serraf A, Litvinova A, Lambert V, Piot JD, et al. Late outcome after arterial switch operation for transposition of the great arteries. Circulation 2001; 104:I121-26

44. Marino BS, Wernovsky G, McElhinney DB, Jawad A, Kreb DL, Mantel SF, et al. Neo-aortic valvar function after the arterial switch. Cardiol Young 2006; 16: 481-89

45. Losay J, Touchot A, Capderou A, Piot JD, Belli E, Planché C, et al. Aortic valve regurgitation after arterial switch operation for transposition of the great arteries: Incidence, risk factors, and outcome. J Am Coll Cardiol 2006; 47:2057-62

46. Angeli E, Formigari R, Pace Napoleone C, Oppido G, Ragni L, Picchio FM, et al. Long-term coronary artery outcome after arterial switch operation for transposition of the great arteries. Eur J Cardiothorac Surg. 2010; 38:714-20

47. Wypij D, Newburger JW, Rappaport LA, duPlessis AJ, Jonas RA, Wernovsky G, et al. The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg. 2003; 126:1397-403

48. Bellinger DC, Wypij D, Rivkin MJ, DeMaso DR, Robertson RL Jr, Dunbar-Masterson C, et al. Adolescents with d-transposition of the great arteries corrected with the arterial switch procedure: neuropsychological assessment and structural brain imaging. Circulation. 2011; 124:1361-9

49. Wypij D, Jonas RA, Bellinger DC, Del Nido PJ, Mayer JE Jr, Bacha EA, et al. The effect of hematocrit during hypothermic cardiopulmonary bypass in infant heart surgery: results from the combined Boston hematocrit trials. J Thorac Cardiovasc Surg. 2008; 135:355-60

50. Kussman BD, Wypij D, Laussen PC, Soul JS, Bellinger DC, DiNardo JA, et al. Relationship of intraoperative cerebral oxygen saturation to neurodevelopmental outcome and brain magnetic resonance imaging at 1 year of age in infants undergoing biventricular repair. Circulation. 2010; 122:245-54



51. Petit CJ, Rome JJ, Wernovsky G, Mason SE, Shera DM, Nicolson SC, et al. Preoperative brain injury in transposition of the great arteries is associated with oxygenation and time to surgery, not balloon atrial septostomy. Circulation. 2009; 119:709-16

52. Andropoulos DB, Hunter JV, Nelson DP, Stayer SA, Stark AR, McKenzie ED, et al. Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-fl ow bypass and cerebral oxygenation monitoring. J Thorac Cardiovasc Surg. 2010; 139:543-56



Univentricular Heart – Perioperative management strategy*Vishal K Singh, DCH, MD, DNB(Pediatrics), **Amit Varma, MBBS, AB Internal Medicine (Critical Care Medicine Perinatal and

Neonatal), *** Rajesh Sharma, MS, MCH (Cardiothoracic Surgery)*Senior Consultant, **Pediatric Critical Care **Director Critical Care, ***Director & Head Pediatric Cardiac Surgery,

Fortis Escorts Heart Institute, Okhla Road, New Delhi

Correspondence:Dr. Vishal K SinghSenior Consultant Pediatric Critical Care MedicineFortis Escorts Heart Institute, Okhla Road, New Delhi-110025.Mb: +919971000328; Fax: +911126825048Email: [email protected]

ManuscriptUniventricular heart (UVH) is a term used to describe a wide range of structural cardiac anomalies, with a functional single ventricular chamber1.Van Praagh et al defi ne UVH as one ventricular chamber that receives both tricuspid and mitral valves or a common atrioventricular (AV)valve2

Anderson et al suggested that the entire atrio ventricular junction is connected to one ventricular mass, thus including hearts with tricuspid or mitral atresia, which are excluded in Van Praagh’s defi nition. As a consensus the STS-Congenital Heart Surgery and the European study group database proposed that nomenclature of UVH should include double inlet left and right ventricles, absence of one AV connection, common AV valves, and hearts with only one well developed ventricle as unbalanced AV canal and complex conditions such as heterotaxy syndromes.

This nomenclature excludes Hypoplastic left heart syndrome (HLHS), pulmonary atresia with intact ventricular septum and certain other biventricular hearts which undergo stages of univentricular palliation.

Table 1: Diagnostic Terms for Patients with Functionally Univentricular Hearts1. Single ventricle, DILV2. Single ventricle, DIRV3. Single ventricle, Mitral atresia4. Single ventricle, Tricuspid atresia5. Single ventricle, Unbalanced AV canal6. Single ventricle, Heterotaxia syndrome7. Single ventricle, other8. Single ventricle + TAPVC9. HLHS10. Aortic valve atresia

Abbreviations: AV, atrioventricular; DILV, double inlet left ventricle; DIRV, double inlet right ventricle; HLHS, hypoplastic left heart syndrome; TAPVC, total anomalous pulmonary venous connection.

The physiology of UVH in a neonate depends upon certain key anatomical factors3. These are 1) Obstruction to systemic or pulmonary outfl ows

AbstractThe term univentricular heart encompasses a wide variety of heart defects that functionally and physiologically, constitute a single ventricle chamber. The disease variants comprising this spectrum are not amenable to biventricular repair, and require staged palliation culminating in cavopulmonary connection. Broadly, the management hinges on controlling pulmonary blood fl ow in early infancy, by means of aortopulmonary shunting in pulmonary atresia or stenosis or pulmonary artery banding for excess pulmonary blood fl ow situations. Concomitant repair of associated anomalies, requires addressal. Neonates and early infancy patients with hypoplastic left heart syndrome(HLHS), undergo staged Norwood procedure, resulting in eventual total cavo pulmonary connection with the right ventricle as the functional systemic chamber. The current review focuses on basics of univentricular physiology, periooperative management and with a brief discussion on the current guidelines for medical managementKey words: Univentricular Heart, Fontan and Bidirectional glenn, Norwood


2) Obstruction to ventricular infl ow and atrial septum, with abnormal systemic or pulmonary venous return

3) Amount of pulmonary blood fl ow and pulmonary vascular resistance

4) AV valve regurgitation

Obstruction to systemic outfl owWhen there is severe obstruction to the systemic outfl ow (HLHS and its variants, UVH with severe aortic valve or arch obstruction, the neonate is duct dependent on the ductus arteriosus for systemic circulation. If the condition is diagnosed antenatally, the baby should be delivered in a tertiary care facility, capable of neonatal cardiac interventions,and prostaglandin E2 (PGE2) is started immediately to ensure ductal patency. If undiagnosed previously, these infants often have a catastrophic presentation, with severe acidosis and shock, following ductal closure. Occasionally these babies can present late, and hence it is essential that a four limb pulse oximetry screening before discharge is a norm. This alongwith four limb BP, would help expedite the diagnosis and allow intervention before clinical deterioration sets in. Since, physiologically there is complete mixing at atrial and ventricular level, with the entire output ejected in pulmonary artery, the balance of systemic vascular resistance(SVR) and pulmonary vascular resistance (PVR ) is crucial to systemic cardiac output.

Obstruction to pulmonary outfl owUVH with critical pulmonary outfl ow obstruction (pulmonary atresia) is an important ductal dependent neonatal congenital heart disease. If associated with heterotaxy syndromes, this is associated with abnormalities in systemic and pulmonary venous return, along with other systemic anomalies. The babies in this spectrum, present usually with increasing cyanosis associated with ductal closure and hence pulse oximetry screening before discharge is important. Once ductus is opened using PGE2, the balance between SVR and PVR determines the pulmonary blood fl ow in parallel circulation

Obstruction to systemic and pulmonary venous return or ventricular infl owsPulmonary venous obstruction, as a component of UVH results in severe pulmonary hypertension, due to back pressure changes in pulmonary capillary bed, and requires early correction4. Similarly, severe mitral and tricuspid stenosis or atresia, as component of UVH, present with pulmonary venous hypertension and back pressure systemic venous congestion. An unrestricted Atrial septal defect (ASD) is essential to maintain systemic output and oxygen saturation and prevent systemic or pulmonary venous congestion. If restrictive it needs to be widened either by balloon septostomy in cases with severe cyanosis and pulmonary venous congestion before surgery, especially in a critically ill infant with metabolic compromise or by surgical septectomy during fi rst stage of repair.

Clinical featuresClinical manifestations hinge on the presence or absence of pulmonary outfl ow obstruction. Without pulmonary stenosis, infants with low pulmonary vascular resistance present with signs and symptoms suggestive of large left to right shunt, congestive heart failure and failure to thrive with cyanosis apparent only on excessive crying5. Aortic outfl ow obstruction may compound already excessive pulmonary blood fl ow and worsen congestive heart failure. Some patients may have a favourable streaming pattern which limits cyanosis (eg: DILV with L-looped ventricles), but severe cyanosis is observed in a subset of patients due to poor streaming of oxygenated blood in the systemic circulation (eg: right side subaortic hypoplastic right ventricle, straddling AV valve, with TGA like physiology).6

In the setting of univentricular heart, a certain degree of pulmonary stenosis is physiologically desirable to prevent pulmonary overcirculation. Severe Pulmonary stenosis or atresia present with profound hypoxemia and cyanosis.

Diagnostic evaluationElectrocardiogramGiven the heterogenecity of the univentricular heart,

Univentricular Heart – Perioperative management strategyPEDIATRIC CARDIAC INTENSIVE CARE - 2


the ECG appearance is quite variable. Patients with right atrial isomerism, often have two separate sinus nodes, with a P-wave axis that fl uctuates with the prevailing pacemaker. In contrast most hearts with left atrial isomerism, do not have a histologically recognizable sinus node, with consonant slow atrial or junctional escape rates7. The AV conduction system may be displaced, particularly in hearts with AV discordance and AV canal defects. In L-looped single ventricle scenarios, the elongated course of the common bundle renders it susceptible to common AV block. With D-looped ventricles, and a well formed right ventricle the AV node is normally positioned.8

In tricuspid atresia, the PR interval is usually normal with tall and broad P –waves and a characteristic left axis deviation. In the absence of a functional right ventricle, left ventricular forces are unopposed, with small R waves and deep S waves in the right precordial leads and tall R waves in left precordial leads. In the most common subtype of DILV, AV conduction is often abnormal. Besides Q waves may be seen in right precordial leads, and leads II, III and avf.

Radiological featuresThe chest x ray is particularly helpful in assessment of pulmonary arterial vascularisation and confi guration of the great arteries. Because pulmonary stenosis is less common with single left ventricles, increased pulmonary arterial vascularisation evokes this diagnosis5. An enlarged cardiac silhouette refl ects volume overload. Dilation of the main and right pulmonary artery may produce a prominent right upper heart border described as ‘waterfall appearance’. In DILV, the ascending aorta shadow is modifi ed by the position of the rudimentary right ventricle. When located anterior and leftward,a prominent left heart border is visualized, but if its right sided, the aortic silhouette is convex to the right . In patients with moderate to severe pulmonary stenosis, common in univentricular hearts with right ventricular morphology, pulmonary arterial vascularisation may be normal or oligemic. With pulmonary atresia, systemic to pulmonary artery shunting may result in asymmetric vascularisation patterns.9

Non invasive imagingThe diagnosis and morphological subtype may be fully delineated with a systematic and thorough echocardiographic appraisal, with particular attention to apical position, atrial situs, AV relationship and ventricular –arterial alignment. In DILV, there are usually two separate patent AV valves, but either may be imperforate, stenotic or regurgitant. Either valve may straddle the bulboventricular foramen. A common AV valve with a 5- leafl et confi guration is commonly found in univentricular hearts with atrial isomerism. In commonest variant of DILV, the rudimentary right ventricular chamber gives rise to the aorta and well formed left ventricle to the pulmonary artery. Left ventricular morphology is usually inferred, when the aorta emanates from an anterosuperior rudimentary chamber. A univentricular heart with a well formed right ventricle can often be surmised to exist on the basis of typical right ventricle morphological features. Comprehensive hemodynamic assessment should include color fl ow imaging and Doppler analysis. An estimate of AV valve stenosis or leak should supplement the status of the AV connection. A restrictive bulboventricular foramen may likewise be assessed by continuous wave Doppler imaging. Cardiac Magnetic resonance imaging (MRI) is a value supplement to echocardiography for demonstrating systemic and pulmonary venous anomalies, aortic arch malformations and proximal pulmonary artery lesions, besides systemic -pulmonary collaterals.10 It also provides important insights in the post operative assessment of patients with univentricular physiology.

Cardiac catheterizationA cardiac catheterization study for univentricular hearts aims at assessment of hemodynamics, systemic and pulmonary venous anatomy, AV and ventriculo arterial connections, ventricular morphology and function, pulmonary vascular resistance (PVR), aortic arch integrity, and systemic-pulmonary collaterals. Patients with univentricular hearts characteristically have a complete mixing of systemic and pulmonary venous blood at ventricular level. If one assumes a pulmonary venous oxygen saturation of 96% and normal systemic blood fl ow,



the arterial oxygen saturation refl ects total pulmonary blood fl ow. As a thumb rule values ≥ 85% and ≤ 75% signify increased and decreased pulmonary blood fl ow respectively.11

Table 2: Calculation of QP :QS in Univentricular physiology

O2 saturation Sao2 / Svo2

Spvo2 / Spao2

Qp /Qs Qp : Qs

75 % 75/50 100/75 25/25 185% 85/60 100/85 25/15 1.795% 95/70 100/95 25/5 5

*Spvo2 values used assume normal oxygen consumption and extraction. In practice, the actual values of Spvo2 obtained from the SVC should be used. QP = pulmonary blood fl ow, QS = systemic blood fl ow, Sao2 = aortic saturation, Svo2 = mixed venous saturation, Spvo2 = pulmonary venous saturation, Spao2 = pulmonary artery saturation

The presence or absence of hemodynamic and anatomic abnormalities such as poor ventricular function, aortic coarctation, pulmonary artery distortion, increased PVR, and abnormal collaterals which may require coil embolisation are relevant to the management plans. After initial palliation, the patients not suitable for Fontan completion, may require repeat catheterization studies to evaluate PVR and magnitude of created shunts, and address complications such as shunt stenosis, pulmonary artery stenosis, and pulmonary arteriovenous (AV) fi stulae.12

ManagementAn ideal patient with UVH, should have good ventricular function, unobstructed venous return, unrestrictive ASD and optimal pulmonary blood fl ow. The single most important principle in UV circulation is that systemic and pulmonary circulation balance each other and the critical balance is maintained by the ratio of respective resistance. The goal of initial surgical palliation is to provide unobstructed systemic outfl ow, restricted pulmonary blood fl ow to maintain normal pulmonary pressures and unobstructed systemic and pulmonary and venous return to the heartIn patients with severe pulmonary obstruction or atresia, the pulmonary blood fl ow is restored with a aortopulmonary shunt such as modifi ed Blalock –Taussig (BT) shunt or bidirectional cavopulmonary anastomosis (Superior Vena Cava(SVC) –Pulmonary

artery(PA))Glenn shunt. If a pulmonary circulation is solely dependent on aortopulmonary collaterals, the patient may require unifocalization of collaterals as a component of staged surgical approach.13 As a staged procedure, all the patients with aortopulmonary shunt, usually undergo a Bidirectional Glenn shunt (BDG)preferably in late infancy, after a cardiac catheterization study to evaluate the pulmonary pressure and anatomy of the pulmonary arteries, and to occlude aortopulmonary collaterals, that may complicate the post BDG course. Careful evaluation of the systemic venous anatomy is imperative, especially for the presence of a left sided superior vena cava (LSVC) or a levo-atrio-cardinal vein and its communication with the right SVC. If detected it is closed at the time of surgery. In presence of LSVC, the patient undergoes a bilateral, bidirectional Glenn procedure (LSVC-LPA, RSVC-RPA). There is a lot of variable opinion regarding whether to leave a little forward fl ow through the pulmonary valve creating a ‘pulsatile’ Glenn.14 Proponents argue that the pulsatility encourages normal growth of the pulmonary tree, wheras the opponents suggest that the competing pulmonary fl ow, hampers smooth SVC fl ow to branch pulmonary arteries. It is imperative to address the restrictive atrial communication in DILV situations, mitral or tricuspid atresia, to enable adequate mixing and optimise preload preventing retrograde congestion.The fi nal stage of conversion to series circulation involves total cavopulmonary connection(TCPC) or Fontan procedure. This is ideally performed between 18 months of age to 4 years. The Choussat criteria for successful Fontan completion has stood the test of time and has been revisited and revised to the current scenario.15

Choussat original criteria proposed for fontan completion1. Age ≥ 4yrs to≤15 years2. Normal Sinus rhythm3. Normal right atrial volume 4. Mean Pulmonary artery pressure ≤15 mm Hg5. Pulmonary arteriolar resistance ≤4 Wood units /

m2 body surface area6. Pulmonary artery to aortic diameter ratio≥0.757. Left ventricular ejection fraction ≥0.60



8. Competent Mitral valve9. Absence of pulmonary artery distortionDespite revisions, the criteria refl ect that after repair the left atrial pressure should be low (determined by good ventricular function) and the transpulmonary gradient (SVC (surrogate of PA pressure)-LA pressure) must be low (determined by the pulmonary vasculature).Current cardiac criteria for successful fontan circulation are:1. Unobstructed ventricular infl ow (No AV valve

stenosis or regurgitation)2. A reasonable ventricular function with basal end

diastolic pressure ≤ 12mm hg3. Unobstructed systemic outfl ow (no subaortic

obstruction, no coarctation, no arterial hypertension). The Pulmonary component includes:

4. A non restrictive communication between the systemic veins and the pulmonary arteries (unobstructed Fontan circuit),

5. Good sized pulmonary arteries without distortion (at repair and later during growth),

6. A well developed distal vascular bed, 7. Pulmonary vascular resistance ≤ 4 wood units/m2,

with estimated mean PA pressures ≤ 12-15mm hg, 8. Unobstructed pulmonary venous return.As a norm, cardiac catheterization is usually performed in most centers before Fontan completion to evaluate pulmonary artery pressures, and resistance, to occlude aortopulmonary or systemic venous collaterals and evaluate ventricular function and end diastolic pressures. TCPC can be performed using either a extra cardiac conduit between the IVC and PA or an intracardiac baffl e. Due to the reduced incidence of new onset arrhythmias, the extracardiac Fontan is the preferred technique in most centers.15A fenestration is usually placed in between the conduit and the atrium as a “pop-off” mechanism especially during the immediate post operative period, when the pulmonary artery (PA) pressures may be temporarily elevated, following CPB induced lung injury. This reduces the incidence and duration of effusions, protein losing enteropathy, related to high venous pressures and early Fontan failure.17 The patient may saturate ≤ 90 % due to right to left shunting across the fenestration. The fenestrations can be closed

using transcatheter techniques, months to years later, once the systemic venous pressures are in acceptable range demonstrated by cardiac catheterization.Patients with unrestricted pulmonary as well as systemic blood fl ow require initial palliation by means of either PA banding, or PA disconnection with creation of an aortopulmonary shunt to limit pulmonary blood fl ow and achieve normal pulmonary artery pressures.18 Pulmonary artery band may lead to development of a subaortic narrowing or restrictive bulboventricular foramen, especially in the DILV physiology, which may require to be corrected in the second stage surgical intervention. The adequacy of PA band in restricting pulmonary circulation and normalising PA pressure is inconsistent and it has been suggested that patients with mean PA pressures more than 25 mm hg and resistance higher than 4 wood units are poor candidates for TCPC, and PA banding is the fi nal palliation in such patients.19 If signifi cant subaortic obstruction observed primarily or due to PA band in a DILV physiology, an aortopulmonary window with endoluminal distal PA banding should be performed early to prevent ventricular hypertrophy and protect pulmonary vasculature. Palliative arterial switch for DILV, is emerging as a better modality to control pulmonary blood fl ow and normalising PA pressures,and also ensuring that LV supports the systemic circulation.20-21

Figure 1: Illustration of Classic Norwood.



Systemic outfl ow obstruction associated with UVH usually necessitate “Norwood Procedure” or its variations. The Norwood repair involves conversion of the pulmonary artery into a ‘neo aorta’. The small native ascending aorta is anastomosed to the ‘neo aorta’ and serves to carry blood retrograde to the coronary arteries. The aortic arch is augmented and then connected to the ‘neo aorta’. The branch pulmonary arteries are transected and connected to the systemic circulation by means of a Goretex aortopulmonary shunt in classic Norwood procedure. The smallest shunt size adequate to supply just enough pulmonary blood fl ow and maintain saturation between 75 -85% is desirable. In the last decade Sano et al suggested a modifi cation where in the aorto pulmonary shunt is replaced by a RV-PA conduit.22 This holds an advantage, in improving post operative hemodynamics as it avoids diastolic run off, observed with aorto pulmonary shunts, resulting in compromised coronary blood fl ow, ventricular dysfunction and death. The rate of composite “serious adverse events (death, acute shunt failure, cardiac arrest, extracorporeal membrane oxygenation (ECMO) or necrotizing colitis (NEC) is reported to be signifi cantly lower with the RV-PA conduit group.23

A hybrid approach , involving creation of the neo aortic arch with stenting of the ductus and a septostomy or atrial stent to widen the atrial communication, with banding of branch pulmonary arteries is performed in a few centers to achieve the same goals .Since it avoids cardiopulmonary bypass and deep hypothermic circulatory arrest, it is advocated for high surgical risk babies, with ventricular dysfunction, late presenters with cardiogenic shock with severe metabolic acidosis and in patients with extremely diminutive ascending aorta.The second stage of the Norwood procedure, namely a Bidirectional Glenn procedure is governed by the same principles as described above. Though the second phase becomes complex in case the fi rst intervention is a hybrid cath procedure., as it involves extensive aortic and pulmonary artery reconstruction, with removal of ductal and/or atrial stent. The fi nal stage of Norwood procedure is the TCPC with resultant separation of the systemic and pulmonary circulation. It must be noted that the long

term outlook for a morphological single left ventricle is better than a single ventricle of RV morphology

Preoperative stabilisation and postoperative managementUniventricular physiology and decreased pulmonary blood fl owA subset of patients with duct dependent pulmonary blood fl ow can present in the neonatal period with signifi cant desaturation due to closing ductus, metabolic acidosis and myocardial dysfunction with signs of cardiogenic shock. Besides the immediate stabilisation, involving PGE1 infusion to keep ductus patent at 0.05 to 0.1 microgram/kg/min, correction of metabolic acidosis, establishing mechanical ventilation and titrating Fi02 to a oxygen saturation > 60-65%, fl uids and inotropic supports with vasopressors for cardiogenic shock, it is also important to assess if the atrial septal defect is restrictive. This may result in poor mixing and compromise systemic cardiac output as in tricuspid atresia and occasionally warrant a balloon atrial septostomy (BAS) if the child is extremely sick.In relatively stable patients a open heart atrial septectomy is done with aortopulmonary shunt Post aortic-pulmonary artery shunt, it is essential to maintain an adequate shunt fl ow and systemic blood pressure (SBP), with fl uids titrated to fi lling pressures and inotropic supports. Besides anticoagulation is initially maintained with heparin with target ACT ≤ 180-200, and later with aspirin at 5mg/kg/day. It is essential to document a functional shunt clinically and with non invasive 2D Echo study with Doppler. In the neonatal period and early infancy, Occasionally with a larger shunt, one may observe a signifi cant diastolic run off, with impaired coronary perfusion with increased preload to LV and pulmonary congestion with increased vascularity. The diagnosis of Shunt Overfl ow is based on the wide pulse pressure, clinical features of congestive heart failure and the xray revealing increased vascularity. A 2D echocardiography with color Doppler confi rms the diagnosis with a dilated LA and LV, with unrestricted shunt fl ow. The management involves reduction in FiO2 to ↑ PVR and restrict shunt fl ow, systemic afterload reduction to improve systemic output (inodilators like



dobutamine, milrinone recommended) and moderate diuresis. Clipping of the shunt should be considered only if the optimal medical management fails, and the patient is symptomatic and fails to be weaned off ventilation. It is imperative that even after extubation, the patients with shunt overfl ow are maintained in room air, accepting saturation between 75-85%.A neonate with duct dependent systemic blood fl ow can present with catastrophic cardiogenic shock and impaired perfusion, especially if not diagnosed antenatally, and delivered in a competent facility.The priority in cardiopulmonary resuscitation is to maintain ductal patency with PGE2 infusion , besides titrating the Qp:Qs ratio to improve systemic cardiac output with mechanical ventilation, strategies to augment PVR, augmentation of CO with inotropes and decrease SVR before early surgical intervention. Though if the neonate is clinically well surgery is planned in the late fi rst week with a declining PVR. The focus in post operative management is to lower systemic vascular resistance, which improves stroke volume, Qs and Qp, with a marked increase in systemic DO224 bronicki et al. After the Norwood procedure, an early2D echocardiography should be performed, intraoperatively to assess for the adequacy of repair, in particular arch assessment for any signifi cant gradient, adequacy of pulmonary venous return, myocardial contractility and AV valve regurgitation. The neonates and infants are usually shifted out with open sternum, and with initial inodilator therapy involving dobutamine at 5-7.5mcg/kg/min or milrinone at 0.5-0.7 mcg/kg/min with adrenaline 0.05-0.1mcg/kg/min. In case the patient lapses into refractory low cardiac output state(LCOS) he may require pressors temporarily, intravenous steroids and T3 where available, with extracorporeal membrane oxygenation (ECMO) for mechanical support as a standby. Occasionally the patients may require therapeutic hypothermia to tide over LCOS, to curtail the metabolic demands. It is important to ventilate with a target to achieve a mixed venous oxygen saturation(MVO2) monitored by near infra red spectroscopy between 50-55%. One should guard against hyperventilation, and titrate Fio2 to maintain saturation between 75-85%.It is important to prevent acute fl uctuations in PVR and hence it is essential to keep the child calm with opoid

infusion with neuromuscular blockade intermittently, especially before airway suction and interventions to avoid agitation. If the patient desaturates one should revert to gentle manual ventilation temporarily, while the shunt functioning is confi rmed, and assess that the patient has no acute stimuli precipitating the event.The patient if stabilised with no signifi cant third spacing and reasonably good urine output 1-3ml/kg/hour, with good myocardial recovery and normal lactate and MVO2, is considered for chest closure after 48-72 hours. It is important to keep a watch for desaturation due to shunt compression, which may require chest reopening. Also it is essential to go up on the delivered tidal volume marginally to ensure adequate chest expansion, as chest compliance is reduced after sternal closure. The patients are initially receiving the basic surgical antimicrobial prophylaxis, but a high index of suspicion for evolving sepsis is imperative and one should closely watch for acute hemodynamic instability, worsening gas exchange with parenchymal changes in x ray, worsening thrombocytopenia, abdominal distension, metabolic issues like hypoglycemia or hyperglycemia with elevated serum lactate, as indicators of sepsis. The patient will require thorough investigation with biomarkers and cultures and antibiotics upgraded based on the local fl ora with sensitivity patterns. The patient is not fed enterally for the initial 72-96 hours, and trophic feeds are initiated only once the patient is consistently hemodynamically stable with no abdominal distension or hemorrhagic gastric aspirate. Early use of TPN with complete asepsis precautions is relevant to the Norwood physiology. But once the patient is consistently stable after chest closure, enteral feeding should be started and gradually built up.Once the patient is stable hemodynamically post chest closure with a good urine output, gradual ventilator weaning is attempted. Post extubation, these cases require non invasive continuous positive airway pressure (CPAP) support to prevent atelectasis, often in view of airway issues subsequent to prolonged ventilation. They also require nasogastric feeds (NG) for an extended duration due to impaired suck-swallow coordination,and demand prokinetics and antirefl ux measures and micronutrients to ensure high calorie and protein



feeds in the recuperation phase.

Post operative care of the bidirectional Glenn Shunt (BDG)

Figure 2: Illustration of Bidirectional Glenn (BDG)

The Bidirectional Glenn shunt involves anastomosis of the cardiac end of the superior vena cava to the right pulmonary artery, but maintains the confl uence of pulmonary arteries.26 The Bidirectional glenn shunt provides effective pulmonary blood fl ow and unlike a aortopulmonary shunt does not increase the ventricle volume load. It is a preferred procedure for infants with a primary presentation in late infancy with UVH with decreased pulmonary blood fl ow, if the pulmonary arteries are not severely hypoplastic. In patients with interrupted inferior vena cava, a BDG constitutes the fi nal palliation (Kawashima procedure). In a post Norwood scenario, this also involves the removal of the aortopulmonary shunt or the RV-PA conduit. The aim of this procedure is selective unloading of the single functioning ventricle and augment pulmonary blood fl ow with improvement in oxygen saturation. A lot of centers across the world, except for in a post Norwood scenario, have started practising the Glenn shunt as a off –CPB procedure. Intraoperative and post operative Near infra red spectroscopy (NIRS) to estimate Cerebral mixed venous oxygen saturation (range-50-60%) is practised in advanced centers, to ensure that cerebral perfusion is not compromised during procedure. Early or on table extubation is the norm after BDG as the Glenn shunt fl ow is promoted in absence of positive pressure ventilation. The patient is nursed at a 45degree head up position to augment SVC fl ow with gravity. The patient is rarely on any inotropic support unless systemic hypotension is reported unresponsive to volume augmentation. The primary challenge is hypoxemia in a few cases due to pulmonary venous admixture, systemic venous collaterals, pulmonary arteriovenous malformations or inadequate Qp or scenarios with borderline elevated PVR. It is advisable to maintain permissive hypercapnia (PaCo2 ≥ 45mm hg) as it augments cerebral blood fl ow, by decoupling it with cerebral metabolism and improves SVC fl ow, without affecting PVR adversely and decreased systemic vascular resistance with improved DO2.27 Once the infant is de escalated the patient is maintained on aspirin (5mg/kg/day) and mild diuresis.

Post operative care after Fontan procedure


Table 3: Manipulation of Hemodynamics in the Post Operative Norwood Patient25

↓SVRAvoid anxiety, shiveringMilrinone NitroprussidePhenoxybenzamine

↑ SVR

Systemic vasoconstrictorsVasopressin epinephrine (≥0.1mcg/kg/min), nor epinephrine, phenylephrineComment-generally required temporarily to counter aggressive systemic vasodilatation, especially vasopressin to counter phenoxybenzamine (irreversible α blocker but does not affect V1 receptors).

↑PVR

↓FiO2

Increase PEEP above FRCInduce respiratory acidosis (controlled hypoventilation, increased dead space, but avoid hypoxia as it may lead to ↓DO2, if systemic output not suffi cientHypothermiaHematocrit≥45%

↓PVR

Increase FiO2Induce respiratory alkalosisAdministration of Nitric OxideSedation, paralysisOptimize lung recruitment

↑CO

Restoration of AV synchrony through pacingDecrease VO2-through sedation, paralysis, avoid hyperthermia Optimize positive pressure ventilation (↓systemic afterload) without excessive PEEP or mean airway pressureAdequate preloadA balanced usage of inotropes and inodilators


Figure 3: Illustration of Extra Cardiac Fontan

The basic principles of post operative care for Fontan procedure hinge around:1. Adequate central venous fi lling pressure to counter

LCOS due to inadequate ventricular preload2. Intravascular volume repletion with a balance

of crystalloids and colloids. Keep Hematocrit around 35-40, and a bit higher for the deeply polycythemic patient substrate. Titrate volume to a SVC pressure of approx 13-15 mm hg

3. The Fontan position (head up 45 degress, and the leg end up with knees bent to facilitate venous return)

4. If the patient is having signifi cant post operative drainage, the blood products have to be supplemented to counter the loss, and one may require to repeat protamine dosing. In a deeply polycythemic patient, platelets will also need to be replaced. It is essential to maintain the heart rate in the physiological limits, as these patients do not tolerate tachycardia or arrhythmias well, and the hemodynamics suffer.

5. Vasopressors and inotropes should be used judiciously in Fontan patients for a brief duration, only if the LCOS is not improving with the routine measures, or sepsis is complicating the clinical behaviour.

6. Mixed venous oxygen saturation, serum lactate levels, metabolic acidosis and urine output are surrogate markers of a good myocardial function, confi rmed by post operative 2D echocardiography with color Doppler.

7. Positive pressure ventilation, is detrimental to Fontan physiology, as it decreases systemic venous

return, increases PVR, decreases ventricular fi lling.28

Hence early extubation is preferred, once the patient is observed to have stable hemodynamics with no signifi cant drainage.If brief duration of positive pressure ventilation is required due to hemodynamic instability or drainage, it is maintained with a SIMV rate 14-16/min,tidal volume 6-8ml/kg/ with PEEP 3-4 and Fio2 ≤0.6, to avoid over distension of alveoli, and avoid rapid changes in PVR. Inhaled nitric oxide with inodilators (milrinone or dobutamine) may be required, if high PVR is exacerbating LCOS.1. Once the patient is deintensifi ed, Tab Enalapril

to facilitate ↓systemic afterload and improved ventricular dynamics may be considered. The Pediatric Heart Network conducted a multicenter, double blind, placebo controlled trial involving 230 infants with single ventricle to receive enalaapril or placebo and followed up to 14 months of age. The analysis concluded that administration of enalapril does not improve somatic growth, ventricular function, or heart failure severity.29 In cases with borderline high PVR, Sildenafi l by virtue of its effect on reducing PVR, which is a critical determinant of pulmonary blood fl ow is also being evaluated.Tunks et al evaluated effect of sildenafi l exposure on hemodynamics in post fontan single ventricle palliation, and detected a signifi cant decrease in SVR and PVR, with improved cardiopulmonary dynamics.30

2. Normally these patients are on modest diuresis, but if evidence of high venous pressure, with persistent pleural drainage and ascites, the diuretics protocol needs to be revisited. A few cases may require metalozone besides the regular diuretics for a brief duration. It is imperative to keep a check on electrolytes when the diuretic dosing is altered.

3. Enteral nutrition is encouraged, though hypoalbunemia patients with increased third space drainage may require intermittent intravenous albumin supplements in the immediate post operative period. The goals of nutrition therapy is to provide atleast 100-125kcal/kg/day with 3



g/kg/day of protein intake. In case of chylous drainage, the saturated fats are restricted and replaced with medium chain triglycerides based diet. A few resistant cases may benefi t from short duration therapy with IV somatostatin analogues.

Complications and natural history of Fontan circulationCurrent data from the long term post operative evaluation of Fontan circulation patients continues to demonstrate satisfactory results. Most surviving patients report a subjective improvement in their quality of life and exercise tolerance. But a few cases fare less well with diminished exercise tolerance and ventricular dysfunction, due to inability to sustain preload. Conditional long term survival beyond 20 years of procedure is around 69-83%. The long term outcome is not only determined by the age of intervention and technique of Fontan procedure, but also by the morphology of single ventricle. The hemodynamic abnormalities, arrhythmias, plastic bronchitis and protein losing enteropathy result due to obstruction of caval or atriopulmonary connections, pulmonary artery distortion or hypoplasia, pulmonary vascular obstructive disease, pulmonary venous obstruction, myocardial dysfunction signifi cant AV valve regurgitation and residual left to right shunts with thrombembolic events.

ArrhythmiaAtrial arrhythmias,occur in about 45% of patients in a 10 year follow up, but over the last two decades, with extra cardiac Fontan procedure the reported incidence is on the decline. Elevated right atrial pressure with distension of atrial wall precipitates supraventricular tachycardia, requiring anti arrhythmics and occasional electrophysiology intervention like radiofrequency ablation. Intra atrial re-entrant tachycardia (IART)or ‘scar related atrial fl utter’, the most commonly encountered arrhythmia in Fontan substrate, is facilitated by extensive atrial fi brosis, suture lines, and /or anatomic features. Besides predisposing to LCOS, it also increases the propensity for thrombus formation. Older age, prior septectomy and sinus node dysfunction, are the risk factors for IART31

Sinus node dysfunction secondary to extensive suture lines around the sinus node with damaged vascular supply, may present with fatigue and exercise intolerance, or occasionally with tachybrady arrhythmia, requiring pacemaker.

ThromboembolismThrombosis in patients with Fontan circulation is due to multiple factors, including a low fl ow cavopulmonary circuit, with a hypercoagulable state,due to altered balance of procoagulant and anticoagulant factors with low levels of protein C., protein S, antithrombin III and factors II,V,VII, and X. Liver dysfunction, protein losing enteropathy and atrial arrhythmias are contributing risk factors32. The incidence of thrombo embolic events is maximum in the fi rst year and peaks again after 10 years. Anticoagulation strategy varies between platelet aggregation inhibitors (clopidogrel) with or without aspirin to anticoagulants like warfarin. Warfarin is defi nitely indicated in patients with documented thrombosis, poor hemodynamics and atrial arrhythmias.

Pleural effusionPleural effusions and extended pleural drainage still persist as the most important cause of extended hospital stay for Fontan patients. Besides infl ammatory response (post CPB), increased hydrostatic pressure in the circuit due to borderline high PVR or AV asynchrony and hormonal factors like aggravated renin- angiotensin axis play an important role in pathophysiology. Besides lower preoperative oxygen saturation, presence of post operative sepsis, smaller conduit size with ventricular diastolic dysfunction, may contribute to this dreaded scenario. Dietary modifi cations (high protein restricted fat (predominant medium chain triglycerides) with fl uid restriction and diuretics form the main stay of therapy. Somatostatin analogues (Octreotide at 10 mcg/kg/dose 8 hrly or as infusion)may be required. Chest tubes are removed once the drainage is less that 2ml/kg/day.

Protein losing enteropathyProtein losing enteropathy is characterised by excessive



loss of proteins from serum into the intestinal lumen, possibly due to the impedance to drainage of thoracic duct secondary to high SVC pressure associated with mesenteric vascular infl ammation. Manifestations include edema, immunodefi ciency, ascites, fat malabsorption, hypercoagulopathy, hypocalcemia and hypomagnesemia. Over a 10 year old follow up, its incidence is reported to be around 13%, with a 20% 10 yr survival after diagnosis..Treatment includes a low salt diet, high in calories and proteints (essential amino acids) and medium chain triglycerides. Diuretics, heparin and somatostatin analogues may provide temporary symptomatic relief.33

SepsisSepsis, gram negative predominantly and occasionally gram positive or fungal, is a grim reality in developing nations. Post Fontan procedure, besides post CPB immunosuppression, the associated complications exacerbating protein losses, further accentuate the risk. Concomitant presence of heterotaxy and splenic dysfunction compound the problem. Besides the immediate control of sepsis based on standard protocols, immunoprophylaxis counselling is imperative.

Plastic bronchitisPlastic Bronchitis (PB) can be a debilitating complication of Fontan procedure with airway casts(mucinous, acellular) being demonstrated either by expectoration or bronchoscopy. Early onset PB is associated with increased risk of death34 Schumacher et al. The predisposing risk factors are prolonged post operative chest tube drainage, chylous drainage, ascites and development of signifi cant aortopulmonary collaterals after Fontan. The pathophysiology is related to bronchial mucosa ischemic injury and increase in mediastinal lymphatic pressure. Bronchoscopy to relieve acute airway obstruction, with mucolytics like n-acetyl cysteine and inhaled Tissue plasminogen activator, dornase alpha are the therapeutic strategies to deal with this life threatening complication. The role of pulmonary vasodilators like sildenafi l and bosentan, which may improve fontan circulation, holds promise and is

currently being investigated. Thoracic duct ligation may be required in resistant case scenarios

Pulmonary edemaPulmonary edema or hemorrhage may be observed in a few cases with development of hemodynamically signifi cant aortopulmonary collaterals, which may require corrective measures during cardiac catheterization

Exercise performanceBesides reduced heart rate variability, elevated neurohumoral activity and abnormal cardiovascular response to exercise are well established variables in regular follow up of Fontan circulation patients. A maximal aerobic capacity after Fontan procedure is reported between 33% to 60% of normal. Peak oxygen uptake, peak heart rate and peak oxygen saturation all decline over a prolonged follow up.

Neurodevelopment With improved survival, neurodevelopmental assessment is a important tool, especially for neonatal interventions. With improvement in perfusion techniques, surgical expertise and post operative care, the neurological outcomes have improved in the last two decades. An increased incidence of attention defi cit /hyperactivity disorder in the HLHS substrate especially is reported, besides a variety of adaptive behaviour, fi ne motor skills and communication defi cits.

PregnancyWith improved survival, deranged ovarian function, with menstrual disorders and infertility are reported due to a combination of chronic hypoxia before intervention and chronic venous congestion after Fontan. If pregnancy ensues, the most common complications are premature labor and neonatal death. Hemodynamic changes observed in pregnancy are detrimental to women with Fontan physiology and 20% of pregnancies are complicated with arrhythmias. A multidisciplinary approach in a specialised unit is imperative for care of these patients.



Fontan FailureFontan failure is defi ned as any process leading to death, takedown of the Fontan or need for transplantation, with signs and symptoms of heart failure in the absence of ventricular systolic dysfunction. This is usually associated with symptoms of congestive hepatopathy, hepato renal and hepato pulmonary syndrome with cirrhotic cardiomyopathy, manifesting with low cardiac output symptoms with systolic heart failure, exercise intolerance, ascites, pleural effusion and edema. It is recommended to involve a hepatology consult annually for patients being followed up more than 15 years after Fontan, due to an increased risk of hepatocellular carcinoma and portal hypertension. It is also recommended if liver enzymes deranged for > six months, to evaluate for associated hepatic etiology. Makato Mori et al.33 ACE inhibitors may be of benefi t for children with low ejection fraction and beta blockers may benefi t by non selective reduction in portal hypertension. In a failing Fontan, a serum creatinine >2mg/dl has been associated with a hazard ratio of 8 for major outcomes like death or transplantationOrthotopic cardiac transplantation though has shown encouraging short term results, but the long term morbidity and mortality rates, have still not warranted consideration of cardiac transplantation as the primary surgical management for univentricular hearts.

Conclusion Management of Univentricular hearts continues to evolve, but it still poses a major challenge for the clinicians, with a myriad of issues which demand solutions periodically. Heart transplantation in developing nations, is not common place. Hence pre emption of expected complications with timely intervention and regular follow up with a multidisciplinary approach, is the key to ensure that a child with univentricular heart develops into an adult with a reasonably good quality of life.

References1. Anderson RH, Cook AC. Morphology of the functionally

univentricular heart. Cardiol Young 2004; 14 (Suppl.1): 3-122. Van Praagh R. Nomenclature and classifi cation: Morphologic

and segmental approach to diagnosis.In: Moller JH, Hoffman

JIE (eds). Pediatric Cardiovascular Medicine. New York, Churchill Livingstone 2000, pp275-288

3. Krishnan U. Univentricular Heart: Management Options. Indian Journal of Pediatrics,Volume 72 - June 2005, pp: 519-524

4. Ishiwata T, Kondo C, Nakanishit, Nakazawa M, Imai Y, Momma K. Non obstructive ASD creation to qualify patients for the Fontan operation: effects on pulmonary hypertension due to restrictive left atrioventricular valve and interatrial communication. Catheter Cardiovasc Interv 2002; 56(4): 528-532

5. Marin-Garcia J, Tandon R, Moller JH, Edwards JE.Common (single) ventricle with normally related great vessels. Circulation. 1974; 49: 565-73

6. Macartney FJ, Partridge JB, Scott 0, Deverall PB.Common or single ventricle: an angiocardiographic and hemodynamic study of 42 patients, Circulation. 1976; 53: 543-554

7. Momma k,Takao A, Shibata T. Characteristics and natural history of abnormal atrial rhythms in left isomerism. Am J Cardiol.1990; 65:231-36

8. Wilkinson JL, Dickinson D, Smith A, Anderson RH. Conducting tissues in univentricular heart of right ventricular type with double or common inlet. J Thorac Cardiovasc Surg.1979; 77:691-698

9. Elliott LP, Gedgaudas E. The roentgenologic fi ndings in common ventricle with transposition of the great vessels. Radiology.1964; 82:850-865

10. Festa P, Ait Ali L, Bernabei M, De Marchi D. The role of magnetic resonance imaging in the evaluation of the functionally single ventricle before and after conversion to the Fontan circulation.Cardiol Young 2005; 15(Suppl 3): 51-56

11. Lock JE,Keane JF, Fellows KE. The use of catheter intervention procedures for congenital heart disease. J Am Coll Cardiol.1986; 7:1420-1423

12. Khairy P, Poirier N, Mercier Lise-Andree.Univentricular Heart. Circulation.2007; 115: 800-812

13. Sullivan ID, Wren C, Stark J, De Leval MR, Macartney FJ, Deanfi eld JE. Surgical unifocalization in pulmonary atresia and ventricular septal defect: a realistic goal ? Circulation. 1988; 78(5 Pt 2); III5-III13

14. Caspi J, Pettitt TW, Ferguson TB Jr, Stopa AR, Sandhu SK. Effects of controlled antegrade pulmonary blood fl ow on cardiac function after bidirectional cavopulmonary anastomosis. Ann Thorac Surg 2003; 76(6):1917-1921; discussion 1921-2

15. Choussat A, Fontan F, Besse B, Vallot F, Chauve A, Bricaud H. Selection criteria for Fontan’s procedure. In: Anderson RH, Shinebourne EA, eds. Pediatric Cardiology. New York: Churchill Livingstone; 1978: 559-566

16. Nurnberg JH, Ovroutski S, Alexi -Meskishvili V, Ewert P, Hetzer R, Lange PE. New onset arrhythmias after the extracardiac conduit fontan operation compared with the intra atrial lateral tunnel procedure,early and mid term results. Ann Thorac Surg 2004; 78(6): 1979-1988

17. Lemler MS, Scott WA, Leonard SR,Stromberg D,Ramaciotti C. Fenestration improves clinical outcome of the fontan



procedure: a prospective randomized study. Circulation 2002; 105(2):207-212

18. Jensen RA Jr, Williams RG, Laks H, Drinkwater D, Kaplan S. Usefulness of banding of the pulmonary trunk with single ventricle physiology at risk of subaortic obstruction. Am J Cardiol 1996; 77(12): 1089-1093

19. Chowdhury UK, Airan B, Kothari SS, Sharma R, Subramaniam GK, Bhan A et al.Surgical outcome of staged univentricular –type repairs for patients with univentricular physiology and pulmonary hypertension. Indian Heart J 2004; 56(4): 320-327

20. Katewa A, Marwah A, Singh V, Sharma R. Palliative arterial switch operation in the context of multiple VSD, potentially univentricular and biventricular hearts with malposed great arteries. A review of 15 cases. World Journal of Pediatric and congenital heart surgery 2012; Vol (3): 295-300

21. Gil jaurena JM, Zabala JI, Albert DC, Castilo R, Gonzalez M, Miro L. Palliative arterial switch as fi rst line treatment before Fontan procedure in patients with single ventricle physiology and subaortic stenosis. Rev. Esp Cardiol 2013; 66(7): 553-555

22. Sano S, Ishino K, Kawada M, Honjo O. Right ventricle-pulmonary artery shunt in fi rst stage palliation of hypoplastic left heart syndrome. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2004; 7:22-31

23. Mair R,Tulzer G, Sames E, et al: Right ventricle to pulmonary artery conduit instead of modifi ed Blalock-Taussig shunt improves post operative hemodynamics in newborns after the Norwood operation. J Thorac Cardiovasc Surg 2003; 126: 1378-1384

24. Bronicki RA, Chang CA. Management of the post operative pediatric cardiac surgical patient. Crit Care Med 2011; 39(8): 1974-1984

25. Lowry AW. Resuscitation and perioperative management of the high risk single ventricle patient: First stage Palliation. Congenital Heart Disease 2012; 7(5): 466-478

26. Allen DH,Driscoll DJ,Shaddy RE,Feltes TF.Moss and Adams Heart disease in infants , children and adolescents, Edition 8; Vol.II: 1175-1194

27. Hoskote A,Li J, Hickey C, et al: The effects of carbon dioxide on oxygenation and systemic, cerebral and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis. J Am Coll Cardiol 2004; 44: 1501-1509

28. Chang AC, Hanley FL, Wernovsky G,Wessel Dl. Pediatric Cardiac Intensive Care.Chap 18.1998: 281-84

29. Hsu TD, Zak V, Mahony L, Sleeper LA, Atz AM, Levine CJ. Enalapril in infants with single ventricle. Results of a Multicenter Randomized Trial.Circulation. 2010; 122: 333-340

30. Tunks RD, Barker Piers CA, Benjamin KD Jr, Cohen –Wolkowiez M, Fleming GA, Laughon M. Sildenafi l exposure and hemodynamic effect after fontan surgery. Pediatr Crit Care Med 2014; 15: 28-34

31. Stephenson EA, Lu M, Berul CI, et al. Arrhythmias in a contemporary Fontan cohort: Prevalence and clinical associations in a multicenter cross-sectional study. J Am Coll Cardiol. 2010; 56: 890-896.

32. Odegard KC, Zurakowski D, Di Nardo JA, et al. Prospective longitudinal study of coagulation profi les in children wit hypoplastic left heart syndrome from stage 1 through Fontan completion. J Thorac Cardiovasc Surg. 2009; 137: 934-941.

33. Nayak S, Booker PD. The Fontan Circulation. Contin Edu Anaesth Crit Care Pain (2008) 8 (1): 26-30

34. Schumacher KR, Singh TP, Kuebler J, Aprile K, O’ Brien M, Blume ED. Risk factors and outcome of Fontan- Associated Plastic bronchitis: A case control study. J Am Heart Assoc. 2014; 3:1-6

35. Mori M, Aguirre JA, Elder RW, Kashkouli A, Farris AB, Ford RM, et al. Beyond a Broken Heart: Circulatory dysfunction in the Failing Fontan. Pediatr Cardiol 2014; 35: 569-579.



Pediatric Mechanical Circulatory SupportMichael A. Maymi, CPNP-AC*, Dipankar Gupta, M.D.**, Wendy E. Barras, CPNP-AC***, Joseph Philip, M.D.****,

Frederick Jay Fricker, M.D.*****, Mark S Bleiweis, M.D.******, Jai P Udassi, M.D.****Pediatrics, Cardiology, Intensive Care unit and Congenital Heart Center, Shands Childrens Hospital, University of

Florida College of Medicine, Gainnesville, Florida, *Pediatric Intensive Care Unit Nurse Practitioner, **Fellow Pediatric Cardiology & Critical Care Medicine, Department of Pediatrics, Congenital Heart Center,

***Pediatric Intensive Care Unit, UF Health Shands Children’s Hospital, Gainesville, FL****Assistant Professor, Division of Cardiology, Congenital Heart Center, *****Professor & Chief, Division of Pediatric Cardiology,

******Professor & Cardiothoracic Surgeon & Director Congenital Heart Center, University of Florida College of Medicine, Gainesville, Florida, USA

Correspondence:Jai P Udassi, MD, University of Florida,Department of Pediatrics, Congenital Heart Center, 1600 SW Archer Road - Box 100296, Gainesville, FL 32610-0296, USA.Tel: 352-273-5422; Fax: 352-273-5927E-mail: [email protected] .edu

Key words: ECMO, Mechanical circulatory support, Ventricular assist device, Syncardia, Berlin EXCOR

IntroductionHistory: Today the use of mechanical circulatory support (MCS) has become essential in the survival of the child with severe heart failure refractory to medical management. The two methods to provide MCS in children are: (a) Extracorporeal membrane oxygenation (ECMO) and (b) ventricular assist devices (VAD). Although ECMO has been widely used in pediatric patients over the past several decades, the fi rst ventricular assist device in an adults goes back almost fi fty years. Dr. Hall made the fi rst attempt implementing the fi rst VAD in an adult patient in 1963 with the fi rst successful surgical placement in 1966 by Dr. Debakey1. The development of the ventricular assist device for the adult population has grown tremendously over the past several decades offering a wide variety of devices. Some older children with heart failure have benefi ted from the currently available adult sized devices. In 1991 the Berlin Heart was made available to pediatric patients, fi rst using adult sized VAD’s and now with smaller pediatric sized devices1. It is now more common to bridge to transplant with pediatric ventricular assist devices, however there continues the need for more sophisticated technology to be able to improve outcomes further. The use of VADs can successfully

bridge a child while awaiting transplants especially for the longer waiting periods for available donors.

ECMO was fi rst used in 1975 and was developed primarily to support the neonate with respiratory failure2. It was later expanded to be used in patients that could not be weaned off cardiac bypass, children with low cardiac output syndrome following cardiac surgery, and in children who had developed unrelenting cardiac arrest. The use of ECMO has some advantages. Firstly, it can be rapidly deployed and it can be initiated in the operating room or at the bedside. Unlike VADs that only offer cardiac support, ECMO can provide both pulmonary and cardiac support. ECMO has a longer history of use, whichgives us the advantage of more experience with the technology. The main disadvantage is that it is generally limited to short term use due to the risks of infection, bleeding, and thrombosis2.

IndicationsBefore a child can be placed on MCS, an evaluation should be conducted at a transplant center3. The assessment and timing are critical during the evaluation process of MCS. The standards used for cardiac transplant evaluation have not changed signifi cantly over the last 15 years3. But there is still debate on what is the most optimal time to initiate MCS. There are no defi ned guidelines in place at the present time but there does seem to be a consensus on MCS selection and initiation. The decision in pediatrics is individualized and dependent upon each centers experiences with MCS. Centers for Medicare & Medicaid Services have necessary


requirements for destination therapy which include life expectancy < 2 years, not a candidate for heart transplantation, failure to respond to optimal medical management for at least 60 of the last 90 days, left ventricular ejection fraction < 25%, and continued need for intravenous inotropic therapy limited by symptomatic hypotension, decreasing renal function, or worsening pulmonary congestion3. Indications for MCS are going to differ depending on which type of therapy is utilized. ECMO is initiated for short-term cardiac or pulmonary support. Indications include malignant arrhythmias, decompensation requiring cardiopulmonary resuscitation, acute cardiac infectious processes including myocarditis and Kawasaki Disease, acute cardiac graft rejection, inability to wean from cardiopulmonary bypass, and when there is uncertainty regarding the candidate for long-term VAD placement1. VAD placement is considered for short or long-term cardiac support. VAD indications include severe left ventricular dysfunction, chronic complication from myocarditis or endocarditis, chronic cardiomyopathy, refractory cardiogenic shock, end-stage congenital heart disease, and as a bridge to transplantation4.

ContraindicationsContraindications should be considered when considering MCS. In pediatrics this has been an area of great debate with the introduction of long-term therapy now available. There are clear absolute contraindications, which include irreversible conditions including multi-system organ failure, severe neurological damage, renal failure, hepatic failure, irreversible septic shock, and incurable malignancy5. There are relative contraindications that include signifi cant bleeding or coagulopathy, major intracranial hemorrhage (> grade I), and neurological disorders with poor quality of life6.

ComplicationsMCS is associated with several complications with some being device-specifi c. ECMO complications primarily include hemorrhage, severe hemolysis, hypotension, air in the circuit, embolism, and infections. VAD complications are associated with neurological, hematologic, gastrointestinal, and immunological issues5. Complications of the Berlin

Heart include neurological events including stroke, hemorrhage after implantation, and infections7. Thoratec complications include infections, prolonged ventilation, bleeding, neurological complications, and severe hypertension during support7. HeartMate complications include bleeding, infection, and neurologic events7

Complications with MCS should be evaluated on an individualized basis and centers should have in place an algorithm on when to discontinue MCS. For example if a severe neurological injury occurs while a patient is on MCS, a multidisciplinary approach including the family should be used to determine if MCS should be discontinued and how this is going to be accomplished.

Short term mechanical circulatory supportECMO in general is used for short-term support. As mentioned earlier it can be rapidly deployed. It requires either a veno-venous (VV) or veno-arterial (VA) canulation. The utilization of VV ECMO is primarily for pulmonary support with gas exchange occurring as it passes across the membrane oxygenator. The use of VA canulation offers both cardiopulmonarysupport and assists systemiccirculation6. It delivers an increased partial pressure of oxygen in arterial blood at much lower fl ow rates. ECMO does not inherently decompress the systemic ventricle in congenital heart disease patients that have had a two-ventricle repair. However it does decrease the blood fl ow entering the pulmonary vasculature and returns it to arterial blood thereby decreasing workload of the myocardium and decreasing oxygen consumption. Additional left atrial canulation is needed to decrease compression of left sided heart structures6. ECMO comes with its disadvantages such as bleeding, thrombosis, infection, end organ dysfunction, decreased mobility, and limited time to use2. In regards to bleeding patients, there is increased exposure to blood products. This can become a long-term problem for organ allocation due to the increased development of panel reactive antigens (PRA), allosensitization and human leukocyte antigen (HLA) incompatibilities.

Pediatric Mechanical Circulatory SupportPEDIATRIC CARDIAC INTENSIVE CARE - 2


Centrifugal pumpsThe centrifugal pump is placed via cannulas that arise from sternal or thoracotomy incision and can provide both univentricular or biventricular support4. There are both adult and pediatric sized VAD’s that can be used to offer most pediatric patients. LevitronixCentrimag (Fig 1) and PediMag (Fig 2) are the most popular centrifugal pumps at this time. The pediatric VAD can be used on patients 10 kg or less2. It is designed for short-term use. The VAD uses a magnet and rotor cones, which spin to create a centrifugal force to move blood into and out of the device. The rotors are shaped to accelerate blood circumferentially and move it to the outer rim of the pump4. The adult Centrimag has the capability to provide fl ows of about 10 liters/min whereas the pediatric PediMag can fl ow as low as 0.4 liters to 1.7 liters/min. Advantages of the centrifugal pumps are that they do not require an oxygenator, there is a lower priming volume compared to other MCS devices, there is decreased risk of hemolysis, adequate decompression of the left ventricle, patients can be easily transported, and the operational expenses are lower1,4.

Figure 1: Centrimag (Reprinted with the permission of Thoratec Corporation)

Figure 2: Pedimag (Reprinted with the permission of Thoratec Corporation)

Intra-aortic balloon pump (IABP)The IABP is used in adults for acute left ventricular dysfunction. The IABP has not been widely used in children due to the availability of ECMO and other VADs, the diffi culty in placing the catheter, aortic elasticity in children, and balloon timing synchronization with higher heart rates8. However for adolescents the IABP may be a viable choice. The catheter is placed in the femoral artery with the tip of the catheter positioned just above the renal artery and approximately two centimeters below the left subclavian artery. Cardiac output is augmented with the timing of balloon infl ation during diastole, which is identifi ed on the monitor screen with the dicrotic notch. This balloon infl ation creates backpressure to perfuse the coronary arteries. Once the balloon is rapidly defl ated, the left ventricle is assisted with forward fl ow and decreases myocardial workload. The IABP also aids in decreasing myocardial consumption, lowers left ventricular end diastolic pressure and left atrial pressure8.

Long term mechanical circulatory supportThe Berlin Heart has become a popular long-term bridge to transplant, ventricular assist device in children. It is a laptop-based unit (Fig 3) that utilizes a pressure and vacuum to move the VAD, gortex to pump blood in and out of the ventricle. The machine offers threecompressors; the fi rst two will drive the right and left VAD while the third is a back up. The

Pediatric Mechanical Circulatory Support PEDIATRIC CARDIAC INTENSIVE CARE - 2


device can be used a single right or left VAD or biventricular VAD. The biventricular VAD can offer synchronous fi lling where both VADs empty and fi ll in concert. There is also asynchronous fi lling where as the right empties and the left fi lls9. This is a very good option for very small children with limited space in the chest cavity. VADS come in a variety of sizes from 10 ml to 80 ml VAD fi ll volumes (Fig4). The internal surface of the cannulas are smooth silicon with the external surface is made up of a Dacron velour. This external surface allows for scar tissue to form and to tightly seal the entrance site to decrease the incidence of ascending infections9.

Figure 3: EXCOR Driving Unit (Courtesy: Berlin Heart, The Woodlands, Texas)

Figure 4: EXCOR Pediatric Pump Range (Courtesy: Berlin Heart, The Woodlands, Texas)

Since the VAD part of the cannulas rest outside the patient’s body they can be assessed for fi brin and clot formation per protocol. Fig 5 shows a Berlin EXCOR BiVAD implanted in a pediatric torso (Fig5). Assessment of the VAD fi lling and emptying can also be observed with a convex and concaved shape of the gortex sheet. The Berlin Heart has its advantages of allowing for long-term cardiac support and is an excellent bridge to transplant option for children of all sizes. It allows for mobility, rehabilitation, and does not require the patient to be intubated4. It does require consistent low dose anticoagulation, which can be diffi cult to maintain therapeutic levels.

Figure 5: EXCOR Pediatric torso (Courtesy: Berlin Heart, The Woodlands, Texas)

Syncardia total artifi cial heartThe FDA approved the Syncardia Total Artifi cial Heart (TAH) in 1994 for use in the United States. It has been used on over 1100 adults nationally. Syncardia is implanted surgically by excising the native right and left ventricles and replacing them with the right and left TAH (Fig 6). Pneumatic cannulas are attached and arise from the chest with surgical closure. The cannulas are connected to device that allows for air pressure to



move the VAD diaphragm, which controls fi lling and emptying of the VAD chamber. Because the native ventricles are removed and replaced by the VAD, the patient no longer has a heart rhythm. There are no arrhythmias, no need to use inotropic medications, no issues with the aortic valve, and no left ventricular thrombus formation. Currently the VAD comes in one size, which is a 70 ml VADand a 50 ml smaller pump is scheduled for use in smaller adults and children (Fig 7). The diaphragm is pneumatically driven, balances left and right-sided output and increases output in response to elevated venous return (Starling-like response). Infl ow valve is 27 mm and outfl ow valve is 25 mm. Due to the size of the VAD, patients have to be screened to ensure the device can be fi tted as per anterior posterior dimensions of the chest via radiographic imaging and CT scan. The Syncardia utilizes a partial fi ll which is about 50 to 60 ml and complete ejection, so that that the

chamber fi lls with enough volume for adequate cardiac output and can completely empty. This eliminates residual blood volume stasis in the device reducing any chances of thrombus formation. There is active ejection with the pneumatic driver pushing air in for ejection. Passive fi lling is used for partial fi lling. The large driver comes with a laptop display to evaluate for partial fi lling and complete ejection. The end user can identify compete ejection with a “fl ag” display at the end of ejection phase. The display also shows heart rate, fi lling volumes, and cardiac output. There are some considerations when using the Syncardia: (a) Central lines cannot be utilized as they may interfere with valve closure on the mechanical valves(b) Peripherally inserted central catheters have been used but are placed in the left upper extremity with the use of fl uoroscopy and only seated in the midline position (c) The patients on the total artifi cial heart need to be on diuretics and should maintain central venous pressures of <10 mmHg to ensure a partial fi ll (d) Blood pressure is managed with the use of vasoconstrictors and vasodilators so that the clinician can manipulate the systemic vascular resistanceto treat hemodynamics (e) Blood product replacement is minimized due to the nature of hemolysis seen with the artifi cial pump. Some centers tolerate hematocrit of about 17-20% as long as the patient is hemodynamically stable and asymptomatic. Syncardia has a Freedom driver, which is a portable, wearable and is undergoing FDA-approved investigational device exemption clinical study in the USA (Fig 8).

Figure 8: Syncardia TAH with Freedom Driver (Courtesy SynCardia Systems, Inc.)

Figure 6: SynCardia Implantation (Courtesy SynCardia Systems, Inc.)

Figure 7: 70 & 50 cc Total Artifi cial Hearts (Courtesy SynCardia Systems,Inc.)



Axial fl ow devicesThe Heart Mate II is an axial fl ow device that creates fl ow by a rotational impeller that has an internal impeller, which spins about 8000 rpms1. The device also is anchored in the apex of the left ventricle with a conduit that pumps blood to the aorta. It is the most commonly implanted device worldwide with more than 10,000 patients already implanted. It offers continuous fl ow for a left ventricular assist device. The FDA has approved Heartmate II to be used as a bridge to transplant or destination therapy. The advantages of the Heart Mate II are that it is smaller, with lower energy requirement and reduced cost (Fig 9,10). It does not require a large priming volume and it is very portable allowing the patient to have an improved quality of life while awaiting transplantation.

Figure 9: Heartmate II (Reprinted with the permission of Thoratec Corporation)

One of the newer devices available on the market is the Heart Ware left ventricular assist device. It utilizes centrifugal continuous fl ow with the use of a hybrid magnetic bearing1. The device also is anchored in the apex of the left ventricle with a conduit that pumps blood to the aorta.

Other devices that will be available soon are the DebakeyHeart Assist 5, which is currently in clinical trials.The University of Pittsburgh is currently working on the PediaFlow device, which is a pediatric VAD that utilizes axial fl ow. It is intended to have better biocompatibility because there is less blood contact with the impeller. It is a smaller design compared to other axial fl ow devices with size dimension of about two AA batteries. This device incorporates a valveless turbo design that limits the amount of blood contact with the device.

Figure 10: Heart Mate II with external equipment (Courtesy Thoratec Corporation)

AnticoagulationAnticoagulation while on MCS is integral part of the management. The blood has continuous contact with foreign substances and this produces a cascade of events causing a shift from normal homeostasis to a hypercoaguable state. Anticoagulation and monitoring will depend on the device implanted. Unfractioned Heparin (UFH) is still the gold standard of laboratory management10. Heparin is reliable and predictable anticoagulant in use however requires the patient to be on a drip continuously. AntithrombinIII (AT III) is produced in the liver and is a natural inhibitor of most clotting factors. Most of its anticoagulation effects are with inhibiting thrombin and factor Xa. Once AT III is bound to unfractionated heparin it has a 1000 times greater inhibitory effect10.



Unfractionated heparin increases antithrombotic effect of tissue factor pathway inhibitor (TFPI) by 2-4 times through increasing the affi nity of factor Xa10. Additional anticoagulation monitoring includes activated clotting time (ACT), activated partial thrombaplastin time (aPTT), thromboelastography (TEG) and platelet function testing. Baseline coagulation studies should be completed prior to initiation of MCS. (Fig 11)

Figure 11: TEG Analysis (Reprinted from Transfusion Medicine Reviews Vol 26(1), Bollinger D, et al. Pg 1-13, 2012, with permission from Elsevier

The Impella 2.5 uses Heparin and follows Factor Xa levels 0.3-0.5 and aPTT 45-55s11. This is typically initiated concurrently with implantation of device. The Rotafl ow VAD uses Heparin and follows Factor Xa level between 0.3-0.5 with aPTT 55-65 s or ACT 180-20011. Anticoagulation is started within 24-48 hrs after surgery, once postoperative bleeding has stopped. Heparin is usually started at 10-15 units/kg/hr and titrated according to the PTT goal. The Berlin Heart EXCOR VAD follows the Edmonton Antithrombotic Protocol, which includes low molecular weight heparin (LMWH) with a target anti-Xa 0.35-0.510. No anticoagulation is typically started in the fi rst 24 hours. For chronic management patient is usually transitioned toLovenoxfor children < 12 months with a goal anti-Xa 0.6-1.0 and Warfarin for children > 12 months with an international normalized ratio 2.7-3.510. Antiplatelet therapy with dipyridamole and aspirin are also used in this protocol10. Antiplatelet and TEG monitoring are followed very closely10. The HeartMate II uses LMWH and follows UFH and aPTT 55-65 s or 1.5 – 1.8x normal11. Long-term therapy utilizes warfarin and antiplatelet therapy. INR is targeted at 1.5-2 and antiplatelet monitoring

with TEGs, platelet mapping (with ADP suppression and arachidonic acid suppression)11.

ConclusionEarlier ECMO was the primary mode of cardiac support however technological advancements have made available multiple VAD options for pediatric patients. As the organ availability is limited and the waiting time for heart transplants is increasing, use of VADs has seen a rapid increase. As newer devices are manufactured which are smaller and more suited to the needs of pediatric population we anticipate a signifi cant decline in the morbidity and mortality associated with use of VADs.

References1. Stiller, B., I. Adachi, and C. D. Fraser, Jr. “Pediatric

Ventricular Assist Devices.” [In eng].PediatrCrit Care Med 14, no. 5 Suppl 1 (Jun 2013): S20-6.

2. Jaquiss, R. D., and R. A. Bronicki. “An Overview of Mechanical Circulatory Support in Children.” [In eng].PediatrCrit Care Med 14, no. 5 Suppl 1 (Jun 2013): S3-6.

3. Wilson, S. R., G. H. Mudge, Jr., G. C. Stewart, and M. M. Givertz. “Evaluation for a Ventricular Assist Device: Selecting the Appropriate Candidate.” [In eng].Circulation 119, no. 16 (Apr 28 2009): 2225-32.

4. Hazinski, Mary Fran. Nursing Care of the Critically Ill Child. 3rd ed. St. Louis, Mo.: Elsevier/Mosby, 2013.

5. O’Connor, M. J., and J. W. Rossano. “Ventricular Assist Devices in Children.” [In eng]. CurrOpinCardiol29, no. 1 (Jan 2014): 113-21.

6. Reuter-Rice, Karin, and Beth Bolick. Pediatric Acute Care: A Guide for Interprofessional Practice. Burlington, MA: Jones & Bartlett Learning, 2012.

7. Fuchs, A., and H. Netz. “Ventricular Assist Devices in Pediatrics.” [In eng]. Images PaediatrCardiol3, no. 4 (Oct 2001): 24-54.

8. Collison, S. P., and K. S. Dagar. “Mechanical Circulatory Support for Acute Cardiac Failure in Children: The Options Available.” [In eng].Indian Heart J 58, no. 4 (Jul-Aug 2006): 345-9.

9. Gazit, A. Z., S. K. Gandhi, and C. Canter C. “Mechanical Circulatory Support of the Critically Ill Child Awaiting Heart Transplantation.” [In eng].CurrCardiol Rev 6, no. 1 (Feb 2010): 46-53.

10. Annich, G., and I. Adachi. “Anticoagulation for Pediatric Mechanical Circulatory Support.” [In eng].PediatrCrit Care Med 14, no. 5 Suppl 1 (Jun 2013): S37-42.

11. Cooper, D. S., and R. Pretre. “Clinical Management of Pediatric Ventricular Assist Devices.” [In eng].PediatrCrit Care Med 14, no. 5 Suppl 1 (Jun 2013): S27-36.



Heart Transplantation in PediatricsDipankar Gupta, MD*, Frederick Jay Fricker, MD**, Mark S Bleiweis, MD***, Jai P Udassi, MD****

*Fellow Pediatric Cardiology & Critical Care Medicine, **Professor & Chief, Division of Pediatric Cardiology, ***Professor & Cardiothoracic Surgeon &Director ,****Assistant Professor, Division of Pediatric Cardiology

Congenital Heart Center, University of Florida College of Medicine, Gainesville, Florida, USA

Correspondence:Dipankar Gupta, MDUniversity of Florida, Department of Pediatrics, Congenital Heart Center, 1600 SW Archer Road – Box 100296, Gainesville, FL 32610-0296, USATel: 352-273-5422; Fax: 352-273-5927E-mail [email protected] .edu

Keywords: Heart Transplantation, pediatrics

IntroductionOver the last fi ve decades, pediatric cardiac transplantation has been performed as treatment for palliated Congenital Heart Disease (CHD) and Cardiomyopathy refractory to surgical and medical therapy. Recent advancements and availability of life support technologies, improved pre and peri-operative management of these critically ill patients, refi nement of surgical techniques and enhanced understanding of immunology and robust immunosuppression, has lead to a remarkable improvement in event free survival after heart transplantation.

Historical perspectiveThe fi rst human heart transplant was performed on December 3rd, 1967 at Cape Town, South Africa by Dr. Christian Barnard1, 2,3. Three days later, the fi rst pediatric human heart transplant was accomplished in Brooklyn, New York on a 19-day-old infant with severe Ebstein’s anomalyafter a failed central shunt4. “We stand on the shoulders of those that have gone before us”.These words are certainly true as we refl ect on the advances made in pediatric heart transplantation. Early pediatric heart transplantation was successfully accomplished at Stanford University in the late 1970’s, when only azathioprine and corticosteroids were available for immune suppression. Nonetheless, morbidity and mortality associated with pediatric

heart transplantation remained high due to a lack of adequate immune suppression. The introduction of Cyclosporine by a pioneer of solid organ transplantation, Dr. Thomas Starzel, made heart transplantation a reality as it greatly simplifi ed the immune suppression management, decreased the morbidity due to corticosteroids and made heart transplantation economically feasible. In the decade of the 1980’s, Stanford, Columbia University and the University of Pittsburgh were the referral centers for pediatric heart transplantation. Nonetheless, their early success resulted in the exponential growth in the number of centers performing pediatric heart transplantation. A major advance in pediatric heart transplantation occurred at Loma Linda University when their program, led by Dr. Leonard Bailey, focused nearly entirely on heart transplantation of the infant with Hyopoplastic Left Heart disease (HLHS). The result of Norwood palliation was dismal, thus infant transplantation was a welcomed option. In 1993, the Pediatric Heart Transplant Study (PHTS) group was founded by six pediatric heart transplant centers to advance the clinical science and treatment of children after listing for heart transplant. The purpose was to establish and maintain an event driven database for heart transplantation, which could be used to stimulate basic and clinical research in the fi eld of pediatric heart transplantation. As of March 2014, there are 46 participating centers contributing data on over 6000 listing and nearly 5000 pediatric heart transplants. The PHTS has created a body of literature that has had a major impact on the care of infants and children after heart transplantation. Based on data reported by the ISHLT, the trend of pediatric heart transplantation has shown a steady increase in the last 20 years (Figure 1).


Indications for heart transplantationPrimary indications for heart transplantation are: end stage palliated congenital heart disease, primary transplantation in lethal congenital heart malformations, i.e. HLHS, pulmonary atresia with intact ventricular septum and sinusoids, and Cardiomyopathy. The indication for pediatric heart transplantation varies across different age groups, with CHD being the primary indication of heart transplant for infants, while cardiomyopathy is the primary indication of heart transplantation for older children (Figure 2)10, 11.The past consensus guidelines for heart transplantation have included12-15:Ongoing need for intravenous inotropic or mechanical circulatory supportComplex CHD not amenable to surgical palliation or repair or if it carries a higher risk/mortality than transplantationProgressive decline of ventricular function or functional status despite optimal medical management with diuretics, digitalis, angiotensin-converting enzyme

inhibitors and beta-blockers.Malignant arrhythmia or survival after cardiac arrest, which is unresponsive to medical therapy, ablation or implantable defi brillator.Progressive pulmonary hypertension due to systemic ventricular failure precluding transplantation at a later date.Growth failure secondary to severe congestive heart failure (CHF) despite optimal medical management.Very poor quality of life secondary to severe CHF.Progressive decline in functional status and/or high-risk conditions with fontan palliation.The American Heart Association (AHA) formulated a working group to better outline the indications for heart transplantation16. Level A evidence for indications of heart transplantation is lacking, however there is Level B evidence available as depicted in Table116. Due to improved surgical repair of CHD, the prevalence of adult CHD will continue to increase. As such, there will be a continuous evolution of the indications for transplantation specifi c for this group

NOTE: This fi gure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of hearts transplanted worldwide has increased and/or decreased in recent years.Figure 1. Recipient Age Distribution by Year of Transplant (From Dipchand AI, Kirk R, Edwards LB, et al. The ISHLT 16th pediatric heart transplantation report-2013;. J Heart Lung Transplant. 2013 Oct; 32(10): 979-88, with permission from Elsevier)

Heart Transplantation in PediatricsPEDIATRIC CARDIAC INTENSIVE CARE - 2


of patients. The AHA has suggested that presence of severe hypoplasia of the pulmonary arteries or veins and non-reactive severe elevations of pulmonary vascular resistance (PVR) would preclude orthotopic heart transplantation (OHT).

Organ allocation and matchingUnited Network for Organ Sharing (UNOS) maintains a network (UNet) accessible to all transplant professionals, linking all transplant centers and organ procurement organizations (OPO). Upon identifi cation of an organ donor, transplant coordinator from an OPO enters the donor information in UNet. These data are used to create a ranked list of potential recipients, called a “match run”. Factors infl uencing the list include tissue match, ABO type, waiting list duration, immune status, degree of medical urgency and distance between the potential recipient & donor17-18. Other factors infl uencing the acceptance of a donor heart offer

Figure 2: Recipient Diagnosis by Age (2006-6/2012) (From Dipchand AI, Kirk R, Edwards LB, et al. The ISHLT 16th pediatric heart transplantation report-2013; J Heart Lung Transplant. 2013 Oct; 32(10):979-88, with permission from Elsevier)

Table 1: Level B evidence for heart transplantation16

Stage D heart failure with systemic ventricular dysfunction in pediatric patients with cardiomyopathies or previous repaired/palliated CHD

Stage C heart failure withsignifi cant growth failure attributable to the heart disease in above population

Not a feasible standard therapy for any specifi c congenital heart lesion

Moderate graft vasculopathy with normal or abnormal ventricular function

Pulmonary vascular resistance (PVR)<6 Woods units/m2 or the transpulmonary gradient to <15 mm Hg actual or with inotropic support or pulmonary vasodilators

Effi cacy not established for patients with previous infection with hepatitis B or hepatitis C or with HIV infection

Effi cacy not established for patients with history of illicit drugs or tobacco or a recent history of alcohol abuse

Effi cacy not established for patients with history of psychological, behavioral, or cognitive disorders; poor family support structures; or documented noncompliance with previous therapies


include: the need for a non-lung donor for a patient that requires extensive reconstruction of pulmonary arteries or re-routing of systemic venous return and HLA incompatibility based on virtual crossmatch.


ABO compatibility has been the standard of care in solid organ transplantation for all age groups. Recently, ABO incompatible heart transplants have been performed in infants have an immature immune system with lower levels of anti-A & anti-B antibodies. Hence, infants have lower probability of antibody formation against donor ABO antigens, as demonstrated by current medical evidence showing no difference in mortality, morbidity and graft failure in ABO incompatible (ABOi) vs ABO compatible (ABOc) heart transplantation19-22. According to the PHTS database, there is equivalent one-year survival and survival from rejection in ABOi and ABOc transplantation21.Pediatric heart transplant candidates who have not received a heart transplant before their 18th birthday shall continue to qualify for medical urgency status based on Organ Procurement and Transplantation Network (OPTN) guidelines. A heart from an organ donor < 18 years of age is allocated to a pediatric heart recipient candidate before being allocated to an adult candidate. A heart transplant candidate who is under 18 years of age at the time of listing is assigned the status code as shown in Table 2.

Donor managementManagement of the donor heart is a critical part in the process of transplantation. Organ donation can be after declaration of brain death or cardio-circulatory death (DCD donor)23. Brain death is followed by an intense catecholamine surge, causing peripheral vasoconstriction, tachycardia and hypertension and, in turn, increased myocardial oxygen demand. This results in myocytolysis, contraction band necrosis, subendocardial hemorrhage, edema & interstitial mononuclear infi ltration24. Subsequently, hypotension and circulatory collapse occurs secondary to decreased systemic vascular resistance (SVR) requiring fl uid resuscitation and high doses of inotropes. Also, brain death leads to alterations in hormone levels secondary to loss of central regulation and primarily includes low antidiuretic hormone, depletion of cortisol, free T3 and insulin. Usual protocol used for optimizing the management of a potential donor includes25-27:Maintain CVP 6-10 mm Hg, correct acidosis (pH 7.40-7.45), correct hypoxemia (pO2> 80 mm Hg &

O2 saturations > 95%), correct anemia (Hematocrit ≥ 30%), inotropes to maintain MAP ≥ 60 mmHg (target dopamine or dobutamine< 10 μg/kg/min).Echocardiogram to rule out structural anomalies Hormonal resuscitation if LVEF < 45%T3: Bolus 4 μg + infusion @ 3 μg/hourVasopressin: 1 unit bolus + infusion @ 0.5-4 units/hour (titrate to SVR of 800-1200)Methylprednisolone: 15 mg/kg bolusInsulin: 1 unit/hour (titrate blood glucose to 120-180 mg/dL)

Use of high dose dopamine or dobutamine (> 20 μg/kg/min) and/or epinephrine > 0.1 μg/kg/min is predictive of donor heart failure.Transplantation after cardio-circulatory death is ethically controversial and debatable23,27, hence DCD heart donors has not achieved widespread application.

Evaluation and management of the patient awaiting heart transplantationEvaluation of the patient awaiting a heart transplant includes15:Cardiac catheterization: Hemodynamic assessment and measurement of left and right heart pressures, pulmonary vascular resistance (PVR). In presence of

Table 2: Transplantation status justifi cationStatus 1A1. Requires assistance with a ventilator2. Requires assistance with a mechanical assist device (e.g., ECMO,

LVAD)3. Requires assistance with a balloon pump4. Patient< 6 months old with congenital or acquired heart disease

exhibiting reactive pulmonary hypertension at > 50% systemic level.

5. Requires infusion of high dose or multiple inotropes (dobutamine ≥ 7.5 μg/kg/min or milrinone ≥ 0.5 μg/kg/min)

6. Patient not meeting above criteria with a life expectancy without a heart transplant of less than 14 days (refractory arrhythmia)

Status 1B1. Requires infusion of low dose single inotropes 2. Less than six months old and does not meet the criteria for Status

1A3. Growth failure i.e., < 5th percentile for weight and/or height,

or loss of 1.5 standard deviations of expected growth (height or weight) per NCHS curves

Status 21. Does not meet the criteria for Status 1A/1B

Status 31. Temporarily unsuitable to receive a thoracic organ transplant.



elevated PVR, reactivity is elicited with 100% oxygen, nitric oxide, prostacyclin prior to listing28. PVR > 6 Wood units/m2 and a trans-pulmonary gradient (TPG) >15 mmHg with non-reactive PVR is suggestive of a high-risk candidate for transplantation.Exercise test: Exercise treadmill test (Bruce protocol) is used to evaluate maximal oxygen consumptions (MVO2) in ambulatory heart failure patients. Patients with MVO2 < 12 ml/kg/minhave very poor 1 year survival rate, 12-14 ml/kg/min have severe clinical limitations and MVO2> 14 ml/kg/min are considered to have preserved exercise capacity and exhibit similar or higher survival rates as expected after transplantation15,29,30.Assessment of end-organ function: Pre-existing renal and hepatic dysfunction must be assessed due to toxicity of immunosuppression therapy post-transplant. The interactions between various medications must be evaluated closely with special attention to systemic side effects15.Infectious disease evaluation: IgG and IgM serologies for CMV, EBV, Toxoplasma Gondii, hepatitis viruses, HIV and HSV must be obtained. Patient must receive PPD and vaccines including varicella, measles, mumps, rubella, H. infl uenza, pneumococcus, hepatitis A and B prior to transplantation.HLA sensitization: HLA antibodies to Class I and II are determined and reported as panel reactive antibodies (PRA). PRA > 10% is considered positive and is associated with lower survival compared to non-sensitized patients. Previous blood transfusions, childbirth, cryopreserved tissue valves, allograft conduits and organ transplants increase the risk of sensitization31,32.Psychosocial assessment: Assessment for reliable & strong support system due to mandatory clinical follow up & medication compliance is also critical. Illicit drug use and previous behaviors of non-compliance can prevent allocation of this limited and valuable resource to a particular patient.Patient management is individualized except for the basic principles of care of any critically ill patient in the intensive care unit.Hemodynamic assessment and data obtained by catheterization guides patient management with the goal of optimizing preload and afterload. Milrinone is the inotrope of choice in patients awaiting

transplantation33, 34. Milrinone has a long half-life, is excreted by kidneys and should be used cautiously in patients with hypotension, renal disease and arrhythmias. In our experience, low dose dobutamine (5-10 μg/kg/min) or epinephrine (0.01-0.05 μg/kg/min) is benefi cial in patients who are not stabilized on monotherapy with milrinone38. Diuresis is necessary to prevent pulmonary edema and fl uid overload; however, patients may need to be on continuous infusion for gentle diuresis. Patients with poor cardiac function are prone to pulmonary and systemic thrombosis, and embolization, making anticoagulation necessary. Heparin is the preferred drug as it can be easily reversed if a donor heart becomes available. Warfarin is an acceptable option for anticoagulation. We have used direct thrombin inhibitors like bivalrudin and argatroban in patients on ventricular assist devices with inability to achieve therapeutic levels despite maximal doses of heparin or with history of heparin induced thrombocytopenia (HIT). Bivalrudin is unique in undergoing non-organ elimination by proteolysis with a short half-life (t ½) of about 25 minutes35.Mechanical support: ECMO (Extracorporeal membrane oxygenation) or Ventricular Assist Device (VAD). Progressive end organ dysfunction despite maximal medical management is an indication for mechanical support. This can essentially be used as a bridge to recovery or bridge to transplantation. Mechanical support can be used in patients with cardiogenic shock due to myocarditis with anticipation of recovery of function or as a bridge to transplantation19, 36. Current options for pediatric VAD use are limited due to the pump sizes required for pediatric patients. Currently, Thoratec, Berlin Heart EXCOR VAD, and DeBakey centrifugal pump are the only VADs available for pediatric use. Survival at 12 months post transplant in patients supported with EXCOR was similar to overall pediatric heart transplants and higher than patients supported with ECMO36,37. In our experience at the Congenital Heart Center at University of Florida, EXCOR VAD has been used extensively in children of all age groups, including newborns to older children, as a bridge to transplant. We have implanted the Syncardia “Total Artifi cial Heart” in an adolescent patient



who presented with cardiogenic shock secondary to coronary allograft vasculopathy (CAV). The support devices have enabled us to aggressively rehabilitate our patients prior to transplantation.The techniques for performing an orthotopic heart transplant were pioneered at Stanford University by Dr. Norman Shumway and his colleagues15,39: The following two techniques are used: Orthotopic heart transplantation (OHT, Figure 3, a and b): OHT using bi-atrial technique is the most commonly used approach39,40. Bi-cavalanastomosis has been described and shown to preserve sinus node function41-43.Heterotopic heart transplantation (HHT, Figure 3, c): In this technique the donor heart is implanted adjacent to the recipient. The indications for HHT currently are donor/recipient size mismatch (weight ratio < 75%) and elevated PVR as an untrained donor right ventricle may be unable to pump against high pulmonary pressures. HHT has been shown to be associated with lower overall survival and higher rates of complications, especially atelectasis, thrombosis in native heart, mitral & tricuspid regurgitation and malignant ventricular arrhythmias in the native heart15, 44-47. This procedure is rarely performed today.

Post-operative managementImmediate post-operative care includes supportive respiratory management with early extubation, unless there is a contraindication. Usually, a fi xed cardiac output is observed with heart rates ranging from 90-110 bpm, which may be inadequate for newborns. In our experience, isoprotenol can be titrated to achieve an acceptable heart rate and augment cardiac output38,48. Catechoamines should always be continued for a minimum of 72 hours after transplantation. Hypertension can be seen if the donor heart is oversized for the recipient or in the presence of increased SVR due to long-standing heart failure with normal stroke volume of the new heart allograft. Systemic hypertension should be aggressively treated with after-load reduction because of the potential for abdominal and cerebral re-perfusion injury. All transplanted hearts have diastolic dysfunction due to ischemic injury, but improve rapidly in the initial hours and days after transplant. Diastolic dysfunction needs to be considered when giving bolus fl uid resuscitation or blood transfusion49. PVR Index (transpulmonary

gradient/ cardiac index) > 9 can be predictive of lower 30-day survival post transplant50.Postoperative temporary pacing can be initiated in case of junctional rhythm or sinus node dysfunction. Permanent pacing is recommended if sinus or atrial rhythm does not return spontaneously within 2 weeks.

RejectionRecipient’s immune response to the foreign antigens manifests as rejection. Rejection can be hyperacute, acute cellular rejection (ACR), antibody-mediated rejection (AMR) or chronic rejection. Hyperacute rejection is rare, manifests within minutes to hours after transplantation and is associated with presence of preformed antibodies to donor antigens (especially blood group or anti-HLA antibodies)15. ACR is a host T-cell mediated response to allograft and is

Figure 3. Techniques of heart transplantation. (a) Bi-atrial OHT. (b) BicavalOHT (c) Heterotopic heart transplantation (From Alkhaldi A, Chin C, Bernstein D. Pediatric cardiac transplantation. Semin Pediatr Surg 2006; 15: 188–96; with permission from Elsevier)



characterized by varying degrees of lymphocytic infi ltrate and myocyte necrosis on biopsy specimens. AMR or B-cell mediated rejection is characterized by micro vascular injury and can be seen in the absence histologic evidence of ACR51. ACR classifi cation is based on revised ISHLT criteria into no rejection (0R), mild (1R), moderate (2R), and severe (3R) rejection. AMR is classifi ed based on the presence of histopathologic or immunopathologic (CD68+ or C4d+) features alone or in combination52.

ImmunosuppressionFollowing solid organ transplantation, antigen-presenting cells (APC, leukocytes/dendritic cells) are presented to recipient with the allograft and sensitize the recipient. T-cells are signaled by the APC to proliferate, causing migration of the CD3+ cells to the graft and, in the presence of complement, cause myocyte injury (Cellular rejection). Calcineurin (Tacrolimus/Cyclosporine) inhibitors block recognition between APC and T cells, preventing lymphocyte proliferation. Administration of IL-2 receptor blocker or small doses of Tacrolimus before implantation blocks this signaling process. The potential for AMR has different implications and management.Allosensitization53 can lead to two-fold higher mortality in the fi rst year after transplantation. UNOS recommends routine screening for alloreactive antibodies (PRA) in patients’ serum. The management of the sensitized donor in the perioperative and post-operative period presents a signifi cant challenge. Pre-operative and intra-operative plasmapheresis is critical to preventing hyperacute allograft injury. Modifi cation of maintenance immune suppression is also indicated. In many situations, the introduction of B cell and plasma cell therapy is necessary to maintain good allograft function.The protocols for immune suppression have an induction and maintenance phase. The protocols are center specifi c and usually consist of a combination of steroids, antiproliferative agents (mycophenolatemofetil or azathioprine) and Calcineurin inhibitor (tacrolimus or cyclosporine). Steroids benefi t by immunosuppression, membrane-stabilization and antioxidant properties38.The immune suppression strategy used at our center is outlined in Tables 3 and 4. The induction

protocol used consists of high dose corticosteroids, IL-2 receptor antagonist (simulant), anti-thymocyte globulin (ATG) followed by calcineurin inhibitors (CNI) cyclosporine or tacrolimus. Simulect is administered at a dose of 12 mg/m2 followed by methylprednisolone (10mg/kg, maximum 500mg), one dose prior to cardiopulmonary bypass and another dose just after release of aortic cross clamp. Rabbit ATG (1.5 mg/kg) is started in the fi rst 24 hours after transplantation for 3-7 days. Methylprednisolone is used at high doses (10 mg/kg) in the initial 24 hours and tapered to 1 mg/kg/day 7-10 days after transplant. Tacrolimus is usually initiated on the second day after transplantation with target levels between 10-15 ng/dL. Cyclosporine is generally used in patients with tacrolimus intolerance or in infant transplants. In the maintenance phase, we attempt to wean the steroids within the fi rst 6 months after transplant. Based on the clinical course, other immune suppression medication, such as CNI, mycophenolatemofetil (MMF), are added and dose titrated for target levels (Table 4). Sirolimus (rapamycin (mTOR) inhibitor) is an alternative medication for patients with high risk of CAV and rejection to standard therapy (after one month as it can impair wound healing).In a recent report from ISHLT, 71% of pediatric hearts transplant recipients received induction therapy of which 47% received ATG and 25% IL-2-R antagonists. Polyclonal therapy was shown to have better survival than IL-2R receptor alone. Induction therapy did not infl uence frequency of rejection up to one year after transplantation, freedom from CAV or lymphoma10. Highest risk of acute cellular rejection (ACR) is in the fi rst month after transplantation. There has been a gradual increase in use of tacrolimus from 52% (2001-2006) to 78% (2007 onwards). Use of MPA also increased to 86% from 64% with a decline in azathioprine. Steroids are still prescribed to 71% of patients on discharge. ISHLT 16th Pediatric Heart Transplant Report shows that 95% of patients 5 years post transplant were on CNI, of which 71% were on tacrolimus10.

Follow up Surveillance endomyocardial biopsies (EMB) & hemodynamic measurements (right atrial pressure,



mean pulmonary artery pressure, pulmonary capillary wedge pressure, thermodilution cardiac output) are performed in the cardiac catheterization laboratory starting about 2 weeks after transplantation. The risk of rejection is highest in the fi rst year after transplant and can be subclinical (signifi cant lymphocytic infi ltrate without clinical or echocardiographic changes). EMB’s are considered gold standard for diagnosis. Acute cellular rejection is classifi ed as mild; moderate or severe54; any rejection episode moderate to severe is treated with a course of steroids followed by repeat EMB.

Survival10

Heart transplant during infancy shows a higher median survival rate as compared to older children (Figure 4). From early 1980s to current era, there has been a signifi cant improvement in survival primarily in the early post-operative period (Figure 5). Pre-transplant diagnosis of cardiomyopathy in infants had a favorable prognosis as compared to CHD. Survival rates for CHD have fared similar to re-transplant10. ECMO support as bridge to transplant has a poor survival compared to VAD or TAH (Figure 6).In most centers, graft survival in the fi rst year approaches 100%. Primary graft failure followed by

Table 3: Induction Immune suppressionAgent/Class Mechanism of action Dose Monitoring Side EffectsInductionBasiliximab (Monoclonal antibody)

Binds IL-2 receptor 12 mg/m2 >35 kg: 20 mg <35 kg: 10mg

CBC Anaphylaxis

Corticosteroids ↓ IL-2 production,↓ macrophage response to signaling, Lymphocyte redistribution

D1: 10 mg/kg/dose Q 8 D2: 5 mg/kg/dose Q 8 D3: 1 mg/kg/dose Q 8 D4: 1 mg/kg/dose QD Start weaning

Glucose ↑ BP, ↑ Glucose, hyperlipidemia, sepsis

Anti-thymocyte globulin (ATG)

Nonspecifi c T-cell lysis 1.5 mg/kg/day (5 days) T-lymphocyte subsets

↓ Platelets, allergic reaction, sepsis, serum sickness

Tacrolimus (CNI) Prefer oral use

Inhibit T-cell activation & proliferation, blocks signal transduction

IV: 0.01-0.03 mg/kg/d PO: 1 mg NG

Target level: 10-15 ng/mL

Sepsis,↑ BP, ↑ K, Nephrotoxicity, Neurotoxicity, ↑ Glucose

Cyclosporine (CNI) Prefer oral use

Inhibit T-cell activation & proliferation, blocks signal transduction

IV: 1-3mg/kg/day Q8-12 PO: 3 times IV dose

Target level: 300-450ng/mL

Nephrotoxicity, Seizures, ↑ BP, gum hyperplasia, hirsutism

Table 4: Maintenance immune suppressionAgent/Class Mechanism of Action Dose Monitoring Side EffectsMaintenance Prednisone 0.25-1 mg/kg/day Wean to

off by 6 monthsCushingoid features, Adrenal suppression

Tacrolimus 0.3-0.5 mg/kg/d divided BID

Target level:5-15 ng/mL

Cyclosporine 5-20 mg/kg/day BID or TID Target level: 100-450ng/mL (Age & rejection based)

Sirolimus (Avoid 1 month after surgery as impairs wound healing)

Inhibition of mTOR, Inhibits T-cell activation & proliferation, Inhibits B-cell differentiation into antibody producing cells

Adult: 6 mg Day 1 then 2 mg/day Pediatric: D1: 3 mg/m2/day then 1 mg/m2/day

Target level: 5-10 ng/mL

↑ BP, ↓ WBC, hyperlipidemia, ↓ Platelets, Nephrotoxicity, ↑ Glucose, PTLD

Mycophenolate mofetil

Inhibits lymphocyte purine synthesis

600mg/m2/dose BID (Maximum 1 gm BID)

WBC > 4000ANC >1200 ↓ Platelets

PTLD: Post transplant lymphoproliferative disease, mTOR: mammalian Target of Rapamycin, WBC: White blood cells/mm3, ANC: Absolute neutrophil count, CNI: Calcineurin inhibitor



rejection was the leading cause of early death. Early discontinuation of prednisone has been clearly shown to have a long-term survival benefi t (Figure 7). CAV is the major cause of late graft loss and mortality. Freedom from CAV (%) post-transplant is shown in Figure 8. In our experience, patients who have had any episode of hemodynamically signifi cant rejection are more prone to develop CAV.

Long-term complicationsInfections55, 56

Various pre-operative and intra-operative factors predispose to infections, like failure to thrive, immune suppression, associated illnesses, prolonged indwelling lines and donor factors. Prophylactic pre-operative antibiotics are used, not recommend beyond 24 hours. Strict isolation is maintained and a high index of suspicion is observed. Bacterial infections are most commonly seen; CMV infection is the most commonly seen viral infection.

Renal dysfunctionAbout 5% of patients required renal replacement therapy (dialysis or renal transplant) at 11 years post-transplant. The most common etiology is nephrotoxicity secondary to CNI use.,. Renal dysfunction was more common in adolescents (14%) compared to infants and young children (5-7%)10. Hypertension due to CNI use, steroid effects and cardiac denervation is seen in 60-90% of children57.

MalignancyAccording to the latest ISHLT report, 18% of patients develop malignancy by 15 years post-transplant. Lymphoma is the most common malignancy in this population; higher incidence has been observed with the use of tacrolimus10,58.

Coronary allograft vasculopathy (CAV)CAV is a major cause of morbidity and mortality due to chronic graft dysfunction. It is seen in 8% of the patients by year 1, 30% after 5 years and 50% patient’s 10 years

Figure. 4. Kaplan-Meier Survival by age, Jan1982 – June 2011 (From Dipchand AI, Kirk R, Edwards LB, et al. The ISHLT 16th pediatric heart transplantation report—2013;. J Heart Lung Transplant. 2013 Oct; 32(10): 979-88, with permission from Elsevier)



Figure 5. Kaplan-Meier Survival by Era (From Dipchand AI, Kirk R, Edwards LB, et al. The ISHLT 16th pediatric heart transplantation report-2013; J Heart Lung Transplant. 2013 Oct; 32(10): 979-88, with permission from Elsevier)

Figure 6. Kaplan-Meier Survival by Mechanical Circulatory Support (From Dipchand AI, Kirk R, Edwards LB, et al. The ISHLT 16th pediatric heart transplantation report—2013;. J Heart Lung Transplant. 2013 Oct;32(10):979-88, with permission from Elsevier)



post transplant60. Coronary angiography is routinely performed in patients’ post-transplant for detection of CAV with the exception of infants. Noninvasive tests like stress testing and multislice coronary computed tomography angiography61 have been evaluated; however, coronary angiography still remains the gold standard. Accelerated fi bro- proliferative changes, which affect the coronary arteries, cause CAV63. HLA-DR mismatches, older donor, hypertension in donor, younger recipient, diabetes, hyperlipidemia and obesity in recipient are common risk factors for CAV59,62. HMG -CoAreductase inhibitors (statins) like pravastatin or atorvastatin have been shown to improve lipid profi le, decrease rejection, improved survival and decreased incidence of CAV64-68. CAV can present as multiple sequential lesions; diffuse narrowing, pruning of distal vessels or focal lesions of proximal vessels (Figure 9). After detection of CAV, patients need to be closely monitored, with long-term cardiac retransplantation being the therapeutic option with 1 and 5-year survival of 56% and 38%63, respectively. Sirolimus (rapamycinmTOR inhibitor)

can prevent development or delay progression of CAV by inhibiting arterial smooth muscle and endothelial cell proliferation69,70. Atrialtachyarrhythmias have been associated with increased incidence of rejection or undiagnosed CAV (8%)71. In a recent retrospective study from St. Louis Children’s hospital, intra-atrial reentry and ectopic atrial tachycardia were the most common rhythm disturbances identifi ed after heart transplantation without increased incidence of rejection72.

Neurodevelopmental outcomes & Functional statusDevelopmental outcomes can be in the low-normal range after transplantation and are similar after surgery for CHD73. School performance has been shown to be sub-optimal with a 10-15 point lower score on IQ testing73. Depression is seen in 50% of patients one year after heart transplantation74. Commonly encountered problems after transplantation are school or cognitive problems related to memory in 15.3% children, attention in 12.6%, missed school days in

Figure 7. Kaplan-Meier Survival Based on Prednisone Use, conditional on survival to one year (From Dipchand AI, Kirk R, Edwards LB, et al. The ISHLT 16th pediatric heart transplantation report-2013;. J Heart Lung Transplant. 2013 Oct; 32(10): 979-88, with permission from Elsevier)



12.4%, and trouble with mathematics in 20% children. No signifi cant differences were observed in emotional and social mean scores between transplant and patients post-surgery for CHD75.It is of paramount importance to identify and intervene in a timely manner for any cognitive disability to optimize the outcomes.

ConclusionWith improved immune suppression, organ support technologies, ventricular assist devices, improved surgical and cardiopulmonary bypass techniques the morbidity associated with transplantation is reduced and the survival rates improve. However, limited availability of organs makes it important to allocate them to the sickest and the patients who will benefi t the most. Future research will need to focus on decreasing chronic rejection, CAV and malignancy. As the surgical techniques are improving and more complex CHDs are repaired, the prevalence of patients with adult congenital heart disease is increasing. Many of these patients may need transplantation in the future.

Mechanical circulatory support is also an evolving fi eld, providing the patients with additional time to allow for bridge to transplantation or recovery.

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58. Dayton JD, Richmond ME, Weintraub RG, et al. Role of immunosuppression regimen in post-transplant lymphoproliferative disorder in pediatric heart transplant patients. J Heart Lung Transplant 2011; 30: 420–5

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60. Rahmani M, Cruz RP, Granville DJ, McManus BM. Allograft vasculopathy versus atherosclerosis. Circ Res 2006; 99: 801-15

61. Barthelemy O, Toledano D, Varnous S, et al. Multislice computed tomography to rule out coronary allograft vasculopathy in heart transplant patients. J Heart Lung Transplant 2012; 31: 1262–68

62. Nagji AS, Hranjec T, Swenson BR, et al. Donor age is associated with chronic allograft vasculopathy after adult heart transplantation: implications for donor allocation. Ann ThoracSurg 2010; 90: 168 –75

63. Radovancevic B, McGiffi n DC, Kobashigawa JA, et al. Retransplantation in 7,290 primary transplant patients: a 10-year multi-institutional study. J Heart Lung Transplant 2003; 22: 862-8

64. Seipelt IM, Crawford SE, Rodgers S, et al. Hypercholesterolemia is common after pediatric heart transplantation: initial experience with pravastatin. J Heart Lung Transplant 2004; 23: 317-22

65. Chin C, Gamberg P, Miller J, et al. Effi cacy and safety of atorvastatin after pediatric heart transplantation. J Heart Lung Transplant 2002; 21: 1213-7

66. Cutts JL, Bankhurst AD. Reversal of lovastatin-mediated inhibition of natural killer cell cytotoxicity by interleukin 2. J Cell Physiol 1990;145:244-52



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68. Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 1995;333: 621-7

69. Meiser BM, Billingham ME, Morris RE. Effects of cyclosporin, FK506, and rapamycin on graft-vessel disease. Lancet 1991;338: 1297-8

70. Eisen HJ, Tuzcu EM, Dorent R, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003;349:847-58

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Best EvidenceJournal Scan

Indira Jayakumar*, Rajeswari Natraj*, Sathish KumarKandath*,Ravi Kumar Thambithurai**, Suchitra Ranjit*

*Senior Consultant,**Junior consultant, Department of Pediatric Emergency and Intensive Care,Apollo Childrens Hospital, Chennai

1. Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle.Balas MC, Vasilevskis EE, Olsen KM, et al. Crit Care Med. 2014 May; 42(5): 1024-36.

ObjectiveThe debilitating and persistent effects of ICU-acquired delirium and weakness warrant testing of prevention strategies. The purpose of this study was to evaluate the effectiveness and safety of implementing the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle into everyday practice.

DesignEighteen-month, prospective, cohort, before-after study conducted between november 2010 and may 2012.

SettingFive adult ICUs, one step-down unit, and one oncology/hematology special care unit located in a 624-bed tertiary medical center.

PatientsTwo hundred ninety-six patients (146 prebundle and 150 postbundle implementation), who are 19 years old or older.

InterventionsAwakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle.

Measurements and main resultsFor mechanically ventilated patients (n = 187), we examined the association between bundle implementation and ventilator-free days. For all patients, we used regression models to quantify

the relationship between awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle implementation and the prevalence/duration of delirium and coma, early mobilization, mortality, time to discharge, and change in residence. Safety outcomes and bundle adherence were monitored. Patients in the postimplementation period spent three more days breathing without mechanical assistance than did those in the preimplementation period (median [interquartile range], 24 [7-26] vs 21 [0-25]; p = 0.04). After adjusting for age, sex, severity of illness, comorbidity, and mechanical ventilation status, patients managed with the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle experienced a near halving of the odds of delirium (odds ratio, 0.55; 95% ci, 0.33-0.93; p = 0.03) and increased odds of mobilizing out of bed at least once during an ICU stay (odds ratio, 2.11; 95% ci, 1.29-3.45; p = 0.003). No signifi cant differences were noted in self-extubation or reintubation rates.

ConclusionsCritically ill patients managed with the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle spent three more days breathing without assistance, experienced less delirium, and were more likely to be mobilized during their ICU stay than patients treated with usual care.

Editorial comments by John Devlin and Anne Pohlman, Crit Care Med. 2014: 42(5):1280-811. The time is right to evaluate current pain and

sedation practices in your ICU. Every patient, in every unit, should be assessed every day for the evidence-based practice interventions contained in the ABCDE bundle.


2. Some of your ICU colleagues may need to be educated about the deleterious effects that sedative-associated coma, prolonged immobility, and delirium have on both short- and long-term patient outcomes.

3. For ICU bedside clinicians, it is no longer a question of “if” but a question of “when” the ABCDE bundle interventions will be completed each day.

4. The awakening and breathing coordination, delirium monitoring/ management, and early exercise/mobility (ABCDE) bundle is an evidence-based, multicomponent, and multidisciplinary strategy to reduce sedative exposure, promote liberation from mechanical ventilation, and improve post-ICU functionality and cognitive function.

5. Failure to titrate the sedatives and analgesics that we routinely administer in the ICU to optimize patient comfort to a light, rather than deep, level of sedation will prolong mechanical ventilation and increase delirium. ICU-acquired weakness will be potentiated

6. Rigorous controlled studies have demonstrated that use of daily awakening, spontaneous breathing trials (DA-SBTs) and early mobilization protocols are not associated with safety concerns and will reduce duration of mechanical ventilation, lower the prevalence of coma and delirium, and improve post-ICU to improve post-ICU outcome

7. Although the recent sccm practice guidelines strongly recommend the use of both da-sbt and early mobilization strategies these interventions are not routinely implemented on a daily basis in most ICUs.

8. The authors conclude that patients managed with the ABCDE bundle spent three more days breathing without mechanical assistance, were twice as likely to be mobilized out of bed during their ICU stay, and were half as likely to develop delirium. No safety concerns, such as a greater rate of patient self-extubation, were noted.

9. This important study of integrating the ABCDE bundle into everyday practice has many strengths.

10. This study focused on establishing effi ciency of ABCDE bundle interventions with bedside clinicians and no additional staff or resources to

help maintain compliance with it. 11. How can you boost the use of the ABCDE bundle

in your ICU? As with any ICU multifaceted quality improvement effort, it is critical to identify the correct interdisciplinary team prior to implementation.

12. An ICU culture that promotes team work, accountability, and consistency are key ingredients to the success of any quality improvement bundle.

Pediatric studies are required to measure the impact of the ABCDE bundle on PICU patients, but there is no reason to suggest that it may be different.The ABCDE approach is a great quality initiative shown to decrease vent days and costs

2. Inhaled antibiotics target superbugs better: Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit.Palmer LB, Smaldone G. Am J Respir Crit Care Med, 2014: 189 (10), 1225-1233

SummaryThe intensive care unit is a haven for multidrug-resistant organisms, some of which are diffi cult to eradicate. Routine use of systemic antibiotics inevitably lead to super-infections. Palmer et al suggest aerosolized antibiotics (AA), which achieve local concentrations in the airway 100-fold greater than the minimal inhibitory concentration that will eradicate resistant bacteria in the proximal airways without systemic toxicity or furthering bacterial resistance.They conducted a double-blind placebo-controlled study enrolling patients aged more than 18years and mechanically ventilated. Patients with more than three risk factors for mul ti drug resistant organism(MDRO)were enrolled. They were randomized based on presence of purulent secretions and clinical pulmonary infection score >6. Using a well-characterized aerosol delivery system, AA or saline placebo was given for 14 days or until extubation. Sputum samples were taken for gram stain and semi quantitative culture before initiation of therapy and at the end of treatment. Based on the gram stain results, patients received vancomycin hydrochloride, 120 mg every 8 hours

BEST EVIDENCE Journal Scan


for gram positive infections and gentamicin sulfate 80mg every 8 hours or amikacin 400mg every 8 hours for gram negative organisms. Both vancomicin and aminoglycosides were considered for combined infection. Two ml saline was used for placebo.Aerosol treatment was given for 14 days or until the patient was extubated.Findings revealed similar demographic variables, systemic antibiotic appropriateness (defined by susceptibility and at least 5 days of treatment) in both the groups. Apache scores being greater in the AA group (20.9 vs. 14.1 p=0.0007).Aerosolized antibiotics were associated with greater eradication of bacteria present at randomization 26/27 vs. 2/23 (p<0.001). Eradication of original resistant bacteria on culture and gram stain at end of treatment was 14/16 vs. 1/11 (p<0.001). AA reduced clinical pulmonary infection score (mean ± sem)9.3 ± 2.7 to 5.3 ± 2.6 vs. 8.0 ± 23 to 8.6 ± 2.10; (p = 0.0008). No drug resistance to AA was noticed.Placebo was associated with increased development of resistant organisms (p=0.03).

CommentsMultidrug-resistant organisms (MDRO) are the dominant airway pathogens in the intensive care unit and represent a major treatment challenge to intensivists. The American Thoracic Society(ATS) Guidelines recommend inhaled antibiotics for vap caused by MDRO only when intravenous antibiotics have failed. However prophylactic use of aerosolized nebulization at the onset of treatment based on gram stain analysis in ventilated patients at risk for MDRO would prevent emergence of these multidrug resistant organisms. This study was well randomized and showed inhaled antibiotics eradicated resistant organisms in tracheal secretions and reduced the development of new resistance to systemic agents. However, the fl aw in the study was non-respiratory sites were not included to determine overall effect on antibiotic resistance. It is also important to note that the device selected to deliver the drug should be well characterized for particle size and efficiency. To achieve high concentrations of drug in the airways, aerosols should be delivered during controlled inspiratory breaths bypassing the humidifi cation system.

RecommendationLarger studies are required to recommend routine

use of aerosolized nebulizations at the onset of therapy in patients with high risk for MDRO to eradicate resistant airway organisms and include non respiratory sites to prove the effi cacy of AA in preventing emergence of new resistance to systemic antimicrobials.

3. Daily chlorhexidine bathing to reduce bacteremia in critically ill childrenAaron M Milstone, Alexis Elward, Xiao Yansong, et al For the pediatric scrub trial study group.The lancet 2013; 381:1099-1106

SummaryThe pediatric scrub trial group conducted this well designed multicentre study to assess whether daily bathing in chlorhexidine gluconate (ChG) compared with standard bathing practices reduced bacteremia in critically ill children. 10 pediatric intensive-care units at 5 hospitals in the United States participated in this unmasked, cluster-randomised, two-period crossover trial. 4072 of 4947 enrolled patients were randomly assigned a daily bathing routine, for either standard bathing practices or using a cloth impregnated with 2% ChG, for a 6-month period. Units switched to the alternative bathing method for a second 6-month period. Patients were not eligible if they were younger than 2 months of age, had an indwelling epidural or lumbar drain, severe skin disease, burns, or allergy to ChG.The fi ndings in this study revealed that there was a 36% reduction in the incidence of bacteremia in patients receiving daily ChG bathing (3·28 per 1000 days, 2·27–4·58) compared with standard practices (4·93 per 1000 days, 3·91–6·15; adjusted incidence rate ratio(AIRRO) 0·64, 0·42–0·98. Furthermore, daily ChG bathing was well tolerated and only 12 patients (1%) withdrew because of ChG related irritation with no serious adverse reaction.

CommentsHealth care associated infections pose a signifi cant burden to life and resources. The longer the patient remains in the ICU the more likely colonization occurs and colonization is the fi rst step to invasive infections. Studies attempting to decolonize patients



have demonstrated reduced rates of infection. Chlorhexidine gluconate is a water soluble antiseptic preparation with a broad activity against bacteria, yeast and viruses . Routine ChG bathing has not been studied previously in pediatric population. More than 4900 patients were included, making this one of the largest clinical trials in critically ill children. The strength of this study was incorporating a cluster randomization crossover into the design which enabled estimation of treatment effect by comparing each unit with itself during treatment and control periods.

RecommendationChlorhexidine bathing is a simple, easily implementable and safe adjunctive intervention that can be added to the existing armamentarium of infections control practices in intensive care units {Current CDC(Center for disease control) recommendation to reduce blood stream infections and MRSA: Methicillin resistant Staphylococcus}

4. A randomised trial of protocol -based care for early septic shockThe ProCESS investigators. The New England Journal of Medicine 2014; 370(18): 1683-1693

Summary This well designed multicentric randomised control study was done in 31 emergency departments in the United States to assess whether all elements of a standard emergency goal directed therapy (EGDT) are necessary in the management of septic shock and was done by comparing three different strategies - protocol based EGDT, protocol based standard care and usual care. EGDT group was similar to rivers et al. Standard care was a 6 hr time limited intervention protocol developed by investigators where in fl uid replete state was decided by the study clinician, PRBC goal was for Hb 7.5 g/dl, Central venous catherization and scvo2 were not mandatory. In both protocolised groups prompts were given by the study coordinator for interventions. Usual care was given as per the treating physician. The primary endpoint was 60 day mortality.1341 patients were enrolled and randomly assigned to the three groups. Inclusion criteria were suspected sepsis and refractory hypotension or lactate > 4mmol/l and patients enrolled within 2 hrs of shock

recognition. All groups were identical in their demographics. Adherence to protocol was good. Central lines were placed in 93.2 % in EGDT group vs about half of the patients in the other 2 groups. Scvo2 monitoring in EGDT was 93.6 % compared less than 5 % in the other 2 groups. During the study, standard group received maximum fl uids, whereas EGDT group received more dobutamine and PRBCs. Both protocol based groups received more vasopressors. The mortality at 60 days was similar for all three groups (21%, 18.2%, and 18.9%). There was no signifi cant difference at 90 day,1yr mortality or need for organ support amongst the groups.The study concluded no advantage of protocol based care over usual care and no benefi t of central venous line and invasive hemodynamic monitoring.

CommentsThe improved mortality compared to Rivers et al can be attributed to differences in study population (more co morbidities and lower scvo2 of 49% in the rivers study). Most importantly, in ProCESS study, recognition of shock was very early, 75 % patients got antibiotics and about 2l of fl uids before randomization. Even though the results of the study are negative for a difference in mortality it provides a conclusive evidence about the above mentioned key elements of resuscitation.There is no difference of outcomes between protocolised groups and usual care group. Usual care has changed from Rivers et al study to now. With increased septic shock awareness (including the surviving sepsis campaign), streamlined and quick care is being delivered to patients in the emergency department and has resulted in signifi cant drop in mortality. All the participating units were academic centres where usual care is expected to be at par with standard of care world wide.Moving away from protocolised approach may result in loss of inroads made in septic shock outcome. But more care may not always mean better care.

Recommendations All hospital emergency rooms must have strategies in place for early recognition of septic shock, aggressive and adequate fl uid resuscitation and early administration of appropriate antibiotics to maximize outcomes in septic shock.Early invasive lines and invasive hemodynamic



monitoring including continuous scvo2 may not be necessary for all. Arise and promise trials may provide further evidence to this extent.Generalisation of these to children should be done with caution in relation to noninvasive bp measurement (inaccurate readings of nibp due to a signifi cant proportion presenting with high svr cold shock) and also safety of trying to persist with peripheral lines in children with inherent diffICUlt access.

5. Controlled rapid sequence induction and intubation - an analysis of 1001 children. Neuhaus d, Schmitz a, Gerber a, Weiss M. Paediatr Anaesth. 2013; 23(8):734-40.

BackgroundClassic rapid sequence induction(RSI) puts pediatric patients at risk of cardiorespiratory deterioration and traumatic intubation due to their reduced apnea tolerance and related shortened intubation time. A ‘controlled’ rapid sequence induction and intubation technique (CRSII) with gentle facemask ventilation prior to intubation may be a safer and more appropriate approach in pediatric patients. The aim of this study was to analyze the benefi ts and complications of CRSII in a large cohort.

MethodsRetrospective cohort analysis of all patients undergoing CRSII according to a standardized institutional protocol between 2007 and 2011 in a tertiary pediatric hospital. By means of an electronic patient data management system, vital sign data were reviewed for cardiorespiratory parameters, intubation conditions, general adverse respiratory events, and general anesthesia parameters.

ResultsA total of 1001 patients with CRSII were analyzed. Moderate hypoxemia (spO2 80-89%) during CRSII occurred in 0.5% (n = 5) and severe hypoxemia (spO2 <80%) in 0.3% of patients (n = 3). None of these patients developed bradycardia or hypotension. Overall, one single gastric regurgitation was observed (0.1%), but no pulmonary aspiration could be detected. Intubation was documented as ‘diffi cult’ in two patients with expected (0.2%) and in three

patients with unexpected ‘diffi cult’ intubation (0.3%). The further course of anesthesia as well as respiratory conditions after extubation did not reveal evidence of ‘silent aspiration’ during CRSII.

ConclusionControlled RSII with gentle facemask ventilation prior to intubation supports stable cardiorespiratory conditions for securing the airway in children with an expected or suspected full stomach. Pulmonary aspiration does not seem to be signifi cantly increased.

CommentsThe aim of RSI is primarily to prevent aspiration and achieve excellent intubating conditions such that desaturation during the apnoiec period is minimized. To this end, standard teaching of rapid sequence induction (RSI) includes cricoid pressure and avoidance of any positive pressure bag-mask ventilation during the procedure. However many reports indicate that cricoid pressure can worsen, can interfere with laryngoscopic view and increase intubating diffi culty. Moreover, children can desaturate quickly after the onset of apnea, especially in the presence of parenchymal pathology and lowered functional residual capacity. In these cases, desaturation can be prevented by gentle bag-mask ventilation while awaiting complete muscle relaxation for laryngoscopy.This is a swiss study that examined 1001 children undergoing RSI for non-cardiac surgery. They used a ‘controlled rapid sequence induction and intubation (CRSII)’ approach for children assumed to have full stomachs. This procedure followed most of the principles of RSI the way it is currently done in many modern critical care settings, with special emphasis on the following:• No cricoid pressure at any stage• Ketamine for induction if hemodynamically

unstable• A non-depolarising neuromuscular blocker rather

than succinylcholine• Gentle facemask ventilation to maintain

oxygenation until intubation conditions achieved• Intubation with a cuffed tracheal tubeThe main fi nding was that CRSII demonstrated a considerably lower incidence of oxygen desaturation and consecutive hemodynamic adverse events during



anesthesia induction than shown by a previous study on classic RSI in children. Furthermore, there was no incidence of pulmonary aspiration during induction, laryngoscopy, and further course of anesthesia.These fi ndings may be especially relevant in the pediatric emergency room and PICU settings where intubation for hypoxemic child with altered lung mechanics may pose a signifi cant risk when traditional RSI is performed.

6. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock Morelli A, Ertmer C, Westphal M et al. JAMA. 2013; 310(16): 1683-91

SummaryMorelli et al did an open labelled randomized control trial in a single centre to evaluate the effect of intravenous beta blockers esmolol in improving the outcome involving patients(154 patients) in septic shock with a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain a mean arterial pressure of 65 mm hg or higher after achieving other EGDT(Emergency goal directed therapy) goals. The study defi ned primary outcome as reduction in heart rate below the predefi ned threshold of 95/min and to maintain heart rate between 80/min and 94/min by esmolol treatment over a 96-hour period. Secondary outcomes included hemodynamic and organ function

measures;Norepinephrine dosages at 24, 48, 72, and 96 hours; and adverse events and mortality occurring within 28 days after randomization. The study showed use of esmolol vs standard care was associated with reductions in heart rates to achieve target levels, without increased adverse events in septic patients. They also showed that esmolol resulted in increase stroke volume, maintained map, and reduce norepinephrine requirements without increasing the need of inotropic support or causing adverse effects on organ function with an associated improvement in 28-day survival.

CommentsExcessive adrenergic stress in septic shock has multiple adverse effects.High plasma catecholamine levels, the extent and duration of catecholamine therapy, and tachycardia are all independently associated with poor outcomes in critically ill patients. This study has shown that measures to reduce heart rate reduction using short acting esmolol may also benefi t. Limitations of the study are several: 1. Its a single centre adult study 2.It is non-blinded.3 selection of an arbitrary predefi ned heart rate threshold rather than an individualized approach.Recommendation:This is an interesting lead trial which needs further studies in large randomized control trials to identify mortality benefi ts, other organ dysfunction as primary outcomes. Plus studies in pediatric population are required for validation asheart rate ranges are different and furthermore, hypotension is a late feature in this age group compared to adults.



Critical Th inkingPICU Quiz

Nameet Jerath, MDSenior Consultant, Pediatric Intensivist Pulmonologist

IP Apollo Hospital, New Delhi

1. A 9-month-old boy presents with diffi culty breathing. His mother states that he has been treated for croup twice already in the last 4 months with similar symptoms. He has had 2 days of upper respiratory tract infection symptoms and now has expiratory stridor on examination. Which of the following is correct?a. Recurrent acute laryngotracheobronchitis

(croup) needs further investigation and should not be ignored

b. Intrathoracic airway obstruction is typically worse during inspiration

c. Extrathoracic airway obstruction is typically worse during inspiration

d. Croup (viral laryngotracheobronchitis) is typically characterized by intrathoracic airway obstruction

e. All are true

2. A patient with acute respiratory distress syndrome has been managed with high-frequency oscillatory ventilation for the past 2 hours. A blood gas study shows pH of 7.48, PaCO2 of 30 mm Hg, PaO2 of 70 mm Hg, bicarbonate level of 22 mEq/L, and oxygen saturation of 97% on a FIO2 of 0.6. Which of the following is the most appropriate intervention?a. Wean the mean airway pressure.b. Increase the delta P.c. Decrease the frequency.d. Increase the mean airway pressure.e. Increase the frequency.

3. A 2 year old child is ventilated for 3 days with bronchiolitis. You extubate him today and almost immediately notice a signifi cant stridor. Which of the following is true of this condition?

a. Occurs in 50% of children.b. Begins within 18 hours, peaks at 48 hours,

andresolves by 5 days.c. Patients with active coughing and very light

sedation are less likely to develop this

d. More prevalent in children above 5 years of agewho have undergone neck surgery.

e. All of the above.

4. A 12 year 48 kg boy with deep burns to about 85% body surface area involving most of trunk and lower extremities is admitted to your ICU, intubated and ventilated. His ventilatory parameters are: Synchronized intermittent mandatory ventilation+Pressure Control/Pressure Support, rate 25, pressures (Peak inspiratory pressure over PEEP/PEEP) 32+6/6, (Tidal volume generated 160ml) Inspiratory time 0.9 sec, FiO2 1. ABG shows pH 7.2, pCO2 82, pO2 52, HCO3 18.Chest Radiograph: clear fi elds.What is the most appropriate measure?a. Acceptable parameters, continue on same

settings avoiding further injury to lungsb. Escharotomy of chest woundc. Increase PEEP, likely developing ALI (Acute

lung injury)d. Switch to High Frequency Oscillatory

Ventilation (HFOV), needs higher Mean Airway Pressure

e. Bronchoscopic toilet of lungs

5. A 15-day-old child is brought in respiratory distress. A Chest radiograph done shows markedly increased pulmonary vascularity. The echocardiogram shows Double Inlet Right Ventricle(DIRV) and confi rms torrential pulmonary fl ows. The vitals: HR 178, BP 50/28, RR 90, SPO2-98%.ABG: pH 7.25, pCO2 35, pO2 90, BE -13, lactate 6.The child is intubated and initiated on mechanical ventilation. The cardiologist and surgeons plan for pulmonary artery banding which can only happen the next morning. Over the next few hours the child has drop in urine output and the ABG on room air shows- pH 7.20, pCO2 40, pO2 84, BE -17, lactate 9.


Which of the following is the most appropriate step?a. iNOb. Nitrogenc. Epinephrine infusiond. Increase FiO2e. NaHCO3 infusion

6. A 9 month old girl presents to the ED with stridor and respiratory distress for the last 2 days, no fevers. She was recently discharged from the hospital about 3 weeks back when she was admitted for sepsis, hypernatremia and encephalopathy needing mechanical ventilation for 4 days during her PICU stay. She was normal on discharge. A laryngoscopy done shows signifi cant obstruction below the cords. Which of the following is likely to be associated with her condition?a. Sepsisb. Larger endotracheal tubec. Gastroesophageal refl uxd. Eosinophilic esophagitise. All of the above

7. A 4 year old child has been on ventilator for streptococcus pneumonia for the last 3 days and is improving in lung condition.Ventilator settings are down and FiO2 requirement is only 0.25. You are worried that he might fail extubation as he has SIADH and positive fl uid balance in past 24 hours. You decide to extubate him from the ventilator. Which of the following statements holds true for his condition?a. SIADH is likely to improve with improving

pneumonia and with discontinuation of positive pressure ventilation.

b. Concurrent frusemide must be given to improve chances of successful extubation

c. Low dose dopamine should be commenced to offset the increase in afterload on extubation

d. Infi ltrates would worsen after extubation with higher chances of reintubation than usual

8. A 7 year old child is admitted in your PICU with fevers, yellow discoloration of eyes and altered sensorium over the last week. On examination you fi nd him deeply icteric, drowsy with fl exion response to painful stimulus. The lab reports show an INR of 4.3. All of the following are appropriate

for this child except?a. Tracheal intubationb. IV antibioticsc. Lactulosed. Vitamin Ke. 3% NaCl

9. All of the following are true regarding peri-extubation corticosteroids and stridor/ reintubation excepta. Steroids given prophylactically have not

shown any benefi t in infants b. Steroids have shown a benefi t in children with

airway abnormalitiesc. Multiple doses begun 12-24 hours before

extubation are of benefi t in adultsd. Steroids before extubation reduces the risk of

reintubation in adultse. All are true

10. A 15 kg child is on Total parenteranl nutrition(TPN) in your unit. He is getting 1100ml of TPN in a day giving him a total of 1250 kcal, through a central line. He is on 2gm/kg of proteins and 3gm/kg of fats. All of the following statements are true for this child except ?a. An adequate ratio of non-protein calorie is

required to avoid oxidation of exogenous proteins

b. The protein to non-protein calorie ratio is around 1: 30 and adequate

c. The Nitrogen to non-protein calorie ratio is around 1: 200 and adequate

d. This concentration of TPN should not be given through a central line

e. All the statements are true

Quiz: Answers and explanations 1. Answer: c

Acute laryngotracheobronchitis presents with inspiratory stridor and is typical of extrathoracic obstruction. Extrathoracic obstruction worsens during inspiration. Obstruction increases the velocity of air and hence drops the pressures intraluminally (Venturi principle). The surrounding atmospheric pressure collapses the airway during inspiration because of a more negative intraluminal pressure.

CRITICAL THINKING PICU Quiz


2. Answer: eA child with ARDS is hyperventilated on the HFOV as suggested by the pH and the PaCO2 levels. The SpO2 is reasonable on 60% FiO2 and attempts to wean mean airway pressure would be a little premature. Ventilation (CO2 washout) is a function of tidal volume (read delta P) and frequency on the HFOV. Increasing delta P would washout CO2 even further by increasing the swing of the piston and the tidal volume. Contrary to conventional ventilation, frequency has an inverse relationship to CO2 and increasing the frequency (hertz) would increase the PaCO2.

3. Answer: e This is the condition of postextubation croup. It occurs in approximately 5% of intubated children and usually resolves in 24 hours. It is more common in patients with frequent coughing episodes and in patients who are more agitated and moving frequently while intubated. It has been shown to be more prevalent in children 1–4 years or age, particularly in association with any type of surgery in the head/neck area.

4. Answer: bThe scenario is of extrinsic restriction of lung expansion most likely due to eschar formations on trunk. Escharotomy of all circumferential burns should be undertaken as an emergency. Some incomplete eschars may need excision too to help chest expansion.

5. Answer: bThis is a situation of single ventricle physiology. Unrestricted pulmonary blood fl ows is causing systemic hypoperfusion and shock.Pulmonary artery(PA) banding is the emergency procedure of choice but in a situation that it cannot be performed immediately inhaled nitrogen or carbon dioxide can be used to induce hypoxemic pulmonary vasoconstriction to improve systemic blood fl ow.

6. Answer: eSubglottic stenosis is an uncommon complication of tracheal intubation. A larger than adequate tube is the most common association but sepsis, GER and eosinophilic esophagitis have all been implicated in the formation of subglottic stenosis.

7. Answer: aLung infection and positive pressure ventilation both cause an inappropriate increase of ADH and cause the body to hold on to free water. Extubation would reverse this and cause spontaneous diuresis. For a child who has improved, use of Frusemide or Dopamine cannot be justifi ed.

8. Answer: cThe child has fulminant hepatic failure. Control of airways in a comatose child, hemodynamic support, prophylactic antibiotics and antiedema measures are all accepted treatment modalities for the child. Lactulose is not preferred because of the risks of aspiration, ileus and lack of outcome benefi ts and is no longer recommended.

9. Answer: dThe Cochrane metanalysis and review on this topic (Khemani RG, Randolph A, Markovitz B. Corticosteroids for the prevention and treatment of post-extubation stridor in neonates, children and adults. Cochrane Database of Systematic Reviews 2009) shows that steroids may be of benefi t in infants and children with airway abnormalities in reducing post extubation stridor. Steroids begun pre-extubation in adults does reduce the incidence of stridor but not of reintubation.

10. Answer: dAn adequate ratio of nitrogenous to total calories is justifi ed to ensure proper utilization of exogenous proteins. The desired ratio of N: NonNitrogen calorie of 1: 250-350 is generally recommended. This is the same as having a protein: non-protein calorie ratio of 1: 25-35. This calorie concentration can be safely given through the central line.

CRITICAL THINKING PICU Quiz



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