Christian F. Poets Axel Franz Petra Koehne. Controversies around treatment of the open duct

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1 Christian F. Poets Axel Franz Petra Koehne Controversies around treatment of the open duct

2 Christian F. Poets Axel Franz Petra Koehne Controversies around treatment of the open duct 123

3 Christian F. Poets Universitätsklinikum Tübingen Neonatologie Calwerstr Tübingen Petra Koehne Charité Universitätsmedizin Berlin Klinik für Neonatologie Augustenburger Platz Berlin Axel Franz Universitätsklinikum Tübingen Neonatologie Calwerstr Tübingen ISBN Springer-Verlag Berlin Heidelberg New York Bibliographic information Deutsche Bibliothek The Deutsche Bibliothek lists this publication in Deutsche Nationalbibliographie; detailed bibliographic data is available in the internet at < This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable to prosecution under the German Copyright Law. SpringerMedizin Springer-Verlag GmbH ein Unternehmen von Springer Science+Business springer.de Springer-Verlag Berlin Heidelberg 2011 The use of general descriptive names, registered names, trademarks, etc. in this publications does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Planning: Diana Kraplow Project management: Diana Kraplow Cover design: deblik Berlin Typesetting and reproduction of the figures: Fotosatz-Service Köhler GmbH Reinhold Schöberl, Würzburg 18/ SPIN

4 V Preface The patent ductus arteriosus continues to pose a considerable challenge to clinicians and scientists alike. Why does it close spontaneously in most infants but remain open in others? How best can we select those infants who are most likely to benefit from treatment, i.e. are there echocardiographic criteria that would help in defining a more selective treatment approach? Would it be better to take an aggressive approach and prescribe prophylactic treatment to all extremely immature infants and if so, what is the best way to define such a subgroup? Or should we rather be more restrictive in applying the current treatment indications and adopt a wait and see policy in most, if not all, premature infants? Finally, are there data to suggest that one of the treatment approaches that are available to close the patent ductus arteriosus is superior to the other? These and other pressing questions were addressed during a meeting on the treatment of the patent ductus arteriosus, convened on September 30 to October 1, 2010, in Stuttgart, Germany. Presentations given during this meeting have been summarized by the authors for this book; they are supplemented by a report on the discussions that followed each lecture. This endeavour was made possible by the generous support of Orphan Europe; however, the contents of this book do not necessarily reflect the views of the company. We hope that readers find the data presented here helpful in arriving at appropriate decisions when faced with the dilemma of how to deal with the patent ductus arteriosus best in their patients. Our sincere thanks to all the authors for their contributions without their efforts this book would not have been possible. Tübingen and Berlin, May 2011 Christian F. Poets, MD, Axel Franz, MD, and Petra Koehne, MD

5 VII Table of Contents Ductal Closure After Birth Morphological Aspects and New Insights R. Bökenkamp Introduction Developmental Background Ductal Maturation Postnatal Anatomical Remodelling PDA in Premature Infants Morphologic Aspects Signalling Related to Ductal Closure Genetic and Environmental Risk Factors for PDA in Premature Infants Prevention of DA Closure in Neonates with CHD Conclusion References Treatment Results After Ductal Closure in Extremely Low Gestational Age Infants P. Koehne Factors Determining Outcome of Very Low Birth Weight Infants 12 Impact of Patent Ductus Arteriosus Intervention for Outcome.. 12 Prophylactic Cyclooxygenase Inhibitor Treatment Prophylactic Ligation of the Ductus Arteriosus Therapeutic Use of Cyclooxygenase Inhibitors for Patent Ductus Arteriosus Intervention Surgical Ligation of Patent Ductus Arteriosus After Failed Pharmacological Intervention Conclusions and Perspectives References Echocardiographic Assessment of the Patent Ductus Arteriosus in the Preterm Infant N. Evans Introduction Doppler Ultrasound

6 VIII Table of Contents Is the Ductus Arteriosus Patent? How Wide is the Ductus Arteriosus? What is the Direction and Velocity of the Shunt? What is the Hemodynamic Significance of the PDA? Impact of the Ductal Shunt on the Lungs Impact of the Ductal Shunt on the Systemic Circulation Prediction of Spontaneous and Therapeutic Ductal Closure Summary References Evaluation of the Open Duct Using Systolic Time Intervals and Doppler Sonography of Peripheral Arteries E. Robel-Tillig Systolic Time Intervals Definitions of the Ejection Time and the Pre-Ejection Period How to Measure the Ejection Time and the Pre-Ejection Period? 58 Reference Ranges for the Ejection Time and the Pre-Ejection Period Doppler Sonographic Blood Flow Parameters of Peripheral Arteries Measurement of Blood Flow Parameters of Peripheral Arteries.. 60 Descending Aorta Anterior Cerebral Artery Superior Mesenteric Artery Renal Artery Summary and Conclusion References Competitive Inhibition of Bilirubin-Albumin Binding by Ibuprofen L. Desfrère, C. Huon Introduction Hyperbilirubinemic Encephalopathy in Preterm Infants Measurement of Unbound Bilirubin Concentrations Bilirubin-Albumin Binding and Bilirubin Displacers IBU Concentrations During Treatment of hspda Bilirubin-Albumin Displacing Effect of IBU in Vitro

7 Table of Contents IX Bilirubin-Albumin Displacing Effect of IBU in Vivo Conclusions References Controversies Around Treatment of the Open Duct B. Van Overmeire Introduction Fluid Restriction for PDA? Which Drug Should Be Used? A Choice Based on Side Effects? Optimal Dosing of Indomethacin and Ibuprofen? Is There a Role for Prophylaxis? Conclusion References High-Dose Therapy with Cyclooxygenase-Inhibitors for Symptomatic Persistent Ductus Arteriosus in Preterms.. 93 B. Beedgen Treatment Options Pharmacological Treatment High-Dose Therapy with Indomethacin Effectiveness and Side Effects of Escalating High-Dose Therapy Long-Term Follow-up Follow-up Results Conclusions Critical Perspective Concerning High-Dose Therapy with Indomethacin High-Dose Therapy with Ibuprofen Outlook References Risks and Benefits of Aggressive and Conservative Approaches to the Management of the Patent Ductus Arteriosus in Premature Infants S. Aliaga, M.M. Laughon Introduction PDA and Clinical Outcomes

8 X Table of Contents PDA and Bronchopulmonary Dysplasia PDA and Necrotizing Enterocolitis PDA and Neurodevelopmental Impairment Other systematic reviews Risks of Treatment Indomethacin Ibuprofen Surgical Ligation Center (Centre) Variation in Treatment of the PDA Conclusion References Missing Data for an Evidence-Based Approach to the Treatment of a Patent Ductus Arteriosus A Small Selection of What We Do not Know Yet A. Franz Prophylactic Interventions Therapeutic Interventions The Problem of Indications for Treatment, i.e., the Definition of a PDA Requiring Therapy The Problem of Contamination The Lack of Data on Long-Term Outcome Further Open Questions Summary References Summary of the Discussions During the International Workshop on Controversies Around Treatment of the Patent Ductus Arteriosus P. Herrmann Subject Index

9 XI List of Contributors Sofia Aliaga, MD, MPH School of Medicine Division of Neonatal-Perinatal Medicine The University of North Carolina at Chapel Hill Chapel Hill, NC Bernd Beedgen, MD Klinik Kinderheilkunde IV (Schwerpunkt Neonatologie), Zentrum für Kinderund Jugendmedizin, Universitätsklinikum Heidelberg Im Neuenheimer Feld Heidelberg, Germany uni-heidelberg.de Regina Bökenkamp, MD Abteilung Kinderheilkunde III Pädiatrische Kardiologie und Pädiatrische Intensivmedizin Medizinische Hochschule Hannover Carl-Neuberg-Straße Hannover Luc Desfrère, MD Service de Néonatologie Hôpital Louis Mourier, AP HP Colombes Université Paris 7 Faculté de Médecine Denis Diderot Paris France Nick Evans DM, MRCPCH Department of Newborn Care Royal Prince Alfred Hospital Missenden Rd, Camperdown, Sydney, New South Wales 2111 Australia nevans@med.usyd.edu.au Axel Franz, MD Universitätsklinikum Tübingen Neonatologie Calwerstr Tübingen Pricilla Herrmann, MA Center for Pediatric Clinical Studies Frondsbergstraße Tübingen Petra Koehne, MD Charité Universitätsmedizin Berlin Klinik für Neonatologie Augustenburger Platz Berlin petra.koehne@charite.de Matthew M. Laughon, MD, MPH School of Medicine Division of Neonatal-Perinatal Medicine The University of North Carolina at Chapel Hill Chapel Hill, NC matt_laughon@med.unc.edu

10 XII List of Contributors Eva Robel-Tillig, MD Klinikum St. Georg Fachbereich Neonatologie/ Pädiatrische Intensivmedizin Delitzscher Str Leipzig Bart Van Overmeire, MD, PhD Head of Neonatal Intensive Care Unit Professor of Paediatrics Erasmus Hospital ULB, Université Libre de Bruxelles Brussels Belgium