20, 2012 Health Technology Assessment Extracorporeal Membrane Oxygenation (ECMO) Final Evidence Report February 12, 2016 Health Technology Assessment Program (HTA) Washington State Health Care Authority PO Box 42712 Olympia, WA 98504-2712 (360) 725-5126 www.hca.wa.gov/hta [email protected] FINAL APPRAISAL DOCUMENT Extracorporeal Membrane Oxygenation (ECMO) February 12, 2016 Karin U. Travers, DSc Research Director Elizabeth Russo, MD Research Scientist Patricia Synnott, MALD, MS Research Associate Rick Chapman, PhD, MS Director of Health Economics Steven D. Pearson, MD, MSc President Daniel A. Ollendorf, PhD Chief Scientific Officer WA – Health Technology Assessment February 12, 2016 Contents List of Acronyms........................................................................................................................................ ii About ICER ............................................................................................................................................... iii Acknowledgements ................................................................................................................................. iv Executive Summary ............................................................................................................................. ES-1 ICER Integrated Evidence Ratings ...................................................................................................... ES-38 1. Background ........................................................................................................................................... 1 2. Washington State Agency Utilization Data ........................................................................................... 3 3. Treatment Strategies: Interventional and Conventional ...................................................................... 4 4. Clinical Guidelines and Training Standards ........................................................................................... 8 5. Medicare and Representative Private Insurer Coverage Policies ....................................................... 12 6. Previous Health Technology Assessments and Systematic Reviews .................................................. 14 7. Ongoing Comparative Studies ............................................................................................................ 17 8. Methods .............................................................................................................................................. 20 9. Results ................................................................................................................................................. 25 ICER Integrated Evidence Ratings ........................................................................................................... 52 Appendix A: Milestones in the Development of ECMO .......................................................................... 63 Appendix B: Literature Search Strategy .................................................................................................. 64 Appendix C: Summary Evidence Tables .................................................................................................. 66 Appendix D: ICER Integrated Evidence Ratings ...................................................................................... 91 Extracorporeal Membrane Oxygenation: Final Evidence Report Page i WA – Health Technology Assessment February 12, 2016 List of Acronyms AED Automated external defibrillators ARDS Acute respiratory distress syndrome AV Arteriovenous avECCO2-R Arteriovenous extracorporeal carbon dioxide removal CADTH Canadian Agency for Drugs and Technology in Health CI Confidence interval CMS Centers for Medicare and Medicaid COPD Chronic obstructive pulmonary disease CPB Cardiopulmonary bypass CPR Cardiopulmonary resuscitation ECCO2-R Extracorporeal carbon dioxide removal ECMO Extracorporeal membrane oxygenation ECLS Extracorporeal life support ED Emergency department ELSO Extracorporeal Life Support Organization FiO2 Fraction of inspired oxygen HR Hazard ratio ICU Intensive care unit iLA Interventional lung assist IQR Interquartile range LOS Length of stay LV Left ventricle NICE National Institute for Health and Care Excellence NIV Noninvasive ventilation NS Not significant OR Odds ratio PaC O2 Partial pressure of arterial CO2 PaO2 Arterial oxygen pressure pECLA Pumpless extracorporeal lung assist PEEP Positive end-expiratory pressure PICO Population, Intervention, Comparators, Outcomes PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses RCT Randomized controlled trial RR Relative risk SD Standard deviation SLR Systematic literature review SPO2 Oxygen saturation USPSTF united States Preventive Services Task Force VA Veno-arterial VAD Ventricular assist device VA-ECMO Veno-arterial ECMO VV Veno-venous VV-ECMO Veno-venous ECMO Extracorporeal Membrane Oxygenation: Final Evidence Report Page ii WA – Health Technology Assessment February 12, 2016 About ICER The Institute for Clinical and Economic Review (ICER) is an independent non-profit health care research organization dedicated to improving the interpretation and application of evidence in the health care system. ICER directs three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). For more information about ICER, please visit ICER’s website, www.icer-review.org. Extracorporeal Membrane Oxygenation: Final Evidence Report Page iii WA – Health Technology Assessment February 12, 2016 Acknowledgements ICER would like to thank the following individuals for their expert opinions as well as peer review of draft documents: Eileen Bulger, MD FACS Professor of Surgery Chief of Trauma University of Washington Harborview Medical Center Michael Mulligan, MD Professor of Cardiothoracic Surgery Director of Lung Transplant Program Director of Advanced Lung Disease Surgery Program University of Washington Medical Center We would also like to thank Shanshan Liu of ICER for her contributions to this report. Extracorporeal Membrane Oxygenation: Final Evidence Report Page iv WA – Health Technology Assessment February 12, 2016 Executive Summary Background Extracorporeal membrane oxygenation (ECMO) is a form of life support that provides cardiopulmonary assistance outside the body. ECMO may be used to support lung function for severe respiratory failure or heart function for severe cardiac failure. An ECMO circuit can be set up as veno-venous (VV) or veno- arterial (VA). VV-ECMO provides external gas exchange, bypassing the lungs and protecting them from high tidal volumes of ventilation that would otherwise be needed to oxygenate and ventilate the patient. VV-ECMO is indicated for patients with potentially reversible respiratory failure, including those with severe acute respiratory distress syndrome (ARDS), primary graft dysfunction following lung transplant, and trauma to the lungs. VA-ECMO provides the same external gas exchange as VV-ECMO, but also augments blood flow in settings of severe cardiac injury. VA-ECMO is indicated for patients with cardiac failure, including cardiogenic shock unresponsive to typical intensive care medicines and cardiac arrest that does not respond to cardiopulmonary resuscitation (CPR). VA-ECMO may also be used for patients following heart surgery or as a bridge to heart transplantation. Both VA- and VV-ECMO may be used intraoperatively as a planned alternative to traditional cardiopulmonary bypass in selected patient populations (e.g., lung or heart transplantation). Other external gas exchange systems provide similar functions without the pump component of VV- or VA-ECMO. These arteriovenous extracorporeal lung assist devices bypass the lungs, but not the heart, and use the patient’s blood pressure in order to sustain circulation of externally oxygenated blood.1-3 Because of the requirement for adequate cardiac function in candidate patients, these systems have more limited application. These devices are known by a variety of names, including pumpless extracorporeal lung assist (pECLA), arteriovenous extracorporeal membrane carbon dioxide removal (avECCO2-R), or interventional lung assist (iLA). In this report, we refer to these devices by the name used by their clinical investigators, although these devices are functionally equivalent. Over the past 30 years, ECMO has become a well-established treatment for infants with lung and heart failure and has become a standard of care in many pediatric care centers.4 A large multicenter randomized controlled trial published in 1996 demonstrated a clear survival benefit with ECMO as well as a reduction in risk of severe disability in neonatal patients with severe respiratory failure.5 In contrast, early studies of ECMO in adults showed poor survival rates, and its use was limited for many years to pediatric populations with life-limiting illness.6,7 The lack of demonstrated benefit from these studies, published in 1979 and 1994, halted enthusiasm for widespread ECMO use. However, several developments have prompted renewed interest and wider utilization of ECMO in recent years.8 First, technological advancements have improved the safety of the technique and broadened the application.9 These improvements include heparin-coated cannulae, new oxygenators, and more efficient pump technology.10