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Extracorporeal Membrane Oxygenation in Children with Coronavirus Disease 2019: Preliminary Report from the Collaborative European Chapter of the Extracorporeal Life Support Organization Prospective Survey

2020; Lippincott Williams & Wilkins; Volume: 67; Issue: 2 Linguagem: Inglês

10.1097/mat.0000000000001309

1538-943X

Matteo Di Nardo, Aparna Hoskote, Tim Thiruchelvam, Jon Lillie, Marie Horan, Sylvia Belda Hofheinz, Laurent Dupic, R. Gimeno, Maria Elena De Piero, Valeria Lo Coco, Peter P. Roeleveld, Marc D. Davidson, Tim Jones, Lars Mikael Broman, Roberto Lorusso, Jan Bělohlávek,

Cardiac Structural Anomalies and Repair

Since the declaration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic,1 a small percentage of children with coronavirus disease 2019 (COVID-19) infection have required intensive care unit (ICU) admission with an even smaller percentage needing extracorporeal membrane oxygenation (ECMO) support.2,3 To provide contemporaneous data on ECMO utilization and activity during the COVID-19 pandemic, the European Chapter of the Extracorporeal Life Support Organization (EuroELSO) established a prospective survey among European neonatal and pediatric centers from the 15th of March to the end of June 2020. The survey was approved by the Maastricht University Medical Centre Ethics Committee. Centers reported anonymized data weekly through the EuroELSO website (www.euroelso.org). We report the preliminary data from 52 neonatal and pediatric ECMO centers across Europe during the first wave of the COVID-19 pandemic. Seven children ( 2,000, endomyocardial biopsy: lymphocytic infiltrate consistent with partially treated myocarditis 5/United Kingdom VA RIJV-CA 87 hours 7 Yes: IVIG, steroids, infliximab Yes Thrombus in right atrium Survived VA to VV Troponin: 110 6/United Kingdom VA RIJV-CA NA 7 No NA None Survived 7/Spain VA Fem-Fem 24 hours 30 Yes: Anakinra, convalescent plasma, mesenchymal stromal cells Yes Pulmonary embolism and cardiac arrest Died VA to VV Troponin: 24.7 Pulmonary embolism Units of measure: Troponin: ng/L (normal value <26 ng/L).ACA, anterior cerebral artery; CA, carotid artery; ECMO, extracorporeal membrane oxygenation; Fem, femoral; IVIG, intravenous immunoglobulin; Jug, jugular; MCA, middle cerebral artery; NA, not applicable; RIJV, right internal jugular vein; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VA, venoarterial; VV, venovenous. The management of ECMO was standard with staff in full personal protective equipment, and enhanced vigilance for thrombotic complications was maintained by the treating centers. All children were anticoagulated with unfractionated heparin as per their institutional protocol. Two children (patients 3 and 5) developed thrombosis while on ECMO despite having activated partial thromboplastin time ratios of 1.6 and 2.7, respectively, before clot formation. All with PIMS-TS presentation were treated with intravenous immunoglobulin (IVIG) and steroids. Among these, one (patient 4) underwent a cardiac biopsy at the time of left atrial decompression procedure that showed an infiltration of lymphocytes suggestive of partially treated myocarditis. Two children required continuous renal replacement therapy, both died. Three patients (43%) received antiviral therapy: lopinavir/ritonavir pre-ECMO and then remdesivir on ECMO, two survived. Immunomodulation with tocilizumab, anakinra, or infliximab (Table 2) was used in three patients (43%), two survived. Convalescent plasma and infusion of mesenchymal stromal cells were administered to the child post HSCT. Surfactant therapy, plasma exchange, or cytokine adsorption filters were not used. Five children (71%) were successfully decannulated, but four (57%) survived to hospital discharge. The median ECMO duration was 7 days (range 7–11 days) with a median ICU stay of 16 days (range 7–20 days). Three children (43%) died—two died on ECMO and a third died post decannulation before pediatric intensive care unit discharge (Table 2). The child post HSCT (patient 7) died for refractory cardiac arrest due to pulmonary embolism after 30 days of ECMO. Patient 3 reported an ischemic stroke involving both the anterior and middle cerebral artery on day 2 of ECMO, while patient 2 reported severe intraventricular and intraparenchymal hemorrhages after 7 days of ECMO. In these three patients, high d-dimers levels 13,500 mcg/L (range 2,200–14,994 mcg/L) were reported suggesting an abnormal activation of the hemostatic system. In contrast to adult data,4 we report that the use of ECMO in children with COVID-19 infection patients in Europe is both scarce and of diverse etiology. An age-specific immune-protective mechanism5 to SARS-CoV-2 may explain this low occurrence of severe disease. Our survey has highlighted: 1) SARS-CoV-2 infection may be associated with comorbid conditions in children, 2) a temporal increase in the ECMO utilization may have been associated with the emergence of PIMS-TS, 3) the risk of thrombotic complications is high when on ECMO support, and 4) the role of adjunctive therapies (antiviral and immunomodulation therapy) remains unclear, however, IVIG and judicious use of steroids may benefit those presenting with PIMS-TS. Early referral before circulatory collapse and multiple organ dysfunction may be advocated in these children. The EuroELSO has provided a collaborative platform for shared learning of the most severe forms of a novel infection with variable presentation and outcome. ACKNOWLEDGMENT The authors thank all the centers who participated to this survey/study and the EuroELSO Social Media Team for their support in spreading the survey/study. EuroELSO Neonatal & Pediatric Working Group & collaborators on COVID-19: Giacomo Cavallaro, MD (Mangiagalli Neonatal Respiratory ECMO Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy); Rosanna Zanai, MD and Salvatore Agati, MD (Centro Cardiologico del Mediterraneo, Bambino Gesù Hospital, Taormina, Messina, Italy); Matteo Di Nardo, MD and Antonio Amodeo, MD (Bambino Gesù Children's Hospital, Rome, Italy); Ferdinando Luca Lorini and Lorenzo Grazioli, MD (A.O.U. Anestesia e Rianimazione 2, Ospedale Papa Giovanni XXIII, Bergamo, Italy); Andrea Moscatelli, MD (U.O.S.D. Terapia Intensiva Neonatale e Pediatrica, Ospedale Gaslini, Genoa, Italy); Angela Amigoni, MD (Pediatric Intensive Care Unit, University Hospital Padova, Padova, Italy); Olivier Brissaud, MD and Nadir Tafer, MD (SAR Sud Hopital Haut Léveque, CHU Bordeaux, Bordeaux, France); Jerome Rambaud, MD, PhD and Pierre-Louis Leger, MD (Hopital Armand-Trosseau [Hospitaux Universitaire Est Parisienne], Service de Reanimation neonatal Pediatrique, Paris, France); Pierre Tissieres, MD, PhD (Hopitaux de Paris, Pediatric Intensive Care e Neonatal Medicine, Paris, France); Capucine Didier, MD (Hopital Femme Mere Enfant, Lyon, France); Angele Boet, MD (Hopital Marie Lannelongue, Paris, France); Stephane Lebel, MD (Hopital de la Timone, Marseille, France); Lionel Berthomieu, MD (Centre Hospitalier Universitaire de Toulouse, Toulouse, France); Anne-Sophie Guilbert, MD (CHU Strasbourg, Strasbourg, France); Pierre Bourgoin, MD (Intensive Care Unit, Nantes Cedex, France); Enno D. Wildschut, MD (Intensive Care Unit, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands); Peter P. Roeleveld, MD (Intensive Care-Universitar Medical Center, Leiden, The Netherlands); Martin Kneyber, MD (Beatrix Children's Hospital–UMC, Groeningen, The Netherlands); Lars Mikael Broman, MD, PhD (Pediatric Perioperative Medicine and Intensive Care-Astrid Lindgren Children's Hospital, Karolinska University Hospital, Solna, Sweden); Oliver Miera, MD (Kinderkardiologie-Universitatmedizin, Berlin, Germany); Matthias Kumpf, MD (Pediatric Intensive Care, Tübingen, Germany); Ralf Knies, MD (University of Bonn, Bonn, Germany); Thomas Schaible, MD (Klinik fur Neonatologie, Uniklinik Mannheim, Mannheim, Germany); Brigitte Stiller, MD (Herzzentrum Freiburg, Bad Krozingen, Germany); Vaclav Vobruba, MD, PhD (Pediatric Department, Charles University, Prague, Czech Republic); Jesus Lopez- Herce, MD, PhD (Hospital General Universitario Gregorio Maranon, Madrid, Spain); Susana Segura Matute, MD (Servicio de Cuidados intensivos pediatricos, Hospital Saint joan de Deu, Barcelona, Spain); Joan Balcells, MD (University Hospital Vall d'Hebron, Barcelona, Spain); Vicent Modesto I Alapont, MD (UCI Pediatrica, Hospital Universitari I Politecnic La Fe, Valencia, Spain); Sylvia Belda and Elena Montanes, MD (ICC-Hospital 12 de Octubre, University of Zaragoza, Madrid, Spain); Janos Schnur, MD and Veronika Maraczi, MD (Heim Pal National Pediatric Institute, Budapest, Hungary); Malaika Mendonca, MD (Pediatric Intensive Care, Bern, Switzerland); Judit Llevadias, MD (Department of Pediatric Cardiology, The Newcastle upon Tyne Hospital, NHS Foundation Trust, Newcastle upon Tyne, United Kingdom); Mark Davidson, MD (Paediatric Intensive Care, Royal Hospital for Children, Glasgow, United Kingdom); Claire Westrope, MD (University Hospital of Leicester Children Hospital, NHS Trust, Leicester, United Kingdom); Aparna Hoskote, MD and Tim Thiruchelvam, MD (Great Ormond Street Hospital (GOSH), London, United Kingdom); Ajay Desai, MD (Royal Brompton Hospital, London, United Kingdom); David Ellis, MD, Margaret Farley, RN, and Tim Jones, MD (Pediatric Intensive Care, Birmingham Children's Hospital, NHS Foundation Trust, Birmingham, United Kingdom); Adrian Humphrey, MD (Pediatric Intensive Care, Bristol Royal Hospital for children, Bristol, United Kingdom); Jonathan Lillie, MD (Evelina London Children's Hospital, London, United Kingdom); Marie Horan, MD (Pediatric Intensive Care Unit, Alder Hey Children's Hospital, Liverpool, United Kingdom); Laurent Dupic, MD (Necker Children's Hospital, Paris, France); Paula Rautiainen, MD (Pediatric Intensive Care Unit, University of Helsinki, Helsinki, Finland); Francisco Abecasis, MD (Pediatric Intensive Care, Centro Hospetalar Universitario Lisboa Norte, Lisbon, Portugal); Dirk Vlasselaers, MD and Leen Vercaemst, Perfusionist (University Hospital Leuven, Leuven, Belgium); Jef Willems, MD (Department of Intensive Care, Universitair Ziekenhuis Ghent, Ghent, Belgium); Caroline Kelly, MD and Sunimol Joseph, MD (Our Lady Children's Hospital, Dublin, Ireland); Uri Pollak, MD (Hadassah University Medical Center, Jerusalem, and other centers [Petah, Ramat, Holon] Israel); Burkhard Simma, MD (Pediatric Intensive Care Academic Teaching Hospital, Feldkirch, Austria); Martin Schweiger, MD (University of Zurich, Zurich, Switzerland); Angeliki Gkouziouta, MD (Athens Onassis Heart Centre, Athens, Grecee); and Laurent Storme, MD (CHRU de Lille, Hôpital Jeanne de Flandre, Lille, France).