Extracorporeal Membrane Oxygenation in COVID-19-related Acute Respiratory Distress Syndrome – a EuroELSO international survey Sebastian Mang1,2, Armin Kalenka3, Lars Mikael Broman4, Alexander Supady5, Justyna Swol6, Guy Danziger1,2, André Becker1,2, Sabrina I Hörsch1,7, Thilo Mertke1,7, Ralf Kaiser1,2, Hendrik Bracht8, Viviane Zotzmann5, Frederik Seiler1,2, Robert Bals1,2, Fabio Silvio Taccone9, Onnen Moerer10, Roberto Lorusso11, Jan Bělohlávek12, Ralf M Muellenbach13, and Philipp M Lepper1,2 for the COVEC-Study Group* pe er re v iew ed 10 Interdisciplinary COVID-19-Center, University Medical Centre, Saarland University, Homburg/Saar, Germany Department of Internal Medicine V - Pneumology, Allergology and Critical Care Medicine, University Medical Centre, Saarland University, Homburg/Saar, Germany Department of Anaesthesiology and Intensive Care Medicine, District Hospital Bergstrasse, University Hospital Heidelberg, Heppenheim, Germany ECMO Centre Karolinska, Department of Pediatric Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Department of Pneumology, Allergology and Sleep Medicine, and Intensive Care Medicine, Paracelsus Medical University, General Hospital Nuremberg, Nuremberg, Germany Department of Anaesthesiology, Critical Care Medicine and Pain Medicine, University Medical Centre, Saarland University, Homburg/Saar, Germany Department of Anaesthesiology and Critical Care Medicine, University Hospital of Ulm, Ulm, Germany Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium 10 Department of Anaesthesiology, University Hospital of Göttingen, Göttingen, Germany 11Cardio-Thoracic Surgery Department - Heart & Vascular Centre - Maastricht University Medical Centre, Maastricht, Netherlands 12 2nd Department of Internal Cardiovascular Medicine, General University Hospital, Prague, Czech Republic 13 Department of Anaesthesiology and Critical Care Medicine, Campus Kassel of the University of Southampton, Kassel, Germany rin tn ot ep * Members of the study group are listed in the appendix Word count: 2,544 Keywords: COVID-19, SARS-CoV-2, ECMO, survey, CARDS Pr 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 Running title: ECMO for COVID-19 induced ARDS – EURO-ELSO-Survey This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey Correspondence to: 50 51 52 53 54 55 56 57 58 59 Philipp M Lepper, MD Department of Internal Medicine V – Pneumology, Allergology and Intensive Care Medicine and ECLS Center Saar University Hospital of Saarland Kirrberger Str 100 66421 Homburg Germany Phone: +49-6841 16 15000 Fax: +49-6841 16 15208 Email: philipp.lepper@uks.eu Pr ep rin tn ot pe er re v iew ed 49 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al Background: Extracorporeal membrane oxygenation (ECMO) is a means to 61 support patients with acute respiratory failure Initially, recommendations to treat 62 severe cases of pandemic Coronavirus Disease 2019 (COVID-19) with ECMO have 63 been restrained In the meantime, ECMO has been shown to produce similar 64 outcomes in patients with severe COVID-19 compared to existing data on ARDS 65 mortality iew ed 60 Objective: We performed an international email survey to assess how ECMO 67 providers worldwide have previously used ECMO during the treatment of critically ill 68 patients with COVID-19 pe er re v 66 69 Methods: A questionnaire with 45 questions (covering e.g indication, 70 technical aspects, benefit and reasons for treatment discontinuation), mostly 71 multiple-choice, was distributed by email to ECMO centers The survey was 72 approved by the European branch of the Extracorporeal Life Support Organization 73 (ELSO) Results: 276 centers worldwide responded that they employed ECMO for 75 very severe COVID-19 cases, mostly in veno-venous configuration (87%) The most 76 common reason to establish ECMO was isolated hypoxemic respiratory failure 77 (50%), followed by a combination of hypoxemia and hypercapnia (39%) Only a 78 small fraction of patients required veno-arterial cannulation due to heart failure (3%) 79 Time on ECMO varied between less than two and more than four weeks The main 80 reason to discontinue ECMO treatment prior to patient’s recovery was lack of clinical 81 improvement (53%), followed by major bleeding, mostly intracranially (13%) Only 82 4% of respondents reported that triage situations, lack of staff or lack of oxygenators 83 were responsible for discontinuation of ECMO support Most ECMO physicians (66% 84  26%) agreed that patients with COVID-19 induced ARDS (CARDS) benefitted from 85 ECMO Overall mortality of COVID-19 patients on ECMO was estimated to be about 86 55%, scoring higher than what has previously been reported for Influenza patients on 87 ECMO (29 – 36%) 89 tn rin Conclusion: ECMO has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure Age and multimorbidity limited the use of ECMO Triage situations were rarely a concern Pr 90 ep 88 ot 74 91 ECMO providers stated that patients with severe COVID-19 benefitted from ECMO This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey An increasing use in patients with respiratory failure in a future stage of the 93 pandemic may be expected Pr ep rin tn ot pe er re v iew ed 92 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al 94 Introduction iew ed 95 96 Early in 2020, countries worldwide have been facing a surge of patients with 97 acute respiratory distress syndrome (ARDS) due to pandemic Severe Acute 98 Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) disease 2019 (COVID-19) 99 Survival of those most severely affected by COVID-19-related ARDS (CARDS) might 100 depend on extracorporeal membrane oxygenation (ECMO) as bridge to recovery1 In this global pandemic, hospitals and healthcare systems have been pushed 102 to the verge of collapse During the first phase of the COVID-19 pandemic, the 103 number of critically ill patients requiring invasive ventilation often exceeded ventilator 104 capacities, creating a need for ICU triage2 In this scenario, it was highly unlikely that 105 ECMO would be broadly recommended to critical care providers to treat COVID-19, 106 given its high demands on personnel and resources3 In its initial guidance 107 document, ELSO considered to offer ECMO only to specific patients not responding 108 to maximal conventional therapy, including proning and neuromuscular blockade4 109 Additionally, early reports suggested mortality rates could be higher than 90% in 110 COVID-19 patients supported with ECMO5 pe er re v 101 A recent trial reported that ECMO reduced 60-day mortality in non-COVID-19 112 related ARDS to 35% in the ECMO group versus 46% in the conventional 113 management group (relative risk 0.76, 95% CI 0.55–1.04; p=0.09)6 The study 114 highlighted that ECMO can facilitate protective ventilation of ARDS patients with 115 reduced tidal volumes, plateau and driving pressures, mostly due to effective 116 extracorporeal CO2 removal CARDS might not differ as much from non-COVID 117 ARDS as was previously expected7 Physiological considerations make it thus 118 reasonable to think about ECMO as a bail-out strategy in critically ill patients with 119 CARDS A recently published retrospective data suggested that mortality of patients 120 with CARDS receiving ECMO might be comparable to past ARDS cohorts8 Given 121 that COVID-19 pathophysiology is still poorly understood, little is currently known 123 tn rin about how to tailor ECMO treatment to meet COVID-19 specific challenges, e.g hypercoagulable state9, or how long ECMO should be continued when patients fail to improve Pr 124 ep 122 ot 111 125 We therefore designed an online survey to elicit how ECMO providers 126 worldwide have previously employed ECMO to treat critically ill COVID-19 patients This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey Our survey was approved by the European branch of the Extracorporeal Life Support 128 Organization (EuroELSO) Pr ep rin tn ot pe er re v iew ed 127 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al 129 Methods iew ed 130 131 We created a questionnaire consisting of 45 questions and distributed it to 132 4,193 physicians that had published on an ECMO-related topic since the year 2000 133 in a PubMed-listed journal with an available E-Mail using a commercially available 134 internet survey platform (SurveyMonkey Inc., San Mateo, California) 135 136 The ethical committee (Ärztekammer des Saarlandes) waived the need for a formal approval since the questionnaire did not retrieve actual patient data 138 pe er re v 137 Questionnaire 139 The questionnaire was composed of two sections: the first dealt with general 141 questions regarding contact information, details on hospital and ICU capacity as well 142 as years of ECMO experience The second part was designed to elicit most common 143 indications for ECMO use in COVID-19, details about ECMO circuit configuration as 144 well as complications and reasons for possible treatment discontinuation We did not 145 ask for any patient-specific data For conformity reasons and to facilitate participation 146 in the survey, most of the questions were multiple choice with two to nine possible 147 answers per question The last eight items requested the participant to express his 148 extent of agreement with a specific statement about ECMO therapy in the context of 149 COVID-19 on a visual analogue scale The survey is partly available in the 150 Supplementary Material 151 The survey questions and multiple-choice responses with their respective 152 organization in the different sections were circulated and consented between a group 153 of 23 very experienced physicians in this field When consensus of all questions and 154 answers was reached, the survey was transferred to an online platform 155 (SurveyMonkey Inc., San Mateo, California) Automatic data retrieval and descriptive 156 statistics were retrieved through this platform More than one answer from centers 158 tn rin were possible This was allowed, as many centers comprise several departments with physicians from different backgrounds (e.g anesthesiology and surgery) Results from multiple-choice questions are expressed in median, participants’ Pr 159 ep 157 ot 140 160 extent of agreement or disagreement in mean and standard deviation in percent The 161 survey was launched on 8th, deadline for return was 20th of June, 2020 Final This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey analysis of results was performed using an extrapolation tool provided by 163 SurveyMonkey as well as SPSS iew ed 162 164 Participants were given the opportunity to be listed as collaborators Those 165 participants who did not supply hospital or contact information or who did not 166 complete the survey could not be included in the list of collaborators 167 168 Results 169 General data on ECMO centers and treatment capacities pe er re v 170 276 ECMO professionals from 98 centers in 30 different countries on four 172 continents (North America, South America, Europe, Asia) responded to the survey, 173 yielding a response rate of 6.6% Sixty-four percent of responding centers were 174 ELSO members As it was possible to skip questions, sometimes the denominator is 175 less than 276 In this case, the number of respondents is given in brackets 176 Centers’ median number of years with ECMO experience was 14, mainly in ECMO 177 treatment of adults or adult and pediatric patients (85%) Only 1.3% of participants 178 were exclusively specialized in neonatal ECMO Most common numbers of patients 179 supported with ECMO per year prior to COVID-19 in the participants’ centers ranged 180 from 21 to 50, 13% of centers having even supported more the 100 patients on 181 veno-venous ECMO (VV-ECMO) per year prior to the pandemic ot 171 182 Numbers of patients with COVID-19 with or without ECMO tn 183 The majority of ECMO providers (30%) stated that to patients with COVID- 185 19 had received ECMO in their center, 85% of all centers having supported a 186 maximum of 15 patients on ECMO by survey deadline ECMO treatment had mostly 187 been initiated in the participants’ hospitals (63%), only a minority of patients was 188 retrieved on ECMO by mobile ECMO retrieval teams from other hospitals 190 191 Indication for ECMO and circuit configuration The most common reason to initiate ECMO for COVID-19 was isolated hypoxemia (50%), followed by a combination of hypoxemia and hypercapnia (39%) Pr 192 ep 189 rin 184 193 Isolated hypercapnia was rarely a reason to cannulate a patient (3%) Only 6% 194 stated that ECMO was started to facilitate lung-protective ventilation (n = 105) The 195 majority of ECMO cannulations (88%) were performed in veno-venous configuration This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al Eight percent of centers used veno-arterial configuration (VA-ECMO) in one or more 197 patients and 3% had to extend to a V-AV-circuit in at least one case (one venous 198 draining cannula, one arterial returning cannula, one venous returning cannula) In 199 those cases, where an arterial cannulation was required, the indications were 200 specified as biventricular failure (n = 2) and, in one case, right heart failure due to 201 pulmonary embolism (n = 1) See also Figure 1, panel A and B iew ed 196 202 203 Anticoagulation management Targeting anticoagulation therapy in patients with COVID-19 on ECMO, 60% 205 of participants (n = 110) stated that they did not change their standard 206 anticoagulation strategy compared to cases of ARDS due to other causes Forty 207 percent used higher doses of anticoagulants than usual, monitored by higher 208 prothrombin time or higher activated clotting time Only one of 110 ECMO providers 209 stated that they deliberately used lower doses of anticoagulants than usual for 210 ECMO in COVID-19 Antiplatelet therapy was also rarely used (1%) to prevent 211 clotting The details of the anticoagulants or antiplatelet agents administered were 212 not part of the survey See also Figure C 213 214 Reasons to abstain from ECMO pe er re v 204 The two main reasons to refrain from ECMO initiation were patient age (74%) 216 and comorbidities (85%, not further specified) 28% of participants stated that ECMO 217 was withdrawn due to a patient’s known or suspected wishes Nine percent decided 218 against ECMO because it was not actively recommended for COVID-19 induced 219 ARDS by responsible scientific societies at that time Seven percent reported that a 220 surge of COVID-19 patients and overwhelming workload made ECMO impracticable 221 Only 5% of participants reported that they had to abstain from ECMO initiation due to 222 a shortage of oxygenators, machines or ECMO cannulas Pr ep rin tn ot 215 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey 223 Duration of ECMO support Most patients were supported with ECMO for less than two weeks However, 225 50% of all participants stated that they had also treated patients with ECMO for more 226 than four weeks (Figure D) iew ed 224 227 228 Reasons for ECMO discontinuation Seventy-two percent of participants confirmed that their center would 230 withdraw ECMO if there was no perspective for a COVID-19 patient to recover If 231 ECMO treatment was discontinued prior to recovery, futility was mostly stated as the 232 reason (n = 50 from 94 responses, 53%) ECMO-related complications were the 233 second most important reason for treatment discontinuation Fourteen percent of 234 ECMO providers stated that they had terminated ECMO due to major bleeding (n = 235 15), mainly intracranial hemorrhage (n = 13) and, less frequently, extracranially In 236 1% of cases, not further specified technical issues led to ECMO withdrawal The 237 question also offered ‘lack of staff’ as a possible answer, which was not chosen 238 However, 2% of participants (n = 2, Germany and France) stated that a triage 239 situation forced physicians to discontinue ECMO prior to the patient’s possible 240 recovery Two percent of respondents named lack of ECMO oxygenators, ECMO 241 machines or consumables as the reason for ECMO discontinuation See also Figure 242 E ot pe er re v 229 243 Estimation of patients’ outcome tn 244 When asked to estimate the percentage of patients who died while on ECMO 246 due to COVID-19, average mortality was estimated to be 55%, meaning that 45% of 247 patients had survived on ECMO at least until the end of the survey 249 250 251 252 The last eight questions were designed to investigate a participant’s opinion on certain statements about ECMO and COVID-19, measured in percentage of agreement Participants agreed to 63%  24% on average that patients were longer on ECMO due to COVID-19 compared to other causes of ARDS The claim that Pr 253 ECMO providers’ opinions on COVID-19 and ECMO ep 248 rin 245 254 CARDS patients on ECMO required more sweep gas flow than what the individual 255 ECMO physician was used to was accepted by 58%  25% The statement that 10 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey Canada 466 iew ed 465 467 David Bracco, McGill University Health Center, Montreal, Canada; 468 Yiorgos Alexandros, Cavayas Hôpital du Sacré-Coeur de Montréal, Montréal, 469 Canada; Ari Joffe, Stollery Children's Hospital, Alberta, Canada; 471 A Dave Nagpal, London Health Sciences Centre, London, Canada; 472 Ying Sia, University Institute of Cardiology and Respirology of Quebec, Quebec, 473 Canada; 474 475 United Kingdom 476 pe er re v 470 477 Georg Auzinger, King's College Hospital London, United Kingdom; 478 Vasileios Zochios, University Hospitals of Leicester NHS Trust, Glenfield Hospital 479 ECMO Unit, Lecester, United Kingdom; 480 481 United States of America 482 Alejandro Garcia, Johns Hopkins University, Baltimore, Maryland, United States; 484 Katja Gist, University of Colorado, Boulder, Colorado, United States; 485 Dana Lustbader, ProHEALTH an OPTUM Company, New York, New York, United States; tn 486 ot 483 Demetris Yannopoulos, University of Minnesota, Minneapolis, Minnesota, United 488 States; 489 R Scott Stephens, Johns Hopkins University, Baltimore, Maryland, United States; 490 Joseph Tonna, University of Utah, Salt Lake City, Utah, United States; 491 Linda Paxton, St Mary's Hospital, Richmond, Virginia, United States; 492 Hitoshi Hirose, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, 494 United States; Bo Kim, Johns Hopkins University, Baltimore, Maryland, United States; Pr 495 ep 493 rin 487 496 Sweden 497 498 Magnus Dalén, Karolinska University Hospital and Karolinska Institutet, Sweden; 20 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al 499 Czech Republik 501 Martin Balik, Complex Cardiac Center, General University Hospital, Prague, Czech Republic; 502 503 iew ed 500 David Janak, Charles University of Prague, Department of Cardiovascular Surgery, Prague, Czech Republic; 504 505 506 Chile pe er re v 507 508 Luis Castillo, Hospital Barros Luco, Santiago, Chile; 509 Alejandro Bruhn; Pontificia Universidad Catolica de Chile, Santiago, Chile; 510 511 Colombia 512 513 Jorge Luis Alvarado Socarras, Fundacion Cardiovascular de Colombia, Bucaramanga, Santander, Colombia; 514 515 516 South Korea 517 Taeyun Kim, Seongnam Citizens Medical Center, Seongnam, South Korea; 519 Hyoung Soo Kim, Hallym University Sacred Heart Hospital, Seoul, South Korea; 520 Joung Hun Byun, Gyeongsang National University College of Medicine, Changwon, tn ot 518 South Korea; 521 523 524 Brazil rin 522 Guilherme Mainardi, Hospital São Camilo, Brazil; 526 Pedro Mendes, Hospital das Clinicas de São Paulo HC-FMUSP, São Paulo, Brazil; 527 528 Switzerland Pr 529 ep 525 530 Raphaël Giraud, Geneva University Hospitals, Geneva, Switzerland; 531 532 21 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey 533 Portugal iew ed 534 535 Philip Fortuna, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal; 536 Japan 537 538 Tatsuma Fukuda, University of the Ryukyus, Nakagami District, Okinawa, Japan; 539 540 The Netherlands 542 pe er re v 541 Jacinta Maas, Leiden University Medical Center, Leiden, The Netherlands; 543 544 Poland 545 546 Dariusz Maciejewski, Regional Teaching Hospital, Bielsko-Biała, Poland; 547 548 India 549 550 Deblal Pandit, Medica Superspecialty Hospital Kolkata, Calcutta, India; 551 Israel ot 552 553 Yosv Psz, General Intensive Care Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 555 556 Slovenia rin 557 558 559 Peter Radsel, University Medical Center Ljubljana, Slovenia; 562 China Gangfeng Yan, Children's Hospital of Fudan University, China; Pr 563 ep 560 561 tn 554 22 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al References iew ed 564 Savarimuthu, Sugeevan; BinSaeid, Jalal; Harky, Amer (2020) The role of ECMO in COVID-19: Can it provide rescue therapy in those who are critically ill? Journal of cardiac surgery 35:6;1298–1301 569 570 571 Phua, Jason; Weng, Li; Ling, Lowell, et al (2020) Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations Lancet Respir Med 2020 May; 8(5): 506–517 572 573 574 575 MacLaren, Graeme; Fisher, Dale; Brodie, Daniel et al (2020) Preparing for the Most Critically Ill Patients With COVID-19: The Potential Role of Extracorporeal Membrane Oxygenation JAMA DOI: 10.1001/jama.2020.2342 576 577 578 Bartlett, Robert H.; Ogino, Mark T.; Brodie, Daniel (2020) Initial ELSO Guidance Document: ECMO for COVID-19 Patients with Severe Cardiopulmonary Failure ASAIO Journal 66(5):472-474 579 580 581 582 583 Henry, Brandon Michael; Lippi, Giuseppe (2020) Poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19): Pooled analysis of early reports Journal of critical care, 58:27–28 DOI: 10.1016/j.jcrc.2020.03.011 584 585 586 587 Combes, Alain; Hajage, David; Capellier, Gilles et al (2018) Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome The New England journal of medicine, 378:21;1965–1975 DOI: 10.1056/NEJMoa1800385 588 589 590 591 Ferrando, Carlos; Suarez-Sipmann, Fernando; Mellado-Artigas, et al (2020) Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS Intensive care medicine DOI: 10.1007/s00134-020-06192-2 592 593 594 595 Barbaro, Ryan P.; MacLaren, Graeme; Boonstra, Philip S et al (2020) Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry The Lancet DOI: 10.1016/S0140-6736(20)32008-0 596 597 598 Iba, Toshiaki; Levy, Jerrold H.; Levi, Marcel; Connors, Jean Marie; Thachil, Jecko (2020) Coagulopathy of Coronavirus Disease 2019 Critical care medicine DOI: 10.1097/CCM.0000000000004458 ot tn rin ep 10 Amato, Marcelo B P; O Meade, Maureen; Slutsky, Arthur S et al (2015) Driving pressure and survival in the acute respiratory distress syndrome The New England Journal of Medicine, 19;372(8):747-55 Pr 599 600 601 pe er re v 565 566 567 568 602 603 604 605 11 Ranucci, Marco; Ballotta, Andrea; Di Dedda, Umberto et al (2020) The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome Journal of thrombosis and haemostasis,18:7;1747–1751 DOI: 10.1111/jth.14854 23 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey 12 Bemtgen, Xavier; Zotzmann, Viviane; Benk, Christoph; et al (2020) Thrombotic circuit complications during venovenous extracorporeal membrane oxygenation in COVID-19 Journal of thrombosis and thrombolysis DOI: 10.1007/s11239-020-02217-1 610 611 612 13 Wang, Dawei; Hu, Bo; Hu, Chang et al (2020) Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China JAMA DOI: 10.1001/jama.2020.1585 613 614 615 616 14 Chen, C.; Yan, J T.; Zhou, N.; Zhao, J P et al (2020) Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19 Zhonghua xin xue guan bing za zhi, 48:0, E008 DOI: 10.3760/cma.j.cn112148-20200225-00123 617 618 619 620 15 Lippi, Giuseppe; Lavie, Carl J.; Sanchis-Gomar, Fabian (2020) Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis Progress in cardiovascular diseases DOI: 10.1016/j.pcad.2020.03.001 621 622 623 624 16 Esposito, Antonio; Palmisano, Anna; Natale, Luigi; Ligabue, Guido; Peretto, Giovanni; Lovato, Luigi et al (2020) Cardiac Magnetic Resonance Characterization of Myocarditis-Like Acute Cardiac Syndrome in COVID-19 In : JACC Cardiovascular imaging DOI: 10.1016/j.jcmg.2020.06.003 Pr ep rin tn ot pe er re v iew ed 606 607 608 609 24 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al 628 629 Sebastian Mang1,2, Armin Kalenka3, Lars Mikael Broman4, Alexander Supady5, 630 Justyna Swol6, Guy Danziger1,2, André Becker1,2, Sabrina I Hörsch1,7, Thilo 631 Mertke1,7, Ralf Kaiser1,2, Hendrik Bracht8, Viviane Zotzmann5, Frederik Seiler1,2, 632 Robert Bals1,2, Fabio Silvio Taccone9, Onnen Moerer10, Roberto Lorusso11, Jan 633 Bělohlávek12, Ralf M Muellenbach13, and Philipp M Lepper1,2 for the COVEC-Study 634 Group* pe er re v iew ed 627 Extracorporeal Membrane Oxygenation in COVID-19-related Acute Respiratory Distress Syndrome – a EuroELSO international survey 626 635 636 Supplementary Data 637 638 Results – Details on participating ECMO centers 639 Countries with most replies were Germany (32), the United States of America 641 (32), Italy (16), France (15) and Canada (11) (Supplementary Figure 1) 642 Participants were mostly ECMO providers at larger hospitals and tertiary care 643 centers, the majority having a capacity of over 1,000 beds in total, 60% having at 644 least 21 ICU beds on their ward ICUs employing ECMO were mostly 645 interdisciplinary (66%) and, to a lesser extent, surgical (18%) or non-surgical (16%) 646 ECMO wards were mainly run by critical care physicians (59%), followed by Cardiac 647 surgeons (19%) and Anesthesiologists (9%) The vast majority of ECMO providers 648 (70%) stated that their center had previously increased ECMO capacity in the face of 649 COVID-19, in median by 25 – 50% 19% managed to double their ECMO capacity 650 (Supplementary Table and 2) 653 654 655 tn Results – Numbers of critically-ill patients with or without ECMO By survey deadline, most centers had treated a median of 21-40 patients with COVID-19 (both intensive and normal care units), 73 of 149 had treated more than 100 patients Those centers experiencing a high emergence of COVID-19 patients Pr 656 rin 652 ep 651 ot 640 657 were mostly localized in countries which were most severely affected by the 658 pandemic at that time (France 18%, Italy 17%, USA 14% and Germany 11%) 41% 25 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey of centers reported that 51 or more patients with COVID-19 required intensive care 660 (n = 145) since the outbreak of the pandemic 661 662 Results – Time on ECMO 663 iew ed 659 While 70 out of 104 participants stated that CARDS patients were on ECMO support 665 for less than two weeks, 52 out of 104 centers reported patients being on ECMO for 666 at least weeks 45% even confirmed that some patients required more than one 667 ECMO run during hospitalization pe er re v 664 668 669 Results – Decision making in ECMO indication and discontinuation 670 We further asked by whom the decision for or against a continuation of ECMO was 672 made in respective cases 50% of participants (51 of 102) stated that the decision 673 was made primarily by the team of treating physicians without noteworthy 674 participation of a third person (see Supplementary Table 3) 13% said that, in 675 addition to physicians’ opinion, a second institution (e.g hospital’s ethical committee) 676 or another clinical department (e.g palliative care) was consulted prior to therapy 677 withdrawal Only 4% stated that the decision was made by a family member or next 678 of kin, provided the patient was not sui juris at that time 31% stated that physicians’ 679 decision to discontinue ECMO treatment had to be backed up by an additional 680 professional or the patient’s family Advanced healthcare directives or a patient’s will 681 as witnessed by their family was chosen by 3% of participants The answer ‘external 682 COVID-19 committee’ was offered but not chosen However, 10% stated that a 683 regulatory authority was involved in decision-making of how COVID-19 patients 684 should be treated, mostly in centers from Canada, China, South Korea, France and 685 Italy tn rin ep Pr 686 ot 671 26 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ot pe er re v iew ed Mang et al Pr ep 692 Figure A – C - ECMO circuit configuration, indication and anticoagulation strategy * measured in higher or reduced prothrombin time (PTT) or ** activated clotting time (ACT) ***were specified as direct thrombin inhibition (n = 1) and Anti-Xa-activity (n = 1) rin 688 689 690 691 tn 687 27 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ot pe er re v iew ed ECMO for COVID-19 induced ARDS – EURO-ELSO Survey 693 Figure D – E – Duration of ECMO therapy and reasons for treatment discontinuation * were specified as futility (n = 2), intractable septic shock (n = 1), multi-organ failure (n = 3) and bleeding other than intracranial (n = 1) tn 694 695 696 698 Pr ep 699 rin 697 28 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 700 Figure – Participants’ extent of agreement to statements about COVID-19 and ECMO therapy = full disagreement, 100% = full agreement Results are expressed in Box-plots The left box barrier equals the 25th percentile, the right barrier equals the 75th percentile Median is expressed by the full line inside the box, mean is marked as an ‘x’ Pr 701 702 703 704 705 ep rin tn ot pe er re v iew ed Mang et al 706 29 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 pe er re v iew ed ECMO for COVID-19 induced ARDS – EURO-ELSO Survey 707 708 709 710 Supplementary Figure 1: Geographical distribution of survey responses 98 centers in 30 different countries on four continents (North America, South America, Europe, Asia) responded to the survey Pr ep rin tn ot 711 30 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al Supplementary Table – General information about participating ECMO centers Questions Answers What is your hospital’s level of care? Number Percentage a Tertiary Care / University Hospital / Academic b Non-Academic c General Hospital d Community Hospital 176 94% 2% 3% 1% a Non-government b Government c mixed 41 109 36 22% 59% 19% 112 63 64% 36% a less than 250 b 250 to 500 c 501 to 750 d 751 to 1000 e more than 1000 33 32 31 74 3% 19% 18% 18% 42% a to beds b to 12 beds c 13 to 16 beds d 17 to 20 beds e 21 to 40 beds f more than 40 beds 17 25 20 53 53 5% 10% 14% 11% 30% 30% a Surgical b Non-surgical c Interdisciplinary 32 29 116 18% 16% 66% a Yes b No 124 53 70% 30% a Less than 10% b 10 to 25% c 25 to 50% d 50 to 75% e 75 to 100% f more than 100% 16 37 22 17 23 4% 13.5% 31% 18.5% 14% 19% a Yes b No 78 94 45% 55% a less than 10% b 10 to 25% c 25 to 50% d 50 to 75% e 75 to 100% f more than 100% 18 20 15 8% 23.5% 26% 12% 10.5% 20% Responded: 187 How is your institution funded? Responded: 186 a Yes b No Is your institution an ELSO center? Responded: 175 Skipped: 87 How many beds does your hospital have in total? Responded: 175 Skipped: 87 What is your ICU’s capacity? Responded: 176 Skipped: 86 What is the type of your ICU? Responded: 177 Skipped: 85 Did you increase ICU capacity for COVID19? Skipped: 85 ot Responded: 177 By how much did you increase ICU capacity for COVID-19? tn Responded: 120 Skipped: 142 Did you increase ECMO capacity for COVID-19? rin Responded: 172 Skipped: 90 By how much did you increase ECMO capacity for COVID-19? ep Responded: 76 Skipped: 186 ECMO – Extracorporeal membrane oxygenation / EuroELSO – European Extracorporeal Life Support Organization / ICU – Intensive care unit / COVID-19 – Coronavirus disease 2019 Pr 713 714 Skipped: 76 pe er re v 10 Skipped: 75 iew ed 712 715 716 31 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey Questions Answers How many patients with COVID-19 have been treated in your hospital in total up to now?* e up to f to 20 g 21 to 40 h 41 to 60 i 61 to 80 j 81 to 100 k more than 100 Responded: 147 Skipped: 115 How many of these COVID-19 patients needed intensive care? Responded: 145 Skipped: 117 How many of these COVID-19 patients have been or are still on ECMO?* Responded: 116 Skipped: 146 Where was ECMO initiated in patients with COVID-19 treated at your center? Responded: 120 iew ed Supplementary Table – ECMO centers’ experience with COVID-19 and ECMO Number Percentage 17 18 15 11 73 11.5% 12% 10% 7.5% 3% 6% 50% 10 17 12 11 26 60 7% 12% 8% 6% 8% 18% 41% c d to e to 10 f 11 to 15 g 16 to 20 h 21 to 50 i 51 to 70 j 71 and more 26 35 20 18 11 22% 30% 17% 15.5% 4% 9.5% 0% 1% a In my own hospital b In another hospital (e.g community hospital) c Both, in own hospital and externally 75 41 63% 3% 34% d e to f to 10 g 11 to 15 h 16 to 20 i 21 to 50 j 51 and more pe er re v 717 Skipped: 142 *Survey deadline was 20th June, 2020 719 ECMO – Extracorporeal membrane oxygenation / ICU – Intensive care unit / COVID-19 – Coronavirus disease 2019 Pr ep rin tn ot 718 32 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 Mang et al Questions Answers What was the indication to initiate ECMO support in COVID-19 patients? Responded: 105 What was the main ECMO circuit configuration in COVID-19 patients? VV – veno-venous; VA – veno-arterial; VVA – veno-venous-arterial (1 venous draining cannula; venous returning cannula, arterial returning cannula) Responded: 106 Have COVID-19 patients been supported on ECMO for less than weeks? Responded: 104 rin If the decision to discontinue ECMO was made, what there the reasons? Pr 10 Responded***: 94 (87) 93 4* 2* 87.5% 7.5% 3% 2% k no l more anticoagulation** m less anticoagulation** n inhibition of platelet aggregation o other changes in anticoagulation management 60 44 1 55.5% 40.5% 1% 1% 2% d Age e Comorbidities f Patient’s will g Shortage of oxygenators, cannulas, machines h ECMO not recommended for COVID-19 by scientific societies i Surge of COVID-19 patients (workload to high) j Other 80 92 30 10 74% 85% 28% 5.5% 9% 12 7.5% 11% a Yes b No 79 30 72.5% 27.5% a Yes b No 70 34 67% 33% a Yes b No 52 52 50% 50% a Yes b No 47 58 45% 55% a Triage situation b Patient’s failure to recover c Patient’s assumed or legal representative’s will d Shortage of oxygenators, cannulas, machines e Lack of staff f Prespecified duration met g Bleeding (Intracranial Bleeding; ICH) h Bleeding (other than ICH) i Technical issues j Other (including: patient’s recovery: 2) 50 13 11 2% 53% 5% 2% 0% 1% 14% 2% 1% 12% a Treating physician / treating team b Treating physician + additional person (e.g 51 13 50% 13% Skipped: 157 ep k VV l VA m V-VA n Other* Skipped: 158 Did your center support COVID-19 patients with more than one ECMO run? Responded: 105 49.5% 3% 39% 5.5% 0% 2% 1% Skipped: 158 Have COVID-19 patients been supported on ECMO for more than weeks? Responded: 104 52 41 Skipped: 153 tn Skipped: 154 Does your center withdraw therapy due to futility? Responded: 109 l Hypoxemia m Hypercapnia n Combination of hypoxemia / hypercapnia o To facilitate lung-protective ventilation p Right heart failure q Biventricular failure r Pulmonary embolism Skipped: 152 State reasons why patients with COVID-19 were not offered ECMO support despite qualification (multiple selection possible)! Responded: 108 Percentage Skipped: 156 Did your center use a different anticoagulation strategy in patients with COVID-19 on ECMO compared to other patients on ECMO? Responded: 108 Number pe er re v Skipped: 157 iew ed Supplementary Table – Details on ECMO initiation and treatment for COVID-19 ot 720 Skipped: 168 Who decides on withdrawal of treatment in COVID-19? 33 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ECMO for COVID-19 induced ARDS – EURO-ELSO Survey 11 Skipped: 160 Was a regulatory authority outside of the hospital involved in how to treat COVID-19 patients? Responded: 107 a Yes b No Skipped: 155 31 4% 30% 3% 0% 11 96 10% 90% iew ed Responded: 102 hospital ethical committee, palliative care) c Family or next of kin d Has to be in agreement with a or b and c e Advanced directive / patient’s living will or expressed as witnessed by the family f External COVID-19 committee *Two participants chose “other” One was not included since he or she stated that ECMO was not employed at all for COVID-19 The second specified their circuit to be V-AV, which was hence counted as V-VA 723 ** Measured by prothrombin time / activated clotting time 724 725 *** 94 participants answered, but specified reasons for treatment discontinuation without previously choosing “other” as an answer 726 727 ECMO – Extracorporeal membrane oxygenation / EuroELSO – European Extracorporeal Life Support Organization / ICU – Intensive care unit / COVID-19 – Coronavirus disease 2019 Pr ep rin tn ot pe er re v 721 722 34 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860 ... 627 Extracorporeal Membrane Oxygenation in COVID- 19- related Acute Respiratory Distress Syndrome – a EuroELSO international survey 626 635 636 Supplementary Data 637 638 Results – Details on participating... Ligabue, Guido; Peretto, Giovanni; Lovato, Luigi et al (2020) Cardiac Magnetic Resonance Characterization of Myocarditis-Like Acute Cardiac Syndrome in COVID- 19 In : JACC Cardiovascular imaging... 462 Saudi Arabia 463 464 Salman Abdulaziz, King Saud Medical City, Saudi Arabia; 19 This preprint research paper has not been peer reviewed Electronic copy available at: https://ssrn.com/abstract=3739860