Anticoagulation Practices during Venovenous Extracorporeal Membrane Oxygenation for Respiratory Failure. A Systematic Review.
The optimal anticoagulation strategy for venovenous extracorporeal membrane oxygenation (VV-ECMO) is not known.



To evaluate the safety of anticoagulation strategies and monitoring during VV-ECMO for respiratory failure.



We conducted a systematic review to evaluate the association between anticoagulation strategies during VV-ECMO and prespecified outcomes, including major bleeding episodes, thrombotic events, and in-hospital mortality. We included articles published between 1977 and January 30, 2015. Study quality was assessed using the Newcastle-Ottawa scoring system. A separate meta-analysis was not planned.



Data were independently extracted by two authors and collected on a standardized report form.



A total of 18 studies (n = 646) were included; 17 studies enrolled patients with acute respiratory distress syndrome. Across all studies, the duration of VV-ECMO support ranged from 4 to 20 days. Patients received an average of 2.3 (±3.9) units of transfused red blood cells per day. The bleeding rate across all studies was 16%, and the rate of thrombosis was 53%. Among seven studies (199 patients) targeting a specified activated partial thromboplastin time (aPTT), there were 37 (19%) major bleeding episodes and 53 (27%) major thromboses. Among five studies (43 patients) with aPTT targets of 60 seconds or greater, there were 24 (56%) bleeding episodes and 3 (7%) clotting events. Three studies (156 patients) with an aPTT target under 60 seconds reported 13 (8%) and 50 (32%) significant bleeding and thrombotic events, respectively. The most commonly reported thrombotic events were circuit-related clotting and deep-vein thrombosis. Mortality during VV-ECMO varied across the studies, ranging from 0 to at least 50% at heterogeneous time points. The total number of deaths for all studies combined was 186 (29%).



The role and optimal therapeutic targets for anticoagulation during VV-ECMO are unclear. Previously published studies are limited by retrospective, observational design, small cohorts, and patient heterogeneity. The clinical significance of reported thrombotic complications is largely unknown. This systematic review underscores the need for randomized controlled trials of anticoagulation strategies for patients undergoing VV-ECMO for respiratory failure.
1 Department of Anaesthesia, University of Toronto, Toronto, Ontario, Canada.|2 Interdepartmental Division of Critical Care, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
Michael C
MC
Sklar
3 Department of Critical Care, Regina General Hospital, Regina, Saskatchewan, Canada.|4 Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.|5 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Eric
E
Sy
6 Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada; and.
Laurance
L
Lequier
2 Interdepartmental Division of Critical Care, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
Eddy
E
Fan
5 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.|7 Division of Critical Care Medicine, Department of Medicine, University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Hussein D
HD
Kanji
D000925:Anticoagulants / Q000009:adverse effects*; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D006470:Hemorrhage / Q000453:epidemiology*; D006801:Humans; D012128:Respiratory Distress Syndrome / Q000150:complications; D012131:Respiratory Insufficiency / Q000401:mortality / Q000628:therapy*; D013927:Thrombosis / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology
D000925:Anticoagulants
anticoagulants; extracorporeal membrane oxygenation; heparin; respiratory failure