Anticoagulation and associated complications in Veno-Arterial Extracorporeal Membrane Oxygenation in Adult Patients: A Protocol for a Systematic Review and Meta-Analysis

Background Veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a rapidly expanding therapy with a relatively limited evidence base. Due to both quantitative and qualitative acquired coagulopathies in VA-ECMO, bleeding remains a major complication and with potentially catastrophic outcomes. Simultaneously, coagulation activation occurs via blood contact with the extracorporeal circuit, which risks not only vital organ emboli, but also the circuit viability. This carries the risk of equally catastrophic complications. As such, VA-ECMO patients are routinely anticoagulated. A large variation in practice exists surrounding anticoagulation in VA-ECMO. Despite an increasing uptake in the therapy, the evidence base is limited and current guidelines surrounding anticoagulation practice are based on expert opinion. We will perform a study level systematic review and meta-analysis of VA-ECMO patients comparing anticoagulation strategies, including the agent of anticoagulation, the method of monitoring and the targeted degree of anticoagulation to assess the association between described anticoagulation strategies and bleeding and thrombotic complications. Methods We will perform a study level meta-analysis of randomised controlled trials (RCTs) and cohort studies that report on bleeding and thrombotic complications in VA-ECMO. Our primary objective is to describe the incidence of bleeding and thrombotic complications associated with individual anticoagulation strategies. In order to be included, a study must report the anticoagulant drug used, the method of monitoring used, or the anticoagulation target used, and at least one outcome of interest. Four databases will be systematically reviewed by two authors. Two authors will extract and assess for risk of bias using the Cochrane Risk of Bias tool for RCTs and the ROBINS-I tool for observational studies. Data will be analysed via incidence rates of bleeding and thrombotic complications, with a subgroup analysis of each anticoagulation strategy where able. The study will be reported in line with PRISMA guidelines.