(219) Reliability of Systemic Anticoagulants During Extracorporeal Membrane Oxygenation

Introduction: Anticoagulation is often utilized during extracorporeal membrane oxygenation (ECMO), yet the optimal agent has not been defined. Empirical evidence suggests direct thrombin inhibitors (DTIs) may produce more favorable hemostatic outcomes compared to heparin in ECMO, however their efficiency of use is unknown. The objective of this systematic review was to assess the dosing reliability of systemic anticoagulant infusions used during ECMO.

Methods: We systematically searched Ovid Cochrane Central Register of Clinical Trials, Embase, MEDLINE, Scopus, CINAHL, ClinicalTrials.gov, International Clinical Trials Registry Platform, and Web of Science following an a priori registered protocol. Articles were included if they were randomized trials or observational studies comparing DTIs to heparin for maintenance anticoagulation during ECMO in human subjects of any age and reported on any dosing reliability outcomes. The primary outcome was the percentage of time spent within therapeutic goal range. Meta-analysis was performed using the inverse variance method to estimate the mean differences with 95% confidence intervals.

Results: After screening the 587 search results, 28 articles met the inclusion criteria, including 16 full manuscripts and 11 conference abstracts, all of which were observational studies. Additionally, one randomized trial registration record that reported results was identified and included. Bivalirudin was the DTI used in most studies, except for 3 reporting on argatroban. Nine full manuscripts reported sufficient data for pooling and were included in the meta-analysis. DTIs experienced a greater percentage of time in therapeutic range than heparin (mean difference 22.87%, 95% CI 6.98-38.75, p < 0.01). Heparin-based ECMO required a longer time to achieve therapeutic anticoagulation compared to DTIs (mean difference 8.28 hours, 1.68-14.88, p = 0.01). The proportion of patients experiencing subtherapeutic anticoagulation ranged from 2.5-48% for DTIs and from 16-63% for heparin.

Conclusions: During ECMO support, DTIs achieved therapeutic anticoagulation targets faster and offered a greater amount of time within therapeutic anticoagulation goal ranges compared to heparin. The beneficial signals supporting DTIs during ECMO warrant the conduct of randomized trials.