Impact of Anticoagulation and Circuit Technology on Complications During Extracorporeal Membrane Oxygenation

Abstract

The objective of this study is to evaluate the impact a change in anticoagulation protocol and circuit technology had on bleeding and thrombotic complications in patients supported on extracorporeal membrane oxygenation (ECMO). A retrospective review at a tertiary, academic pediatric intensive care unit was undertaken. The anticoagulation protocol changed from targeting an activated clotting time (ACT) to anti-Xa level. Significant changes in the ECMO circuit were undertaken concurrently. One-hundred and fifty-two ECMO runs in 129 patients in the ACT target group were compared with 122 ECMO runs in 101 patients in the anti-Xa target group. Improved probability of survival by ECMO duration, decreased rate of surgical exploration, increased time to first surgical exploration, decreased incidence of intracranial hemorrhage, increased time to identification of intracranial hemorrhage, decreased blood loss and transfused product volumes, decreased rate of circuit changes, and increased time to first circuit change were all observed in the anti-Xa targeted group. Heparin dosing was similar in both groups with fewer bolus doses of heparin and fewer changes in the infusion rate in the anti-Xa targeted group. The change in anticoagulation protocol and circuit technology was associated with an improvement in survival, a decrease in hemorrhagic complications, and a decrease in circuit changes.

Anticoagulation and Antithrombin in Veno-venous Extracorporeal Membrane Oxygenation

“…Retrospective clinical studies in extracorporeal membrane oxygenation and non-extracorporeal membrane oxygenation adults and children have demonstrated that use of an anti-Xa monitoring strategy may improve patient outcomes, including survival. 7 In this study, Protti et al 5 report that 49% of centers measured antithrombin concentration with routine supplementation in 38.1% if the target was not reached (51%), or if antithrombin was lower than 70% (49%). Not surprisingly, due to the cost of antithrombin, multivariate analyses demonstrated antithrombin supplementation was associated with national income and less likely to be prescribed in lower income countries.…”

“…Anti-Xa monitoring, which measures heparin concentration and activity in the ex vivo test sample, is demonstrated to decrease transfusion requirements thrombosis and bleeding and circuit changes. 7 Complicating the clinician's test choice for patient management is the lack of correlation of PTT, activated clotting time, and anti-Xa concentration. 8 Discussions continue among experts as to the appropriate monitoring tests whether PTT, anti-Xa, or measuring global hemostasis using thromboelastography are more reflective of in vivo clinical state.…”

“…Heparin use in extracorporeal membrane oxygenation in ill neonates is complicated as upwards of 40 U • kg -1 • h -1 of heparin is often required. Evidence-based guidance on use of antithrombin supplementation in children, and adults, on extracorporeal membrane oxygenation is conflicting, with some retrospective pediatric studies demonstrating decreased thrombotic events with supplementation, 7,9 but not in others. 10,11 Thus, the benefit of antithrombin replacement in extracorporeal membrane oxygenation patients has not been established, with costs as much as $3.50 (USD) per unit and some patients being replaced with more than 500 units per administration, which could be on a daily basis or more.…”

Traditional and non-traditional anticoagulation management during extracorporeal membrane oxygenation

“…A large, retrospective single-center investigation of 365 pediatric ECMO patients showed a reduction in the incidence of bleeding and transfusion requirements, as well as decreased numbers of circuit replacement due to clotting after implementing an anti-factor Xa target of 0.3-07 IU/mL, daily AT level control and AT replacement, when heparin demand exceeded 60 U/kg/h (27). Additionally, another large, retrospective single-center investigation in pediatric patients compared an ACT-based protocol (target 160-200 seconds) with an anti-factor Xa-based protocol (target 0.5-0.7 IU/mL) (28). The analysis included 152 ECMO runs in the ACT group and 122 ECMO runs in the anti-factor Xa group.…”

Anti-Factor Xa–Based Anticoagulation during Extracorporeal Membrane Oxygenation: Potential Problems and Possible Solutions

“…The vast majority of studies where anti-FXa has been used for titrating UFH dose in ECMO report a target value of 0.3 to 0.7 IU/mL, 10,13 but higher ranges (lower limit: 0.4-0.5 IU/mL; upper limit: 0.8 IU/mL) have also been proposed. 7,11,44 Lower ranges (0.2-0.4 IU/mL) have been proposed as well. 45 The range 0.3 to 0.7 IU/mL, proposed by the Extracorporeal Life Support Organization 46 in 2014, simply reflects the range traditionally considered adequate for UFH treatment and prevention of venous thrombosis.…”