Hamzah, Mohammed

OBJECTIVES: To assess the wholistic costs of systemic anticoagulation delivery in heparin versus bivalirudin-based maintenance of adult patients supported on extracorporeal membrane oxygenation (ECMO). DESIGN: Single-center retrospective cohort study. SETTING: Large academic ECMO center. PATIENTS: Adults on ECMO receiving heparin or bivalirudin for primary maintenance systemic anticoagulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electronic data were abstracted from a database maintained by our ECMO center, which transitioned to a preferred bivalirudin-based anticoagulation management in 2017. The pretransition group consisted of 126 patients (123 heparin and three bivalirudin), whereas the posttransition group included 275 patients (82 heparin and 193 bivalirudin). Drug costs were estimated using the wholesale acquisition cost, and laboratory assays costs were estimated using reimbursement fee schedules. Cost data were normalized to the duration of the ECMO run and reported in U.S. Dollar per ECMO day. Following the practice change, bivalirudin patients were less likely to receive AT supplementation (31.0 vs 12.4%; p < 0.0001) and had fewer coagulation assays ordered (6.1 vs 5.4 per ECMO day; p = 0.0004). After the transition, there was a dramatic decrease in costs related to AT assay assessments ($11.78 [interquartile range {IQR}, $9.48–$13.09] vs $1.03 [IQR, $0–$5.75]; p < 0.0001) and AT supplementation ($0 [IQR, $0–$312.82] vs $0 [IQR, $0–$0]; p < 0.0001) per ECMO day. Unadjusted survival at 28 days was higher posttransition (64.3 vs 74.9%; p = 0.0286). CONCLUSIONS: Antithrombin assays and supplementation compromise a significant proportion of heparin-based anticoagulation costs in ECMO patients and is substantially reduced when a bivalirudin-based anticoagulation strategy is deployed. A favorable association exists between the aggregate cost of administration of bivalirudin compared with heparin-based systemic anticoagulation in adults supported on ECMO driven by reductions in antithrombin activity assessments and the cost of antithrombin replacement.

Bivalirudin offers several important advantages of relevance to the management of extracorporeal membrane oxygenation (ECMO) patients. This multicenter retrospective analysis evaluated the bivalirudin dosing in pediatric ECMO and correlated these doses with the severity of renal dysfunction. A total of 75 patients were included in this analyses: estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m2 (n = 29), eGFR 30–60 (n = 18), eGFR < 30 (n = 28), and of those 23 were on renal replacement therapy (RRT). The initial bivalirudin dose used to reach therapeutic anticoagulation in patients with eGFR > 60 was significantly higher than the dose required in those with renal impairment (0.25 mg/kg/hr in patients with eGFR > 60 and 0.19 mg/kg/hr in patients on RRT, 0.18 mg/kg/hr in patients with eGFR 30–60 and 0.13 mg/kg/hr in patients with eGFR < 30 with no RRT). Progressive dose escalations (two to threefold increase) were required to maintain therapeutic range over the initial 4 days of ECMO that coincided with improving renal creatinine clearance during that same time period. Establishing an initial starting dose of bivalirudin contingent upon eGFR is essential for the rapid achievement of target anticoagulation intensity. Further dose adjustments guided by laboratory monitoring is necessary given the dynamic changes in creatinine clearance following ECMO initiation.