Bivalirudin Anticoagulation Dosing Protocol for Extracorporeal Membrane Oxygenation: A Retrospective Review

Abstract

Anticoagulation with unfractionated heparin during extracorporeal membrane oxygenation (ECMO) is common, but alternative agents are being evaluated for safety and efficacy. The objective of this analysis was to assess if a comprehensive bivalirudin dosing and monitoring protocol effectively guides dose adjustments and monitoring of bivalirudin in patients during ECMO. Our analysis included 11 patients who received bivalirudin during ECMO therapy and had dosing managed using our hospital derived protocol. Patients treated over a 1-year period were included in this retrospective analysis. Clinical characteristics and changes in activated partial thromboplastin time (aPTT) were evaluated from medical records to determine the efficacy of the dosing protocol. ECMO was initiated for acute respiratory distress syndrome in eight (72.7%) patients and for cardiac arrest in three (27.3%) patients. A total of 178 protocol guided dose adjustments were made during the study. Among the dose adjustments, 56 (31.5%) attained the protocol predicted aPTT level change, 96 (53.9%) of the measured aPTT changes were less than predicted, and 26 (14.6%) of the measured aPTT changes were more than predicted. On average, patients were within their defined therapeutic aPTT target range 66.3% of the time. All patients reached their designated aPTT target range within the first 24 hours of therapy. Significant bleeding was documented in eight (72.7%) patients. No clinically evident thromboembolic events were identified in vivo while cannulated. This analysis suggests that bivalirudin can be managed using a dosing protocol to provide anticoagulation therapy to patients during ECMO and can provide foundational guidance for dose adjustment and monitoring for other institutions.

Comparison of Bivalirudin Versus Heparin for Maintenance Systemic Anticoagulation During Adult and Pediatric Extracorporeal Membrane Oxygenation

“…Although the use of nonheparin anticoagulants remains atypical during ECMO, DTIs have been used when UFH is contraindicated, and a growing body of evidence exists to support both its safety and potential clinical superiority (14–25). Compared with other DTIs, bivalirudin offers a short half-life with limited reliance on organ function for clearance (26).…”

Anticoagulation strategy with bivalirudin plus aspirin combination during extracorporeal membrane oxygenation for COVID-19-associated acute respiratory distress syndrome

“…[19] To date, only a single center has reported a dosing protocol for anticoagulation with bivalirudin to monitor and guide coagulation parameters. [20] There has been a growing number of reports on the use of bivalirudin, with varying target anticoagulation parameters and ensuing complications in patients with or without COVID-19-associated ARDS. [11,21] In another study comparing bivalirudin and heparin in critically ill patients with severe COVID-19, bivalirudin displayed similar rates of hospital mortality and thromboembolic complications.…”

Extracorporeal Cardiopulmonary Resuscitation

“…Some centers report the use of direct thrombin inhibitors, such as bivalirudin, as an alternative to unfractionated heparin infusions [31]. Direct thrombin inhibitors (DTI) have the advantage of not requiring ATIII for action and can inhibit clotbound thrombin.…”