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as compared to unfractionated heparin( UFH) [ 5 ]. Current literature reports fewer bleeding events within the first 48 h of ECMO and a longer time within goal range with bivalirudin than heparin [ 7, 8 ]. Thus, our institution adopted bivalirudin as the primary anticoagulant for use during ECMO. There are limited published data and protocols regarding dosing, which calls for further description and study into the optimal approach [ 9, 10 ]. Furthermore, there is limited literature available describing the use of bivalirudin in patients with coronavirus disease 2019( COVID-19) receiving ECMO support [ 11, 12 ].
A cross-sectional review of all ECMO patients who received bivalirudin as their primary anticoagulant was conducted in 2018 to evaluate safety( systemic and circuit-related thrombotic events) and efficacy at our institution, in order to standardize dosing and monitoring recommendations for this patient population. Several protocol optimizations were identified, including minimizing various initial doses and initial prescribing of aPTT goals, which resulted in changes to the pharmacist-directed direct thrombin inhibitor( DTI) protocol. Since that time, all patients initiated on ECMO at this institution who have received bivalirudin as the systemic anticoagulant have utilized standardized doses and aPTT goals based on the new ECMO-specific protocol. The results of this initial review represent the pre-group of the present study. The intent of this study was to evaluate the updated pharmacist-directed ECMO bivalirudin protocol and its efficacy and safety, as well as describe dosing patterns in patients on ECMO with COVID-19.
Materials and methods Study design
This was a retrospective, single-center, pre-post study. It was undertaken as a Health Care Delivery Improvement Project, and as such was not reviewed as Human Subjects Research by the Institutional Review Board.
Intervention groups
In the 2018 cross-sectional review, adult patients who received bivalirudin for systemic anticoagulation during ECMO were evaluated from January 1, 2015, to July 31, 2018. The current study’ s pre-group was comprised of this cohort. Institutional practice during this time was for initial bivalirudin dosing and aPTT goal ranges to be set by the ordering provider, individualized for each patient. Following initiation, doses were adjusted by the pharmacist per a general DTI protocol, which was not specific to ECMO patients. The primary objectives of the initial study were to characterize the patient population receiving bivalirudin for ECMO and to describe the institutional prescribing patterns. The study identified an opportunity to standardize target aPTT ranges and bivalirudin dosing, and thus, a pharmacist-directed protocol for patients on ECMO was developed and implemented in January 2019.
Patients in the post-group were included from May 1, 2019, to June 30, 2021. Adult patients 18 years of age or older who were admitted to our institution and received ECMO support
Figure
1. Study flow diagram for patient exclusion and primary endpoint.
for at least 24 h were included. Patients were excluded if they received a systemic anticoagulant other than bivalirudin for ECMO anticoagulation or if they received Impella Ò( Johnson & Johnson MedTech, Danvers, MA, USA) support( Figure 1).
Institutional protocol
Bivalirudin for mechanical circulatory support is dosed based on a pharmacist-directed dosing protocol at our institution. The recommended initial bivalirudin rate chosen by the pharmacist is based on creatinine clearance, which is automatically calculated within the electronic health record utilizing the Cockroft-Gault equation. A low intensity( aPTT 45--60), high intensity( aPTT 60--80), or custom aPTT goal is chosen at the discretion of the cardiothoracic surgery team based on patient-specific and device-specific factors( Table 1). Once two consecutive aPTTs are within therapeutic range, aPTT monitoring may align with scheduled ECMO labs drawn every six hours instead of every two or four-hour monitoring. Two nomograms for the low and high intensity aPTT goals guide pharmacist-directed bivalirudin dose adjustments based on the aPTT( Tables 2 and 3). Study outcomes and data collection
Patient baseline and ECMO characteristics were collected. Baseline coagulopathy was defined as an international normalized ratio( INR) greater than 1.5 or platelets less than 50 K / lL. Incidence of renal failure during ECMO was defined as initiation of continuous renal replacement therapy( CRRT) or acute kidney injury as defined by the KDIGO guidelines [ 13 ]. For our non-ECMO bivalirudin protocol, aPTT monitoring decreases to