Argatroban dosing requirements in extracorporeal life support and other critically ill populations

Argatroban is a parenteral direct thrombin inhibitor that requires close monitoring to ensure safety and efficacy. Limited data exist to describe its effect in critically ill patients. This was a retrospective, single-center, cohort study that aimed to compare argatroban dosing requirements in those receiving extracorporeal life support (ECLS), continuous renal replacement therapy (CRRT), or neither. Organ dysfunction was assessed using a modified version of the Sequential Organ Failure Assessment (modSOFA) that incorporated the use of extracorporeal support systems. Eighty patients were included in the study (n = 20, 20, 40 in the ECLS, CRRT, and support-free groups, respectively). The majority of patients were Child-Pugh classification B (73%). Median modSOFA scores were higher in the ECLS (16.5) and CRRT (15.5) groups than in the support-free group (7.5) (P < .001). There was no difference in the primary outcome of first therapeutic argatroban dose between the three groups (0.5 mu g/kg/min for each; IQRs 0.25-0.50, 0.11-0.50, and 0.25-0.50, respectively; P = .455). The ECLS group had the lowest mean (0.39 mu g/kg/min), minimum (0.20 mu g/kg/min), and final (0.43 mu g/kg/min) doses. ECLS patients had more supratherapeutic aPTTs and dose changes overall, supporting the need for more frequent anticoagulation monitoring or dose reductions in this population. Total modSOFA score demonstrated a moderate inverse correlation with first therapeutic dose (dose = 0.54 - (modSOFA score x 0.012); R = -0.342, P = .002). Overall, initial argatroban doses of 0.3-0.5 mu g/kg/min appear to achieve therapeutic aPTT values in the studied populations.