Argatroban dosing in extracorporeal membrane oxygenation and other critically ill populations
Dingman S, Peters M, To L, and Smith Z. Argatroban dosing in extracorporeal membrane oxygenation and other critically ill populations. Crit Care Med 2019; 47(1).
Crit Care Med
Learning Objectives: Argatroban is a potent parenteral direct thrombin inhibitor that requires close monitoring to ensure safety and efficacy. Limited data exist to describe its effect in critically ill patients. The objective of this study was to compare argatroban dosing requirements in those receiving extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT), or neither. Methods: This was a retrospective, single-center, cohort study. Adult patients initiated on argatroban while in an intensive care unit were matched on Child-Pugh classification and assigned to one of three groups based on type of extracorporeal support received: ECMO, CRRT, or support-free group. The primary outcome was comparing the first argatroban dose to achieve three consecutive therapeutic aPTTs according to a pharmacist-directed dosing guideline amongst the three study groups. Other outcomes included mean, final, minimum, and maximum argatroban doses. Organ dysfunction was assessed using a modified version of the Sequential Organ Failure Assessment (modSOFA) that incorporated the use of extracorporeal support systems. Linear regression was performed to correlate modSOFA score and therapeutic argatroban dose. Results: Eighty patients were included in the study (n = 20, 20, 40 in the ECMO, CRRT, and support-free groups, respectively). The majority of patients were Child-Pugh classification B (73%). Median modSOFA scores were higher in the ECMO (16.5) and CRRT (15.5) groups than in the support-free group (7.5) (P <0.001). The primary outcome of first therapeutic dose was 0.5 mcg/kg/min in all three groups (IQRs 0.25-0.50, 0.11-0.50, and 0.25-0.50, respectively; P = 0.455), with the ECMO group having the lowest mean (0.39 mcg/kg/min), minimum (0.20 mcg/kg/min), and final (0.43 mcg/kg/min) doses. ECMO patients had more supratherapeutic aPTTs and dose changes overall. Total modSOFA score demonstrated a moderate inverse correlation with first therapeutic dose (dose = 0.54 - (modSOFA score ∗ 0.012); R = -0.342, P = 0.002). Conclusions: In the studied population, initial argatroban doses of 0.3-0.5 mcg/kg/min achieved therapeutic PTT values. No initial argatroban dosing requirement differences were noted amongst groups receiving ECMO, CRRT, or the support-free group. ECMO patients demonstrated greater dosing instability, which supports the need for more frequent anticoagulation monitoring or dose reductions in this population. Future studies are warranted on this subject matter.