기타학회
| Evaluation of Argatroban Dosing in Critically Ill Patients: Impact of Organ Dysfunction and Extracorporeal Support | ||
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Department of Pharmacy, Asan Medical Center, South Korea
Background and importance Argatroban, a direct thrombin inhibitor primarily metabolized in the liver, is widely used in the management of heparin-induced thrombocytopenia (HIT). In critically ill patients, dosing is complicated by organ dysfunction and altered pharmacokinetics. While hepatic impairment is an established determinant of dose adjustment, evidence on dosing in patients receiving extracorporeal support (ECMO, CRRT) remains limited.
Aim and objectives This study aimed to evaluate the impact of organ dysfunction and extracorporeal support on argatroban dosing requirements in critically ill patients.
Materials and methods We performed a retrospective, single-center study of ICU patients treated with argatroban for ≥24 hours between January 2015 and December 2024. Data included demographics, organ dysfunction, extracorporeal support, argatroban dosing, aPTT monitoring, and bleeding or thrombotic events. Argatroban doses were compared by organ dysfunction and extracorporeal support using the Mann-Whitney test. Independent predictors of mean argatroban dose were assessed by multiple linear regression.
Results A total of 46 patients were included. The mean initial dose was 0.19±0.28 mcg/kg/min, and the therapeutic dose (dose achieving two consecutive target aPTTs) was 0.38±0.42 mcg/kg/min. Patients with hepatic dysfunction (n=28) required significantly lower therapeutic and mean doses than those without (p=0.023 and p=0.032, respectively). Renal dysfunction, ECMO, and CRRT did not significantly influence dosing, although higher aPTT values were observed in CRRT patients. Multivariate analysis confirmed the Child-Pugh score as an independent predictor of mean dose (p=0.018).
Conclusion and relevance In critically ill patients, argatroban should generally be initiated at ≤0.5 mcg/kg/min, with further reductions in hepatic dysfunction. Extracorporeal support did not significantly alter dosing requirements, reinforcing hepatic function as the key determinant for adjustment. These findings support individualized argatroban therapy and provide practical guidance for HIT management in the ICU. |
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