Association between nafamostat mesylate infusion dose and dialysis circuit occlusion in continuous renal replacement therapy: a retrospective cohort study

Abstract Background Circuit occlusion during treatment is detrimental in patients undergoing continuous renal replacement therapy (CRRT), leading to treatment interruption, reduced clearance efficiency, and increased healthcare costs. Nafamostat mesylate (NM) is an anticoagulant commonly used during CRRT, particularly in patients with a high risk of bleeding, owing to its short half-life and reversible anticoagulant effects. However, its optimal dose range remains unclear. We aimed to investigate whether differences in the hourly dose of NM are associated with differences in the circuit occlusion rate of CRRT in patients who are critically ill. Methods We conducted a retrospective cohort study in the intensive care unit of Shonan Kamakura General Hospital between April 2022 and June 2024. Adult patients requiring CRRT with NM as the sole anticoagulant were included in this study. The primary outcome was the ratio of circuit occlusions within 24 h. A multivariate logistic regression analysis was performed to account for confounding clinical factors. The secondary outcome was the occurrence of bleeding events until hospital discharge. We also performed subgroup analyses and stratified and compared the patient- and device-side factors thought to affect circuit occlusion. Results We included 70 patients (mean age, 72 years; 44 males [62.9%]). The median NM dose was 30 mg/h (interquartile range [IQR]: 30–40 mg/h). There was no significant association between NM dose and occlusion (odds ratios [OR] 1.39; 95% confidence interval [CI] 0.71–2.89) or bleeding events (OR 1.39; 95% CI 0.55–4.35). Subgroup analysis suggested that the association between a higher NM dose and circuit occlusion events was generally consistent across strata, although some subgroups (such as patients with higher sequential organ failure assessment scores, bleeding risk, sepsis, or different filter types) showed possible heterogeneity in the effect estimates. However, no statistically significant interactions were observed. Conclusions In this study, the continuous NM infusion dose was not significantly associated with circuit occlusion in CRRT. Future randomized trials comparing different NM doses and alternative anticoagulants are needed to define the optimal anticoagulation strategies.