Comparison of total versus ideal body weight-based remimazolam dosing for sedation in overweight and obese patients undergoing knee arthroplasty under spinal anesthesia: a randomized controlled trial

Background: Obesity poses sedation challenges owing to altered pharmacokinetics. However, the optimal weight scalar for remimazolam administration in overweight and obese patients remains controversial. This study compared the efficacy and safety of total body weight (TBW)- vs. ideal body weight (IBW)-based remimazolam dosing. Methods: In this patient- and outcome assessor-blinded randomized trial, 110 patients of body mass index (BMI) ≥ 25 kg/m2 undergoing elective knee arthroplasty under spinal anesthesia received TBW- or IBW-based remimazolam. A 0.075 mg/kg loading dose was followed by continuous infusion to maintain moderate sedation. The primary outcome was the incidence of intraoperative respiratory depression. Secondary outcomes included sedation quality, recovery profiles, and pharmacokinetic/pharmacodynamic simulations. Results: Of 102 analyzed patients, respiratory depression was significantly more frequent in the TBW group (45.1% vs. 25.5%; relative risk [RR] 1.77; 95% CI 1.02 to 3.06; P = 0.038). TBW-based dosing, older age, and male sex were independent risk factors. Recovery times were longer in the TBW group (median difference 5.0 min, 95% CI 1.0 to 10.0, P = 0.016). This difference was numerically larger in patients with BMI ≥ 30 kg/m2 (mean difference 14.2 min), but no subgroup comparison remained significant after Benjamini-Hochberg adjustment. Post-hoc Eleveld model simulations generally underestimated sedation depth. The estimated loading dose associated with a 10% risk of respiratory depression was 0.024 mg/kg. Conclusions: TBW-based remimazolam dosing increased the risk of transient respiratory depression and prolonged recovery compared to IBW-based dosing in overweight and obese patients. Conservative IBW-based dosing appeared safer under the present protocol; further loading-dose reduction remains an exploratory hypothesis requiring dose-finding and pharmacokinetic validation.