The Impact of Sex on the Median Effective Dose of Dexmedetomidine for Preoperative Sedation in Adults Undergoing Upper Limb Surgery: An Up-and-Down Sequential Allocation Study

Purpose: Prospective evidence on sex-based variability in the sedative potency of dexmedetomidine remains limited. This study aimed to estimate and compare the median effective dose (ED 50 ) of dexmedetomidine for preoperative sedation in adult men and women undergoing elective upper limb surgery. Patients and Methods: In this prospective, single-center, assessor-blinded, dose-finding study, adult patients aged 18 to 60 years scheduled for upper limb surgery were allocated to male and female dexmedetomidine groups according to biological sex. Dexmedetomidine was administered intravenously over 15 minutes using a modified Dixon’s up-and-down sequential method (initial dose 1.0 μg/kg; step size 0.05 μg/kg). Adequate sedation was defined as a Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale score < 3 at 26 minutes from infusion start. The primary endpoint was the Dixon-derived ED 50, with supportive analyses including probit regression, bootstrap validation, and multivariable logistic regression adjusted for baseline covariates. Secondary outcomes included sedation depth and adverse events. Results: Forty-six patients (23 per group) were enrolled. The Dixon-derived ED 50 (95% confidence interval) was 1.26 μg/kg (1.17– 1.35) in men and 1.28 μg/kg (1.17– 1.38) in women, with overlapping confidence intervals. Probit regression and bootstrap-validated ED 50 estimates were consistently similar between groups. In multivariable analysis, sex was not independently associated with adequate sedation ( P = 0.275), whereas dexmedetomidine dose was a significant predictor. At 26 minutes, neither MOAA/S scores nor bispectral index (BIS) values differed significantly between sexes. Bradycardia occurred in 39.1% of males versus 34.8% of females, and hypertension in 13.0% versus 4.3%, respectively; all adverse events were transient and safely managed. Conclusion: No clinically meaningful sex-related difference was observed in dexmedetomidine ED 50 under standardized preoperative conditions. These findings do not support routine sex-based dose adjustment for preoperative sedation in relatively healthy adults. Keywords: dexmedetomidine, adrenergic alpha-2 receptor agonists, preanesthetic medication, dose–response relationship, drug, sex factors A Letter to the Editor has been published for this article .