Abstract / Summary
Background and Objectives: Remimazolam is an ultra-short-acting benzodiazepine suitable for continuous infusion; however, evidence regarding its maintenance infusion rate for moderate sedation during spinal anesthesia across age strata is limited. We aimed to estimate and compare the continuous maintenance median effective dose (ED50) of remimazolam across three prospectively defined age groups. Materials and Methods: In this prospective, single-center dose-finding study (ClinicalTrials.gov NCT05379777), 60 patients undergoing lower-extremity orthopedic surgery under spinal anesthesia were stratified into Group A (<60 years), Group B (60–74 years), and Group C (≥75 years) (n = 20 each). After a loading infusion (1.0 mg/kg/h) to achieve moderate sedation (Modified Observer’s Assessment of Alertness/Sedation [mOAA/S] score ≤ 3), maintenance rates were assigned using Dixon’s up-and-down method; success was defined as maintaining mOAA/S ≤ 3 until the end of surgery without dose titration. The maintenance ED50 was estimated using centered isotonic regression with 90% confidence intervals (CIs). Safety outcomes were evaluated in all patients. Results: Sedation was maintained at the assigned rate in 13, 13, and 14 patients in Groups A, B, and C, respectively, and all failures were managed by upward titration. The maintenance ED50 was 0.238 (90% CI, 0.152–0.336), 0.233 (90% CI, 0.170–0.301), and 0.178 (90% CI, 0.092–0.245) mg/kg/h in Groups A, B, and C, respectively; the CIs overlapped, and no statistically significant difference was observed. Hypotension requiring vasopressors occurred in 25.0% and respiratory depression requiring airway management in 23.3% of patients, without significant intergroup differences; no patient had peripheral oxygen saturation < 90% or required flumazenil. Conclusions: The maintenance ED50 of remimazolam for moderate sedation during spinal anesthesia was numerically lower in patients aged ≥75 years, without a statistically significant difference among age groups. A conservative initial maintenance rate may be considered in this age group; this hypothesis-generating suggestion requires confirmation in adequately powered studies.