Remimazolam Concentration and Sedation Depth During Lower Extremity Surgery Under Spinal Anesthesia

Condition(s) studied

Investigational drug(s) / intervention(s)

Remimazolam: Remimazolam besylate is prepared at 1 mg/mL. After spinal anesthesia, 2.5 mg is infused intravenously over 1 minute, followed by 0.2 mg/kg/h. MOAA/S is assessed at 1-5 minutes after loading and then every 5 minutes. Increase by 0.05 mg/kg/h for MOAA/S \>3; decrease by 0.05 mg/kg/h for MOAA/S \<=2, maintaining the minimum rate if already at 0.05 mg/kg/h. Permitted range: 0.05-0.8 mg/kg/h. Stop infusion for MOAA/S \<=1 or airway/respiratory impairment; resume at the minimum rate after recovery, with flumazenil if clinically indicated. Stop remimazolam and consider another sedative if MOAA/S remains \>3 at the maximum rate. Stop infusion at the start of muscle-layer closure. Assess MOAA/S every 5 minutes after cessation until MOAA/S 5. Opioids and other sedatives are not coadministered during the study regimen.

Study summary

This study will examine how the amount of remimazolam predicted to reach its site of action relates to the depth of sedation during lower extremity surgery under spinal anesthesia. Remimazolam is a sedative used to help patients relax and feel sleepy during surgery. People may respond differently to the same amount of this medicine, and age may explain some of these differences.

Sixty adults will be enrolled at Seoul National University Hospital, with 20 participants in each age group: 19-49 years, 50-69 years, and 70 years or older. All participants will receive remimazolam using the same stepwise dose-adjustment rules. The dose will be adjusted according to repeated assessments of responsiveness. Researchers will record sedation scores, medication delivery, brain-wave signals, vital signs, recovery, and side effects.

After surgery, a computer model will estimate the remimazolam concentration at its site of action. These estimates will not be available to the clinical team during surgery. The main goal is to measure how much the concentration associated with the target level of sedation varies between patients. The study will also examine the effect of age and whether early responses can help predict an individual patient's later response.

Eligibility

Primary outcome measure(s)

• Between-Patient Coefficient of Variation in Model-Predicted Effect-Site Concentration Associated With Target Sedation — During intraoperative remimazolam sedation, from loading through infusion cessation on the day of surgery
  Between-patient variability in the remimazolam effect-site concentration associated with target sedation (Modified Observer's Assessment of Alertness/Sedation \[MOAA/S\] \<=3), expressed as a coefficient of variation (%). Eleveld model-predicted concentrations are reconstructed after surgery from dosing histories and patient covariates. The protocol specifies maintenance observations at MOAA/S 3 and an ordinal mixed-effects concentration-response analysis to estimate variability at the MOAA/S \<=3 threshold. MOAA/S ranges from 0 (no response to painful stimulus) to 5 (readily responsive to a name spoken in a normal tone); lower scores indicate deeper sedation.

Trial sites (1)

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