Remimazolam Concentration and Sedation Depth During Lower Extremity Surgery Under Spinal Anesthesia
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age19+
SponsorSeoul National University Hospital
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Age 19 years or older.
Scheduled for lower extremity surgery under spinal anesthesia.
American Society of Anesthesiologists (ASA) physical status I-III.
Agrees to intraoperative sedation and provides written informed consent.
Disqualifiers
Refusal to participate.
Contraindication to spinal anesthesia, including refusal, increased intracranial pressure, infection at the puncture site, underlying neurological disease, severe hypovolemia, aortic or mitral stenosis, thrombocytopenia, or coagulopathy.
Contraindication or history of hypersensitivity to remimazolam, including acute narrow-angle glaucoma, severe respiratory failure, or dextran 40 hypersensitivity.
Contraindication or history of hypersensitivity to flumazenil.
Trial design
Design model
Single group
Treatments tested in this trial
Remimazolam
DrugRemimazolam 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.
Treatment groups
60 Participants
are divided into 1 treatment groupGroup A: Titrated Remimazolam SedationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Between-Patient Coefficient of Variation in Model-Predicted Effect-Site Concentration Associated With Target Sedation
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.
Time frame
During intraoperative remimazolam sedation, from loading through infusion cessation on the day of surgerySecondary outcomes
1
Ratio of Individual Representative Effect-Site Concentration to the Eleveld Sedation Target
For each participant, the median model-predicted effect-site concentration at maintenance MOAA/S 3 observations divided by the Eleveld model sedation target (1.75 times the age-adjusted Ce50).
Time frame
During remimazolam administration on the day of surgery2
Age-Adjusted Residual Between-Patient Coefficient of Variation
Residual between-patient variability in the concentration associated with target sedation after adjustment for age as a continuous covariate, expressed as a coefficient of variation (%).
Time frame
During remimazolam administration on the day of surgery3
MOAA/S Score
Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score, measured at baseline before remimazolam, at 1, 2, 3, 4, and 5 minutes after completion of loading, every 5 minutes during infusion, and every 5 minutes after infusion cessation until a score of 5 is reached in the operating room or PACU. Scores are also recorded at infusion cessation, end of surgery, operating-room discharge, and PACU admission. MOAA/S ranges from 0 (no response to painful stimulation) to 5 (readily responds to a name spoken in a normal tone); lower scores indicate deeper sedation.
Time frame
From baseline before remimazolam until MOAA/S 5 after infusion cessation on the day of surgery4
Remimazolam Infusion Rate
Remimazolam infusion rate (mg/kg/h), measured at 5-minute intervals from the end of the loading dose until infusion cessation. The rate after any adjustment at each assessment is recorded.
Time frame
From the end of the remimazolam loading dose until infusion cessation on the day of surgerySponsors and contacts
Click on the lead sponsor to view all of their trials.
Seoul National University Hospital
Lead sponsor
National Research Foundation of Korea
Collaborator
Ministry of Science and ICT, Republic of Korea
Collaborator
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: