ED50 of Remimazolam for Anesthesia Induction in Frail Elderly Patients

The physiological decline associated with frailty in elderly patients presents significant challenges for anesthesia induction. Remimazolam tosilate, an ultra-short-acting benzodiazepine, offers a promising safety profile, yet its optimal dosing in frail populations remains undefined. This prospective, up-and-down sequential allocation trial was conducted at the Second Hospital of Hebei Medical University. 58 patients aged ≥65 years undergoing elective surgery were stratified into two groups: an Elderly Group (Clinical Frailty Scale \[CFS\] < 5) and a Frail Elderly Group (CFS ≥ 5). The initial remimazolam induction dose was set at 0.15 mg/kg for the elderly group and 0.13 mg/kg for the frail group, with dose adjustments based on the previous patient's response. A non-invasive RVM was employed to continuously monitor Tidal Volume (VT) and detect early hypoventilation.

• Remimazolam Tosilate (Drug): The initial induction dose was set at 0.15 mg/kg administered as a single intravenous bolus over 30 seconds. The dose adjustment gradient for consecutive patients was 0.02 mg/kg based on the Dixon up-and-down method.
• Remimazolam Tosilate (Drug): The initial induction dose was set at 0.13 mg/kg administered as a single intravenous bolus over 30 seconds. The dose adjustment gradient for consecutive patients was 0.01 mg/kg based on the Dixon up-and-down method.

Primary outcomes

• Sedation Success (Loss of Consciousness) [up to 2 minutes]: Defined as the achievement of Loss of Consciousness (LOC) confirmed by loss of eyelash reflex, no response to verbal commands, Ramsay Sedation Score ≥ 5, and MOAA/S score < 1.

Secondary outcomes

• Median Effective Dose (ED50) of Remimazolam [Perioperative/Periprocedural]: The ED50 calculated via probit analysis based on the Dixon up-and-down sequential allocation method.
• Changes in Tidal Volume (VT) [Baseline, 30 seconds, 60 seconds, 90 seconds, and up to 120 seconds post-administration]: Continuous assessment of spontaneous Tidal Volume (VT) utilizing a non-invasive Respiratory Volume Monitor (RVM) to evaluate subclinical respiratory depression.
• Mean Arterial Pressure (MAP) [Baseline and up to 2 minutes post-administration]: Changes in Mean Arterial Pressure (MAP) during the induction period, measured in mmHg.
• Heart Rate (HR) [Baseline and up to 2 minutes post-administration]: Changes in Heart Rate (HR) during the induction period, measured in beats per minute.

Sex: All, ages: 65 Years to any

Inclusion Criteria:

* Aged ≥65 years;
* Scheduled for elective surgery under general anesthesia with endotracheal intubation;
* American Society of Anesthesiologists (ASA) physical status II or III;
* Body Mass Index (BMI) between 18 and 30 kg/m².

Exclusion Criteria:

* Known allergy to benzodiazepines;
* History of severe respiratory or cardiovascular disease (e.g., acute heart failure, severe COPD);
* Long-term use of sedatives, analgesics, or alcohol abuse;
* Known neuromuscular disorders (e.g., myasthenia gravis);
* Inability to communicate for sedation assessment.