ED50 of Remimazolam for Anesthesia Induction in Frail Elderly Patients

Significantly Reduced Median Effective Dose (ED50) of Remimazolam for Anesthesia Induction in Frail Elderly Patients: A Prospective Dose-Finding Clinical Trial With Respiratory Volume Monitoring

This study aimed to determine the median effective dose (ED50) of remimazolam for loss of consciousness (LOC) in elderly and frail elderly patients using the Dixon up-and-down method, while utilizing a novel Respiratory Volume Monitor (RVM) to detect subclinical respiratory depression.

Study Overview

• Status: Completed
• Conditions: Frailty; Anesthesia Induction
• Intervention / Treatment: Drug: Remimazolam Tosilate; Drug: Remimazolam Tosilate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Second Hospital of Hebei Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elderly Group (Non-Frail); Patients with a Clinical Frailty Scale (CFS) score < 5.	Drug: Remimazolam Tosilate; 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.; Drug: Remimazolam Tosilate; 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.
Experimental: Frail Elderly Group; Patients with a Clinical Frailty Scale (CFS) score ≥ 5.	Drug: Remimazolam Tosilate; 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.; Drug: Remimazolam Tosilate; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sedation Success (Loss of Consciousness)	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.	up to 2 minutes

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The First Hospital of Hebei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2025
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: March 1, 2026
• First Submitted That Met QC Criteria: March 8, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Frailty; Anesthesia Induction; Dixon Up-and-Down Method; Remimazolam Tosilate; Median Effective Dose (ED50); Respiratory Volume Monitor (RVM)
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Frailty
• Other Study ID Numbers: 2025-R031

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No