Effects of Remimazolam on Breathing Patterns, Respiratory Drive, and Inspiratory Effort in Mechanically Ventilated Patients

Sedatives and analgesics are usually given for analgesic, anxiolytic, or sedating purposes for patients with critical illness, while they inevitably inhibit respiratory and circulatory function. Sometimes, patients receive deep sedation to induce hypoventilation or suppress spontaneous respiratory effort. The sedation level in clinical practice is usually assessed with subjective sedation scoring systems, such as the Richmond Agitation Sedation Scale (RASS). However, studies have found that sedation depth based on RASS is not a reliable marker of respiratory drive during critical illness. In recent years, researchers have proposed to monitor the effects of sedatives and analgesics on respiratory indicators and to implement lung-protective sedation, such as airway occlusion pressure (P0.1), airway occlusion pressure (Pocc). However, different pharmacological characteristics, different depths of sedation, and different sedation regimens among different sedatives and analgesics make a great difference in their effects on respiration. Remimazolam is a new benzodiazepine sedative developed by adding a methyl propionate side chain to the structure of midazolam. As an organic weak base, remimazolam forms a salt with benzenesulfonic acid, which enhances its solubility and stability. The sedative effect of remimazolam primarily occurs through binding to γ-aminobutyric acid type A (GABAA) receptors, opening chloride channels, promoting chloride ion influx, hyperpolarizing neuronal membranes, and thereby suppressing neuronal excitability. The drug acts rapidly, achieving maximum sedation within three minutes after administration. Research on adverse effects of remimazolam remains limited, particularly regarding its impact on respiratory function. Therefore, this study aims to investigate the effects of remimazolam on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients.

Study Overview

• Status: Completed
• Conditions: Mechanical Ventilation; Remimazolam; Sedation and Analgesia
• Intervention / Treatment: Drug: Remimazolam

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients admitted to the ICU after surgery under general anesthesia;
• Patients with an artificial airway and receiving assisted ventilation in pressure support mode;
• Patients expected to achieve a sedation depth corresponding to a Richmond Agitation and Sedation Scale (RASS) score of -2 to +1;

Exclusion Criteria:

• Patients with brainstem tumors or neuromuscular disorders;
• Patients unable to undergo RASS assessment due to various reasons, such as history of psychiatric disorders (schizophrenia, mania, delirium, cognitive impairment), status epilepticus, or coma;
• Patients with known or suspected allergy or contraindication to any component of the study drug or opioids;
• Severe hepatic dysfunction (Child-Pugh class C);
• Chronic kidney disease (estimated glomerular filtration rate < 60 ml/min/1.73 m²);
• Mean arterial pressure (MAP) < 65 mmHg, or requiring norepinephrine infusion > 0.5 μg/kg/min to maintain MAP ≥ 65 mmHg;
• Age <18 years old;
• Pregnant or breastfeeding women;
• Body mass index (BMI) <18 kg/m² or >30 kg/m²

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Remimazolam; The investigators conducted a single-arm, prospective physiological trial to assess the respiratory effects of remimazolam. The study enrolled 20 patients receiving invasive mechanical ventilation. Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h. The primary outcomes were changes in breathing pattern (respiratory rate (RR), tidal volume (VT), and minute ventilation (Vmin)), respiratory drive (airway occlusion pressure (P0.1)), and inspiratory effort (pressure muscle index (PMI) and airway occlusion pressure (ΔPocc)) after 0.15 mg/kg/h infusion of remimazolam.

Drug: Remimazolam; Remimazolam will be infused at 0.15，0.175，0.20，0.225，0.25，0.275, 0.3 mg/kg/h in sequence for 30 minutes at each dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tidal volume	The change in tidal volume 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs.	At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
Respiratory rate	The change in respiratory rate 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs.	At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
Minute ventilation	The change in minute ventilation 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs.	At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
Airway occlusion pressure (P0.1)	The change in P0.1 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs.	At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
Pressure muscle index (PMI)	The change in PMI 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs.	At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
Airway occlusion pressure (Pocc)	The change in Pocc 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs.	At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory rate	Changing trends in respiratory rate during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h	Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, respiratory rate was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
Tidal volume	Changing trends in tidal volume during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h	Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, tidal volume was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
Minute ventilation	Changing trends in minute ventilation during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h	Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, minute ventilation was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
P0.1	Changing trends in P0.1 during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h	Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, P0.1 was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
PMI	Changing trends in PMI during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h	Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, PMI was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
Pocc	Changing trends in Pocc during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h	Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, Pocc was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
Richmond Agitation and Sedation Scale (RASS) score	Changing trends in RASS score during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h. The RASS scale ranges from -5 to +4. The lower the score, the deeper the level of sedation.	Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, RASS score was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h).

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Principal Investigator: Jian-Xin Zhou, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2023
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): March 31, 2025

Study Registration Dates

• First Submitted: November 6, 2026
• First Submitted That Met QC Criteria: November 11, 2026
• First Posted (Actual): November 12, 2026

Study Record Updates

• Last Update Posted (Actual): November 12, 2026
• Last Update Submitted That Met QC Criteria: November 11, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: intensive care unit; mechanical ventilation; respiratory drive; inspiratory effort; breathing pattern
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia; remimazolam
• Other Study ID Numbers: KY2023-182-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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