The Effect of Ciprofol 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 P0.1, Pocc, Pmus, WOB, and PTP. 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. Ciprofol is an analog of propofol, with increased stereoselective effects adding to its anesthetic properties, is increasingly used in the intensive care unit, but its effects on respiration are not well understood. Therefore, this study aims to investigate the effects of ciprofol on respiratory patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients.

Study Overview

• Status: Recruiting
• Conditions: Mechanical Ventilation; Sedation and Analgesia
• Intervention / Treatment: Drug: ciprofol

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

Contacts and Locations

• Study Contact: Name: Jian-Xin Zhou, MD; Phone Number: +8613801183875; Email: zhoujx.cn@icloud.com
• Study Contact Backup: Name: Rui Su; Phone Number: +8618611993866; Email: surui1969@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Recruiting
      • Beijing Tiantan Hospital
      • Contact: Jian-Xin Zhou, MD; Phone Number: 8610 59978019; Email: zhoujx.cn@icloud.com
      • Contact: Rui Su; Phone Number: +8618611993866; Email: surui1969@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The patient received surgery under general anesthesia and admitted into the ICU
• The patient has been intubated and is receiving invasively mechanically ventilated with the mode of pressure support (PSV) or continuous positive airway pressure (CPAP)
• The patient requires sedative medication targeting RASS -2 to +1 for comfort, safety and to facilitate the delivery of life support measures

Exclusion Criteria:

• Age < 18 years
• Body mass index (BMI) <18 or >30 kg/m2
• Pregnancy or lactation
• Brain stem tumors, myasthenia gravis, or neuromuscular diseases
• Acute severe neurological disorder and any other condition interfering with RASS assessment
• Systolic blood pressure < 90 mmHg after appropriate intravenous volume replacement and continuous infusions of 2 vasopressors
• Heart rate < 50 beats per minute or second- or third-degree heart block in the absence of a pacemaker
• Contraindicate or allergic to any of the study medications
• Acute hepatitis or serious hepatic dysfunction (Child-Pugh class C)
• Chronic kidney disease with glomerular filtration rate (GFR) < 60 ml/min/1.73m2
• Alcohol abuse

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: Experimental arm; Before the trial drug administration, included patients will receive a continuous infusion of remifentanil for analgesia, starting at 0.01 μg/kg/min and adjusting infusion rate to target a Critical-care Pain Observation Tool (CPOT) score of 0-1. The experimental drug was not to be administered until it was confirmed that the patient's baseline sedation level had reached a RASS score of ≥ -2. For sedation, the ciprofol was started at the rate of 0.3 mg/kg/h and maintained for 30 minutes. Then, the initial infusion rate was increased to 0.4, 0.5, 0.6, 0.7, and up to 0.8 mg/kg/h every 30 minutes. The infusion of ciprofol would be stopped if the RASS score ≤ -4, respiratory rate < 8 breaths/min, or Saturation of pulse oxygen (SpO2) < 90% before the maximal dose of 0.8 mg/kg/h was achieved.

Drug: ciprofol; Ciprofol will be infused at 0.3，0.4，0.5，0.6，0.7，0.8 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
Explore the effect of ciprofol on tidal volume	Change from baseline in tidal volume (ml) at 30 minutes after infusion of ciprofol	At baseline (before sedation with ciprofol) and 0.3 mg/kg/h ciprofol continuous infusion for 30 minutes
Explore the effect of ciprofol on respiratory rate	Change from baseline in respiratory rate (breaths/min) at 30 minutes after infusion of ciprofol	At baseline (before sedation with ciprofol) and 0.3 mg/kg/h ciprofol continuous infusion for 30 minutes
Explore the effect of ciprofol on minute ventilation	Change from baseline in minute ventilation (L/min) at 30 minutes after infusion of ciprofol	At baseline (before sedation with ciprofol) and 0.3 mg/kg/h ciprofol continuous infusion for 30 minutes
Explore the effect of ciprofol on P0.1	Change from baseline in P0.1 (cmH2O) at 30 minutes after infusion of ciprofol	At baseline (before sedation with ciprofol) and 0.3 mg/kg/h ciprofol continuous infusion for 30 minutes
Explore the effect of ciprofol on PMI	Change from baseline in PMI (cmH2O) at 30 minutes after infusion of ciprofol	At baseline (before sedation with ciprofol) and 0.3 mg/kg/h ciprofol continuous infusion for 30 minutes
Explore the effect of ciprofol on ΔPocc	Change from baseline in ΔPocc (cmH2O) at 30 minutes after infusion of ciprofol	At baseline (before sedation with ciprofol) and 0.3 mg/kg/h ciprofol continuous infusion for 30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explore the effect of ciprofol on tidal volume	Change from baseline in tidal volume (ml) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on respiratory rate	Change from baseline in respiratory rate (breaths/min) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on minute ventilation	Change from baseline in minute ventilation (L/min) at 30 minutes after infusion of ciprofol at different infusion rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on P0.1	Change from baseline in P0.1 (cmH2O) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on PMI	Change from baseline in PMI (cmH2O) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on ΔPocc	Change from baseline in ΔPocc (cmH2O) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on systolic blood pressure	Change from baseline in systolic blood pressure (mmHg) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.3，0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on diastolic blood pressure	Change from baseline in diastolic pressure (mmHg) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.3，0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on mean arterial pressure	Change from baseline in mean arterial pressure (mmHg) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.3，0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on heart rate	Change from baseline in heart rate (beats/min) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.3，0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on saturation of pulse oxygen	Change from baseline in saturation of pulse oxygen (%) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.3，0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on end-tidal carbon dioxide pressure	Change from baseline in end-tidal carbon dioxide pressure (mmHg) at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.3，0.4，0.5，0.6，0.7，0.8 mg/kg/h)
Explore the effect of ciprofol on RASS score	Change from baseline in RASS score at 30 minutes after infusion of ciprofol at different rates	At baseline (before sedation with ciprofol) and 30 minutes following each infusion rate adjustment (0.3，0.4，0.5，0.6，0.7，0.8 mg/kg/h)

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: December 11, 2023
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Estimated): February 29, 2024

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: mechanical ventilation; sedation; analgesia; respiratory drive; inspiratory effort; respiratory patterns
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration
• Other Study ID Numbers: KY2023-182-03

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