Efficacy and Safety of Esketamine Combined With Dexmedetomidine for Sedation Iof Mechanically Ventilated Patients

Sponsor

The First Affiliated Hospital with Nanjing Medical University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05466708

Collaborator

(none)

120

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A prospective, randomized controlled study was conducted to compare the effects of esketamine combined with dexmedetomidine in the sedation and analgesia treatment of mechanically ventilated patients in the ICU on the time to awaken, time to extubation, time to mechanical ventilation, time in the ICU, and on delirium.

Condition or Disease	Intervention/Treatment	Phase
Dexmedetomidine Ketamine Analgesia Intensive Care Units Mechanical Ventilation	Drug: Esketamine combined with dexmedetomidine Drug: Dexmedetomidine	Phase 4

Detailed Description

Dexmedetomidine is a highly selective α2-adrenoceptor agonist with rapid onset of action, easy to wake up, no accumulation in the body, little inhibition of respiration, sedative, hypnotic and anxiolytic effects, and also has a certain analgesic effect.Clinical studies have shown that the use of dexmedetomidine for sedation in ICU patients is beneficial in reducing the duration of mechanical ventilation and the incidence of delirium is low, but the sedative effect of dexmedetomidine is relatively weak, and has the side effects of slowing down heart rate and lowering blood pressure, so its clinical application is limited.Esketamine is an isomer of ketamine, its effect is stronger than ketamine, and glutamate N-methyl D-aspartate (NMDA) receptor binding, play a sedative, hypnotic, analgesic effect, rapid onset, strong effect, and small respiratory inhibition, bronchodilator effect, the disadvantage is that there is a vasoconstrictor effect can cause increased blood pressure, increased heart rate.

The combination of esketamine and dexmedetomidine can provide effective sedation and analgesia with the advantages of maintaining hemodynamic stability, maintaining stable spontaneous breathing and reducing psychiatric symptoms, and has been successfully used in clinical operations such as endoscopy, pediatric anesthesia and outpatient tooth extraction.

The effectiveness and safety of esketamine in combination with dexmedetomidine for the sedation of mechanically ventilated patients in the ICU has not been evaluated. In this study, a prospective, randomized, controlled, single-center study was conducted to evaluate the efficacy and safety of esketamine in combination with dexmedetomidine for the sedation of mechanically ventilated patients in the ICU.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Esketamine Combined With Dexmedetomidine for Sedation Iof Mechanically Ventilated Patients in the ICU: a Prospective, Randomized, Single-center Study

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Esketamine combined with dexmedetomidine Esticketamine was administered at 1mg/kg, IVP, then intravenously pumped at 0.25-1.5mg/ kg (kg×h) in combination with dexmedetomidine 1.0μg/kg for 20 min, followed by continuous intravenously pumped at 0.2-0.7mg/ kg (kg×h), maintaining a RASS score of -2-0.	Drug: Esketamine combined with dexmedetomidine Asic ketamine, injection, 50mg/ bottle, source: hospital pharmacy, production unit: Jiangsu Hengrui Pharmaceutical Co., LTD., validity: 2 years, storage condition: airtight shading, room temperature. Dexmedetomidine, injection, 0.2mg/ bottle, source: Hospital Pharmacy, manufacturer: Jiangsu Hengrui Pharmaceutical Co., LTD., expiration date: 18 months, storage condition: airtight shading, room temperature. Other Names: S-ketamine combined with dexmedetomidine
Active Comparator: Dexmedetomidine Dexmedetomidine was administered at 1.0μg/kg for 20 min, followed by continuous intravenous pumping at 0.2-0.7mg/ kg×h to maintain a RASS score of -2-0	Drug: Dexmedetomidine Dexmedetomidine, injection, 0.2mg/ bottle, source: Hospital Pharmacy, manufacturer: Jiangsu Hengrui Pharmaceutical Co., LTD., expiration date: 18 months, storage condition: airtight shading, room temperature.

Arm

Intervention/Treatment

Experimental: Esketamine combined with dexmedetomidine

Esticketamine was administered at 1mg/kg, IVP, then intravenously pumped at 0.25-1.5mg/ kg (kg×h) in combination with dexmedetomidine 1.0μg/kg for 20 min, followed by continuous intravenously pumped at 0.2-0.7mg/ kg (kg×h), maintaining a RASS score of -2-0.

Drug: Esketamine combined with dexmedetomidine

Asic ketamine, injection, 50mg/ bottle, source: hospital pharmacy, production unit: Jiangsu Hengrui Pharmaceutical Co., LTD., validity: 2 years, storage condition: airtight shading, room temperature. Dexmedetomidine, injection, 0.2mg/ bottle, source: Hospital Pharmacy, manufacturer: Jiangsu Hengrui Pharmaceutical Co., LTD., expiration date: 18 months, storage condition: airtight shading, room temperature.

Other Names:

S-ketamine combined with dexmedetomidine

Active Comparator: Dexmedetomidine

Dexmedetomidine was administered at 1.0μg/kg for 20 min, followed by continuous intravenous pumping at 0.2-0.7mg/ kg×h to maintain a RASS score of -2-0

Drug: Dexmedetomidine

Dexmedetomidine, injection, 0.2mg/ bottle, source: Hospital Pharmacy, manufacturer: Jiangsu Hengrui Pharmaceutical Co., LTD., expiration date: 18 months, storage condition: airtight shading, room temperature.

Outcome Measures

Primary Outcome Measures

Duration of mechanical ventilation [Usually within 14 days]
Duration of mechanical ventilation after endotracheal intubation
Time to extubation [Usually within 14 days]
Daily offline screening, SBT test if eligible, and extubation if SBT is successful
Duration of ICU stay [Usually within 28 days]
Length of stay in ICU
28-day mortality rate [28 days]
Mortality of patients within 28 days from the time of tracheal intubation

Secondary Outcome Measures

Adverse reactions [28 days]
Adverse reactions that patients experience with the medication, such as hypertension, hypotension, rapid heart rate, slow heart rate

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients admitted to ICU for tracheal intubation and mechanical ventilation; Patients aged

18 years and <65 years; Patients with expected mechanical ventilation time >24 hours.

Exclusion Criteria:

Patients with known or suspected hypersensitivity to esketamine, propofol, dexmedetomidine, or remifentanil; Pregnancy, hyperlipidemia, excessive obesity, end-stage patients; Patients with burns or severe trauma; alcoholics; Patients on long-term anti-anxiety medication or sleeping pills; Patients with severe central nervous system diseases; Patients with acute and chronic liver insufficiency; Patients with acute and chronic renal insufficiency requiring dialysis; Patients who do not wish to sign the informed consent form.