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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Dexmedetomidine, Ketamine, Analgesia, Intensive Care Units, Mechanical Ventilation

Intervention / Treatment
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* Drug: Esketamine combined with dexmedetomidine
* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esketamine combined with dexmedetomidine<br>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<br>* 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.<br>* Other names: S-ketamine combined with dexmedetomidine;|
| Active Comparator: Dexmedetomidine<br>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<br>* Dexmedetomidine, injection, 0.2mg/ bottle, source: Hospital Pharmacy, manufacturer: Jiangsu Hengrui Pharmaceutical Co., LTD., expiration date: 18 months, storage condition: airtight shading, room temperature.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse reactions | Adverse reactions that patients experience with the medication, such as hypertension, hypotension, rapid heart rate, slow heart rate | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexmedetomidine, Esketamine, Analgesia, Sedation, Intensive Care Units, Mechanical Ventilation