Safety and Efficacy of Esketamine Combined With Dexmedetomidine for Sedation of Mechanically Ventilated Patients (SEEDS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Analgesia; Ketamine; Dexmedetomidine; Mechanical Ventilation; Intensive Care Units
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Esketamine combined with dexmedetomidine

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zuo Xiangrong; Phone Number: +86 13913979197; Email: zuoxiangrong@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 225500
      • Recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Zuo Xiangrong; Phone Number: +86 13913979197; Email: zuoxiangrong@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Mechanically ventilated with oral endotracheal intubation in the ICU;
• Patients aged >18 years and <70 years;
• Patients with expected mechanical ventilation time >24 hours.

Exclusion Criteria:

• Known or suspected allergy to esketamine, dexmedetomidine, remifentanil, or propofol;
• Pregnancy or lactation periods;
• Obesity defined as Body Mass Index >35kg/m2;
• Extreme hemodynamic or respiratory instability due to severe burn or trauma (defined as Injury Severity Score ≥25);
• Heavy drinking defined by WHO as drinking at least 60g of pure alcohol every day for men and at least 40g for women;
• Terminally ill patients near death, such as patients with extensively metastatic tumor or refractory shock;
• Long-term exposure to sedatives, opioid analgesics or antianxiety drugs;
• Severe central nervous system disease such as cerebrovascular accidents, status epilepsy, or coma;
• Acute or chronic severe liver disease (Child-Pugh class C or history of liver transplant);
• Acute or chronic renal insufficiency needing dialysis;
• Patients or authorized surrogates refuse to provide informed consents;
• Mechanically ventilated for more than 24 hours prior to enrollment (not including the time on ventilators in the operation room).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine combined with dexmedetomidine; Esketamine will be administered at 1mg/kg, IVP, then intravenously pumped at 0.25-1.5mg/kg/h in combination with dexmedetomidine 1μg/kg for 20 min, followed by continuous intravenously pumped at 0.2-0.7mg/kg/h, maintaining a RASS score of -2-0.	Drug: Esketamine combined with dexmedetomidine; Esketamine, 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 will be administered at 1μg/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.; Other Names: Dexmedetomidine Hydrochloride Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation	Duration of mechanical ventilation after endotracheal intubation	Usually within 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Within 28 days
Recovery time	From the stop of sedatives to awakening	Within 14 days
Dose of Propofol	Total dose of rescue propofol	Within 14 days
Occurrence of delirium	The proportion of participants who have at least one positive CAM-ICU	Within 14 days
Adverse reactions	Adverse reactions that patients experience with the medication, such as hypertension, hypotension, rapid heart rate, slow heart rate	Within 28 days

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Study Chair: Zuo Xiangrong, Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 5, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Analgesia; Sedation; Dexmedetomidine; Mechanical Ventilation; Intensive Care Units; Esketamine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Psychotropic Drugs; Antidepressive Agents; Hypnotics and Sedatives; Ketamine; Dexmedetomidine; Esketamine
• Other Study ID Numbers: 2021120884Esketamine

Drug and device information, study documents

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