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

NCT ID: NCT05466708

Last Updated: 2024-05-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-11
• Study Completion Date: 2024-12-01

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.

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.

Conditions

Dexmedetomidine; Ketamine; Analgesia; Intensive Care Units; Mechanical Ventilation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Esketamine combined with dexmedetomidine

Intervention Type: DRUG

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.

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

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

S-ketamine combined with dexmedetomidine; Dexmedetomidine Hydrochloride Injection

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zuo Xiangrong

Role: STUDY_CHAIR

Nanjing Medical University

Locations

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zuo Xiangrong

Role: CONTACT

zuoxiangrong@njmu.edu.cn

+86 13913979197

Facility Contacts

Zuo Xiangrong

Role: primary

zuoxiangrong@njmu.edu.cn

+86 13913979197

References

Zhang W, You J, Hu J, Chen X, Wang H, Li N, Wei C, Tang W, Zuo X. Effect of esketamine combined with dexmedetomidine on delirium in sedation for mechanically ventilated ICU patients: protocol for a nested substudy within a randomized controlled trial. Trials. 2024 Jul 2;25(1):431. doi: 10.1186/s13063-024-08287-3.

Reference Type: DERIVED

PMID: 38956664 (View on PubMed)

Other Identifiers

2021120884Esketamine

Identifier Type: -

Identifier Source: org_study_id