Clinical trial NCT05466708: Safety and Efficacy of Esketamine Combined With Dexmedetomidine for Sedation of Mechanically Ventilated Patients
Official title: Safety and Efficacy of Esketamine Combined With Dexmedetomidine for Sedation of Mechanically Ventilated Patients in the ICU: a Prospective, Randomized, Single-center Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Dexmedetomidine
Ketamine
Analgesia
Intensive Care Units
Mechanical Ventilation
Keywords: Dexmedetomidine
Esketamine
Analgesia
Sedation
Intensive Care Units
Mechanical Ventilation
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2022-07-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Duration of mechanical ventilation
timeFrame: Usually within 14 days
Secondary outcomes:
measure: Time to extubation
timeFrame: Usually within 14 days
measure: Duration of ICU stay
timeFrame: Usually within 28 days
measure: 28-day mortality rate
timeFrame: Within 28 days
measure: Recovery time
timeFrame: Within 14 days
measure: Dose of Propofol
timeFrame: Within 14 days
measure: Occurrence of delirium
timeFrame: Within 14 days
measure: Adverse reactions
timeFrame: Within 28 days
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: Nanjing Medical University
name: Zuo Xiangrong
role: STUDY_CHAIR
References: