Different Doses of Dexmedetomidine Combined With Esketamine in Women Undergoing Cesarean Delivery

Peking University First Hospital120 enrolled

Overview

Esketamine is a commonly used analgesic during cesarean delivery, but may produce transient neuropsychiatric symptoms. Dexmedetomidine has both sedative and analgesic effects. When used in combination with esketamine, dexmedetomidine can reduce esketamine related neuropsychiatric effects after general anesthesia. The investigator speculate that combining low-dose dexmedetomidine with esketamine may also reduce neuropsychiatric adverse effects of esketamine in women undergoing cesarean section. This pilot trial is designed to determine the minimum dose of dexmedetomidine that can effectively prevent neuropsychiatric side effects of antidepressive dose esketamine (0.2mg/kg) in women undergoing cesarean delivery.

Esketamine is a commonly used anesthetic and analgesic drug during the perioperative period. Recent studies found that low-dose esketamine has rapid onset antidepressant effects and reduces postpartum depression when administered during cesarean delivery. However, even low-dose esketamine produces transient neuropsychiatric symptoms. Dexmedetomidine is a high selective alpha2-adrenoceptor agonist and has both sedative and analgesic effects. When used in combination with esketamine, dexmedetomidine reduces esketamine related neuropsychiatric adverse reactions in patients undergoing general anesthesia. The investigator speculate that combining low-dose dexmedetomidine with esketamine may also reduce neuropsychiatric adverse effects of esketamine in women undergoing cesarean delivery. The purpose of this pilot trial is to determine the minimum dose of dexmedetomidine that can effectively prevent neuropsychiatric side effects of antidepressve dose esketamine (0.2mg/kg) in women undergoing cesarean delivery.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

120

Interventions

Esketamine 0.2 mg/kgDRUG

Esketamine 0.2 mg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Esketamine 0.2 mg/kg + dexmedetomidine 0.1 µg/kgDRUG

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.1 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Esketamine 0.2 mg/kg + dexmedetomidine 0.15 µg/kgDRUG

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.15 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Esketamine 0.2 mg/kg + dexmedetomidine 0.2 µg/kgDRUG

A mixture of esketamine 0.2 mg/kg and dexmedetomidine 0.2 µg/kg is diluted in 20 ml normal saline and infused over 40 minutes after clamping the umbilical cord.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion criteria: * Pregnant women aged ≥18 years. * Scheduled for elective or emergency cesarean delivery under neuraxial anesthesia. Exclusion criteria: * A previous history of schizophrenia; * Severe complications of pregnancy, such as pre-eclampsia, placenta accreta spectrum, or HELLP (intravascular haemolysis, elevated liver enzymes, and low platelet count) syndrome; or American Society of Anesthesiologists classification III or higher; * Any contraindications to ketamine or esketamine, such as refractory hypertension, severe cardiovascular disease, or hyperthyroidism; * Any contraindications to dexmedetomidine, such as sick sinus syndrome, severe sinus bradycardia (\<50 beats per minute), or second-degree or above atrioventricular block without pacemaker; * Other conditions that are considered unsuitable for study participation.

Outcomes

Primary Outcomes

Incidence of dissociation within 24 hours.

Dissociative symptoms is assessed with the Clinician-Administered Dissociative States Scale (CADSS; scores range from 0 to 92, with higher score indicating more severe symptoms) at the end of study drug infusion and at 1, 2, and 24 hours after study drug infusion. A CADSS score of \>4 points at any timepoint indicates occurrence of dissociative symptoms.