Effect of Esketamine on Perioperative Negative Mood in Patients Undergoing Cardiac Valve Surgery

Effect of a Single Dose of Esketamine on Perioperative Negative Mood in Patients Undergoing Cardiac Valve Surgery: a Randomized Controlled Trial

A multicenter, randomized controlled, blinded prospective study to investigate the effects of esketamine on perioperative anxiety and depression in patients undergoing cardiac valve surgery.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery; Depression, Anxiety; S-ketamine
• Intervention / Treatment: Drug: Esketamine; Drug: normal saline

Detailed Description

Undergoing surgery can be a traumatic and painful experience for patients, often causing negative moods such as anxiety and depression. The size and type of surgery significantly impact the occurrence of anxiety and depression in patients. Approximately one-third of patients after cardiac surgery experience anxiety or depression, which increases the risk of recurrent cardiovascular events and death.

Ketamine is an anesthetic drug with comprehensive effects, including analgesia, sedation, and amnesia. Its primary mechanism of action is blocking N-methyl-D-aspartate (NMDA) receptors. Esketamine, the pure dextro isomer of ketamine, has a higher affinity for glutamate NMDA receptors and opioid receptors, offering stronger sedative, analgesic, and antidepressant effects. On March 4, 2019, esketamine was approved by the FDA for treatment-resistant depression. Given its analgesic, anesthetic, and antidepressant effects, esketamine may be an ideal drug for improving negative moods in patients undergoing cardiac surgery.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, China
      • First Medical center of Chinese PLA General Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old, male or female
2. Patients undergoing heart valve surgery
3. Patients with ASA grade 1 to 4
4. BMI between 18-30 kg/m²
5. Able to participate in neuropsychological testing and receive follow-up visits
6. Clearly understand and voluntarily agree to participate in the study and sign the informed consent form

Exclusion Criteria:

1. Patients with significant preoperative neuro-psychiatric disease and cognitive impairment
2. Intellectual disability or a MiniMental State Examination (MMSE) score <24, or a speech disorder that may compromise their ability to undergo preoperative assessments
3. History of psychoactive drug abuse

5. Preoperative combined severe hepatic insufficiency or renal insufficiency 6. Any contraindications to ketamine or esketamine, such as refractory hypertension or hyperthyroidism

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine group; Patients who undergo general anesthesia using esketamine.	Drug: Esketamine; A single dose of 0.3mg / kg esketamine during induction of anesthesia.
Placebo Comparator: Control group; Patients who undergo general anesthesia without esketamine	Drug: normal saline; Receiving the same volume of normal saline during induction of anesthesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative anxiety and depreession	The primary outcomes were depression and anxiety, which were assessed using the Hospital Anxiety and Depression Scale (HADS). Perioperative anxiety was measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale, a standardized self-report instrument consisting of 7 items. Patients with a HADS-A score of 8 or more were considered to be experiencing anxiety, with a score of 8 to 10 indicating mild anxiety, 11 to 14 indicating moderate anxiety, and 15 to 21 indicating severe anxiety. Perioperative depression was measured using the Hospital Anxiety and Depression Scale-Depression (HADS-D) subscale. Patients with a HADS-D score of 8 or more were considered to be experiencing depression, with a score of 8 to 10 indicating mild depression, 11 to 14 indicating moderate depression, and 15 to 21 indicating severe depression.	Preoperative day 1, postoperative day 7 and day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Sleep Quality	Postoperative sleep quality was assessed using the Insomnia Severity Index (ISI). The ISI is a simple tool used to screen for insomnia and consists of 7 items to assess the nature and symptoms of the subject's sleep disorder on a 5-point Likert scale, with each item scored from 0 to 4 and the total score ranging from 0 to 28, with higher scores indicating greater severity of insomnia. The sum of the scores with 0-7 indicating insomnia without clinical significance, 8-14 indicating subclinical insomnia, 15-21 indicating clinical insomnia (moderate), 22-28 indicating 'clinical insomnia (moderate), and 22-28 indicating clinical insomnia (moderate). A score of 8 to 14 indicates subclinical insomnia, a score of 15 to 21 indicates clinical insomnia (moderate), and a score of 22 to 28 indicates clinical insomnia (severe).	Preoperative day 1, postoperative day 7 and day 30
Delirium	Delirium was assessed using a combination of the 3-Minute Diagnostic Interview for CAM (3D-CAM) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Patients in the general ward were assessed using the 3D-CAM, while patients in the intensive care unit were assessed using the CAM-ICU. Delirium consists of four main features: acute altered mental status or fluctuating level of consciousness, inattention, disorganized thinking, and altered level of consciousness. Patients were diagnosed with postoperative delirium if both the first and second features were present, and either the third or fourth feature was also present.	Within 7 days after surgery
PONV	Postoperative nausea and vomiting (PONV) were assessed using a visual analogue scale (VAS). This scale consists of a 10-centimeter straight line, with 0 indicating no nausea and vomiting, and 10 indicating the most extreme level of nausea and vomiting that can be endured. The severity of PONV is categorized as follows: mild (1 to 4), moderate (5 to 6), and severe (7 to 10).	Within 2 days after extubation
Postoperative Recovery Quality	Postoperative quality of recovery was evaluated using the Chinese version of the Quality of Recovery-15 (QoR-15) score. This assessment tool comprises 15 items, each scored on a 10-point scale. The total score ranges from 0 to 150, with 0 indicating poor recovery and 150 signifying an excellent quality of recovery.	Postoperative day 7 and day 30
Postoperative Pain	Assessment was conducted using the Numerical Rating Scale (NRS) for pain, which ranges from 0 to 10. On this scale, a score of 0 represents the absence of pain, while a score of 10 represents the most severe pain.	Postoperative day 7 and day 30
Postoperative Quality of Life	Postoperative quality of life was evaluated using the EQ-5D, a five-dimensional health scale. This scale encompasses five key dimensions: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension is rated on a three-point scale: no difficulty, some difficulty, and extreme difficulty. The responses to these levels are then utilized to calculate the EQ-5D Index score, which quantifies the overall health status based on the reported levels of difficulty across the five dimensions.	Postoperative day 7 and day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative inflammatory factor (IL-6)	Inflammatory factor (IL-6 in pg/ml) were from laboratory tests in the patient's medical record.	perioperatively
Perioperative inflammatory factor (CRP)	Inflammatory factor (CRP in mg/dl) were from laboratory tests in the patient's medical record.	perioperatively
Intraoperative blood pressure	Intraoperative blood pressure（MAP in mmHg/SBP in mmHg/DBP in mmHg) at T0 (before induction of anes thesia), T1 (5 min after esketamine or control injection), T2 (30 min after esketamine or control injection), T3 (1 h after esketamine or control injection), T4 (3 h after esketamine or control injection), and T5(at the end of surgery) were included.	During the surgery
Intraoperatively heart rate	Intraoperative heart rate（HR in bmp) at T0 (before induction of anes thesia), T1 (5 min after esketamine or control injection), T2 (30 min after esketamine or control injection), T3 (1 h after esketamine or control injection), T4 (3 h after esketamine or control injection), and T5(at the end of surgery) were included.	During the surgery
Perioperative brain injury-related factor (S100β)	Brain injury-related factor (S100β in ng/ml)	perioperatively
Perioperative brain-derived neurotrophic factor (BDNF)	Brain-derived neurotrophic factor (BDNF in ng/ml)	perioperatively
Perioperative acetylcholine (Ach)	Acetylcholine (Ach in ng/ml)	perioperatively
Perioperative norepinephrine (NE)	Norepinephrine(NE in ng/ml)	perioperatively

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Collaborators: Beijing Tiantan Hospital; The Sixth Medical Center of Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2024
• Primary Completion (Actual): April 7, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: September 19, 2024
• First Submitted That Met QC Criteria: September 19, 2024
• First Posted (Actual): September 23, 2024

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Behavior; Anxiety Disorders; Depression; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Esketamine; Saline Solution
• Other Study ID Numbers: PLAGH-RCT-Esket

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No