Effect of Esketamine on Depressive Symptoms of Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy (EDSOP)

Effect of Intraoperative Esketamine Infusion on Depressive Symptoms of Obese Patients Undergoing Laparoscopic Sleeve Gastrectomy

Esketamine, as a powerful analgesic intravenous anesthetic, has a rapid onset and elimination effect, does not inhibit spontaneous respiration, and can slightly stimulate the circulatory system. It has been confirmed that esketamine can effectively combat opioid related complications, especially life-threatening respiratory suppression. Thus becoming a new powerful perioperative analgesic drug. At the same time, esketamine has been licensed for the treatment of "resistant depression" and emergency treatment for patients in crisis states of depression. But the evidence for its safety and effectiveness is insufficient. We have designed a randomized controlled clinical trial to investigate the effect of an established general anesthesia strategy without opioids by using esketamine on postoperative depressive in obese patients undergoing laparoscopic sleeve gastrectomy.

Study Overview

• Status: Not yet recruiting
• Conditions: Depressive Symptoms
• Intervention / Treatment: Drug: Opioid; Drug: Esketamine hydrochloride

Detailed Description

The bidirectional relationship between obesity and mood disorders is suggested supported by empirical evidence. Obesity increases the risk of depression, and depression predicts the developing of obesity. The associations between atypical depressive symptoms and obesity-related characteristics may consequent to sharing pathophysiologic characteristics in patients with major depressive disorders, such as genetics, and brain circuitries integrating homeostatic and mood regulatory responses.

Bariatric surgery is a remarkably effective and durable treatment for obesity, resulting in considerable weight loss, and reductions in the prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia and sleep apnea at 5 years. Nearly 23-33% of patients undergoing bariatric surgery report a preoperative depression. Meanwhile, bariatric surgery is consistently associated with postoperative decreases in the prevalence of depression (8%-74% decrease) and the severity of depressive symptoms (40%-70% decrease) at 6-month, 12-month, 24-month. In 357 extremely obese patients with a mean BMI of 51.2 kg/m2, 45% of patients are identified as depression before gastric bypass surgery. And by 6-, 12-, 24-month follow-up, by using Beck Depression Inventory, clinically significant depressive symptoms are characterized to 12%, 13% and 18%, respectively. Compared with status prior to surgery, the prevalence of any Axis I psychiatric disorder for DSM-IV at 2 and 3 years after Roux-en-Y gastric bypass or laparoscopic adjustable gastric band surgery is significantly reduced from 30.2% to 16.8% and 18.4%.

Based on the HAMD assessments, we found that the incidence of depressive symptoms was 71.1% in 225 young obese patients (31.0 years-old) before laparoscopic sleeve gastrectomy. The depressive symptoms and severity were improved over time, particular in postoperative 3 months. However, depressive symptoms were still sustained in a proportion of obese patients.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chunxia Huang, PhD; Phone Number: +8613500512159; Email: huangchunxia@ahmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• BMI≥40kg/m2 or BMI>35 kg/m2 with an existing comorbidity
• scheduled for selective LSG
• American Society of Anesthesiologists physical status I-III
• HAMD>7
• with informed consent

Exclusion Criteria:

• Patients diagnosed with significant comorbidities, such as cardiopathy, chronic respiratory conditions, abnormal hepatic and/or renal function, coagulation dysfunction, major psychiatric or neurological disorders
• Patients allergy to esketamine or other drugs used in the study
• Patients are scheduled for/plan to have an additional surgery during the 3-month follow-up period
• Patients suffer from acute or chronic pain with analgesics, or take anticathartic, glucocorticoid medications
• Patients involved in another research study
• Patients will likely have problems, in the judgement of the investigator, with maintaining follow-up
• Any other reasons the investigator feels is relevant for excluding the patient
• lack of patient consent

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
Active Comparator: Control Group: Standardized general anesthesia; The control group is standard of opioid anesthesia including reminfentanil and sufentanil. In addition to dexmedetomidine and transverse abdominal plane block, general anesthesia induction will be induced performed with sufentanil (0.5 μg kg-1), propofol (1.5 mg kg-1), and rocuronium (1 mg kg-1). General anesthesia was maintained with a continuous infusion of remifentanil (5-15 μg kg-1 h-1), cisatracurium (0.1-0.2 mg kg-1 h-1), dexmedetomidine (0.4 μg kg-1 h-1), and sevoflurane exposure guided by bispectral index. Dexmedetomidine administration and sevoflurane inhalation will be completed at 20 minutes before surgery finish. Propofol and remifentanil will be continuously infused till the end of surgery.	Drug: Opioid; A standardized opioid anesthesia will be achieved by using continuous intraoperative infusion of opioids.
Experimental: Intervention Group: A standardized non-opioid anesthesia; Dexmedetomidine (0.5μg kg-1) and esketamine (0.25mg kg-1) was intravenously infused to provide sedation for the bilateral transverse abdominal plane block (0.33% ropivacaine and dexmedetomidine 1μg kg-1). General anesthesia was then induced with esketamine (0.25 mg kg-1 h-1), propofol (1.5 mg kg-1), and rocuronium (1 mg kg-1). Following endotracheal intubation, GA was maintained with a continuous infusion of esketamine (0.25 mg kg-1 h-1), cisatracurium (0.1-0.2 mg kg-1 h-1), dexmedetomidine (0.4 μg kg-1 h-1), and sevoflurane guided by bispectral index. The infusions of esketamine and dexmedetomidine, as well as sevoflurane inhalation will be finished at 20 minutes before surgery completion. Propofol will be continuously infused to maintain appropriate bispectral index.	Drug: Esketamine hydrochloride; A standardized non-opioid anesthesia will be achieved by using continuous intraoperative infusion of esketamine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton depression Rating Scale	The 24-item version of the Hamilton Depression Scale (HAM-D) is used to assess the severity of depression. Each item is rated on the Likert scale, ranging from 0 to 4. The normal value is 0-7 points, the mild depression value is 8-20 points, the moderate depression symptom value is 21-35 points, and the severe depression value exceeds 35 points. The higher scores indicate the worse symptoms.	Before surgery and at the postoperative 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the first rescue antiemetics	The time from extubation to the first rescue antiemetics	At 0-24 hours after surgery
Length of anesthesia	From beginning to the end of anesthesia	At the end of anesthesia
Length of surgery	From beginning to the end of surgery	At the end of surgery
BMI	Body mass index	Before surgery and at the postoperative 3 months
Pittsburgh Sleep Quality Index	Pittsburgh Sleep Quality Index (PSQI) will be assessed the quality of sleep. The higher score means the lower quality of sleep.	Before surgery and at the postoperative 3 months
Postoperative anxiety	Postoperative anxiety	In 3 months after surgery
Hamilton Anxiety Rating Scale	Hamilton Anxiety Rating Scale (HAMA) will be used to assess anxiety. Total score ranges from 0 to 56, the higher the score is, the more serious the anxiety is.	Before surgery and at the postoperative 3 months
Cognition	AVLT, Trail Making Tests, Stroop color and word test, word fluency, Digit span test will be used to evaluate the cognition.	Before surgery and at the postoperative 3 months
The incidence of Postoperative nausea and vomiting	The incidence of Postoperative nausea and vomiting	At 0-24 hours after surgery
Postoperative depressive symptoms	Montgomery-Asberg Depression Rating Scale (MARDS) includes 10 items. The normal value is less than 12 points, the mild depression value is 12-22 points, the moderate depression symptom value is 22-30 points, and the severe depression value is 30-35 points, extreme severe depression value exceeds 35. The higher scores indicate the worse symptoms.	In 3 months after surgery
Postoperative pain	Postoperative incision pain and visceral pain will be assessed by VAS withing 0-10. The higher scores indicate the more pain.	At 0-24 hours after surgery
Time to the first rescue analgesics	The time from extubation to the first rescue analgesics	At 0-24 hours after surgery
Consumption of anesthetics	Total usage of anesthetics during the surgery	During the surgery
QoR-15	The QoR-15 is a convenient patient-reported tool, including 15 items of five domains (pain, comfort, physical independence, psychological support, and emotional state) with each item ranging from 0 to 10. Higher scores suggest better quality of recovery (0-89, poor recovery; 90-121, moderate recovery; 122-135, good recovery; 136-150, excellent recovery)	At 24 hours after surgery
Adverse event rate	The incidence of adverse events	During postoperative 3 months
Gastrointestinal Symptom Rating Scale	Gastrointestinal Symptom Rating Scale (GSRS) will be used to assess gastrointestinal function. The score ranges from 0-45. The higher score means poorer gastrointestinal function.	Before surgery and at the postoperative 3 months
Quality of health and functional status	SF-36 consists of 36 items and is a short questionnaire to evaluate the health and functional status within one month. There are 8 dimensions regarding physiological functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. For each item, the average is 50 points, 0 is the lowest and 100 is the highest. The conversion score for each item is (the exact score minus the suspected lowest score) / (the difference between the expected highest and lowest score) × 100. The total score of the 8 dimensions is the total score of the scale.	Before surgery and at the postoperative 3 months
Brain function	Resting functional magnetic resonance imaging (rs-fMRI) will measure brain structure and functional changes, including gray matter volume, gray matter thickness, functional connectivity.	Before surgery and at the postoperative 3 months

Collaborators and Investigators

• Sponsor: The Second Hospital of Anhui Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 14, 2023
• First Submitted That Met QC Criteria: December 27, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: EDSOP

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