Dexmedetomidine Reduces Sevoflurane MAC-BAR During Pneumoperitoneum

Effect of Dexmedetomidine on Sevoflurane Minimum Alveolar Concentration for Attenuating Adrenergic Response to CO2 Pneumoperitoneum: A Randomized Controlled Trial

This clinical trial aims to learn the impact of dexmedetomidine on the minimum alveolar concentration blunting the adrenergic response (MAC-BAR) of sevoflurane to carbon dioxide pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. It will also learn about the effect of dexmedetomidine on hemodynamic parameters. The main questions are:

• Does dexmedetomidine reduce the MAC-BAR of sevoflurane required to suppress the sympathetic response to carbon dioxide pneumoperitoneum?
• Would dexmedetomidine administration dose-dependently reduce the minimum alveolar concentration blunting the adrenergic response of sevoflurane required to suppress the sympathetic response to carbon dioxide pneumoperitoneum? Researchers will compare low-dose dexmedetomidine to high-dose dexmedetomidine to see if dexmedetomidine works to treat postoperative negative behavior change and emergence delirium.

Participants will:

• Take intravenous dexmedetomidine or 0.9% saline (a look-alike substance that contains no drug)
• Study drug infusions were initiated 15 minutes prior to anesthesia induction, allowing a minimum of 30 minutes to elapse before surgical incision to achieve steady-state plasma and brain concentrations.

Study Overview

• Status: Recruiting
• Conditions: Laparoscopic Cholecystectomy
• Intervention / Treatment: Drug: normal Saline; Drug: Dexmedetomidine low-dose; Drug: Dexmedetomidine high-dose

Detailed Description

Laparoscopic (minimally invasive) surgery has several advantages over open surgery, including less tissue damage, faster recovery, and fewer complications. This has led to widespread use of laparoscopic techniques. However, the inflated carbon dioxide gas used to create the surgical space during laparoscopic surgery causes significant changes in the body's normal blood pressure and heart function.

The anesthetic drug sevoflurane is commonly used during these procedures, but higher doses are needed to adequately block the body's stress response to the inflated gas. The minimum alveolar concentration blunting the adrenergic response (MAC-BAR) measures the minimum anesthetic depth required to suppress the sympathetic/stress response in 50% of patients. Doctors use MAC-BAR values to help determine the appropriate anesthetic dose to maintain hemodynamic stability. Unfortunately, using higher sevoflurane doses to reach the necessary MAC-BAR increases the risk of low blood pressure, reduced heart function, and confusion after surgery.

The drug dexmedetomidine has properties that can help manage the body's stress response during surgery. Researchers wanted to see if dexmedetomidine could allow the use of lower, more stable doses of sevoflurane during laparoscopic procedures by reducing the body's reaction to the inflated gas.

The goal of this study was to evaluate how dexmedetomidine affects the MAC-BAR of sevoflurane needed to block the sympathetic/stress response to the inflated gas used in laparoscopic surgery.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yusheng Yao, MD&PhD; Phone Number: 13559939629; Email: fjslyys@fjmu.edu.cn
• Study Contact Backup: Name: Sisi Chen, MD; Phone Number: 15080109541; Email: css@fjmu.edu.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Provincial Hospital
      • Contact: Yusheng Yao, Doctor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Aged 18-45 years.
• 2. American Society of Anesthesiologists (ASA) grade I - II.
• 3. Patients undergoing elective laparoscopic cholecystectomy.

Exclusion Criteria:

• 1. Inability to provide informed consent;
• 2. History of chronic pain or substance abuse;
• 3. Pregnancy;
• 4. Body mass index (BMI) ≥ 30 kg/m2;
• 5. Known allergies to the study medications;
• 6. Intake of medications within the last 72 hours that potential interfere with the determination of the MAC-BAR;
• 7. Any other condition deemed exclusionary by the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; The control group received volume-matched 0.9% saline infusions at identical rates.	Drug: normal Saline; The control group received volume-matched 0.9% saline infusions at identical rates.
Experimental: Low-dose dexmedetomidine group; The low-dose dexmedetomidine group received a 75 μg/h loading dose over 15 minutes, followed by 60 μg/h maintenance infusion intravenously.	Drug: Dexmedetomidine low-dose; The low-dose dexmedetomidine group received a 75 μg/h loading dose over 15 minutes, followed by 60 μg/h maintenance infusion intravenously.; Other Names: dexmedetomidine hydrochloride Injection
Experimental: High-dose dexmedetomidine group; The high-dose dexmedetomidine group received a 150 μg/h loading dose over 15 minutes, followed by 120 μg/h maintenance infusion intravenously.	Drug: Dexmedetomidine high-dose; The high-dose dexmedetomidine group received a 150 μg/h loading dose over 15 minutes, followed by 120 μg/h maintenance infusion intravenously.; Other Names: dexmedetomidine hydrochloride Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum alveolar concentration of sevoflurane to block the adrenergic response (MAC-BAR)	The MAC-BAR of sevoflurane for each group was determined using an up-and-down sequential allocation technique. One minute after establishing a stable pneumoperitoneum, the sympathetic adrenergic response was evaluated by changes in heart rate and mean artery pressure from pre-insufflation baseline values. A positive response was defined as a ≥ 20% increase in either heart rate or mean artery pressure from baseline.	Within 30 minutes after intubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Adverse events such as bradycardia, tachycardia, hypertension, hypotension, and hypoxia will be recorded during the trial.	Up to 24 hours postoperatively
Change in mean arterial pressure	Change in blood pressure was calculated as the difference between pre-pneumoperitoneum and post-pneumoperitoneum. Pre-pneumoperitoneum mean arterial pressure was averaged from 3 and 1 minutes baseline values, while post-pneumoperitoneum value was averaged over 1 and 3 minutes after establishing insufflation.	Upon arrival in the operating room, at 3, 1 minutes before pneumoperitoneum and 1, 3 minutes after pneumoperitoneum
Change in heart rate	Change in blood pressure was calculated as the difference between pre-pneumoperitoneum and post-pneumoperitoneum. Pre-pneumoperitoneum heart rate was averaged from 3 and 1 minutes baseline values, while post-pneumoperitoneum value was averaged over 1 and 3 minutes after establishing insufflation.	Upon arrival in the operating room, at 3, 1 minutes before pneumoperitoneum and 1, 3 minutes after pneumoperitoneum

Collaborators and Investigators

• Sponsor: Fujian Provincial Hospital
• Investigators: Study Chair: Xiaochun Zheng, MD&PhD, Fujian Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: August 25, 2024
• First Submitted That Met QC Criteria: August 25, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: sevoflurane; dexmedetomidine; laparoscopic surgery; MAC-BAR; α2-adrenergic receptor agonist
• Additional Relevant MeSH Terms: Digestive System Diseases; Peritoneal Diseases; Pneumoperitoneum; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: k2022-12-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication, the individual deidentified participant data underlying published results, the study protocol, and the statistical analysis plan can be accessed upon reasonable request from the corresponding author.
• IPD Sharing Time Frame: The investigators would like to share the individual deidentified participant data from the three months following the publication of the main results.
• IPD Sharing Access Criteria: All the individual participant data collected during the trial, the study protocol, the statistical analysis plan, and the clinical study report can be accessed with approval from the corresponding author.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No