Intraperitoneal Dexmedetomidine Versus Magnesium as Adjuvants to Bupivacaine in Laparoscopic Cholecystectomy

Intraperitoneal Instillation of Dexmedetomidine Versus Magnesium Sulphate as Adjuvants to Bupivacaine in Laparoscopic Cholecystectomy

Although both dexmedetomidine and magnesium sulphate have been individually evaluated as adjuvants to local anesthetics, direct comparisons between the two agents in intraperitoneal instillation during laparoscopic cholecystectomy remain limited. Understanding their relative efficacy and safety could provide valuable guidance for optimizing perioperative analgesia in these patients.

Study Overview

• Status: Recruiting
• Conditions: Dexmedetomidine; Laparoscopic Cholecystectomy; Magnesium Sulfate
• Intervention / Treatment: Other: Bupivacaine 100 mg + dexmedetomidine 1 µg/kg; Other: Bupivacaine 100 mg + magnesium sulphate 50 mg/kg

Detailed Description

Laparoscopic cholecystectomy is one of the most commonly performed minimally invasive procedures worldwide. Despite its advantages over open surgery, such as shorter hospital stay and faster recovery, patients frequently experience postoperative pain, which can delay mobilization, prolong hospital stay, and reduce overall satisfaction [1]. Effective pain management is therefore a critical component of enhanced recovery after laparoscopic cholecystectomy [2].

Intraperitoneal instillation of local anesthetics has been widely used as part of multimodal analgesia to reduce postoperative pain [3]. Bupivacaine, a long-acting amide local anesthetic, is commonly employed due to its favorable safety profile and prolonged duration of action. However, when used alone, its efficacy in providing sustained analgesia is limited, prompting the exploration of adjuvants that may potentiate its effect [4].

Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, has been shown to enhance the analgesic efficacy of local anesthetics by prolonging sensory blockade and providing sedative as well as opioid-sparing effects. Magnesium sulphate, an N-methyl-D-aspartate (NMDA) receptor antagonist, has also been investigated as an adjuvant, with evidence suggesting its role in reducing central sensitization and postoperative pain [5].

Aim of the work The present study aims to compare the analgesic efficacy of intraperitoneal bupivacaine combined with dexmedetomidine versus bupivacaine combined with magnesium sulphate in patients undergoing laparoscopic cholecystectomy.

Primary Outcomes:

1. Postoperative pain scores (VAS) at rest and on movement at 2, 6, 12, and 24 hours after surgery.

2. Quality of recovery (QoR-15 questionnaire).

   Secondary Outcomes:

3. Total postoperative opioid consumption in the first 24 hours.
4. Time to first analgesic request.
5. Incidence of postoperative nausea and vomiting (PONV).
6. Hemodynamic parameters (heart rate, mean arterial pressure).
7. Adverse events related to study drugs.

Patients and Methods Study Settings This study will be conducted in the Gastrointestinal Surgery Department at Alexandria University Main Hospital, a tertiary care center with a high volume of laparoscopic procedures.

Study Design This is a prospective, randomized, double-blind, controlled trial.

Randomization and Blinding

Patients will be randomized using a computer-generated sequence into two equal groups:

Group 1: Intraperitoneal instillation of bupivacaine with dexmedetomidine. Group 2: Intraperitoneal instillation of bupivacaine with magnesium sulphate. Allocation concealment will be ensured using sealed opaque envelopes. Both patients and outcome assessors will be blinded to group allocation. The study solutions will be prepared by an anesthesiologist not involved in patient management or assessment.

Methods:

Preoperative evaluation and preparation:

During preoperative visit, evaluation of patients will be carried out through proper history taking, clinical examination and routine laboratory investigations including complete blood picture, coagulation profile, blood urea, serum creatinine, serum electrolytes, liver function tests and any other investigation needed.

Pre-anesthetic preparation and premedication:

• Informed written consent, from all individual participants who will be included in this study will be taken during preoperative visit.
• Patients should be trained during preoperative visit on a visual analogue scale (VAS), with 0 corresponding to no pain and 10 to the worst pain imaginable.

On arrival to operative theatre, intravenous cannula will be inserted and standard monitoring will be established using multichannel monitor (Carescape Monitor B650, GE Healthcare Finland) to monitor the following in both groups:

• Electrocardiogram (ECG) for heart rate and rhythm. (Beats/min).
• Non-invasive measurement of arterial blood pressure. (Mean blood pressure in mmHg).
• Pulse oxygen saturation. (SpO2%).
• End tidal CO2 tension (in mmHg).

Anesthesia:

After preoxygenation for 3 minutes, anesthesia will be induced in both groups with propofol 2mg/kg of lean body weight until loss of verbal response, fentanyl 2µg/kg and atracurium 0.5 mg/kg intravenously. Anesthesia will be maintained by isoflurane with 50% oxygen in air (1.2-1.5 %) to maintain entropy between 40-60. Mechanical ventilation will be performed with tidal volume of 8 ml/ kg and a respiratory rate of 12-15 cycles/min to maintain the end-tidal carbon dioxide tension between 35 and 40 mmHg and an oxygen saturation of ≥ 98 per cent with 50 percent oxygen in air. Incremental doses of atracurium will be given every 30 minutes to maintain muscle relaxation. In both groups, signs of insufficient analgesia (eg, tachycardia over 20% of the preoperative value occur during anesthesia) or somatic response (eg, movement ,tearing ,or sweating), will be treated with additional boluses of fentanyl 0.5 mcg/kg intraoperatively as needed. Intraoperatively, all patients will receive IV dexamethasone (8 mg), paracetamol (1 g), ketorolac (30 mg).

Intervention At the end of surgery, before trocar removal, the study solution will be instilled intraperitoneally under direct vision.

Group 1: Bupivacaine 100 mg (20 mL, plain bupivacaine HCl 0.5%) + dexmedetomidine (1 µg/kg).

Group 2: Bupivacaine 100 mg (20 mL, plain bupivacaine HCl 0.5%) + magnesium sulphate (50 mg/kg).

Both adjuvants were calculated according to the patients' ideal body weight. The total volume in each group was adjusted to 50 mL with saline.

At the end of surgery, awake extubation, in a semi-sitting position, will be done. Then, the patient will be transferred to the PACU. In PACU, all patients will be assessed for presence and severity of pain; using Visual Analog Scale (VAS). Patients will be prescribed IV nalbuphine 0.15 mg/kg of lean body weight boluses on 4-6 hours basis with a maximum of 20 mg if VAS > 3. Pain control in the ward will be achieved with IV paracetamol 1 g every 6 hours and ketorolac 30 mg every 12 hours.

Sample size calcaulation According to the previous studies [6, 7], the sample size was calculated to detect a 2-point difference in mean pain scores on the Visual Analogue Scale (VAS) postoperatively between the two groups. A two-sided significance level (α) of 0.05, and a power of 80%, the required sample size was estimated to be 32 patients per group using a two-sample t-test. To compensate for potential dropouts, the sample size was increased to 40 patients per group.

Statistical Analysis Data will be analyzed using R Studio (version 4.4.2). Continuous variables will be presented as mean ± standard deviation (SD) or median (interquartile range, IQR) as appropriate and compared using Student's t-test or Mann-Whitney U test. Categorical variables will be expressed as frequencies and percentages, analyzed using chi-square or Fisher's exact test. A p-value < 0.05 will be considered statistically significant.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: sarah m elgamal, MD; Phone Number: 01005496440; Email: sarahelgamal1990@yahoo.com

Study Locations

• Egypt
  • Alexandria, Egypt
    • Recruiting
    • Alexandria University
    • Contact: sarah m elgamal, MD; Phone Number: 01005496440; Email: sarahelgamal1990@yahoo.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients aged 18-60 years
• ASA physical status I-II
• scheduled for elective laparoscopic cholecystectomy under general anesthesia.

Exclusion Criteria:

• Known hypersensitivity to study drugs
• history of cardiac arrhythmias or conduction abnormalities
• severe hepatic/renal impairment
• chronic opioid or analgesic use
• pregnancy
• conversion to open surgery
• drain insertion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1; Bupivacaine 100 mg (20 mL, plain bupivacaine HCl 0.5%) + dexmedetomidine (1 µg/kg).	Other: Bupivacaine 100 mg + dexmedetomidine 1 µg/kg; 20 ml bupivacaine + 1 µg/kg dexmedetomidine . The total volume will be adjusted to 50 mL with saline.; Other Names: group 1
Active Comparator: group 2; Bupivacaine 100 mg (20 mL, plain bupivacaine HCl 0.5%) + magnesium sulphate (50 mg/kg).	Other: Bupivacaine 100 mg + magnesium sulphate 50 mg/kg; 20 ml bupivacaine + 50 mg/kg magnesium sulphate . The total volume will be adjusted to 50 mL with saline.; Other Names: group 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain scores (VAS)	at rest , at movement	postoperative day 1
Quality of recovery	QoR-15 questionnaire	postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total postoperative opioid consumption	mg	postoperative day 1
Time to first analgesic request.	minutes	postoperative day1
Incidence of postoperative nausea and vomiting	number	postoperative day 1

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Principal Investigator: sarah m elgamal, MD, Alexandria University

Publications and helpful links

General Publications

• Taki-Eldin A, Badawy AE. OUTCOME OF LAPAROSCOPIC CHOLECYSTECTOMY IN PATIENTS WITH GALLSTONE DISEASE AT A SECONDARY LEVEL CARE HOSPITAL. Arq Bras Cir Dig. 2018 Jun 21;31(1):e1347. doi: 10.1590/0102-672020180001e1347.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2026
• Primary Completion (Estimated): November 3, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: July 4, 2026
• First Submitted That Met QC Criteria: July 4, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 4, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: dexmedetomidine; cholecystectomy; bupivacaine
• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Anilides; Amides; Aniline Compounds; Amines; Inorganic Chemicals; Sulfur Acids; Sulfates; Sulfuric Acids; Magnesium Compounds; Bupivacaine; Dexmedetomidine; Magnesium Sulfate
• Other Study ID Numbers: 0307942 (Registry Identifier: sarah m elgamal)

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