Attenuate the Stress Response in Laparoscopic Cholecystectomy

Dexmedetomidine Versus Fentanyl-Midazolam Combination to Attenuate the Stress Response in Laparoscopic Cholecystectomy

Aims of this study are to compare the effectiveness of dexmedetomidine versus fentanyl-midazolam in attenuating hemodynamic stress response during laparoscopic cholecystectomy (mainly HR). And to assess the recovery profile, the pain and opioid requirements, the sedation profile, and any adverse events during the first 24 hrs postoperatively

Study Overview

• Status: Not yet recruiting
• Conditions: Laparoscopic Cholecystectomy Surgery
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Fentanyl- midazolam

Detailed Description

Induction of general anesthesia, direct laryngoscopy and tracheal intubation induce marked cardiovascular changes as well as autonomic reflex activity. Although the responses of blood pressure and heart rate are short lived, they might have detrimental effects in high-risk patients, especially those with cardiovascular disease (1). These cardiovascular responses are associated with increased plasma levels of catecholamines (2). The main reason for the intubation induced hypertension seems to be a release of noradrenaline and, to a lesser extent, of adrenaline. In addition, increased levels of adrenocorticotrophic hormone (ACTH) and dopamine have also been reported (3).

A variety of factors have been shown to have an effect on this stress response: the choice and dosages of premedication and induction agents (4), the skill of the operator, and probably the technique being used. Numerous studies have demonstrated an increased stress response during direct laryngoscopy, fibreoptic intubation and insertion of the laryngeal mask (5).

• Dexmedetomidine is an Alpha 2 adrenoreceptors agonists may exert its analgesic effect through hyperpolarization of the non-adrenergic neurons which leads to depression of neuronal firing in the locus ceruleous together with suppression of the release of norepinephrine because of the stimulation of the central adrenergic receptors which produces a hypnotic effect without ventilatory depression (6).
• Midazolam is the benzodiazepine with the shortest half-life. It produces sedation and amnesia by acting on the γ-aminobutyric acid type-A receptors; additionally, its combined application in peripheral nerve blocks can increase the convulsive threshold of local anesthetics. It should be noted that GABA enhanced in amplitude by midazolam resulting in inhabitation of projection neurons and antinociception (7).

Fentanyl citrate is an opioid strong analgesic that is particularly well suited for use in anesthesia because of its high potency, rapid onset and short duration of action, absence of emetic activity, and minimal hypotensive activity after intravenous administration. As with other morphine-like analgesics. (8).

Laparoscopic cholecystectomy has increasingly been accepted as the procedure of choice for treatment of symptomatic gallstones and chronic cholecystitis (9). Its role and its timing in the management of acute cholecystitis, however remain controversial. The potential hazard of severe complications as a result of distorted anatomy caused by acute inflammation is a major concern (10)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anas Ahmed Abd elmoaty, resident doctor; Phone Number: +201006318654; Email: anasa1@yahoo.com
• Study Contact Backup: Name: Obey mohamed elhassan Shaker Osman, prof; Phone Number: +201143311373; Email: Obeywafa@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-65 years.
• Both sexes.
• American Society of Anesthesiology (ASA) physical status I - II.

Exclusion Criteria:

• Known allergy to study drugs.
• Uncontrolled, non-correctable comorbidities (hepatic, renal or cardiac such as hypertension & Arrhythmia ).
• History of psychiatric illness or substance abuse.
• Pregnancy or lactation

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
Experimental: Dexmedetomidine Group	Drug: Dexmedetomidine; investigator will give Loading dose 1 mcg/kg IV over 10 min, followed by infusion 0.5 mcg/kg/h until pneumoperitoneum established
Active Comparator: Fentanyl-Midazolam Group	Drug: Fentanyl- midazolam; Investigator will inject Fentanyl 2 mcg/kg IV + Midazolam 0.05 mg/kg IV before induction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamics	Hemodynamics mainly HR	During procedure

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Kum CK, Goh PMY, Isaac JR, et al. Laparoscopic cholecystec tomy for acute cholecystitis. Br J Surg 1994; 81:1651-1654.
• Bass EB, Pitt HA, Lillemoe KD. Cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy. Am J Surg 1993; 165:466-471.
• GARDOCKIJF, YELNOSKYJ. A study of some of the pharmacologic actions of fentanyl citrate. Toxicology and applied Pharmacology 1964; 6: 48-62.
• Kohno T, Kumamoto E, Baba H, et al. Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices. Anesthesiology 2000; 92: 507-515
• Kosugi T, Mizuta K, Fujita T, Nakashima M, Kumamoto E. High concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without alpha(2) adrenoceptor activation. Br J Pharmacol 2010;160: 1662-1676.
• SMITHJE, KINGMJ, YANNY HF, POTTINGER KA, POMIRSKA MB. Effect of fentanyl on the circulatory responses to orotracheal fibreoptic intubation. Anaesthesia 1992;47: 20-3.
• Bucx MJL, VANGEELRTM, SCHECKPAE, STIJNEN T. Cardiovascular effects of forces applied during laryngoscopy. The importance of tracheal intubation. Anaesthesia 1992; 47:
• WEATHERILL D, SPENCE AA. Anaesthesia and disorders of the adrenal cortex. British Journal of Anaesthesia 1984; 56: 741-9.
• DERBYSHIRE DR, CHMIELEWSKI A, FELLD, VATERM, ACHOLA KJ, SMITHG. Plasma catecholamine responses to tracheal intubation. British Journal of Anaesthesia 1983; 55: 85540
• SIEDLECKI J. Disturbances in the function of cardiovascular system in patients following endotracheal intubation and attempts to their prevention by pharmacological blockade of the sympathetic system. Anaesthesia, Resuscitation and Intensive Therapy 1975, 3: 107-23.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 7, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: stress response
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone; Fractures, Stress; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Dexmedetomidine
• Other Study ID Numbers: stress in lap cholecystectomy

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