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

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)

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