Dexmedetomidine vs Midazolam Premedication: Effects on Perioperative Stress in Elective Laparoscopic Cholecystectomy-A Randomized Double-Blind Trial.

PURPOSE: Preoperative anxiety contributes to the perioperative stress response and may influence recovery. Midazolam is commonly used for premedication, while dexmedetomidine has emerged as a potential alternative with a different safety profile. This study aimed to compare their effects on perioperative stress and clinically relevant outcomes. DESIGN: Prospective, randomized, double-blind controlled trial. METHODS: Fifty-nine ASA I-II adult patients undergoing elective laparoscopic cholecystectomy were randomized to receive intravenous dexmedetomidine (0.3 µg/kg) or midazolam (0.03 mg/kg) for premedication. Plasma adrenocorticotropic hormone (ACTH) levels were measured at baseline, pre-induction, and 2 hours postoperatively. Secondary outcomes included hemodynamic parameters, postoperative pain scores, neutrophil-to-lymphocyte ratio, and perioperative adverse events, while anxiety was assessed preoperatively. FINDINGS: ACTH concentrations decreased over time in both groups. Preinduction ACTH concentrations were lower in the midazolam group (2.9 [2.1-4.5] vs 4.3 [2.6-7.9] pmol/L; P= .040), whereas no between-group differences were observed at baseline or 2 hours postoperatively. Hemodynamic parameters, anesthetic and opioid requirements, and postoperative pain scores were comparable between groups. Hypotension and bradycardia were more frequent with dexmedetomidine but without statistical significance. No significant associations were observed between anxiety, ACTH levels, and inflammatory markers. CONCLUSIONS: No statistically significant differences were observed between low-dose dexmedetomidine and midazolam in the measured perioperative clinical outcomes. Although midazolam resulted in lower pre-induction ACTH concentrations, this isolated finding was not accompanied by differences in postoperative ACTH concentrations or clinical outcomes. These findings suggest that the measured psychological, neuroendocrine, and inflammatory components of the perioperative stress response may not be directly correlated, and provide one of the first direct comparisons of pre-induction ACTH responses between dexmedetomidine and midazolam.