Clonidine Provides Superior Hemodynamic Stability and Analgesia over Midazolam-fentanyl under Monitored Anesthesia...

Monitored anesthesia care (MAC) combines local anesthesia with sedoanalgesia to maintain patient comfort and hemodynamic stability. This study aimed to compare the analgesic efficacy, sedation quality, and hemodynamic changes between clonidine and midazolam-fentanyl combinations during varicose vein surgery and to assess the effect of catechol-O-methyltransferase (COMT) gene polymorphism (rs4680) on postoperative pain modulation.

In this prospective, randomized controlled trial, 50 American Society of Anesthesiologists I-II patients were equally divided into two groups. Group I (clonidine) received 2 μg/kg bolus followed by 0.2 μg/kg/h infusion, while Group II (midazolam-fentanyl) received 0.06 mg/kg midazolam and 1 μg/kg fentanyl followed by 0.2 mL/kg/h infusion. Hemodynamic variables, pain scores (Visual Analog Scale [VAS]), sedation (Ramsay and Observer's Assessment of Alertness/Sedation), and recovery (Aldrete) were assessed. The COMT rs4680 polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism.

Baseline characteristics were comparable (P > 0.05). Mean heart rate (HR), systolic, diastolic, and mean arterial pressures (MAPs) were significantly lower in the clonidine group at 10-60 min intraoperatively (e.g. HR: 70.04 ± 3.77 vs. 78.60 ± 2.97 beats/min; P < 0.001; MAP: 79.88 ± 7.48 vs. 91.29 ± 4.88 mmHg; P < 0.001). Postoperative VAS scores were consistently lower in the clonidine group at 6 h (0.44 ± 0.87 vs. 2.84 ± 1.43; P < 0.001), 12 h (0.00 ± 0.00 vs. 1.60 ± 1.26; P < 0.001), and 18 h (0.00 ± 0.00 vs. 0.84 ± 0.90; P < 0.001). Rescue analgesia was required in 32% versus 56% of patients, respectively (P = 0.114). Respiratory distress occurred only in the midazolam-fentanyl group (16%; P = 0.037). COMT genotypes (CT = 54%, TT = 46%) showed no significant association with pain intensity (P > 0.05).

Clonidine-based MAC provided better intraoperative hemodynamic stability, prolonged analgesia, and reduced postoperative pain compared with midazolam-fentanyl, with minimal respiratory complications. The COMT rs4680 polymorphism did not significantly influence pain perception, highlighting the multifactorial nature of postoperative analgesic response.