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In an attempt to maintain stable levels of an α2-adrenergic agonist throughout the perioperative period, two different oral-transdermal clonidine dosage regimens were administered according to a randomized, double-blind, placebo-controlled study in patients undergoing abdominal surgery. We determined the clinical efficacy of a high- and a low-dose clonidine regimen on sedation, hemodynamic parameters, anesthesia, and analgesia. The low-dose clonidine group of patients (n = 14) received a 7-cm2 clonidine transdermal patch (Catapres-TTS® #2), which was supplemented with oral doses of clonidine ∼3 μg·kg-1 on the evening prior to surgery and on the morning of surgery. The high-dose clonidine group (n = 14) received a 10.5-cm2 clonidine transdermal patch (Catapres-TTS® #3) with oral clonidine ∼4.5 μ·kg-1 at bedtime and 6.0 μ.kg-1 on the morning of surgery. Placebo-treated (control) patients received the same occlusive patch without active ingredient and oral placebo tablets at bedtime and on the morning of surgery. Preanesthetic medication included midazolam 50 μ·kg-1 intramuscularly (im). Anesthesia was induced with alfentanil 30 μ·kg-1 intravenously (iv), thiopental 3 mg. kg-1 iv, and vecuronium 0.1 mg·kg-1 iv, and was maintained with 70% nitrous oxide in oxygen and a continuous infusion of alfentanil 0.5 μg·kg-1·min-1. Isoflurane was added when the blood pressure exceeded 110% of the patient's prestudy value. For pain relief postoperatively, the patients received morphine, 1–2-mg iv boluses, via a patient-controlled analgesia pump. The low-dose clonidine patient group had mean plasma clonidine concentrations that varied from 1.47 ng.ml-1 (preoperative) to 1.32 ng·ml-1 (postoperative day 2). Patients in the high-dose clonidine group had mean clonidine concentrations that varied from 1.93 ng·ml-1 (preoperative) to 1.70 ng.ml-1 (postoperative day 2). Patients in the clonidine treatment groups (both high- and low-dose) were more sedated preoperatively, required significantly less volatile anesthetic intraoperatively to maintain hemodynamic stability, and self-administered less morphine for postoperative analgesia. In addition, the hemodynamic parameters were more stable intraoperatively in both clonidine-treated groups. This study demonstrates the utility and efficacy of oral-transdermal clonidine regimens as a perioperative adjunct in the anesthetic management of surgical patients undergoing major abdominal operations.