Premedication with Oral and Transdermal Clonidine Provides Safe and Efficacious Postoperative Sympatholysis

Abstract

We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a transdermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60-90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia.

Patient attitudes toward granting consent to participate in perioperative randomized clinical trials

“…approached 52 patients on the hospital ward 1 to 2 days after surgery to complete a questionnaire. The patients who were asked to complete the surveys had been recruited previously for a variety of perioperative RCTs at the University of Chicago Hospital, including studies of clonidine sympatholysis in vascular surgery (n ϭ 16), 9 methylnaltrexone for treatment of postoperative nausea and vomiting (n ϭ 17), 10 and an oral fentanyl lozenge for treatment of postoperative pain (n ϭ 10). 11 Nonclinical research personnel had approached patients for RCT consent, provided a verbal explanation of the study, and encouraged patients to ask questions and read the consent form; clinician-investigators later spoke with patients who had agreed to confirm their consent.…”

Prämedikation im Rahmen einer TIVA bei kieferchirurgischen Operationen - Vergleich der perioperativen Verläufe nach Clonidin versus Midazolam

“…und sind in der perioperativen Phase besonders erwünscht (Senkung der perioperativen Streûantwort, sedierender, analgetischer, anästhetikasparender, antiemetischer Effekt sowie eine Senkung der Shiveringinzidenz). Clonidin ist dabei eine der am besten untersuchten Substanzen [13,15,16,29].…”

“…Sowohl die präoperative, als auch die intra-und postoperative Gabe von Clonidin über unterschiedliche Applikalionswege (oral, intravenös, transdermal) wurde von verschiedenen Arbeitsgruppen untersucht [11,13,16,41]. Dabei erwies sich Clonidin als eine im perioperativem Zeitraum sicher anwendbare Substanz mit geringem Nebenwirkungspotential [8].…”

“…Wir entschieden uns zu einer oralen Prämedikation in einer in der Literatur angegebebenen Dosis [6,13,16,17]. Hierbei erwiesen sich 5 g kg ±1 Clonidin gegenüber 100 g kg ±1 Midazolam bezüglich des Sedierungsgrades und des präoperativen Angsterlebens als gleichwertig (s. Tab.…”

Comment on the guidelines for perioperative cardiovascular evaluation for noncardiac surgery of the ACC/AHA

“…Einige Studien untersuchten den Einfluss von α-II-Agonisten (z. B. Clonidin), die eine Reduktion der kardialen Ereignisse bei Patienten mit bekannter KHK zeigten, wenn ein vaskulärer Eingriff durchgeführt wurde[18, 56, 66,86].Es gibt weiterhin sehr wenige randomisierte Studien zum Einsatz einer medikamentösen Therapie vor einer nichtkardialen Operation zur Senkung der perioperativen kardialen Komplikationen. Die verfügbaren Daten reichen nicht aus, um konkrete Schlüsse oder gar Empfehlungen zu geben.…”