EFFECTS OF CLONIDINE ON PROLONGED POSTOPERATIVE SYMPATHETIC RESPONSE

Objective: Surgical trauma results in diffuse sympathoadrenal activati on which is thought to contribute to perioperative cardiovascular comp lications in high risk patients, Regional anesthetic and analgesic tec hniques can attenuate this ''stress response'' and reduce the occurren ce rate of adverse perioperative events; however, their use in the pos toperative period is logistically difficult and costly. The present st udy was undertaken to evaluate whether transdermal administration of t he alpha(2) adrenergic-receptor agonist, clonidine, can be used as a p harmacologic means of blunting the stress response throughout the peri operative period, Design: Double-blind, placebo controlled clinical tr ial in patients undergoing pancreatico-biliary surgery, Setting: Opera ting rooms and surgical intensive care unit of a major university teac hing hospital. Patients: Forty patients scheduled for major upper abdo minal surgery. Interventions: Patients received either clonidine (0.2 mg orally and a clonidine TTS-3 patch the evening before surgery and 0 .3 mg orally on call to the operating room) or matched oral and transd ermal placebo, Measurements and Main Results: Heart rate, systemic art erial blood pressure, plasma catecholamine, clonidine, interleukin-6 c oncentrations, and 24-hr urine cortisol and nitrogen excretion were me asured the day before surgery and daily thereafter for 72 hrs postoper atively, Preoperative transdermal (and oral) clonidine administration resulted in therapeutic plasma clonidine concentrations throughout the perioperative period (1.54 +/- .07 [SEM] mu g/mL). Clonidine reduced preoperative epinephrine and norepinephrine concentrations by 65%, Pla sma catecholamine concentrations increased in both groups following su rgery but were markedly lower throughout the postoperative period in p atients receiving clonidine. Patients receiving clonidine had a reduce d frequency rate of postoperative hypertension, Clonidine had no effec t on plasma interleukin-6 concentration, urine cortisol excretion, or urine nitrogen excretion, No adverse effects of clonidine administrati on were observed. Conclusions: The combined administration of oral and transdermal clonidine effectively attenuated the catecholamine respon se to surgical stress throughout the postoperative study period, Cloni dine administration produced specific sympatholytic effects, since oth er elements of the stress response were not attenuated, Undesirable si de effects were not noted, The sustained sympatholytic effects we obse rved suggest that alpha(2) adrenergic-receptor agonists may offer a ph armacologic means of modifying the sympathoadrenal response to injury, and may be useful in reducing perioperative complications.