PERIOPERATIVE PLATELET REACTIVITY AND THE EFFECTS OF CLONIDINE

Background: Increased postoperative platelet reactivity may contribute to arterial thrombotic complications following surgery. Alpha2 Agonis ts, which are being used increasingly to blunt the stress response of surgery, increase platelet aggregation in vitro. We compared periopera tive changes in platelet reactivity in 21 patients receiving either cl onidine or placebo. Methods. Patients undergoing major abdominal surge ry were randomized to receive oral and transdermal clonidine (n = 11) or placebo (n = 10). All patients received similar perioperative manag ement, including preoperative sedation, general anesthesia without neu raxial opioids, or local anesthetics and postoperative patient-control led intravenous morphine. Blood was obtained for measurement of clonid ine level, fibrinogen concentration, platelet count, and platelet reac tivity (impedance aggregometry and dense granule release) before induc tion and 24, 48, and 72 h postoperatively. Results. Thirteen of the 21 patients had biopsy-proven cancer at surgery, 5 of 11 received clonid ine and 8 of 10 received placebo (NS). Clonidine levels were therapeut ic (1-2 ng/ml) throughout the study period. Clonidine administration h ad no effect on platelet count or platelet reactivity. Therefore, the groups were combined for further analysis. In this group (n = 21), com pared to preoperative values, fibrinogen levels rose maximally (36%) a t 72 h postoperatively and platelet counts decreased 22% at 48 h. Plat elet reactivity (aggregation and degranulation) to collagen, adenosine diphosphate, arachidonic acid, and ristocetin, increased at 24, 48, a nd 72 h postoperatively. Thrombin-induced (supramaximal stimulus) dens e granule release did not change from preoperative values. Conclusions : These data indicate that major abdominal surgery causes increased pl atelet reactivity postoperatively but does not effect maximal degranul ation. This increased platelet reactivity occurs within 48 h of surger y, coinciding with the peak incidence of postoperative arterial thromb otic complications. Clonidine administration has no effect on surgical ly induced changes in platelet reactivity. In this surgical patient po pulation, the use of clonidine should not increase the risk of platele t-induced perioperative arterial thrombosis.