Rosenfeld B A, Faraday N, Campbell D, Dorman T, Clarkson K, Siedler A, Breslow M J, Bell W
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Anesthesiology. 1993 Aug;79(2):255-61. doi: 10.1097/00000542-199308000-00010.
Increased postoperative platelet reactivity may contribute to arterial thrombotic complications following surgery. alpha 2 Agonists, which are being used increasingly to blunt the stress response of surgery, increase platelet aggregation in vitro. We compared perioperative changes in platelet reactivity in 21 patients receiving either clonidine or placebo.
Patients undergoing major abdominal surgery were randomized to receive oral and transdermal clonidine (n = 11) or placebo (n = 10). All patients received similar perioperative management, including preoperative sedation, general anesthesia without neuraxial opioids, or local anesthetics and postoperative patient-controlled intravenous morphine. Blood was obtained for measurement of clonidine level, fibrinogen concentration, platelet count, and platelet reactivity (impedance aggregometry and dense granule release) before induction and 24, 48, and 72 h postoperatively.
Thirteen of the 21 patients had biopsy-proven cancer at surgery, 5 of 11 received clonidine and 8 of 10 received placebo (NS). Clonidine levels were therapeutic (1-2 ng/ml) throughout the study period. Clonidine administration had no effect on platelet count or platelet reactivity. Therefore, the groups were combined for further analysis. In this group (n = 21), compared to preoperative values, fibrinogen levels rose maximally (36%) at 72 h postoperatively and platelet counts decreased 22% at 48 h. Platelet reactivity (aggregation and degranulation) to collagen, adenosine diphosphate, arachidonic acid, and ristocetin, increased at 24, 48, and 72 h postoperatively. Thrombin-induced (supramaximal stimulus) dense granule release did not change from preoperative values.
These data indicate that major abdominal surgery causes increased platelet reactivity postoperatively but does not effect maximal degranulation. This increased platelet reactivity occurs within 48 h of surgery, coinciding with the peak incidence of postoperative arterial thrombotic complications. Clonidine administration has no effect on surgically induced changes in platelet reactivity. In this surgical patient population, the use of clonidine should not increase the risk of platelet-induced perioperative arterial thrombosis.
术后血小板反应性增加可能导致手术后动脉血栓形成并发症。α2激动剂越来越多地用于减轻手术应激反应，但在体外可增加血小板聚集。我们比较了21例接受可乐定或安慰剂治疗患者围手术期血小板反应性的变化。
接受腹部大手术的患者被随机分为口服和经皮给予可乐定组（n = 11）或安慰剂组（n = 10）。所有患者接受相似的围手术期管理，包括术前镇静、不使用神经轴索阿片类药物的全身麻醉或局部麻醉以及术后患者自控静脉注射吗啡。在诱导前以及术后24、48和72小时采集血液，用于检测可乐定水平、纤维蛋白原浓度、血小板计数和血小板反应性（阻抗聚集测定法和致密颗粒释放）。
21例患者中有13例手术时经活检证实患有癌症，11例中5例接受可乐定治疗，10例中8例接受安慰剂治疗（无显著性差异）。在整个研究期间，可乐定水平均处于治疗范围（1 - 2 ng/ml）。给予可乐定对血小板计数或血小板反应性无影响。因此，将两组合并进行进一步分析。在该组（n = 21）中，与术前值相比，纤维蛋白原水平在术后72小时最高升高了36%，血小板计数在术后48小时降低了22%。术后24、48和72小时，血小板对胶原、二磷酸腺苷、花生四烯酸和瑞斯托菌素的反应性（聚集和脱颗粒）增加。凝血酶诱导的（超最大刺激）致密颗粒释放与术前值相比没有变化。
这些数据表明，腹部大手术可导致术后血小板反应性增加，但不影响最大脱颗粒。这种血小板反应性增加发生在手术后48小时内，与术后动脉血栓形成并发症的高发期一致。给予可乐定对手术引起的血小板反应性变化无影响。在该手术患者群体中，使用可乐定不应增加血小板诱导的围手术期动脉血栓形成的风险。
