Komatsu R, Orhan-Sungur M, In J, Podranski T, Bouillon T, Lauber R, Rohrbach S, Sessler D
Outcomes Research Institute, University of Louisville, KY, USA.
Br J Anaesth. 2006 Jun;96(6):732-7. doi: 10.1093/bja/ael101. Epub 2006 May 4.
Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (triggering core temperatures) in humans.
Control (placebo) and ondansetron infusions at the target plasma concentration of 250 ng ml(-1) were studied in healthy volunteers on two different days. Each day, skin and core temperatures were increased to provoke sweating; then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction and shivering thresholds after compensating for changes in mean-skin temperature. Data were analysed using t-tests and presented as means (sds); P<0.05 was taken as significant.
Ondensetron plasma concentrations were 278 (57), 234 (55) and 243 (58) ng ml(-1) at the sweating, vasoconstriction and shivering thresholds, respectively; these corresponded to approximately 50 mg of ondansetron which is approximately 10 times the dose used for postoperative nausea and vomiting. Ondansetron did not change the sweating (control 37.4 (0.4) degrees C, ondansetron 37.6 (0.3) degrees C, P=0.16), vasoconstriction (37.0 (0.5) degrees C vs 37.1 (0.3) degrees C; P=0.70), or shivering threshold (36.3 (0.5) degrees C vs 36.3 (0.6) degrees C; P=0.76). No sedation was observed on either study day.
/b>. Ondansetron appears to have little potential for facilitating induction of therapeutic hypothermia.
昂丹司琼是一种5-羟色胺-3受体拮抗剂，可减轻术后寒战。通常，减轻寒战的药物会损害中枢体温调节控制，因此可能有助于在诱导治疗性低温期间预防寒战。因此，我们确定了昂丹司琼是否会降低人体主要自主体温调节反应阈值（触发核心温度）。
在两个不同的日子对健康志愿者进行研究，以目标血浆浓度250 ng/ml输注对照（安慰剂）和昂丹司琼。每天，升高皮肤和核心温度以引发出汗；然后降低温度以引起外周血管收缩和寒战。在补偿平均皮肤温度变化后，我们确定了核心温度出汗、血管收缩和寒战阈值。使用t检验分析数据，并以均值（标准差）表示；P<0.05被视为具有统计学意义。
在出汗、血管收缩和寒战阈值时，昂丹司琼血浆浓度分别为278（57）、234（55）和243（58）ng/ml；这些相当于约50mg的昂丹司琼，约为用于术后恶心和呕吐剂量的10倍。昂丹司琼未改变出汗阈值（对照37.4（0.4）℃，昂丹司琼37.6（0.3）℃，P=0.16）、血管收缩阈值（37.0（0.5）℃对37.1（0.3）℃；P=0.70）或寒战阈值（36.3（0.5）℃对36.3（0.6）℃；P=0.76）。在任何一个研究日都未观察到镇静作用。
昂丹司琼似乎几乎没有促进诱导治疗性低温的潜力。
