Hamaya Y, Nishikawa T, Dohi S
Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Japan.
Anesthesiology. 1994 Oct;81(4):811-9. doi: 10.1097/00000542-199410000-00007.
Because clonidine, a relative selective alpha 2-agonist, inhibits the action of arginine vasopressin (AVP), the authors examined whether clonidine as an oral preanesthetic medication would induce diuresis and also would affect AVP release and its action during general anesthesia.
Fifty-seven patients (aged 18-65 yr) randomly received oral clonidine either approximately 5 micrograms.kg-1 (n = 19), approximately 2.5 micrograms.kg-1 (n = 19), or none (n = 19) in addition to oral famotidine 20 mg, 90 min before arrival at operating room. Urine volume, urine osmolality, and amount of sodium and potassium excreted into urine were examined every hour for 3 h during minor surgery under general anesthesia with isoflurane and nitrous oxide in oxygen. For 5 patients of each group, plasma AVP and atrial natriuretic peptide concentrations and urine cyclic adenosine monophosphate concentrations as an index of AVP action were also assayed.
Urine output indices (calculated as hourly urine output [milliliters per hour] divided by body weight [kilograms]) were significantly greater in the all periods (P < or = 0.035) after the initiation of anesthesia in the patients receiving clonidine 5 micrograms.kg-1 and only in the 3rd h in those receiving clonidine 2.5 micrograms.kg-1 (P = 0.047) as compared with those in the patients given famotidine alone. The peak effects of diuresis and natriuresis induced by oral clonidine 5 micrograms.kg-1 were both observed at the 2nd h (mean +/- SEM, 2.4 +/- 0.4 ml.kg-1.h-1 and 5.7 +/- 1.5 mEq.h-1 vs. 0.6 +/- 0.1 ml.kg-1.h-1 and 2.2 +/- 0.5 mEq.h-1 in the control subjects; P = 0.001 and P = 0.049). Kaliuresis also increased in the patients receiving clonidine 5 micrograms.kg-1 in the 2nd and 3rd h (P < or = 0.003). Urine osmolality showed a significant reduction over time in patients given clonidine but not in the control subjects. However, plasma AVP and atrial natriuretic peptide levels, and urine cyclic adenosine monophosphate concentrations did not significantly differ among the three groups.
Oral preanesthetic medication of clonidine 2.5 or 5 micrograms.kg-1 caused a significant diuretic effect during surgery under general anesthesia, though it did not apparently relate to AVP action. This effect of clonidine could be related to its pharmacological action as an alpha 2-adrenoceptor agonist not necessarily restricted to the kidney. The diuretic effect of clonidine implicates its clinical importance in the management of patients during anesthesia.
由于可乐定（一种相对选择性的α2 激动剂）可抑制精氨酸加压素（AVP）的作用，作者研究了可乐定作为口服麻醉前用药是否会诱导利尿，以及在全身麻醉期间是否会影响 AVP 的释放及其作用。
57 例年龄在 18 - 65 岁的患者，在到达手术室前 90 分钟，除口服 20mg 法莫替丁外，随机接受约 5μg·kg-1（n = 19）、约 2.5μg·kg-1（n = 19）的口服可乐定或不接受可乐定（n = 19）。在异氟烷和一氧化二氮 - 氧气混合气体全身麻醉下进行小手术期间，每小时检测尿量、尿渗透压以及尿中钠和钾的排泄量，共检测 3 小时。对每组 5 例患者，还检测血浆 AVP 和心钠素浓度以及尿中环磷酸腺苷浓度作为 AVP 作用的指标。
与仅接受法莫替丁的患者相比，接受 5μg·kg-1 可乐定的患者在麻醉开始后的所有时间段（P≤0.035）以及接受 2.5μg·kg-1 可乐定的患者仅在第 3 小时（P = 0.047），尿量指数（以每小时尿量[毫升/小时]除以体重[千克]计算）显著更高。口服 5μg·kg-1 可乐定诱导的利尿和利钠的峰值效应均在第 2 小时观察到（均值±标准误，分别为 2.4±0.4ml·kg-1·h-1 和 5.7±1.5mEq·h-1，而对照组为 0.6±0.1ml·kg-1·h-1 和 2.2±0.5mEq·h-1；P = 0.001 和 P = 0.049）。接受 5μg·kg-1 可乐定的患者在第 2 和第 3 小时尿钾排泄也增加（P≤0.003）。给予可乐定的患者尿渗透压随时间显著降低，而对照组未出现此情况。然而，三组之间血浆 AVP 和心钠素水平以及尿中环磷酸腺苷浓度无显著差异。
口服 2.5 或 5μg·kg-1 可乐定作为麻醉前用药在全身麻醉手术期间可引起显著的利尿作用，尽管这一作用显然与 AVP 的作用无关。可乐定的这一作用可能与其作为α2 - 肾上腺素能受体激动剂的药理作用有关，且不一定局限于肾脏。可乐定的利尿作用提示其在麻醉患者管理中的临床重要性。
