Adams H A, Thiel A, Jung A, Fengler G, Hempelmann G
Abteilung für Anaesthesie und Intensivmedizin, Marienkrankenhaus Trier-Ehrang.
Anaesthesist. 1992 Oct;41(10):588-96.
Clinically used ketamine is a racemic mixture of two isomers, S(+)- and R(-)-ketamine. The anaesthetic potency of S(+)-ketamine was found to be three times higher than that of R(-)-ketamine. It was the aim of this study to compare the effects of racemic ketamine and S(+)-ketamine on endocrine and cardiovascular parameters, recovery and psychomimetic reactions in young healthy volunteers.
6 women and 4 men between 23 and 38 years were investigated twice in a randomized double blind cross-over design receiving injections of 2 mg/kg BW racemic ketamine or 1 mg/kg BW S(+)-ketamine at an interval of at least 7 days. Samples were taken from a central venous catheter before and 1, 3, 5, 10, 15, 30, 60 and 120 min after injection for analysis of adrenaline, noradrenaline (by high pressure liquid chromatography with electrochemical detection), ADH, ACTH, cortisol (by radio immuno assay), glucose, lactate and free glycerol. In addition, SAP, HR, and arterial oxygen saturation were measured, and return of consciousness and orientation were protocoled. Incidence and assessment of dreams were reported by the volunteers.
Adrenaline, noradrenaline, ACTH, cortisol, lactate and free glycerol in plasma as well as SAP and HR increased significantly after injection of both racemic ketamine and S(+)-ketamine. The influence on ADH and glucose was not significant. There were no differences between racemic ketamine and S(+)-ketamine in these parameters. Recovery was significantly improved after administration of S(+)-ketamine. Simple orders were followed after 7.9 +/- 1.1 vs. 9.2 +/- 1.2 min (P = 0.004). Orientation with respect to the person returned after 9.0 +/- 1.8 vs. 11.5 +/- 2.5 min (P = 0.004); with respect to time and location after 10.1 +/- 2.1 min vs. 13.4 +/- 4.0 min (P = 0.007). 18 dreams were reported; assessment was positive in 13 cases and indifferent in 5 cases, none was negative. In 7 of 10 cases, the investigators were able to identify that S(+)-ketamine had been injected.
With respect to endocrine and cardiovascular parameters, the pharmacodynamic effects of racemic and S(+)-ketamine were comparable. Because of the significant improvement in recovery and the reduced quantitative drug load, S(+)-ketamine offers a clear clinical advantage compared with currently used racemic ketamine.
临床使用的氯胺酮是两种异构体S(+)-氯胺酮和R(-)-氯胺酮的外消旋混合物。研究发现S(+)-氯胺酮的麻醉效力是R(-)-氯胺酮的三倍。本研究旨在比较外消旋氯胺酮和S(+)-氯胺酮对年轻健康志愿者内分泌和心血管参数、恢复情况及拟精神病反应的影响。
采用随机双盲交叉设计,对6名女性和4名年龄在23至38岁之间的男性进行了两次研究,两次注射间隔至少7天,分别注射2mg/kg体重的外消旋氯胺酮或1mg/kg体重的S(+)-氯胺酮。在注射前以及注射后1、3、5、10、15、30、60和120分钟,从中心静脉导管采集样本,分析肾上腺素、去甲肾上腺素(采用高压液相色谱电化学检测法)、抗利尿激素、促肾上腺皮质激素、皮质醇(采用放射免疫分析法)、葡萄糖、乳酸和游离甘油。此外,测量收缩压、心率和动脉血氧饱和度,并记录意识和定向恢复情况。志愿者报告梦境的发生率和评估情况。
注射外消旋氯胺酮和S(+)-氯胺酮后,血浆中的肾上腺素、去甲肾上腺素、促肾上腺皮质激素、皮质醇、乳酸和游离甘油以及收缩压和心率均显著升高。对抗利尿激素和葡萄糖的影响不显著。在这些参数方面,外消旋氯胺酮和S(+)-氯胺酮之间没有差异。注射S(+)-氯胺酮后恢复情况显著改善。简单指令执行时间分别为7.9±1.1分钟和9.2±1.2分钟(P = 0.004)。人物定向恢复时间分别为9.0±1.8分钟和11.5±2.5分钟(P = 0.004);时间和地点定向恢复时间分别为10.1±2.1分钟和13.4±4.0分钟(P = 0.007)。共报告了18个梦境;评估为积极的有13例,无差异的有5例,无消极的。在10例中有7例,研究人员能够确定注射的是S(+)-氯胺酮。
在外分泌和心血管参数方面,外消旋氯胺酮和S(+)-氯胺酮的药效学作用相当。由于恢复情况显著改善且药物剂量减少,与目前使用的外消旋氯胺酮相比,S(+)-氯胺酮具有明显的临床优势。