S(+)-氯胺酮可增加人体肌肉交感神经活动，并维持对低血压刺激的神经反应。

S(+)-ketamine increases muscle sympathetic activity and maintains the neural response to hypotensive challenges in humans.

作者信息

Kienbaum P, Heuter T, Pavlakovic G, Michel M C, Peters J

机构信息

Abteilung für Anästhesiologie und Intensivmedizin, Universität Essen, Germany.

出版信息

Anesthesiology. 2001 Feb;94(2):252-8. doi: 10.1097/00000542-200102000-00014.

DOI:10.1097/00000542-200102000-00014

PMID:11176089

Abstract

BACKGROUND

S(+)-Ketamine is reported to exert twofold greater analgesic and hypnotic effects but a shorter recovery time in comparison with racemic ketamine, indicating possible differential effects of stereoisomers. However, cardiovascular regulation during S(+)-ketamine anesthesia has not been studied. Muscle sympathetic activity (MSA) may be an indicator of the underlying alterations of sympathetic outflow. Whether S(+)-ketamine decreases MSA in a similar manner as the racemate is not known. Thus, the authors tested the hypothesis that S(+)-ketamine changes MSA and the muscle sympathetic response to a hypotensive challenge.

METHODS

Muscle sympathetic activity was recorded by microneurography in the peroneal nerve of six healthy participants before and during anesthesia with S(+)-ketamine (670 microg/kg intravenously followed by 15 microg x kg(-1) x min(-1)). Catecholamine and ketamine plasma concentrations, heart rate, and arterial blood pressure were also determined. MSA responses to a hypotensive challenge were assessed by injection of sodium nitroprusside (2-10 microg/kg) before and during S(+)-ketamine anesthesia. In the final step, increased arterial pressure observed during anesthesia with S(+)-ketamine was adjusted to preanesthetic values by sodium nitroprusside infusion (1-6 microg x kg(-1) x min(-1)).

RESULTS

Anesthesia with S(+)-ketamine (ketamine plasma concentration 713 +/- 295 microg/l) significantly increased MSA burst frequency (mean +/- SD; 18 +/- 6 to 35 +/- 11 bursts/min) and burst incidence (32 +/- 10 to 48 +/- 15 bursts/100 heartbeats) and was associated with a doubling of norepinephrine plasma concentration (from 159 +/- 52 to 373 +/- 136 pg/ml) parallel to the increase in MSA. Heart rate and arterial blood pressure also significantly increased. When increased arterial pressure during S(+)-ketamine was decreased to awake values with sodium nitroprusside, MSA increased further (to 53 +/- 24 bursts/min and 60 +/- 20 bursts/100 heartbeats, respectively). The MSA increase in response to the hypotensive challenge was fully maintained during anesthesia with S(+)-ketamine.

CONCLUSIONS

S(+)-Ketamine increases efferent sympathetic outflow to muscle. Despite increased MSA and arterial pressure during S(+)-ketamine anesthesia, the increase in MSA in response to arterial hypotension is maintained.

摘要

背景

据报道，与消旋氯胺酮相比，S(+)-氯胺酮具有两倍的镇痛和催眠效果，但恢复时间更短，这表明立体异构体可能具有不同的作用。然而，S(+)-氯胺酮麻醉期间的心血管调节尚未得到研究。肌肉交感神经活动（MSA）可能是交感神经输出潜在改变的一个指标。S(+)-氯胺酮是否以与消旋体类似的方式降低MSA尚不清楚。因此，作者检验了S(+)-氯胺酮会改变MSA以及肌肉对低血压刺激的交感神经反应这一假设。

方法

在6名健康参与者的腓神经中，通过微神经ography记录S(+)-氯胺酮麻醉前和麻醉期间（静脉注射670μg/kg，随后以15μg·kg⁻¹·min⁻¹）的肌肉交感神经活动。还测定了儿茶酚胺和氯胺酮血浆浓度、心率和动脉血压。通过在S(+)-氯胺酮麻醉前和麻醉期间注射硝普钠（2 - 10μg/kg）来评估MSA对低血压刺激的反应。在最后一步，通过硝普钠输注（1 - 6μg·kg⁻¹·min⁻¹）将S(+)-氯胺酮麻醉期间观察到的动脉压升高调整到麻醉前值。

结果

S(+)-氯胺酮麻醉（氯胺酮血浆浓度713±295μg/l）显著增加了MSA爆发频率（平均值±标准差；从18±6次/分钟增加到35±11次/分钟）和爆发发生率（从32±10次/100次心跳增加到48±15次/100次心跳），并且与去甲肾上腺素血浆浓度加倍（从159±52pg/ml增加到373±136pg/ml）相关，与MSA的增加平行。心率和动脉血压也显著升高。当用硝普钠将S(+)-氯胺酮期间升高的动脉压降低到清醒值时，MSA进一步增加（分别增加到53±24次/分钟和60±20次/100次心跳）。在S(+)-氯胺酮麻醉期间，对低血压刺激的MSA增加完全得以维持。