Engelhardt W, Stahl K, Marouche A, Hartung E, Dierks T
Institut für Anaesthesiologie, Universität Würzburg.
Anaesthesist. 1994 Nov;43 Suppl 2:S76-82.
The potency of S-(+)-ketamine is approximately double that of the racemic ketamine. This study was carried out to investigate the recovery of cerebral electrical function after a bolus of 1.3 mg/kg ketamine or 0.65 mg/kg S-(+)-ketamine and subsequent continuous application of 4 mg/kg h ketamine per h or 2 mg/kg S-(+)-ketamine, per h for 15 min. Furthermore, the centrally acting, cholinergic agonist physostigmine has been reported to antagonize ketamine and to shorten the recovery period. Therefore, after S-(+)-ketamine 0.012 mg/kg physostigmine was tested against saline placebo. METHODS. With their own informed consent and the approval of the ethics committee 12 healthy volunteers were enrolled in a double-blind cross-over study. All drugs were dissolved in identical volumes. On three dates with intervals of at least 1 week between, ketamine/NaCl, S-(+)-ketamine/physostigmine or S-(+)-ketamine/NaCl was administered (Table 1). The sequence was randomized. The EEG was recorded from 20 sites according to the 10/20 system and after Fast-Fourier transformation computed into amplitudes within the delta, theta, alpha, and beta bands and within the total spectrum. The median, the spectral edge frequency and the dominant frequency (dF) were also determined. Mean values of all electrodes before and at 10, 15, 30, 45 and 195 min after the bolus injection were compared using two-dimensional analysis of variance (ANOVA, significance level P < 0.05). RESULTS. The characteristic increase in theta-amplitude and decrease of alpha-amplitude were observed after ketamine and S-(+)-ketamine. Median and dF dropped from the alpha to the theta frequency range. Ketamine led to a greater increase in total, delta, theta and beta amplitude during anaesthesia. 3 hours after ketamine/S-(+)-ketamine anaesthesia a significant decrease in the median and dominant frequency and in total, delta, theta, alpha and beta amplitudes confirmed residual impairment of cerebral function after all study drugs. No differences were found between physostigmine and placebo. DISCUSSION. The EEG changes during ketamine/S-(+)-ketamine administration suggest a slightly deeper anaesthetic level after ketamine. The course of recovery was not different after ketamine and after S-(+)-ketamine. The spectral edge frequency did not differ between measurement points, and is therefore not suitable for assessment of the depth of anaesthesia reached with ketamine/S-(+)-ketamine. The dose of physostigmine tested was probably too low to produce antagonism of S-(+)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side effects, such as nausea, vomiting and bradycardia, and possibly even tonic-clonic seizures.
S-(+)-氯胺酮的效力约为消旋氯胺酮的两倍。本研究旨在探究静脉注射1.3mg/kg氯胺酮或0.65mg/kg S-(+)-氯胺酮，随后持续每小时静脉输注4mg/kg氯胺酮或2mg/kg S-(+)-氯胺酮，持续15分钟后，大脑电功能的恢复情况。此外，据报道，中枢作用的胆碱能激动剂毒扁豆碱可拮抗氯胺酮并缩短恢复期。因此，在注射0.012mg/kg S-(+)-氯胺酮后，对毒扁豆碱与生理盐水安慰剂进行了测试。方法：在获得12名健康志愿者的知情同意并经伦理委员会批准后，将他们纳入一项双盲交叉研究。所有药物均溶解于相同体积的溶剂中。在三个日期进行给药，每次给药间隔至少1周，分别给予氯胺酮/氯化钠、S-(+)-氯胺酮/毒扁豆碱或S-(+)-氯胺酮/氯化钠（表1）。给药顺序随机。根据10/20系统从20个部位记录脑电图，并在快速傅里叶变换后计算出δ、θ、α和β频段以及总频谱内的振幅。还测定了中位数、频谱边缘频率和主频（dF）。使用二维方差分析（ANOVA，显著性水平P<0.05）比较推注给药前及给药后10、15、30、45和195分钟时所有电极的平均值。结果：氯胺酮和S-(+)-氯胺酮给药后均观察到特征性的θ波振幅增加和α波振幅降低。中位数和dF从α频率范围降至θ频率范围。氯胺酮在麻醉期间导致总振幅、δ波、θ波和β波振幅有更大的增加。氯胺酮/S-(+)-氯胺酮麻醉3小时后，中位数、主频以及总振幅、δ波、θ波、α波和β波振幅均显著降低，证实所有研究药物给药后均存在大脑功能的残余损害。毒扁豆碱与安慰剂之间未发现差异。讨论：氯胺酮/S-(+)-氯胺酮给药期间的脑电图变化表明氯胺酮给药后的麻醉深度略深。氯胺酮和S-(+)-氯胺酮给药后的恢复过程无差异。测量点之间的频谱边缘频率无差异，因此不适合用于评估氯胺酮/S-(+)-氯胺酮达到的麻醉深度。所测试的毒扁豆碱剂量可能过低，无法产生对S-(+)-氯胺酮的拮抗作用。毒扁豆碱剂量增加的情况尚待研究，但可能会导致更高的副作用发生率，如恶心、呕吐和心动过缓，甚至可能引发强直阵挛性癫痫发作。
