RACEMIC KETAMINE VERSUS S-(-KETAMINE WI TH OR WITHOUT PHYSOSTIGMINE ANTAGONISM - A QUANTITATIVE EEG-STUDY IN VOLUNTEERS())

The potency of S-(+)-ketamine is approximately double that of the race mic ketamine. This study was carried out to investigate the recovery o f 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 m g/kg h ketamine per h or 2 mg/kg S-(+)-ketamine per h for 15 min. Furt hermore, the centrally acting, cholinergic agonist physostigmine has b een 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 enroll ed in a double-blind cross-over study. All drugs were dissolved in ide ntical volumes. On three dates with intervals of at least 1 week betwe en, 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-Fo urier 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 dete rmined. 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. T he characteristic increase in theta-amplitude and decrease of alpha-am plitude 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 an aesthesia. 3 hours after ketamine/S-(+)-ketamine anaesthesia a signifi cant decrease in the median and dominant frequency and in total, delta , theta, alpha and beta amplitudes confirmed residual impairment of ce rebral function after all study drugs. No differences were found betwe en physostigmine and placebo. Discussion. The EEG changes during ketam ine/S-(+)-ketamine administration suggest a slightly deeper anaestheti c level after ketamine. The course of recovery was not different after ketamine and after S-(+)-ketamine. The spectral edge frequency did no t differ between measurement points, and is therefore not suitable for assessment of the depth of anaesthesia reached with ketamine/S-(+)-ke tamine. The dose of physostigmine tested was probably too low to produ ce antagonism of S-(+)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side ef fects, such as nausea, vomiting and bradycardia, and possibly even ton ic-clonic seizures.