RECOVERY AFTER SHORT ANESTHESIA WITH (S)- KETAMINE OR RACEMIC-KETAMINE IN VOLUNTEERS - A RANDOMIZED, DOUBLE-BLIND, CROSS-OVER STUDY

The anaesthetic potency of the (S)-ketamine isomer is approximately do uble that of racemic ketamine. The aim of this study was to compare th e recovery of cerebral function after a bolus of 1,3 mg/kg racemic ket amine or 0.65 mg/kg (S)-ketamine followed by continuous application of 4 or 2 mg/kg x h over 15 minutes. Methods: With their informed consen t and approval of the local ethics committee 12 healthy volunteers wer e enrolled in a double-blind, cross-over study. All drugs were dissolv ed in identical volumes. On three dates with an interval of one week a t least ketamine/NaCl, (S)-ketamine/physostigmine or (S)-ketamine/NaCl was administered (table 1). The sequence was randomized. In addition, the unspecific antagonistic potential of the centrally acting, cholin ergic agonist physostigmine (0.012 mg/kg) after (S)-ketamine was teste d against saline-placebo. Neuropsychological tests (tests 3-5 of the s yndrome-short-test [Erzigkeit, see references]) were used to quantify cerebral function before and at 45, 75, 105, 135, 165 and 195 min afte r anaesthesia. All data are mean values and standard deviation. Compar isons overtime and between drugs were carried out using two-dimensiona l analysis of variance (ANOVA). Wilcoxon-tests were used post-hoc, p < 0.05 was considered significant. Results: After (S)-ketamine the subj ects were able to carry out the tasks more rapidly than after racemic ketamine (p < 0.05). Mean time to reach preoperative test performance +10% was 117.5 min for (S)-ketamine/physostigmine, 121.3 min for (S)-k etamine/NaCl and 141.6 min for racemic ketamine (p < 0.05 between (S)- ketamine and racemic ketamine). No differences were found between phys ostigmine and placebo. The incidence of side effects (mainly nausea, v omiting) was not different. Discussion: (S)-ketamine offers a shorter recovery time after short anaesthesia compared to racemic ketamine. Th e investigated dose of physostigmine was probably too low to produce a ntagonism of (S)-ketamine. An increased dosage of physostigmine has ye t to be studied, but is likely to cause a higher rate of side effects such as nausea, vomiting, bradycardia and possibly even tonic-clonic s eizures.