[Studies using S-(+)-ketamine on probands. Computerized EEG-analysis and transcranial Doppler ultrasonography]

It has been shown in the recent literature that the anaesthetic potency of the ketamine isomer S(+)-ketamine is twice that of the racemic mixture used in clinical practice. METHODS. With approval of the local ethics committee, we investigated the effects of a bolus injection of 2 mg/kg racemic ketamine or 1 mg/kg S(+)-ketamine, respectively, on the electroencephalogram (EEG) and transcranial Doppler sonography (TCD) of the middle cerebral artery in ten healthy volunteers by means of a randomised, double-blind, cross-over design. Spectral edge frequency, total activity and activity of the alpha, beta, delta, and theta bands were assessed by bihemispheric leads using the Neurotrac system before (MZP 1) and 1, 3, 5, 10, 15, 30, 60, and 120 min after injection (MZP 2-9). Simultaneously, systolic (Vs-MCA), diastolic (Vd-MCA), and mean (Vm-MCA) blood flow velocities in the middle cerebral artery and pulsatility (Vs-Vd)/Vm were recorded. Statistics consisted of two-dimensional analysis of variance with P < 0.05 considered as significant. RESULTS. Racemic ketamine and S(+)-ketamine produced comparable effects on the EEG. Theta- and beta-activities increased between the 1st and 10th min after injection and returned to near baseline values thereafter. 120 min after injection, the absolute delta- and theta-activities were higher following racemic ketamine when compared to the S(+)-ketamine group. However, significant differences between the groups could not be confirmed statistically. TCD variables changed considerably in the course of the study without intergroup differences. Compared to the baseline values, Vs-MCA, Vd-MCA, and Vm-MCA increased significantly for the first 15 min after injection with a maximum at MZP 3. The pulsatility of the obtained Doppler waveform (Vs-Vd)/Vm showed significant decreases at MZP 2-4. CONCLUSIONS. In our study, both racemic ketamine and its isomer S(+)-ketamine produced similar EEG changes consistent with the data from earlier studies. However, the relative lower proportion of slow EEG activity at the end of the study might indicate a better recovery of cortical function following S(+)-ketamine than after racemic ketamine. Assuming a close relationship between cerebral blood flow velocity and cerebral blood flow, our TCD results suggest that both racemic ketamine and S(+)-ketamine will considerably increase cerebral blood flow in spontaneously breathing volunteers. Such an effect has been observed by others and, at least partly, can be explained by a concomitant increase in arterial carbon dioxide partial pressure.