ANALGESIC AND PSYCHOTROPIC EFFECTS OF KET AMINE RACEMATE VERSUS S-(-KETAMINE IN SUBANAESTHETIC DOSES())

The intravenous anaesthetic ketamine is widely used in subanaesthetic doses as a potent analgesic in emergency and disaster medicine. At pre sent, ketamine is commercially available only in its racemic form, alt hough the S(+)-isomer has proved to be approximately three times as po tent than the R(-)-isomer. In first clinical trials in Germany, S(+)-k etamine was reported to be markedly advantageous with regard to analge sia in anaesthetized patients. We therefore evaluated ketamine's analg esic and psychotropic effects in subanaesthetic doses given to healthy volunteers. Materials and methods. After institutional approval of th e study by the university's Ethics Committee, 16 volunteers received k etamine racemate (1 mg/kg) and S(+)-ketamine (0.5 mg/kg) i.m. with 1-w eek intervals between injections in a randomized, double-blind fashion . Analgesia (electric pain stimulation of the median nerve), long-term memory, anterograde amnesia (recognition of simple pictures), motor c oordination (Trieger test), immediate recall (short test of general in telligence) and concentration capacity (CI test: recognition of a pres elected symbol among several symbols) were measured over a 60-min peri od and mean arterial pressure, heart rate, and ketamine plasma levels in venous blood samples were determined. Values were calculated as mea ns and data were analysed by Wilcoxon's paired test for group comparis on. Results. Within 15 min, both agents induced a measurable degree of analgesia. After ketamine racemate, the level of pain toleranted incr eased from 38.8+/-14.0 to 57.0+/-13.7 mA and after S(+)-ketamine, from 36.9+/-10.5 to 53.3+/-15.2 mA. Ketamine racemate did not exert measur able effects on long-term memory, whereas anterograde amnesia was obse rved in 46% and 54% of the study subjects after 15 and 30 min, respect ively. However, after S(+)-ketamine, only 8% of the volunteers demonst rated anterograde amnesia (P < 0.05). Immediate recall also declined i n both groups (baseline: 5 points, after 15 min: 3.5 points for ketami ne racemate, 4 points for S(+)-ketamine), whereas concentration capaci ty worsened from 14.5+/-3.8 s to 35.9+/-18.6 s after ketamine racemate and significantly less, from 14.8+/-2.5 s to 22.9+/-7.6 s, after S(+) -ketamine (P < 0.01). Furthermore, after 15 min, ketamine racemate ind uced an increase in heart rates from 74+/-15 b/min to 97+/-11 b/min, w hile S(+)-ketamine raised heart rates from 74+/-13 b/min to 89+/-11 b/ min only (P < 0.05). Mean arterial pressure increased from 97+/-11 mmH g to 111+/-9 mmHg after ketamine racemate and from 92+/-11 mmHg to 110 +/-13 mmHg after S(+)-ketamine (not significantly different). Conclusi on. S(+)-Ketamine at half-dose of ketamine-racemate is as potent as ke tamine-racemate in subanaesthetic doses with powerful analgesic proper ties. The (+)-isomer exerts less adverse effects on measurable cerebra l functions and induces a significantly smaller increase in heart rate . Since states of impaired consciousness and disorientation are especi ally disturbing under emergency conditions, further investigations sho uld be carried out to define S(+)-ketamine's position as a potent anal gesic for therapeutic use in emergency and disaster medicine.