[Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]

Abstract

The intravenous anaesthetic ketamine is widely used in subanaesthetic doses as a potent analgesic in emergency and disaster medicine. At present, ketamine is commercially available only in its racemic form, although the S(+)-isomer has proved to be approximately three times as potent than the R(-)-isomer. In first clinical trials in Germany, S(+)-ketamine was reported to be markedly advantageous with regard to analgesia in anaesthetized patients. We therefore evaluated ketamine's analgesic and psychotropic effects in subanaesthetic doses given to healthy volunteers. MATERIALS AND METHODS. After institutional approval of the study by the university's Ethics Committee, 16 volunteers received ketamine racemate (1 mg/kg) and S(+)-ketamine (0.5 mg/kg) i.m. with 1-week 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 coordination (Trieger test), immediate recall (short test of general intelligence) and concentration capacity (CI test: recognition of a preselected symbol among several symbols) were measured over a 60-min period and mean arterial pressure, heart rate, and ketamine plasma levels in venous blood samples were determined. Values were calculated as means and data were analysed by Wilcoxon's paired test for group comparison. RESULTS. Within 15 min, both agents induced a measurable degree of analgesia. After ketamine racemate, the level of pain tolerated increased 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 measurable effects on long-term memory, whereas anterograde amnesia was observed in 46% and 54% of the study subjects after 15 and 30 min, respectively. However, after S(+)-ketamine, only 8% of the volunteers demonstrated anterograde amnesia (P < 0.05). Immediate recall also declined in both groups (baseline: 5 points, after 15 min: 3.5 points for ketamine racemate, 4 points for S(+)-ketamine), whereas concentration capacity 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 induced an increase in heart rates from 73 +/- 15 b/min to 97 +/- 11 b/min, while 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 mmHg to 111 +/- 9 mmHg after ketamine racemate and from 92 +/- 11 mmHg to 110 +/- 13 mmHg after S(+)-ketamine (not significantly different). CONCLUSION. S(+)-Ketamine at half-dose of ketamine-racemate is as potent as ketamine-racemate in subanaesthetic doses with powerful analgesic properties. The (+)-isomer exerts less adverse effects on measurable cerebral functions and induces a significantly smaller increase in heart rate. Since states of impaired consciousness and disorientation are especially disturbing under emergency conditions, further investigations should be carried out to define S(+)-ketamine's position as a potent analgesic for therapeutic use in emergency and disaster medicine.