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.