[Studies using S-(+)-ketamine on probands. Endocrine and circulatory reactions, recovery and dream experiences]

Clinically used ketamine is a racemic mixture of two isomers, S(+)- and R(-)-ketamine. The anaesthetic potency of S(+)-ketamine was found to be three times higher than that of R(-)-ketamine. It was the aim of this study to compare the effects of racemic ketamine and S(+)-ketamine on endocrine and cardiovascular parameters, recovery and psychomimetic reactions in young healthy volunteers.

6 women and 4 men between 23 and 38 years were investigated twice in a randomized double blind cross-over design receiving injections of 2 mg/kg BW racemic ketamine or 1 mg/kg BW S(+)-ketamine at an interval of at least 7 days. Samples were taken from a central venous catheter before and 1, 3, 5, 10, 15, 30, 60 and 120 min after injection for analysis of adrenaline, noradrenaline (by high pressure liquid chromatography with electrochemical detection), ADH, ACTH, cortisol (by radio immuno assay), glucose, lactate and free glycerol. In addition, SAP, HR, and arterial oxygen saturation were measured, and return of consciousness and orientation were protocoled. Incidence and assessment of dreams were reported by the volunteers.

Adrenaline, noradrenaline, ACTH, cortisol, lactate and free glycerol in plasma as well as SAP and HR increased significantly after injection of both racemic ketamine and S(+)-ketamine. The influence on ADH and glucose was not significant. There were no differences between racemic ketamine and S(+)-ketamine in these parameters. Recovery was significantly improved after administration of S(+)-ketamine. Simple orders were followed after 7.9 +/- 1.1 vs. 9.2 +/- 1.2 min (P = 0.004). Orientation with respect to the person returned after 9.0 +/- 1.8 vs. 11.5 +/- 2.5 min (P = 0.004); with respect to time and location after 10.1 +/- 2.1 min vs. 13.4 +/- 4.0 min (P = 0.007). 18 dreams were reported; assessment was positive in 13 cases and indifferent in 5 cases, none was negative. In 7 of 10 cases, the investigators were able to identify that S(+)-ketamine had been injected.

With respect to endocrine and cardiovascular parameters, the pharmacodynamic effects of racemic and S(+)-ketamine were comparable. Because of the significant improvement in recovery and the reduced quantitative drug load, S(+)-ketamine offers a clear clinical advantage compared with currently used racemic ketamine.