Pharmacology of Ketamine Isomers in Surgical Patients

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Abstract
To assess the intraoperative and postoperative effects of the optical isomers of ketamine. compared with the racemic mixture as sole anesthetics, equianesthetic doses of racemic ketamine (RK), 2 mg/kg, (+)ketamine (PK), 1 mg/kg, and (−)ketamine (MK), 3 mg/kg, were administered intravenously in a randomized, double-blind fashion to 60 healthy patients undergoing elective outpatient operations. Intraoperative effects, adequacy of anesthesia, and need for adjunctive agents were assessed by the same two anesthesiologists. Psychologic assessment was achieved utilizing a trait anxiety scale, a profile of mood states questionnaire, an open-ended sentence-completion form, and a postoperative check list, as well as observations made by a psychologist in the recovery room. Samples of plasma and urine were obtained for gas chromatographic analysis of ketamine and its major metabolites. The durations of anesthesia (35 ± 4 min) were the same in all three groups; however, the amounts of drug needed ranged from 2.4 mg/kg in the PK group to 8.5 mg/kg in the MK group. At the termination of anesthesia, mean plasma levels of the parent compounds were 0.9 (RK), 0.5 (PK), and 1.7 pg/ml (MK), consistent with a PK:MK potency ratio of 3.4:1. The slopes of the plasma decay curves were not significantly different among the three groups. PK was judged to produce more effective anesthesia than RK or MK (95 vs. 75 vs. 68 per cent). Verbal responses in the postanesthetic period suggested significantly more psychic emergence reactions after MK than after RK or PK (37 vs. 15 vs. 5 per cent). Furthermore, MK produced more agitated behavior than did RK or PK (26 vs. 10 vs. 0 per cent). Postoperative pain occurred more commonly in the RK (10 per cent) and MK (16 per cent) groups than in the PK group (0 per cent). The incidences of dreaming (84 per cent) were the same in all three groups. Relative to preoperatively, fear was decreased to a greater extent postoperatively in the PK group than in the RK and MK groups (43 vs. 13 vs. 30 per cent). Finally, patients found PK more acceptable than either RK or MK (85 vs. 65 vs. 63 per cent). The study disclosed differences in anesthetic potencies, intraoperative effects, analgesia, physical side effects, incidences and types of postanesthetic emergence phenomena, and anesthetic preferences among the optical isomers of ketamine. Parallelism of the plasma decay curves and similarities in the patterns of appearance and excretion of the ketamine metabolites for the three groups suggest that the differences were due to pharmacodynamic factors.

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