Analgesic efficacy of low-dose ketamine. Somatosensory-evoked responses in relation to subjective pain ratings.

Abstract

Low-dose ketamine has been shown to exert analgesic effects. Whether ketamine-induced pain relief may be quantitated by somatosensory evoked cerebral potentials has not been established. Thirty healthy volunteers were assigned randomly to one of three groups. Subjects of group 1 (n = 10, control) were given saline as placebo. In groups 2 (n = 10) and 3 (n = 10), intravenous ketamine (0.25 mg. kg-1 and 0.50 mg. kg-1, respectively) was administered. The following variables were recorded at baseline and for 50 min after drug administration: electroencephalographic (EEG) data, somatosensory-evoked late cortical responses (SEP) elicited by intracutaneous stimulation of the fingertip (2-3 fold pain threshold), heart rate, mean arterial blood pressure, and end-tidal PETCO2 via a tight-fitting mask. Electroencephalographic spectral power in selected frequency bands and frequency percentiles were calculated from the spontaneous EEG segment preceding each somatosensory stimulus. Somatosensory-evoked late cortical response parameters were calculated from the respective poststimulus EEG segments. After recording of each EEG response, subjects were asked to rate the individual pain sensation. In group 1, all variables did not change over time. Ketamine administration resulted in dose-dependent decreases in alpha-activity and increases in theta power (group 2: 190%, group 3: 440%). Electroencephalographic changes were not related to changes in pain perception. For the first 30 min after ketamine injection, a dose-dependent decrease of the long-latency N150-P250 somatosensory-evoked late cortical response component was observed (group 2: 15-20%; group 3: 25-30%). Subjective pain ratings were also different between groups, with a higher degree of pain relief in group 3 for the first 30 min. At the end of the observation period, pain relief and the N150-P250 amplitude were comparable in both ketamine groups. These data indicate that pain relief induced by low-dose ketamine is dose-dependent for the first 30 min after bolus injection. Changes in pain perception may be quantitated by somatosensory-evoked cortical responses. Also, EEG changes are not specific for changes in nociception, but the increase in theta power may reflect the hypnotic effect of low-dose ketamine.