S(+)-ketamine increases muscle sympathetic activity and maintains the neural response to hypotensive challenges in humans

Background: S(+)-Ketamine is reported to exert twofold greater analgesic an d hypnotic effects but a shorter recovery time in comparison with racemic k etamine, indicating possible differential effects of stereoisomers. However , cardiovascular regulation during S(+)-ketamine anesthesia has not been st udied. Muscle sympathetic activity (MSA) may be an indicator of the underly ing alterations of sympathetic outflow. Whether S(+)-ketamine decreases MSA in a similar manner as the racemate is not known. Thus, the authors tested the hypothesis that S(+)-ketamine changes MSA and the muscle sympathetic r esponse to a hypotensive challenge. Methods: Muscle sympathetic activity was recorded by microneurography in th e peroneal nerve of six healthy participants before and during anesthesia w ith S(+)-ketamine (670 mug/kg intravenously followed by 15 mug.kg(-1).min(- 1)). Catecholamine and ketamine plasma concentrations, heart rate, and arte rial blood pressure were also determined. MSA responses to a hypotensive ch allenge were assessed by injection of sodium nitroprusside (2-10 mug/kg) be fore and during S(+)-ketamine anesthesia In the final step, increased arter ial pressure observed during anesthesia with S(+)-ketamine was adjusted to preanesthetic values by sodium nitroprusside infusion (1-6 mug.kg(-1).min(- 1)). Results: Anesthesia with S(+)-ketamine (ketamine plasma concentration 713 /- 295 mug/l) significantly increased MSA burst frequency (mean +/- SD; 18 +/- 6 to 35 +/- 11 bursts/min) and burst incidence (32 +/- 10 to 48 +/- 15 bursts/100 heartbeats) and was associated with a doubling of norepinephrine plasma concentration (from 153 +/- 52 to 373 +/- 136 pg/ml) parallel to th e increase in MSA, Heart rate and arterial blood pressure also significantl y increased. When increased arterial pressure during S(+)-ketamine was decr eased to awake values with sodium nitroprusside, MSA increased further (to 53 +/- 24 bursts/min and 60 +/- 20 bursts/100 heartbeats, respectively). Th e MSA increase in response to the hypotensive challenge was fully maintaine d during anesthesia with S(+)-ketamine. Conclusions: S(+)-Ketamine increases efferent sympathetic outflow to muscle . Despite increased MSA and arterial pressure during S(+)-ketamine anesthes ia, the increase in MSA in response to arterial hypotension is maintained.