Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans

Background: Cardiovascular stimulation and increased catecholamine plasma c oncentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition i n various experimental models. However, direct recordings of efferent sympa thetic nerve activity have not been performed in humans. The authors tested the hypothesis that racemic ketamine increases efferent muscle sympathetic activity (MSA) and maintains the muscle sympathetic response to hypotensiv e challenges. Methods: Muscle sympathetic activity was recorded by microneurography in th e peroneal nerve of six healthy subjects before and during anesthesia with racemic ketamine (2 mg/kg intravenously plus 30 mu g . kg(-1) . min(-1)). C atecholamine plasma concentrations, heart rate, and blood pressure were als o determined. Muscle sympathetic neural responses to a hypotensive challeng e were assessed by injection of sodium nitroprusside (2-10 mu g/kg) before and during ketamine anesthesia. in the final step, increased arterial press ure observed during ketamine anesthesia was adjusted to preanesthetic basel ine by sodium nitroprusside infusion (1-6 mu g . kg(-1) . min(-1)). Results: Ketamine significantly decreased MSA burst frequency (mean +/- SD, 18 +/- 9 bursts/min to 9 +/- 8 bursts/min) and burst incidence (26 +/- 11 bursts/100 heart beats to 9 +/- 6 bursts/100 heart beats). However, when in creased mean arterial pressure (85 +/- 8 mmHg to 121 +/- 20 mmHg) was norma lized to the awake baseline by sodium nitroprusside, MSA recovered (25 +/- 18 bursts/min; 23 +/- 14 bursts/100 heart beats). During ketamine anesthesi a, both epinephrine (15 +/- 10 pg/ml to 256 +/- 193 pg/ml) and norepinephri ne (250 +/- 105 pg/ml to 570 +/- 270 pg/ml) plasma concentrations significa ntly increased, as did heart rate (67 +/- 13 beats/min to 113 +/- 15 beats/ min), Hypotensive challenges similarly increased MSA both in the awake stat e and during ketamine anesthesia. Conclusions: During increased arterial blood pressure associated with ketam ine, sympathetic discharge to muscle blood vessels decreases at the same ti me that plasma concentrations of norepinephrine increase. When this increas e in arterial blood pressure is reversed, MSA during ketamine is not change d from preketamine baseline recordings, Finally, hypotensive challenges sti ll evoke an unchanged sympathetic reflex response. Thus, our results do not support the assumption that ketamine anesthesia increases sympathetic nerv e activity in a generalized fashion.