title: Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans.
abstract: BACKGROUND
  Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent sympathetic 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 hypotensive challenges.
  
  
  METHODS
  Muscle sympathetic activity was recorded by microneurography in the peroneal nerve of six healthy subjects before and during anesthesia with racemic ketamine (2 mg/kg intravenously plus 30 microg x kg(-1) x min(-1)). Catecholamine plasma concentrations, heart rate, and blood pressure were also determined. Muscle sympathetic neural responses to a hypotensive challenge were assessed by injection of sodium nitroprusside (2-10 microg/kg) before and during ketamine anesthesia. In the final step, increased arterial pressure observed during ketamine anesthesia was adjusted to preanesthetic baseline by sodium nitroprusside infusion (1-6 microg x kg(-1) x 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 increased mean arterial pressure (85 +/- 8 mmHg to 121 +/- 20 mmHg) was normalized to the awake baseline by sodium nitroprusside, MSA recovered (25 +/- 18 bursts/min; 23 +/- 14 bursts/100 heart beats). During ketamine anesthesia, both epinephrine (15 +/- 10 pg/ml to 256 +/- 193 pg/ml) and norepinephrine (250 +/- 105 pg/ml to 570 +/- 270 pg/ml) plasma concentrations significantly increased, as did heart rate (67 +/- 13 beats/min to 113 +/- 15 beats/min). Hypotensive challenges similarly increased MSA both in the awake state and during ketamine anesthesia.
  
  
  CONCLUSIONS
  During increased arterial blood pressure associated with ketamine, sympathetic discharge to muscle blood vessels decreases at the same time that plasma concentrations of norepinephrine increase. When this increase in arterial blood pressure is reversed, MSA during ketamine is not changed from preketamine baseline recordings. Finally, hypotensive challenges still evoke an unchanged sympathetic reflex response. Thus, our results do not support the assumption that ketamine anesthesia increases sympathetic nerve activity in a generalized fashion.
authors.affiliation: Abteilung für Anästhesiologie und Intensivmedizin, Universität GH Essen, Germany. peter.kienbaum@uni-essen.de
authors.forename: P
authors.initials: P
authors.lastname: Kienbaum
authors.forename: T
authors.initials: T
authors.lastname: Heuter
authors.forename: M C
authors.initials: MC
authors.lastname: Michel
authors.forename: J
authors.initials: J
authors.lastname: Peters
mesh_terms: D000328:Adult; D000771:Anesthesia, Intravenous; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000009:adverse effects; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000187:drug effects*; D009476:Neurons, Efferent / Q000187:drug effects*; D009599:Nitroprusside / Q000009:adverse effects; D009638:Norepinephrine / Q000097:blood; D010543:Peroneal Nerve
chemical_list: D000778:Anesthetics, Dissociative; D000959:Antihypertensive Agents; D009599:Nitroprusside; D007649:Ketamine; D009638:Norepinephrine; D004837:Epinephrine