title: Ketamine activates breathing and abolishes the coupling between loss of consciousness and upper airway dilator muscle dysfunction.
abstract: BACKGROUND
  Procedural sedation is frequently performed in spontaneously breathing patients, but hypnotics and opioids decrease respiratory drive and place the upper airway at risk for collapse.
  
  
  METHODS
  In a randomized, controlled, cross-over, pharmaco-physiologic study in 12 rats, we conducted acute experiments to compare breathing and genioglossus electromyogram activity at equianesthetic concentrations of ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist that combines potent analgesic with hypnotic action effects, versus propofol. In 10 chronically instrumented rats resting in a plethysmograph, we measured these variables as well as electroencephalography during five conditions: quiet wakefulness, nonrapid-eye-movement sleep, rapid eye movement sleep, and low-dose (60 mg/kg intraperitoneally) and high-dose ketamine anesthesia (125 mg/kg intraperitoneally).
  
  
  RESULTS
  Ketamine anesthesia was associated with markedly increased genioglossus activity (1.5 to fivefold higher values of genioglossus electromyogram) compared with sleep- and propofol-induced unconsciousness. Plethysmography revealed a respiratory stimulating effect: higher values of flow rate, respiratory rate, and duty-cycle (effective inspiratory time, 1.5-to-2-fold higher values). During wakefulness and normal sleep, the δ (f = 6.51, P = 0.04) electroencephalogram power spectrum was an independent predictor of genioglossus activity, indicating an association between electroencephalographic determinants of consciousness and genioglossus activity. Following ketamine administration, electroencephalogram power spectrum and genioglossus electroencephalogram was dissociated (P = 0.9 for the relationship between δ/θ power spectrum and genioglossus electromyogram).
  
  
  CONCLUSIONS
  Ketamine is a respiratory stimulant that abolishes the coupling between loss-of-consciousness and upper airway dilator muscle dysfunction in a wide dose-range. Ketamine compared with propofol might help stabilize airway patency during sedation and anesthesia.
authors: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA. meikermann@partners.org
authors: Matthias
authors: M
authors: Eikermann
authors: Martina
authors: M
authors: Grosse-Sundrup
authors: Sebastian
authors: S
authors: Zaremba
authors: Mark E
authors: ME
authors: Henry
authors: Edward A
authors: EA
authors: Bittner
authors: Ulrike
authors: U
authors: Hoffmann
authors: Nancy L
authors: NL
authors: Chamberlin
mesh_terms: D000758:Anesthesia; D000771:Anesthesia, Intravenous; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009333:Neck / Q000502:physiology; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects*; D012890:Sleep / Q000502:physiology; D014474:Unconsciousness / Q000139:chemically induced*; D014851:Wakefulness / Q000502:physiology
chemical_list: D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D007649:Ketamine; D015742:Propofol