title: Ketamine antagonises alfentanil-induced hypoventilation in healthy male volunteers.
abstract: BACKGROUND
  The effects of ketamine on respiration, alone, or in combination with opioids, have not been completely clarified. Both stimulant and depressant effects have been reported, as well as attenuation of opioid-induced hypoventilation at the expense of increased oxygen consumption. These conflicting results might partly be due to dose-dependent mechanisms. We have, therefore, determined the ventilatory effects of ketamine, in combination with alfentanil, using infusions to different pseudo steady-state concentrations.
  
  
  METHODS
  On two separate days, eight healthy male volunteers were given alfentanil as a continuous computer-controlled infusion, aiming at a plasma concentration of 50 ng x mL(-1). After reaching apparent steady-state for alfentanil, racemic ketamine or placebo was administered in a protocol randomised for the two days. On the ketamine days a computer-controlled infusion, aiming for escalating ketamine plasma concentrations of 50, 100 and 200 ng x mL(-1), was added to the alfentanil infusion. On the placebo days saline was added. Using a face-mask with an occlusion valve, respiratory parameters were measured during air-breathing and after 6 repetitive 30-s CO2 challenges.
  
  
  RESULTS
  The alfentanil infusion induced hypoventilation by decreasing respiratory rate, while tidal volume and respiratory drive were unaffected. This hypoventilation was antagonised by ketamine in a concentration-dependent manner mainly through an increase in respiratory rate. The CO2 response was not affected by alfentanil or ketamine.
  
  
  CONCLUSIONS
  In the dose range of interest for postoperative, intensive-care and pain-clinic settings, ketamine antagonises the resting hypoventilation induced by alfentanil.
authors.affiliation: Division of Anesthesiology, Huddinge University Hospital, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Persson
authors.forename: H
authors.initials: H
authors.lastname: Scheinin
authors.forename: G
authors.initials: G
authors.lastname: Hellström
authors.forename: S
authors.initials: S
authors.lastname: Björkman
authors.forename: E
authors.initials: E
authors.lastname: Götharson
authors.forename: L L
authors.initials: LL
authors.lastname: Gustafsson
mesh_terms: D000328:Adult; D015760:Alfentanil / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000097:blood; D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000097:blood; D002245:Carbon Dioxide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007040:Hypoventilation / Q000139:chemically induced / Q000517:prevention & control*; D007260:Infusion Pumps; D007649:Ketamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D016018:Least-Squares Analysis; D008297:Male; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010919:Placebos; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D009292:Narcotic Antagonists; D010919:Placebos; D002245:Carbon Dioxide; D015760:Alfentanil; D007649:Ketamine