title: Recurrent hypoxia in rats during development increases subsequent respiratory sensitivity to fentanyl.
abstract: BACKGROUND
  In children with a history of significant obstructive sleep apnea who undergo adenotonsillectomy, postsurgical administration of opiates has been alleged to be associated with an increased risk for respiratory complications, including respiratory depression. The authors hypothesize that this association is due to an effect of recurrent hypoxemia that accompanies more severe obstructive sleep apnea on altered responsiveness to subsequent exogenous opiates.
  
  
  METHODS
  The current study was designed to test the effect of recurrent hypoxia in the developing rat on respiratory responses to subsequent administration of the mu-opioid agonist fentanyl. Rats were exposed to 12% oxygen balance nitrogen for 7 h daily for 17 days, from postnatal day 17 to 33, a period equivalent to human childhood. After 17 additional days in room air, rats were given a fentanyl dose and tested for their respiratory response to fentanyl using a whole body plethysmograph. Rats undergoing similar protocols without recurrent hypoxia served as controls.
  
  
  RESULTS
  As compared with controls, rats preexposed to recurrent hypoxia displayed a more profound depression with fentanyl in minute ventilation, respiratory frequency, tidal volume, and tidal volume divided by inspiratory time that represents respiratory drive. These results indicated an increased respiratory sensitivity to fentanyl after recurrent hypoxia.
  
  
  CONCLUSIONS
  Previous recurrent hypoxia increases respiratory sensitivity to subsequent opiate agonists. If these findings are applicable to humans, opiate dosing in children must be adjusted depending on history of recurrent hypoxemia to avoid respiratory depression.
authors.affiliation: Departments of Pediatrics and Physiology, McGill University, The Montreal Children's Hospital, 2300 Tupper Street, Montreal, Quebec H3H 1P3, Canada. immanuela.moss@mcgill.ca
authors.forename: Immanuela Ravé
authors.initials: IR
authors.lastname: Moss
authors.forename: Karen A
authors.initials: KA
authors.lastname: Brown
authors.forename: André
authors.initials: A
authors.lastname: Laferrière
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D005283:Fentanyl / Q000494:pharmacology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists; D012008:Recurrence; D015656:Respiratory Mechanics / Q000187:drug effects*; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D005283:Fentanyl