title: Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing.
abstract: BACKGROUND
  Chronic opioid therapy for pain management has increased dramatically without adequate study of potential deleterious effects on breathing during sleep.
  
  
  METHODS
  A retrospective cohort study comparing 60 patients taking chronic opioids matched for age, sex, and body mass index with 60 patients not taking opioids was conducted to determine the effect of morphine dose equivalent on breathing patterns during sleep.
  
  
  RESULTS
  The apnea-hypopnea index was greater in the opioid group (43.5/h vs 30.2/h, p < .05) due to increased central apneas (12.8/h vs 2.1/h; p < .001). Arterial oxygen saturation (SpO2) in the opioid group was significantly lower during both wakefulness (difference 2.1%, p < .001) and non-rapid eye movement (NREM) sleep (difference 2.2%, p < .001) but not during rapid eye movement (REM) sleep (difference 1.2%) than in the nonopioid group. Within the opioid group, and after controlling for body mass index, age, and sex, there was a dose-response relationship between morphine dose equivalent and apnea-hypopnea (p < .001), obstructive apnea (p < .001), hypopnea (p < .001), and central apnea indexes (p < .001). Body mass index was inversely related to apnea-hypopnea index severity in the opioid group. Ataxic or irregular breathing during NREM sleep was also more prevalent in patients who chronically used opioids (70% vs 5.0%, p < .001) and more frequent (92%) at a morphine dose equivalent of 200 mg or higher (odds ratio = 15.4, p = .017).
  
  
  CONCLUSIONS
  There is a dose-dependent relationship between chronic opioid use and the development of a peculiar pattern of respiration consisting of central sleep apneas and ataxic breathing. Although potentially significant, the clinical relevance of these observations remains to be established.
authors.affiliation: Intermountain Sleep Disorder Center, Pulmonary Division, LDS Hospital, Salt Lake City, UT 84143, USA. james.walker@intermountainmail.org
authors.forename: James M
authors.initials: JM
authors.lastname: Walker
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Farney
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rhondeau
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Boyle
authors.forename: Karen
authors.initials: K
authors.lastname: Valentine
authors.forename: Tom V
authors.initials: TV
authors.lastname: Cloward
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Shilling
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D015992:Body Mass Index; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy*; D017286:Polysomnography; D012119:Respiration; D012189:Retrospective Studies; D012720:Severity of Illness Index; D020182:Sleep Apnea, Central / Q000139:chemically induced* / Q000175:diagnosis*; D020181:Sleep Apnea, Obstructive / Q000139:chemically induced / Q000175:diagnosis