title: Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations.
abstract: BACKGROUND
  Chronic opioid use has been associated with the development of sleep-disordered breathing (SDB) such as central sleep apnea (CSA). Patients receiving chronic opioids may suffer from unrecognized sleep apnea that contributes to opioid-overdose death. Currently, information regarding the perioperative management of patients with chronic opioid-associated CSA is limited. The objectives of this review are to define the clinical manifestations of SDB associated with chronic opioid therapy, especially CSA, and to highlight their prevalence, mechanisms, risk factors, and perioperative management.
  
  
  METHODS
  We searched Medline (1983-2014), Medline In-Process and other nonindexed citations (July 2014), EMBASE (1983-2014), the Cochrane Database of Systematic Reviews (January 2005-2014), the Cochrane Central Registry of Controlled Trials (July 2014), and PubMed basic search for new materials (1983-2014). Anesthesia and Sleep Medicine meeting abstracts were also searched for relevant articles. We included all prospective, retrospective studies and case reports in which CSA and chronic opioid use was confirmed by polysomnography. CSA was defined as the absence of airflow for ≥ 10 seconds with the absence of breathing efforts. A Central Apnea Index ≥ 5 events/h was considered significant.
  
  
  RESULTS
  The search strategy yielded 8 studies which included 560 patients. The overall prevalence of CSA in patients taking chronic opioids was high (24%). The morphine equivalent daily dose (MEDD) was strongly associated with the severity of the SDB, predominantly CSA, with an MEDD of >200 mg being a threshold of particular concern. Concurrent use of benzodiazepines or hypnotics was associated with the severity of CSA in one study. Body mass index was inversely related to the severity of SDB. There were various recommendations regarding the best type of positive airway pressure therapy for the treatment of opioid-associated CSA. Continuous positive airway pressure may be ineffective in eliminating, or may even increase, CSA. Adaptive servoventilation and bilevel positive airway pressure ventilation were effective according to some reports.
  
  
  CONCLUSIONS
  The overall prevalence of CSA in patients taking chronic opioids was 24%. The most important risk factors for severity of CSA were an MEDD >200 mg, and low or normal body mass index. Continuous positive airway pressure is often ineffective for treating CSA. Limited data are available on the perioperative management of patients with CSA associated with chronic opioid use. Further prospective studies on the perioperative risks and management of these patients are needed.
authors.affiliation: From the *Department of Anesthesiology, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; and †University of Utah Health Sciences Center, Intermountain Sleep Disorders Center, Intermountain Healthcare, LDS Hospital, Salt Lake City, Utah.
authors.forename: Denis
authors.initials: D
authors.lastname: Correa
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Farney
authors.forename: Frances
authors.initials: F
authors.lastname: Chung
authors.forename: Arun
authors.initials: A
authors.lastname: Prasad
authors.forename: David
authors.initials: D
authors.lastname: Lam
authors.forename: Jean
authors.initials: J
authors.lastname: Wong
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D019338:Polypharmacy; D011175:Positive-Pressure Respiration / Q000379:methods; D015995:Prevalence; D012307:Risk Factors; D012720:Severity of Illness Index; D020182:Sleep Apnea, Central / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines