title: Pharmacovigilance: a review of opioid-induced respiratory depression in chronic pain patients.
abstract: BACKGROUND
  Opioids may induce life-threatening respiratory depression, but limited knowledge is available on factors that contribute to opioid-induced respiratory depression (OIRD). This is especially true for patients with chronic pain on prolonged opioid therapy. There are no good quality case control studies or randomized controlled trials available on this topic. Here we present and analyze all case series since 1980 on OIRD in chronic pain patients extracted from PubMed.
  
  
  OBJECTIVE
  To describe and understand clinically identified factors involved in life-threatening OIRD in patients receiving opioids for chronic pain relief.
  
  
  METHODS
  A literature search was performed for all relevant case reports on OIRD in chronic pain.
  
  
  METHODS
  We searched PubMed (www.ncbi.nlm.nih.gov) for all available case reports/series on OIRD in adolescent (12 years and older) and adult patients treated with opioids for chronic pain, from which we identified specific commonalities that contributed to OIRD (akin to closed claims analyses). The dataset was post-hoc divided into 2 distinct categories: cases published from 1980 to 1999 and those from 2000 to 2012.
  
  
  RESULTS
  Thirty-four reports describing 42 chronic pain patients experiencing OIRD were retrieved. Cases published before the year 2000 (pre-2000) predominantly involved morphine in cancer patients, whereas cases since 2000 (post-2000) predominantly involved methadone or transdermal fentanyl in non-cancer pain patients. Specific factors that contributed to OIRD were elevated opioid plasma levels due to renal impairment and sensory deafferentiation in pre-2000 cases, and elevated plasma levels due to drug interactions on the cytochrome P450 in post-2000 cases.
  
  
  CONCLUSIONS
  The case series analysis of published case reports imposes limitations in terms of the types of cases presented (only severe cases are published or cases with specific precipitating factors), the journal-related publication strategy, and changes in clinical practice.
  
  
  CONCLUSIONS
  Our case review confirms that life-threatening OIRD in chronic pain patients involves a series of complex often-interacting factors. In spite of the factors identified in this cases series, OIRD remains unpredictable and safe opioid prescribing requires careful titration of opioid dosages and continuous monitoring to prevent life-threatening OIRD.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands. a.dahan@lumc.nl
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.forename: Frank
authors.initials: F
authors.lastname: Overdyk
authors.forename: Terry
authors.initials: T
authors.lastname: Smith
authors.forename: Leon
authors.initials: L
authors.lastname: Aarts
authors.forename: Marieke
authors.initials: M
authors.lastname: Niesters
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects*; D059350:Chronic Pain / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000453:epidemiology*
chemical_list: D000701:Analgesics, Opioid