Pharmacovigilance: A Review of Opioid-Induced Respiratory Depression in Chronic Pain Patients

Background: Opioids may induce life-threatening respiratory depression, but limitedknowledge 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 thistopic. Here we present and analyze all case series since 1980 on OIRD in chronic pain patientsextracted from PubMed.Objective: To describe and understand clinically identified factors involved in life-threateningOIRD in patients receiving opioids for chronic pain relief.Study Design: A literature search was performed for all relevant case reports on OIRD inchronic pain.Methods: We searched PubMed (www.ncbi.nlm.nih.gov) for all available case reports/serieson OIRD in adolescent (12 years and older) and adult patients treated with opioids for chronicpain, from which we identified specific commonalities that contributed to OIRD (akin to closedclaims analyses). The dataset was post-hoc divided into 2 distinct categories: cases publishedfrom 1980 to 1999 and those from 2000 to 2012.Results: Thirty-four reports describing 42 chronic pain patients experiencing OIRD wereretrieved. Cases published before the year 2000 (pre-2000) predominantly involved morphinein cancer patients, whereas cases since 2000 (post-2000) predominantly involved methadoneor transdermal fentanyl in non-cancer pain patients. Specific factors that contributed to OIRDwere elevated opioid plasma levels due to renal impairment and sensory deafferentiation inpre-2000 cases, and elevated plasma levels due to drug interactions on the cytochrome P450in post-2000 cases.Limitations: The case series analysis of published case reports imposes limitations in terms ofthe types of cases presented (only severe cases are published or cases with specific precipitatingfactors), the journal-related publication strategy, and changes in clinical practice.Conclusions: Our case review confirms that life-threatening OIRD in chronic pain patientsinvolves a series of complex often-interacting factors. In spite of the factors identified in thiscases series, OIRD remains unpredictable and safe opioid prescribing requires careful titrationof opioid dosages and continuous monitoring to prevent life-threatening OIRD.Key words: Opioids, opioid-induced respiratory depression, toxicity, pain, chronic pain, caseseries