Risk factors for severe respiratory depression from prescription opioid overdose

Addiction. 2018 Jan;113(1):59-66. doi: 10.1111/add.13925. Epub 2017 Sep 6.


Background and aims: Prescription opioid overdose is a leading cause of injury-related morbidity and mortality in the United States. We aimed to identify characteristics associated with clinical severity in emergency department patients with prescription opioid overdose.

Design: This was a secondary data analysis of adult prescription opioid overdoses from a large prospective cohort of acute overdoses. We examined elements of a typical emergency department evaluation using a multivariable model to determine which characteristics were associated with clinical severity, specifically severe respiratory depression (SRD).

Setting: This study was conducted at two urban academic emergency departments in New York City, USA.

Participants: Adult patients who presented with acute prescription opioid overdose between 2009 and 2013 were included in the current study. We analyzed 307 patients (mean age = 44.7, 42% female, 2.0% mortality).

Measurements: Patient demographics, reported substances ingested, suspected intent for ingesting the substance, vital signs, laboratory data, treatments including antidotes and intubation and outcome of death were recorded by trained research assistants. Intent was categorized into four mutually exclusive categories: suicide, misuse, therapeutic error and undetermined. The primary outcome was SRD, defined as administration of either (a) naloxone or (b) endotracheal intubation (ETI).

Findings: A total of 109 patients suffered SRD with 90 patients receiving naloxone alone, nine ETI alone and 10 both naloxone and ETI. The most common opioids were oxycodone (n = 124) and methadone (n = 116). Mean age was higher in patients with SRD (51.1 versus 41.1, P < 0.001). Opioid misuse was associated with SRD in the multivariable analysis [odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.21-3.55]. The unadjusted relative risk of SRD was high for fentanyl (83.3% SRD) and lowest for codeine (3.6% SRD).

Conclusion: In emergency department patients in the United States with prescription opioid overdose, worse clinical severity was associated with opioid misuse, increased with age and was widely variable, depending on the specific opioid medication involved.

Keywords: Drug abuse; drug overdose; emergency medicine; hypoventilation; naloxone; opioid-related disorders.

MeSH terms

  • Adult
  • Age Factors
  • Analgesics, Opioid / poisoning*
  • Cohort Studies
  • Drug Overdose / complications*
  • Drug Overdose / epidemiology
  • Drug Overdose / therapy
  • Emergency Service, Hospital
  • Female
  • Fentanyl / poisoning
  • Humans
  • Intubation, Intratracheal
  • Male
  • Methadone / poisoning
  • Middle Aged
  • Multivariate Analysis
  • Naloxone / therapeutic use
  • Narcotic Antagonists / therapeutic use
  • Odds Ratio
  • Oxycodone / poisoning
  • Prescription Drug Misuse / statistics & numerical data
  • Prospective Studies
  • Respiration, Artificial
  • Respiratory Insufficiency / chemically induced*
  • Respiratory Insufficiency / epidemiology
  • Respiratory Insufficiency / etiology
  • Respiratory Insufficiency / therapy
  • Risk Factors
  • Severity of Illness Index
  • United States / epidemiology


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Naloxone
  • Oxycodone
  • Methadone
  • Fentanyl