Effectiveness of Opioid Analgesic Medicines Prescribed in or at Discharge From Emergency Departments for Musculoskeletal Pain : A Systematic Review and Meta-analysis

Ann Intern Med. 2022 Nov;175(11):1572-1581. doi: 10.7326/M22-2162. Epub 2022 Oct 18.


Background: The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain.

Purpose: To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting.

Data sources: Electronic databases and registries from inception to 7 February 2022.

Study selection: Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED.

Data extraction: Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.

Data synthesis: Forty-two articles were included (n = 6128). In the ED, opioids were statistically but not clinically more effective in reducing pain in the short term (about 2 hours) than placebo and paracetamol (acetaminophen) but were not clinically or statistically more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) or local or systemic anesthetics. Opioids may carry higher risk for harms than placebo, paracetamol, or NSAIDs, although evidence is very uncertain. There was no evidence of difference in harms associated with local or systemic anesthetics.

Limitations: Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes.

Conclusion: The risk-benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit-risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain.

Primary funding source: None. (PROSPERO: CRD42021275293).

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Acetaminophen / therapeutic use
  • Adult
  • Analgesics / adverse effects
  • Analgesics, Opioid* / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Emergency Service, Hospital
  • Humans
  • Musculoskeletal Pain* / drug therapy
  • Patient Discharge


  • Analgesics, Opioid
  • Acetaminophen
  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal