Qureshi I, Abdulrashid K, Thomas SH, et al. Comparison of intravenous paracetamol (acetaminophen) to intravenously or intramuscularly administered non-steroidal anti-inflammatory drugs (NSAIDs) or opioids for patients presenting with moderate to severe acute pain conditions to the ED: systematic review and meta-analysis. Emerg Med J. 2023 Jul;40(7):499-508. doi: 10.1136/emermed-2022-212869. Epub 2023 May 12. (Systematic review)

OBJECTIVE: Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opiates/opioids, administered parenterally via intravenous or intramuscular route, are widely used to provide analgesia for patients with moderate to severe pain. This systematic review and meta-analysis evaluated the level of analgesia provided by intravenous paracetamol (IVP) alone compared with NSAIDs (intravenous or intramuscular), or opioids (intravenous) alone in adults attending the ED with acute pain.

METHODS: Two authors independently searched PubMed (MEDLINE), Web of Science, Embase (OVID), Cochrane Library, SCOPUS and Google Scholar (3 March 2021-20 May 2022) for randomised trials without any language or date restriction. Clinical trials were evaluated using the Risk of Bias V.2 tool. The primary outcome was mean difference (MD) for pain reduction at 30 min (T30) post analgesia delivery. The secondary outcomes were MD in pain reduction at 60, 90 and 120 min; the need for rescue analgesia; and the occurrence of adverse events (AEs).

RESULTS: Twenty-seven trials (5427 patients) were included in the systematic review and 25 trials (5006 patients) in the meta-analysis. There was no significant difference in pain reduction at T30 between the IVP group and opioids (MD -0.13, 95% CI -1.49 to 1.22) or IVP and NSAIDs (MD -0.27, 95% CI -1.0 to 1.54. There was also no difference at 60 min, IVP group versus opioid group (MD -0.09, 95% CI -2.69 to 2.52) or IVP versus NSAIDs (MD 0.51, 95% CI 0.11 to 0.91). The quality of the evidence using Grading of Recommendations, Assessments, Development and Evaluations methodology was low for MD in pain scores.The need for rescue analgesia at T30 was significantly higher in the IVP group compared with the NSAID group (risk ratio (RR): 1.50, 95% CI 1.23 to 1.83), with no difference found between the IVP group and the opioid group (RR: 1.07, 95% CI 0.67 to 1.70). AEs were 50% lower in the IVP group compared with the opioid group (RR: 0.50, 95% CI 0.40 to 0.62), whereas no difference was observed in the IVP group compared with the NSAID group (RR: 1.30, 95% CI 0.78 to 2.15).

CONCLUSION: In patients presenting to the ED with a diverse range of pain conditions, IVP provides similar levels of pain relief compared with opiates/opioids or NSAIDs at T30 post administration. Patients treated with NSAIDs had lower risk of rescue analgesia, and opioids cause more AEs, suggesting NSAIDs as the first-choice analgesia and IVP as a suitable alternative.


Discipline Area Score
Emergency Medicine 6 / 7
Special Interest - Pain -- Physician 5 / 7
Comments from MORE raters

Emergency Medicine rater

Important and timely review in the context of the opioid crisis and increased scrutiny on pain management in both the ED and prehospital settings. The key issue is that most jurisdictions don't have access to IV paracetamol, although a review such as this can hopefully advance the cause on the regulatory front.

Emergency Medicine rater

In the opioid epidemic era, finding effective and available non-opioid alternatives is a priority. This meta-analysis provides proof that a 1 gram dose of intravenous acetaminophen is equianalgesic to opioids across a range of conditions that cause acute pain, although this formulation of acetaminophen remains unavailable on many hospital formularies. The low quality of the evidence based on GRADE criteria may give pause to clinicians considering a paradigm shift to using IV acetaminophen as first-line or rescue analgesia, but this meta-analysis provides food for thought.

Emergency Medicine rater

This article makes a strong case for using NSAIDs as opposed to opioids for acute pain in the ED.

Special Interest - Pain -- Physician rater

Useful to have an SR identifying the many trials. The variability in protocols for comparators make direct clinical application problematic.

Special Interest - Pain -- Physician rater

Good methodology but pain conditions are very heterogeneous (dysmenorrhea, headache, fractures, etc), which limits the interpretation of the results.
Comments from EvidenceAlerts subscribers

Dr. Craig Benton (7/2/2023 5:50 PM)

Interpretation: Opioids should not be recommended for acute non-specific low-back pain or neck pain given that we found no significant difference in pain severity compared with placebo. This finding calls for a change in the frequent use of opioids for these conditions.