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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
  1. Isma Qureshi1,
  2. Khadiga Abdulrashid2,3,
  3. Stephen H Thomas1,4,
  4. Manar E Abdel-Rahman2,
  5. Sameer A Pathan1,4,5,
  6. Tim Harris1,4
  1. 1 Emergency Medicine, Hamad General Hospital, Doha, Qatar
  2. 2 Public Health, Qatar University College of Health Sciences, Doha, Qatar
  3. 3 Primary Health Care Corporation, Doha, Qatar
  4. 4 Queen Mary University of London Barts and The London School of Medicine and Dentistry, London, UK
  5. 5 School of Public health and Preventive medicine, Monash University, Melbourne, Victoria, Australia
  1. Correspondence to Khadiga Abdulrashid, Public health, Qatar University, Doha 122104, Qatar; ka1305102{at}


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.

PROSPERO registration number CRD42021240099.

  • emergency department
  • analgesia
  • effectiveness
  • efficiency
  • emergency care systems

Data availability statement

Data are available upon reasonable request. Data available upon request.

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Data availability statement

Data are available upon reasonable request. Data available upon request.

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  • Handling editor Gene Yong-Kwang Ong

  • Contributors IQ: searching of databases, trial selection, data extraction, trial quality assessment and manuscript writing; KA: searching of databases, trial selection, data extraction, trial quality assessment, data analysis, manuscript writing, and generation of graphs and tables; SHT: study concept and design and manuscript preparation; MEA-R: statistical analysis and preparation and review of the manuscript; SAP: manuscript preparation, analysis and trial quality assessment; TH: study concept and design, direct supervision of database searches, trial selection, data extraction, trial quality assessment and manuscript review. TH is the article guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.