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Epinephrine (adrenaline) compared to selective beta-2-agonist in adults or children with acute asthma: a systematic review and meta-analysis
  1. Christina Baggott1,
  2. Jo Katherine Hardy1,
  3. Jenny Sparks1,
  4. Doñah Sabbagh1,
  5. Richard Beasley1,2,
  6. Mark Weatherall3,
  7. James Fingleton1,2,3
  1. 1 Medical Research Institute of New Zealand, Wellington, New Zealand
  2. 2 Capital and Coast District Health Board, Wellington, New Zealand
  3. 3 Medicine, University of Otago Wellington, Wellington, New Zealand
  1. Correspondence to Dr James Fingleton, Respiratory Medicine, Capital and Coast District Health Board, Wellington 6023, New Zealand; james.fingleton{at}


Background International asthma guidelines recommend against epinephrine (adrenaline) administration in acute asthma unless associated with anaphylaxis or angio-oedema. However, administration of intramuscular epinephrine in addition to nebulised selective β2-agonist is recommended for acute severe or life-threatening asthma in many prehospital guidelines. We conducted a systematic review to determine the efficacy of epinephrine in comparison to selective β2-agonist in acute asthma.

Methods We included peer-reviewed publications of randomised controlled trials (RCTs) that enrolled children or adults in any healthcare setting and compared epinephrine by any route to selective β2-agonist by any route for an acute asthma exacerbation. The primary outcome was treatment failure, including hospitalisation, need for intubation or death.

Results Thirty-eight of 1140 studies were included. Overall quality of evidence was low. Seventeen studies contributed data on 1299 participants to the meta-analysis. There was significant statistical heterogeneity, I2=56%. The pooled Peto’s OR for treatment failure with epinephrine versus selective β2-agonist was 0.99 (0.75 to 1.32), p=0.95. There was strong evidence that recruitment age group was associated with different estimates of the odds of treatment failure; with studies recruiting adults-only having lower odds of treatment failure with epinephrine. It was not possible to determine whether epinephrine in addition to selective β2-agonist improved outcomes.

Conclusion The low-quality evidence available suggests that epinephrine and selective β2-agonists have similar efficacy in acute asthma. There is a need for high-quality double-blind RCTs to determine whether addition of intramuscular epinephrine to inhaled or nebulised selective β2-agonist improves outcome.

PROSPERO registration number CRD42017079472.

  • asthma
  • asthma guidelines
  • critical care
  • emergency medicine
  • paediatric asthma

Data availability statement

Data are available upon reasonable request. Data extracted from included studies as part of full-text review are available upon reasonable request to the corresponding author.

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Data availability statement

Data are available upon reasonable request. Data extracted from included studies as part of full-text review are available upon reasonable request to the corresponding author.

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  • Twitter @jamesfingleton

  • Contributors JF, CB, DS, JKH and RB proposed the systematic review. JF, CB, DS, JKH and JS screened the studies and extracted the data. MW conducted the meta-analysis. JF wrote the first draft of the manuscript. All authors had access to the data and read and approved the final version of the manuscript. JF is guarantor of the data.

  • Funding The MRINZ is supported by Independent Research Organisation funding from the Health Research Council of New Zealand. Grant/award number not applicable.

  • 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.