The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis

J R Soc Med. 2010 Oct;103(10):403-11. doi: 10.1258/jrsm.2010.090441.


Objective: To determine whether antipyretic treatment for influenza infection influences the risk of mortality in animal models and humans.

Design: A systematic search of Medline, Embase and the Cochrane Register of Controlled Trials was undertaken to identify randomized placebo-controlled trials of antipyretic use in influenza infection in animal models or humans that reported mortality. A quantitative meta-analysis of the risk of death using Peto's one step odds ratio with calculation of the pooled risk of death and standard evaluation of heterogeneity was undertaken.

Setting: Not applicable.

Participants: Not applicable.

Main outcome measures: Risk of mortality associated with antipyretic use in influenza infection.

Results: Eight studies from three publications met the inclusion criteria. No human studies were identified. The risk of mortality was increased by antipyretic use in influenza-infected animals with a fixed effects pooled odds ratio of 1.34 (95% CI 1.04-1.73). An increased risk was observed with aspirin, paracetamol and diclofenac.

Conclusion: In animal models, treatment with antipyretics for influenza infection increases the risk of mortality. There are no randomized placebo-controlled trials of antipyretic use in influenza infection in humans that reported data on mortality and a paucity of clinical data by which to assess their efficacy. We suggest that randomized placebo-controlled trials of antipyretic use in human influenza infection are urgently required, and that these are sufficiently powered to investigate a potential effect on mortality.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Acetaminophen / adverse effects*
  • Analgesics, Non-Narcotic / adverse effects*
  • Animals
  • Aspirin / adverse effects*
  • Diclofenac / adverse effects*
  • Disease Models, Animal
  • Humans
  • Influenza, Human / drug therapy
  • Influenza, Human / mortality*
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / mortality*


  • Analgesics, Non-Narcotic
  • Diclofenac
  • Acetaminophen
  • Aspirin