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Meta-Analysis
. 2010 Oct;103(10):403-11.
doi: 10.1258/jrsm.2010.090441.

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

Sally Eyers  1 , Mark Weatherall, Philippa Shirtcliffe, Kyle Perrin, Richard Beasley
Affiliations
Meta-Analysis

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

Sally Eyers et al. J R Soc Med. 2010 Oct.

Abstract

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.

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Figures

Figure 1
Figure 1
QUOROM statement showing the flow of study selection
Figure 2
Figure 2
The forest plot shows the point estimates for each trial (in the centre of the shaded box) and its confidence interval (the ends of the lines). The size of the box is inversely proportional to the individual study variance. Studies with high variance have smaller boxes. The studies with small variance (large boxes) contribute more to the pooled study estimate, represented by the diamond. The odds ratios for risk of mortality are presented on the logarithm scale and the trials are ranked in order of the size of the odds ratio. The pooled estimate presented is the fixed effect estimate
See this image and copyright information in PMC

References

    1. Centers for Disease Control and Prevention Interim Guidance for Novel H1N1 Flu (Swine Flu). Atlanta, GA: CDC; 2009. See www.cdc.gov
    1. Department of Health, British Thoracic Society, British Infection Society, Health Protection Agency Clinical guidelines for patients with an influenza like illness during an influenza pandemic. London: Department of Health; 2006
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    1. Russell FM, Shann F, Curtis N, Mulholland K. Evidence on the use of paracetamol in febrile children. Bull World Health Organ 2003;81:367–72 - PMC - PubMed
    1. Shann F. Antipyretics in severe sepsis. Lancet 1995;345:338. - PubMed

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