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

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.