The effect of antipyretic medications on mortality in critically ill patients with infection: a systematic review and meta-analysis.

BACKGROUND Antipyretic medications are widely used in critically ill patients with infection despite evidence supporting a protective, adaptive role of fever. OBJECTIVE To assess the mortality risk of antipyretic medications among critically ill patients with infection. METHODS A systematic search of MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and PubMed was undertaken to identify randomised controlled trials (RCTs) of antipyretic use among critically ill patients with suspected or confirmed infection that reported mortality. A quantitative meta-analysis of the risk of death was carried out with calculation of the pooled risk of death and standard evaluation of heterogeneity. RESULTS Six RCTs investigating the use of paracetamol (1) and non-steroidal anti-inflammatory medications (5) met the inclusion criteria for meta-analysis. The trials were heterogeneous in terms of study populations and interventions, were not primarily designed to evaluate antipyretic effect on mortality risk, and significant confounding was present from the use of other concomitant antipyretic strategies. The pooled estimates of odds ratios for mortality with antipyretic treatment were 0.96 (95% CI, 0.68-1.34) and 1.08 (95% CI, 0.60-1.96) for fixed effects and random effects, respectively, and the I-squared value was 34.9 (95% CI, 0.0-73.9). CONCLUSION The studies included in this review were insufficient to allow a robust estimate of the effect of pharmacological antipyresis on mortality in critically ill patients with suspected infection. Further RCTs are required to resolve this important area of clinical uncertainty.