Antipyretic Therapy in Critically Ill Patients with Established Sepsis: A Trial Sequential Analysis

Background and objective: antipyretic therapy for patients with sepsis has long been debated. The present study aimed to explore the beneficial effect of antipyretic therapy for ICU patients with sepsis. Design: systematic review and trial sequential analysis of randomized controlled trials. Database: Pubmed, Scopus, EBSCO and EMBASE were searched from inception to August 5, 2014. Methods: Mortality was dichotomized as binary outcome variable and odds ratio (OR) was chosen to be the summary statistic. Pooled OR was calculated by using DerSimonian and Laird method. Statistical heterogeneity was assessed by using the statistic I2. Trial sequential analysis was performed to account for the small number of trials and patients. Main results: A total of 6 randomized controlled trials including 819 patients were included into final analysis. Overall, there was no beneficial effect of antipyretic therapy on mortality risk in patients with established sepsis (OR: 1.02, 95% CI: 0.50–2.05). The required information size (IS) was 2582 and our analysis has not yet reached half of the IS. The Z-curve did not cross the O’Brien-Fleming α-spending boundary or reach the futility, indicating that the non-significant result was probably due to lack of statistical power. Conclusion: our study fails to identify any beneficial effect of antipyretic therapy on ICU patients with established diagnosis of sepsis. Due to limited number of total participants, more studies are needed to make a conclusive and reliable analysis.