Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis
Drewry AM, Ablordeppey EA, Murray ET, et al. Crit Care Med. 2017; 45: 806-13.
Study Question: Do antipyretics reduce mortality in critically ill septic patients?
Study Description: This meta-analysis included randomized controlled trials and observational studies that assessed antipyretic use in adult patients. Studies that reported mortality data on septic patients were included. The primary outcome was 28-day mortality. Secondary outcomes included early mortality, which was defined as mortality within the ICU or mortality on or prior to day 14 after enrollment.
Results: Four randomized studies (n = 1507) compared antipyretic therapy to control. The RR of 28-day mortality was 0.93 (95% CI 0.77-1.13; no p-value provided) and the hospital mortality pooled RR was 0.93 (95% CI 0.79 -1.09; no p-value provided). A significant decrease in early mortality was noted in the secondary analysis of patients receiving antipyretic therapy (RR 0.68; 95% CI 0.49–0.92; no p-value provided). Six observational studies (n = 2058) showed a pooled OR for 28-day/hospital mortality of 0.90 (95% CI 0.54-1.51; no p-value provided).
Conclusion(s): Use of antipyretics in critically ill septic patients does not reduce 28-day or hospital mortality.
Perspective: Treatment of fever is commonplace in the critical care setting, despite the lack of compelling evidence for improved clinical outcomes. This meta-analysis showed that although effective at reducing hyperthermia, the administration of antipyretics conferred no 28-day mortality benefit in patients with sepsis. As such, the finding of a reduction in early mortality means little in terms of overall patient benefit. This analysis calls into question the theoretical benefit of treating fever to reduce metabolic demands, as no significant difference in heart rate or minute ventilation was found. A clinical trial would need to enroll 29,000 patients to have the power to detect a difference in the primary outcome, an enrollment criteria that is likely not feasible. Therefore, this robust meta-analysis provides practical information to the bedside clinician regarding lack of proven clinical benefit with antipyretic therapy for critically ill septic patients.