Impact of fever on the outcome non-anoxic acute brain injury patients: a systematic review and meta-analysis

Fever is a common condition in intensive care unit (ICU) patients, with an incidence between 30 and 50% in non-neurological ICU patients and up to 70–90% in neurological ICU patients. We aim to perform systematic review and meta-analysis of current literature to assess impact of fever on neurological outcomes and mortality of acute brain injury patients. We searched PubMed/Medline, Scopus and Embase databases following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and we included both retrospective and prospective observational studies, interventional studies, and randomized clinical trials that had data on body temperature and fever during ICU admission. The primary endpoints were neurological outcome and mortality at any time. Secondary outcomes included: early neurological deterioration, delayed cerebral ischemia (DCI, only for patients with subarachnoid hemorrhage), large infarct or hemorrhage size, hemorrhagic transformation (only for patients with ischemic stroke). This study was registered in PROSPERO (CRD42020155903). 180 studies from 14692 records identified after the initial search were included in the final analysis, for a total of 460,825 patients. Fever was associated with an increased probability of unfavorable neurological outcome (pooled OR 2.37 [95% CI 2.08–2.71], I2:92%), death (pooled OR 1.31 [95% CI 1.28–1.34], I2:93%), neurological deterioration (pooled OR 1.10 [95% CI 1.05–1.15]), risk of DCI (pooled OR 1.96 [95% CI 1.73–2.22]), large infarct size (pooled OR 2.94 [95% CI 2.90–2.98]) and hemorrhagic transformation (pooled OR 1.63 [95% CI 1.34–1.97]) and large hemorrhagic volume (pooled OR 2.38 [95% CI 1.94–2.93]). Fever was associated with poor neurological outcomes and mortality in patients with acute brain injury. Whether normothermia should be targeted in the management of all neuro critically ill patients warrants specific research.