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.
Background: Pain assessment is a challenge in critically ill patients, in particular those who are unable to express movements in reaction to noxious stimuli. The purpose of the study was to compare the pupillary response and skin conductance to pain stimulation in critically ill unconscious patients. Methods: This observational study included adult patients admitted to the intensive care unit (ICU) with acute brain injury (Glasgow Coma Scale < 9 with a motor response < 5) and/or requirements for deep level of sedation. Automated pupillometry (Algiscan, ID-MED, Marseille, France) was used to determine pupillary reflex dilation during tetanic stimulation. The maximum intensity of the stimulation value allowed the determination of a pupillary pain index score ranging from 1 (no nociception) to 9 (high nociception): a pupillary pain index (PPI) score of ≤4 was used to reflect adequate pain control. For skin conductance (SC), the number of SC peaks per second (NSCF) was collected concomitantly to tetanic stimulation. An NSCF of ≤0.07 peak/second was used to reflect adequate pain control. Results: Of the 51 included patients, there were 32 with brain injury and 19 receiving deep sedation. Mean PPI score was 5 (Interquartile Range= 2–7); a total of 28 (55%) patients showed inadequate control of the nociceptive stimulation according to the PPI assessment. Only 15 (29%) patients showed a detectable skin conductance, with NSCF values from 0.07 to 0.47/s. No correlation was found between skin conductance algesimeter (SCA)-derived variables and PPI score or pupillary dilation to pain. Conclusions: Detection of inadequate pain control might vary according to the method used to assess nociception in ICU patients. A poor agreement between quantitative pupillometry and skin conductance was observed.
