Circadian brain temperature fluctuation in patients with traumatic brain injury

Introduction: Circadian disruption and elevated brain temperature (TBr) are key factors in neural compromise, but how human TBr varies around the clock is unknown. TBr is measured via intracranial probe in patients with traumatic brain injury (TBI). Taking advantage of pre-existing, high-temporal-resolution data (https://www.center-tbi.eu/), we explored time-dependent variations in TBr. Methods: A retrospective analysis was performed using data collected from TBI patients at a single ICU. Intracranial probes were fitted for routine monitoring at standard cortical depth in anaesthetized, ventilated patients. Inclusion criteria were minimum 48 hours of continuous TBr data with matched core body temperature (TBo) data. Patients that underwent targeted temperature management protocols were excluded. Time-series data were analysed via non-linear regression in GraphPad Prism 7 and validated in BioDare2 (biodare.ed.ac.uk). Results: For n=51 patients, temperature ranges (mean±SEM) were 36.9±0.15 to 40.4±0.14°C for TBr and 36.3±0.12 to 38.7±0.11°C for TBo. Maximum TBr was significantly greater than maximum TBo (p< 0.0001), and minimum TBr was significantly greater that minimum TBo (p=0.0155). Daily variations in TBr and TBo were observed in several patients, although TBr was sometimes phase-shifted with respect to TBo. Linear regression of temperature by patient age produced a positive slope for minimum TBr that was significantly different from zero (p=0.0187). Conclusion: Preliminary analysis indicates that (1) TBr is consistently higher than TBo, (2) TBr varies with time of day in some patients, and (3) minimum TBr increases with age. TBo is typically used for clinical decision-making. If confirmed in a larger cohort, our findings would suggest that TBo is a poor substitute for TBr — the more relevant parameter in patients with brain injury. Time-of-day effects on TBr could influence interpretation of trends in individual patients, and might partly explain conflicting results of therapeutic hypothermia trials. Future work will extend this analysis to patient outcome. Financial support: N.M.R. was funded by Wellcome (096409/Z/11/Z). Funding sources did not have any involvement in the study design; the collection, analysis and interpretation of data; writing of or the decision to submit the abstract.