Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study

Abstract

Background: After traumatic brain injury (TBI), fever is frequent. Brain temperature (BT), which is directly linked to body temperature, may influence brain physiology. Increased body and/or BT may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome.

Methods: Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective multicenter longitudinal study on TBI in Europe and Israel, includes a high resolution cohort of patients with data sampled at a high frequency (from 100 to 500 Hz). In this study, simultaneous BT, ICP, and CPP recordings were investigated. A mixed-effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes in ICP and CPP during the episodes of BT changes (Δ BT ≥ 0.5 °C lasting from 15 min to 3 h) up or downward. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test).

Results: Twenty-one patients with 2,435 h of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38 °C and experienced at least one episode of ICP above 20 mm Hg. The linear mixed-effects model revealed an association between BT above 37.5 °C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n = 79) ICP increased, whereas CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n = 70). All these changes were of moderate clinical relevance (increase of ICP of 4.5 and CPP decrease of 7.5 mm Hg for BT rise, and ICP reduction of 1.7 and CPP elevation of 3.7 mm Hg during BT defervescence), even if statistically significant (p < 0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes.

Conclusions: Patients after TBI usually develop BT > 38 °C soon after the injury. BT may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5 °C and a higher ICP was identified but not confirmed for lower BT ranges. The relationship between BT, ICP, and CPP become clearer during rapid temperature changes. During episodes of temperature elevation, BT seems to have a significant impact on ICP and CPP.

Keywords: Brain temperature; Cerebral perfusion pressure; Fever; Hyperthermia; Intracranial pressure; Neuromonitoring; Traumatic brain injury.

Fig. 1

BT (a), ICP (b), and CPP (c) during the first 7 days of monitoring. These color maps show every per-minute average, employing a color scale with gray indicating missing values. BT, brain temperature, CPP, cerebral perfusion pressure, ICP, intracranial pressure

Fig. 2

Comparison between maximal daily BT with the corresponding maximal CT. The image represents 93 available comparisons of maximal daily BT (from HR data) with the corresponding daily maximal CT (recorded manually) in 20 patients. BT and CT dots are connected by the line but, in fact, represent single measurements. In the majority of cases, BT (blue dots/line) are higher than CT (red dots/line) (n = 63, 68%). Maximal difference between BT and CT ranged from − 1.5 to 2 °C. BT, brain temperature, CT, core temperature, HR, high resolution, Max, maximal

Fig. 3

Generalized linear mixed model effects on ICP of six BT ranges. Generalized linear mixed model, including ICP (mm Hg) as dependent variable (predicted values with 95% confidence interval) in six ranges of BT (°C) as independent variable. BT < 36.4 °C was taken as the reference group. The gray area indicates the values below the physiological BT range, which are likely to depend on active treatment. The asterisks indicate the following p values: X, < 1; * < 0.01; ** < 0.001; and *** < 0.0001. BT, brain temperature, ICP, intracranial pressure

Fig. 4

BT elevation/reduction episodes. BT, brain temperature, ΔBT, change in brain temperature, ICP, intracranial pressure

Fig. 5

ICP response to BT changes. ICP at the beginning and end of BT episodes. a ICP during all the BT elevation episodes. b ICP during all the BT reduction episodes. Colored points represent different patients; all measurements in the same patient are the same color. p values for the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test). BT, brain temperature, ICP, intracranial pressure