Prehospital Epidemiology and Treatment of Severe Traumatic Brain Injury: Unraveling the black box

In Chapter 2, the study protocol is described of the BRAIN-PROTECT study, the first Dutch prospective observational study on prehospital epidemiology and treatment of patients with severe traumatic brain injury (TBI). The main objective of this research project was to identify prehospital factors, in particular treatment strategies, associated with beneficial or detrimental outcomes in patients with suspected severe TBI. The BRAIN-PROTECT study inclusion started in 2012 and prehospital inclusion continued until December 2017 (Follow-up until December 2018). In total, 2,589 patients were included (Chapter 3The incidence rate of suspected severe TBI was 3.2 (per 100,000 inhabitants per year) and 2.7 for confirmed TBI. Age ranged between 1 and 97 years and 70.8% were male. The overall 30-day mortality was 39.0% for the overall population of severe TBI and for confirmed TBI 42.4%. In Chapter 5, the results of a retrospective study on neurological deterioration are presented. 13% of 808 patients with initial mild TBI showed a discrepancy between the initial assessment of TBI severity based on the GCS, and the actual TBI severity as determined post hoc. In Chapter 6 face-to-face and telephonic examination of the GOS-E - an extended score on neurological functioning after neurotrauma - were compared. These showed a kappa value of 0.79, which is commonly considered good or substantial agreement, and implies that telephonic assessment is a valid alternative. Most of the prehospital treatments for severe TBI lack a thorough base of evidence. Prehospital airway management is regularly performed, but it’s benefit is not yet fully established. In Chapter 7, a systematic review and meta-analysis was performed to address effects of Prehospital Intubation (PHI) on mortality in patients with severe TBI. Six studies met the inclusion criteria for the meta-analysis. The main finding is that effects of PHI depend on the level of experience of the Emergency Medical Service (EMS)-providers who perform the intervention, and that PHI by EMS-personnel with limited experience in performing PHI is associated with increased mortality. In Chapter 9, the results are described of an inquiry and analysis of the national trauma data registry of the Netherlands. Between 2015 and the end of 2019, almost 9000 patients with severe TBI were studied. In an unadjusted comparison between the groups, mortality was significantly higher when patients were intubated (prehospital) as compared to non-intubated patients. After adjusting for potential confounders, PHI was still significantly associated with an almost 2-fold increase in the odds of mortality in the complete case analysis. Furthermore, the analyses revealed that the relationship of PHI and mortality may depend on whether P-HEMS is involved in the treatment or not. In Chapter 10, analyses were performed on the BRAIN-PROTECT dataset in order to assess the most optimum end-tidal CO2 values regarding mortality. Analyses of the (unadjusted) effects of end-tidal CO2 levels on predicted mortality revealed a statistically significant “L-shaped” association. These results were robust as they were repeated in a multi variable model. This model revealed reasonable end-tidal CO2 values between 35-45mmHg. In Chapter 11, the results of a systematic review and meta-analysis are presented on fluid administration to patients with severe TBI. The meta-analysis on the effects of Hypertonic Saline with Dextran (HSD) versus normal saline on survival did not show any effect. This was the same for the effect of hypertonic saline versus crystalloid fluids. Finally, the role of Tranexamic Acid (TXA) as an anti-fibrinolytic agent was investigated. In the BRAIn-PROTECT study, an increased mortality was observed among patients with isolated severe TBI who had received TXA, whereas no evidence for a relationship between TXA and mortality was observed in the other cohorts after controlling for potential confounders