Gaby Franschman

Epidemiology, severity classification and outcome of moderate and severe traumatic brain injury: A prospective multicenter study

Changes in the demographics, approach, and treatment of traumatic brain injury (TBI) patients require regular evaluation of epidemiological profiles, injury severity classification, and outcomes. This prospective multicenter study provides detailed information on TBI-related variables of 508 moderate-to-severe TBI patients. Variability in epidemiology and outcome is examined by comparing our cohort with previous multicenter studies. Additionally, the relation between outcome and injury severity classification assessed at different time points is studied. Based on the emergency department Glasgow Coma Scale (GCS), 339 patients were classified as having severe and 129 as having moderate TBI. In 15%, the diagnosis differed when the accident scene GCS was used for classification. In-hospital mortality was higher if severe TBI was diagnosed at both time points (44%) compared to moderate TBI at one or both time points (7-15%, p<0.001). Furthermore, 14% changed diagnosis when a threshold (≥6 h) for impaired consciousness was used as a criterion for severe TBI: In-hospital mortality was<5% when impaired consciousness lasted for<6 h. This suggests that combining multiple clinical assessments and using a threshold for impaired consciousness may improve the classification of injury severity and prediction of outcome. Compared to earlier multicenter studies, our cohort demonstrates a different case mix that includes a higher age (mean=47.3 years), more diffuse (Traumatic Coma Databank [TCDB] I-II) injuries (58%), and more major extracranial injuries (40%), with relatively high 6 month mortality rates for both severe (46%) and moderate (21%) TBI. Our results confirm that TBI epidemiology and injury patterns have changed in recent years whereas case fatality rates remain high.

Prognosis in moderate and severe traumatic brain injury: external validation of the IMPACT models and the role of extracranial injuries.

BACKGROUND Several prognostic models to predict outcome in traumatic brain injury (TBI) have been developed, but few are externally validated. We aimed to validate the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic models in a recent unselected patient cohort and to assess the additional prognostic value of extracranial injury. METHODS The Prospective Observational COhort Neurotrauma (POCON) registry contains 508 patients with moderate or severe TBI, who were admitted in 2008 and 2009 to five trauma centers in the Netherlands. We predicted the probability of mortality and unfavorable outcome at 6 months after injury with the IMPACT prognostic models. We studied discrimination (area under the curve [AUC]) and calibration. We added the extracranial component of the Injury Severity Score (ISS) to the models and calculated the increase in AUC. RESULTS The IMPACT models had an adequate discrimination in the POCON registry, with AUCs in the external validation between 0.85 and 0.90 for mortality and between 0.82 and 0.87 for unfavorable outcome. Observed outcomes agreed well with predicted outcomes. Adding extracranial injury slightly improved predictions in the overall population (unfavorable outcome: AUC increase of 0.002, p = 0.02; mortality: AUC increase of 0.000, p = 0.37) but more clearly in patients with moderate TBI (unfavorable outcome: AUC increase of 0.008, p < 0.01, mortality: AUC increase of 0.012, p = 0.02) and patients with minor computed tomographic result abnormalities (unfavorable outcome: AUC increase of 0.013, p < 0.01; mortality: AUC increase of 0.001, p = 0.08). CONCLUSION The IMPACT models performed well in a recent series of TBI patients. We found some additional impact of extracranial injury on outcome, specifically in patients with less severe TBI or minor computed tomographic result abnormalities. LEVEL OF EVIDENCE Epidemiologic/prognostic study,

Prehospital management of severe traumatic brain injury: concepts and ongoing controversies

Purpose of review Prehospital management affects long-term outcome of patients with severe traumatic brain injury (TBI). This article reviews the current concepts and ongoing controversies of prehospital treatment of severe TBI. Recent findings Prehospital management focuses on the prevention of secondary brain injury and rapid transport to a neurotrauma center for definitive diagnosis and life– as well as brain-saving emergency treatment such as decompressive craniotomy. There is a broad consensus that adequate airway management, prevention of hypoxia, hypocapnia or hypercapnia, prevention of hypotension and control of hemorrhage represent preclinical therapeutic modalities that may contribute to improved survival in severe TBI. The precise role of prehospital endotracheal intubation, osmotic agents and early therapeutic hypothermia needs to be clarified in the context of time required for transportation, local infrastructure, geographical factors and availability of experienced emergency teams. Summary Prehospital management of TBI remains challenging. There are no universal objectives suitable to all patients. Randomized, controlled clinical trials are necessary for developing optimal protocols for paramedic and physician emergency medical teams.

Factors influencing intracranial pressure monitoring guideline compliance and outcome after severe traumatic brain injury.

Objective:To determine adherence to Brain Trauma Foundation guidelines for intracranial pressure monitoring after severe traumatic brain injury, to investigate if characteristics of patients treated according to guidelines (ICP+) differ from those who were not (ICP-), and whether guideline compliance is related to 6-month outcome. Design:Observational multicenter study. Patients:Consecutive severe traumatic brain injury patients (≥16 yrs, n = 265) meeting criteria for intracranial pressure monitoring. Measurements and Main Results:Data on demographics, injury severity, computed tomography findings, and patient management were registered. The Glasgow Outcome Scale Extended was dichotomized into death (Glasgow Outcome Scale Extended = 1) and unfavorable outcome (Glasgow Outcome Scale Extended 1–4). Guideline compliance was 46%. Differences between the monitored and nonmonitored patients included a younger age (median 44 vs. 53 yrs), more abnormal pupillary reactions (52% vs. 32%), and more intracranial pathology (subarachnoid hemorrhage 62% vs. 44%; intraparenchymal lesions 65% vs. 46%) in the ICP+ group. Patients with a total intracranial lesion volume of ~150 mL and a midline shift of ~12 mm were most likely to receive an intracranial pressure monitor and probabilities decreased with smaller and larger lesions and shifts. Furthermore, compliance was low in patients with no (Traumatic Coma Databank score I −10%) visible intracranial pathology. Differences in case-mix resulted in higher a priori probabilities of dying (median 0.51 vs. 0.35, p < .001) and unfavorable outcome (median 0.79 vs. 0.63, p < .001) in the ICP+ group. After correction for baseline and clinical characteristics with a propensity score, intracranial pressure monitoring guideline compliance was not associated with mortality (odds ratio 0.93, 95% confidence interval 0.47–1.85, p = .83) nor with unfavorable outcome (odds ratio 1.81, 95% confidence interval 0.88–3.73, p = .11). Conclusions:Guideline noncompliance was most prominent in patients with minor or very large computed tomography abnormalities. Intracranial pressure monitoring was not associated with 6-month outcome, but multiple baseline differences between monitored and nonmonitored patients underline the complex nature of examining the effect of intracranial pressure monitoring in observational studies.

Multicenter Evaluation of the Course of Coagulopathy in Patients with Isolated Traumatic Brain Injury: Relation to CT Characteristics and Outcome

This prospective multicenter study investigated the association of the course of coagulation abnormalities with initial computed tomography (CT) characteristics and outcome in patients with isolated traumatic brain injury (TBI). Patient demographics, coagulation parameters, CT characteristics, and outcome data of moderate and severe TBI patients without major extracranial injuries were prospectively collected. Coagulopathy was defined as absent, early but temporary, delayed, or early and sustained. Delayed/sustained coagulopathy was associated with a higher incidence of disturbed pupillary responses (40% versus 27%; p<0.001) and higher Traumatic Coma Data Bank (TCDB) CT classification (5 (2-5) versus 2 (1-5); p=0.003) than in patients without or with early, but short-lasting coagulopathy. The initial CT of patients with delayed/sustained coagulopathy more frequently showed intracranial hemorrhage and signs of raised intracranial pressure (ICP) compared to patients with early coagulopathy only. This was paralleled by higher in-hospital mortality rates (51% versus 33%; p<0.05), and poorer 6-month functional outcome in patients with delayed/sustained coagulopathy. The relative risk for in-hospital mortality was particularly related to disturbed pupillary responses (OR 8.19; 95% CI 3.15,21.32; p<0.001), early, short-lasting coagulopathy (OR 6.70; 95% CI 1.74,25.78; p=0.006), or delayed/sustained coagulopathy (OR 5.25; 95% CI 2.06,13.40; p=0.001). Delayed/sustained coagulopathy is more frequently associated with CT abnormalities and unfavorable outcome at 6 months after TBI than early, short-lasting coagulopathy. Our finding that not only the mere presence but also the time course of coagulopathy holds predictive value for patient outcome underlines the importance of systematic hemostatic monitoring over time in TBI.

Effect of Secondary Prehospital Risk Factors on Outcome in Severe Traumatic Brain Injury in the Context of Fast Access to Trauma Care

BACKGROUND Prevention of secondary prehospital risk factors such as hypoxia and hypotension is likely to improve patient prognosis in severe traumatic brain injury (TBI). Because the Dutch trauma care organization is characterized by fast access to specialized trauma care due to the geographical situation, we investigated whether and to what extend secondary risk factors, such as hypoxia and hypotension, and measures, such as endotracheal intubation, affect outcome in severe TBI in the context of a region with fast access to trauma care. METHODS The medical records of 339 subsequent computed tomography-confirmed patients with TBI with a Glasgow coma scale (GCS) score≤8 who were primarily referred to a Level I trauma center in Amsterdam or Nijmegen in the Netherlands were retrospectively analyzed. RESULTS Multinomial logistic regression revealed that the strongest outcome predictors in our population were a disturbed pupillary reflex (odds ratio [OR], 5.8), a GCS score of 3 (OR, 4.9), and arterial hypotension (OR, 3.5). Interestingly, we observed no differences between intubated and nonintubated patients with respect to metabolic and respiratory parameters or mortality whereby the injury severity score was slightly higher in endotracheally intubated patients (32 [25-41]) versus nonintubated patients (25 [22-29]). CONCLUSION In agreement with others, GCS, a disturbed pupil reflex, and arterial hypotension were predictive for the prognosis of primarily referred patients with severe TBI in the Netherlands. In contrast, in the perspective of slightly higher injury scores in intubated patients, prehospital endotracheal intubation was not predictive for patient outcome.

Haemostatic and cranial computed tomography characteristics in patients with acute and delayed coagulopathy after isolated traumatic brain injury

Primary objective: To investigate whether the development of coagulopathy at different stages after isolated traumatic brain injury (TBI) is associated with distinct cranial computed tomography characteristics. Research design: Retrospective cohort study in 226 patients with moderate-to-severe isolated TBI who were categorized as subjects without coagulopathy or with acute temporary, acute sustained or delayed coagulopathy. Methods and procedures: Coagulopathy was defined as an activated partial thromboplastin time >40 seconds and/or prothrombin time (PT) >1.2 and/or platelet count <120*109 l−1. Cranial CT scans were assigned to the six-point Traumatic Coma Data Bank (TCDB) CT-classification. Main outcomes and results: Coagulopathy occurred in 44% of patients in the first 24-hours post-trauma. Patients with acute, sustained coagulopathy showed a prolonged PT (1.64 ± 0.89) when compared to patients without (1.03 ± 0.07), acute temporary (1.27 ± 0.22) or delayed coagulopathy (1.08 ± 0.06; p < 0.05). Patients with acute temporary or delayed coagulopathy had the worst TCDB CT classification scores, while mortality rates were the highest in patients with sustained or delayed coagulopathy. Conclusions: Not only the mere presence of coagulopathy, but also the course of haemostatic alterations following neurotrauma may hold predictive value for patient outcome, irrespective of the severity level of cerebral injury.

Causes and Consequences of Treatment Variation in Moderate and Severe Traumatic Brain Injury: A Multicenter Study

Objectives: Although guidelines have been developed to standardize care in traumatic brain injury, between-center variation in treatment approach has been frequently reported. We examined variation in treatment for traumatic brain injury by assessing factors influencing treatment and the association between treatment and patient outcome. Design: Secondary analysis of prospectively collected data. Setting: Five level I trauma centers in the Netherlands (2008–2009). Patients: Five hundred three patients with moderate or severe traumatic brain injury (Glasgow Coma Scale, 3–13). Interventions: We examined variation in seven treatment parameters: direct transfer, involvement of mobile medical team, mechanical ventilation, intracranial pressure monitoring, vasopressors, acute neurosurgical intervention, and extracranial operation. Measurements and Main Results: Data were collected on patient characteristics, treatment, and 6-month Glasgow Outcome Scale-Extended. Multivariable logistic regression models were used to assess the extent to which treatment was determined by patient characteristics. To examine whether there were between-center differences in treatment, we used unadjusted and adjusted random effect models with the seven treatment parameters as dependent variables. The influence of treatment approach in a center (defined as aggressive and nonaggressive based on the frequency intracranial pressure monitoring) on outcome was assessed using multivariable random effect proportional odds regression models in those patients with an indication for intracranial pressure monitoring. Sensitivity analyses were performed to test alternative definitions of aggressiveness. Treatment was modestly related to patient characteristics (Nagelkerke R 2 range, 0.12–0.52) and varied widely among centers, even after case-mix correction. Outcome was more favorable in patients treated in aggressive centers than those treated in nonaggressive centers (OR, 1.73; 95% CI, 1.05–3.15). Sensitivity analyses, however, illustrated that the aggressiveness-outcome association was dependent on the definition used. Conclusions: The considerable between-center variation in treatment for patients with brain injury can only partly be explained by differences in patient characteristics. An aggressive treatment approach may imply better outcome although further confirmation is required.

Adjusting for confounding by indication in observational studies: a case study in traumatic brain injury

Introduction Observational studies of interventions are at risk for confounding by indication. The objective of the current study was to define the circumstances for the validity of methods to adjust for confounding by indication in observational studies. Patients and methods We performed post hoc analyses of data prospectively collected from three European and North American traumatic brain injury studies including 1,725 patients. The effects of three interventions (intracranial pressure [ICP] monitoring, intracranial operation and primary referral) were estimated in a proportional odds regression model with the Glasgow Outcome Scale as ordinal outcome variable. Three analytical methods were compared: classical covariate adjustment, propensity score matching and instrumental variable (IV) analysis in which the percentage exposed to an intervention in each hospital was added as an independent variable, together with a random intercept for each hospital. In addition, a simulation study was performed in which the effect of a hypothetical beneficial intervention (OR 1.65) was simulated for scenarios with and without unmeasured confounders. Results For all three interventions, covariate adjustment and propensity score matching resulted in negative estimates of the treatment effect (OR ranging from 0.80 to 0.92), whereas the IV approach indicated that both ICP monitoring and intracranial operation might be beneficial (OR per 10% change 1.17, 95% CI 1.01–1.42 and 1.42, 95% CI 0.95–1.97). In our simulation study, we found that covariate adjustment and propensity score matching resulted in an invalid estimate of the treatment effect in case of unmeasured confounders (OR ranging from 0.90 to 1.03). The IV approach provided an estimate in the similar direction as the simulated effect (OR per 10% change 1.04–1.05) but was statistically inefficient. Conclusion The effect estimation of interventions in observational studies strongly depends on the analytical method used. When unobserved confounding and practice variation are expected in observational multicenter studies, IV analysis should be considered.