BackgroundTraumatic brain injury (TBI) is a leading cause of death and disability. A reliable prediction of outcome on admission is of great clinical relevance. We aimed to develop prognostic models with readily available traditional and novel predictors.Methods and FindingsProspectively collected individual patient data were analyzed from 11 studies. We considered predictors available at admission in logistic regression models to predict mortality and unfavorable outcome according to the Glasgow Outcome Scale at 6 mo after injury. Prognostic models were developed in 8,509 patients with severe or moderate TBI, with cross-validation by omission of each of the 11 studies in turn. External validation was on 6,681 patients from the recent Medical Research Council Corticosteroid Randomisation after Significant Head Injury (MRC CRASH) trial. We found that the strongest predictors of outcome were age, motor score, pupillary reactivity, and CT characteristics, including the presence of traumatic subarachnoid hemorrhage. A prognostic model that combined age, motor score, and pupillary reactivity had an area under the receiver operating characteristic curve (AUC) between 0.66 and 0.84 at cross-validation. This performance could be improved (AUC increased by approximately 0.05) by considering CT characteristics, secondary insults (hypotension and hypoxia), and laboratory parameters (glucose and hemoglobin). External validation confirmed that the discriminative ability of the model was adequate (AUC 0.80). Outcomes were systematically worse than predicted, but less so in 1,588 patients who were from high-income countries in the CRASH trial.ConclusionsPrognostic models using baseline characteristics provide adequate discrimination between patients with good and poor 6 mo outcomes after TBI, especially if CT and laboratory findings are considered in addition to traditional predictors. The model predictions may support clinical practice and research, including the design and analysis of randomized controlled trials.

We studied the prognostic value of a wide range of conventional and novel prognostic factors on admission after traumatic brain injury (TBI) using both univariate and multivariable analysis. The outcome measure was Glasgow Outcome Scale at 6 months after injury. Individual patient data were available on a cohort of 8686 patients drawn from eight randomized controlled trials and three observational studies. The most powerful independent prognostic variables were age, Glasgow Coma Scale (GCS) motor score, pupil response, and computerized tomography (CT) characteristics, including the Marshall CT classification and traumatic subarachnoid hemorrhage. Prothrombin time was also identified as a powerful independent prognostic factor, but it was only available for a limited number of patients coming from three of the relevant studies. Other important prognostic factors included hypotension, hypoxia, the eye and verbal components of the GCS, glucose, platelets, and hemoglobin. These results on prognostic factors will underpin future work on the IMPACT project, which is focused on the development of novel approaches to the design and analysis of clinical trials in TBI. In addition, the results provide pointers to future research, including further analysis of the prognostic value of prothrombin time, and the evaluation of the clinical impact of intervening aggressively to correct abnormalities in hemoglobin, glucose, and coagulation.

We determined the relationship between secondary insults (hypoxia, hypotension, and hypothermia) occurring prior to or on admission to hospital and 6-month outcome after traumatic brain injury (TBI). A meta-analysis of individual patient data, from seven Phase III randomized clinical trials (RCT) in moderate or severe TBI and three TBI population-based series, was performed to model outcome as measured by the Glasgow Outcome Scale (GOS). Proportional odds modeling was used to relate the probability of a poor outcome to hypoxia (N = 5661), hypotension ( N = 6629), and hypothermia ( N = 4195) separately. We additionally analyzed the combined effects of hypoxia and hypotension and performed exploratory analysis of associations with computerized tomography (CT) classification and month of injury. Having a pre-enrollment insult of hypoxia, hypotension or hypothermia is strongly associated with a poorer outcome (odds ratios of 2.1 95% CI [1.7-2.6], 2.7 95% CI [2.1-3.4], and 2.2 95% CI [1.6-3.2], respectively). Patients with both hypoxia and hypotension had poorer outcomes than those with either insult alone. Radiological signs of raised intracranial pressure (CT class III or IV) were more frequent in patients who had sustained hypoxia or hypotension. A significant association was observed between month of injury and hypothermia. The occurrence of secondary insults prior to or on admission to hospital in TBI patients is strongly related to poorer outcome and should therefore be a priority for emergency department personnel.

We studied the prognostic strength of the individual components of the Glasgow Coma Scale (GCS) and pupil reactivity to Glasgow Outcome Score (GOS) at 6 months post-injury. A total of 8721 moderate or severe traumatic brain injury (TBI) patient data from the IMPACT database on traumatic brain injury comprised the study cohort. The associations between motor score and pupil reactivity and 6-month GOS were analyzed by binary logistic regression and proportional odds methodology. The strength of prognostic effects were expressed as the unadjusted odds ratios presented for all individual studies as well as in meta-analysis. We found a consistent strong association between motor score and 6-month GOS across all studies (OR 1.74-7.48). The Eye and Verbal components were also strongly associated with GOS. In the pooled population, one or both un-reactive pupils and lower motor scores were significantly associated with unfavorable outcome (range 2.71-7.31). We also found a significant change in motor score from pre-hospital direct to study hospital enrollment ( p < 0.0001) and from the first in-hospital to study enrollment scores (p < 0.0001). Pupil reactivity was more robust between these time points. It is recommended that the study hospital enrollment GCS and pupil reactivity be used for prognostic analysis.

Computerized tomography (CT) scanning provides an objective assessment of the structural damage to the brain following traumatic brain injury (TBI). We aimed to describe and quantify the relationship between CT characteristics and 6-month outcome, assessed by the Glasgow Outcome Scale (GOS). Individual patient data from the IMPACT database were available on CT classification (N = 5209), status of basal cisterns ( N = 3861), shift ( N = 4698), traumatic subarachnoid hemorrhage (tSAH) ( N = 7407), and intracranial lesions ( N = 7613). We used binary logistic and proportional odds regression for prognostic analyses. The CT classification was strongly related to outcome, with worst outcome for patients with diffuse injuries in CT class III (swelling; OR 2.50; CI 2.09-3.0) or CT class IV (shift; OR 3.03; CI 2.12-4.35). The prognosis in patients with mass lesions was better for patients with an epidural hematoma (OR 0.64; CI 0.56-0.72) and poorer for an acute subdural hematoma (OR 2.14; CI 1.87-2.45). Partial obliteration of the basal cisterns (OR 2.45; CI 1.88-3.20), tSAH (OR 2.64; CI 2.42-2.89), or midline shift (1-5 mm-OR 1.36; CI 1.09-1.68); >5 mm-OR 2.20; CI 1.64-2.96) were strongly related to poorer outcome. Discrepancies were found between the scoring of basal cisterns/shift and the CT classification, indicating observer variation. These were less marked in studies that had used a central review process. Multivariable analysis indicated that individual CT characteristics added substantially to the prognostic value of the CT classification alone. We conclude that both the CT classification and individual CT characteristics are important predictors of outcome in TBI. For clinical trials, a central review process is advocated to minimize observer variability in CT assessment.