Aziz S. Alali, Nancy Temkin, Monica S. Vavilala, Abhijit V. Lele, Jason Barber, Sureyya Dikmen and Randall M. Chesnut
The aim of this study was to examine the relationship between early arterial oxygenation thresholds and long-term outcome after severe traumatic brain injury (TBI).
In a post hoc analysis of a randomized trial, adults with severe TBI were classified based on exposure to different levels of arterial oxygenation as measured using the average of arterial partial pressure of oxygen (PaO2) values obtained within 24 hours of admission. Potentially important PaO2 thresholds were defined a priori. The primary outcome was Glasgow Outcome Scale–Extended (GOSE) score at 6 months. Secondary outcomes were cognitive outcomes measured using a battery of 9 neuropsychological tests administered at 6 months, and 6-month mortality.
In adjusted analyses, oxygenation thresholds of 150 and 200 mm Hg were associated with better functional outcome at 6 months (adjusted OR for better functional outcome on GOSE 1.82 [95% CI 1.12–2.94] and 1.59 [95% CI 1.06–2.37], respectively) and improved cognitive outcome at 6 months (adjusted beta coefficients for better cognitive percentile across 9 neuropsychological tests: 6.9 [95% CI 1.3–12.5] and 6.8 [95% CI 2.4–11.3], respectively). There was no significant association between oxygenation level and 6-month mortality except at a PaO2 threshold of 200 mm Hg (OR for death 0.36, 95% CI 0.18–0.71). Higher or lower oxygenation thresholds were not associated with functional or cognitive outcome.
In this observational study, the relationship between early arterial oxygenation and long-term functional and cognitive TBI outcomes appears to be U-shaped. Mild levels of hyperoxemia within the first 24 hours after injury were associated with better long-term functional and cognitive outcomes. These findings highlight the importance of examining balanced oxygen supplementation as a potential strategy to improve TBI outcomes in future research.
Aziz S. Alali, David Gomez, Chethan Sathya, Randall S. Burd, Todd G. Mainprize, Richard Moulton, Richard A. Falcone Jr., Charles de Mestral and Avery Nathens
Well-designed studies linking intracranial pressure (ICP) monitoring with improved outcomes among children with severe traumatic brain injury (TBI) are lacking. The main objective of this study was to examine the relationship between ICP monitoring in children and in-hospital mortality following severe TBI.
An observational study was conducted using data derived from 153 adult or mixed (adult and pediatric) trauma centers participating in the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) and 29 pediatric trauma centers participating in the pediatric pilot TQIP between 2010 and 2012. Random-intercept multilevel modeling was used to examine the association between ICP monitoring and in-hospital mortality among children with severe TBI ≤16 years of age after adjusting for important confounders. This association was evaluated at the patient level and at the hospital level. In a sensitivity analysis, this association was reexamined in a propensity-matched cohort.
A total of 1705 children with severe TBI were included in the study cohort. The overall in-hospital mortality was 14.3% of patients (n = 243), whereas the mortality of the 273 patients (16%) who underwent invasive ICP monitoring was 11% (n = 30). After adjusting for patient- and hospital-level characteristics, ICP monitoring was associated with lower in-hospital mortality (adjusted OR 0.50; 95% CI 0.30–0.85; p = 0.01). It is possible that patients who were managed with ICP monitoring were selected because of an anticipated favorable or unfavorable outcome. To further address this potential selection bias, the analysis was repeated with the hospital-specific rate of ICP monitoring use as the exposure. The adjusted OR for death of children treated at high ICP–use hospitals was 0.49 compared with those treated at low ICP-use hospitals (95% CI 0.31–0.78; p = 0.003). Variations in ICP monitoring use accounted for 15.9% of the interhospital variation in mortality among children with severe TBI. Similar results were obtained after analyzing the data using propensity score-matching methods.
In this observational study, ICP monitoring use was associated with lower hospital mortality at both the patient and hospital levels. However, the contribution of variable ICP monitoring rates to interhospital variation in pediatric TBI mortality was modest.
Aziz S. Alali, Nancy Temkin, Jason Barber, Jim Pridgeon, Kelley Chaddock, Sureyya Dikmen, Peter Hendrickson, Walter Videtta, Silvia Lujan, Gustavo Petroni, Nahuel Guadagnoli, Zulma Urbina and Randall M. Chesnut
While existing guidelines support the treatment of intracranial hypertension in severe traumatic brain injury (TBI), it is unclear when to suspect and initiate treatment for high intracranial pressure (ICP). The objective of this study was to derive a clinical decision rule that accurately predicts intracranial hypertension.
Using Delphi methods, the authors identified a set of potential predictors of intracranial hypertension and a clinical decision rule a priori by consensus among a group of 43 neurosurgeons and intensivists who have extensive experience managing severe TBI without ICP monitoring. To validate these predictors, the authors used data from a Latin American trial (n = 150; BEST TRIP). To report on the performance of the rule, they calculated sensitivity, specificity, and positive and negative predictive values with 95% confidence intervals. In a secondary analysis, the rule was validated using data from a North American trial (n = 131; COBRIT).
The final predictors and the clinical decision rule were approved by 97% of participants in the consensus working group. The predictors are divided into major and minor criteria. High ICP would be considered suspected in the presence of 1 major or ≥ 2 minor criteria. Major criteria are: compressed cisterns (CT classification of Marshall diffuse injury [DI] III), midline shift > 5 mm (Marshall DI IV), or nonevacuated mass lesion. Minor criteria are: Glasgow Coma Scale (GCS) motor score ≤ 4, pupillary asymmetry, abnormal pupillary reactivity, or Marshall DI II. The area under the curve for the logistic regression model that contains all the predictors was 0.86. When high ICP was defined as > 22 mm Hg, the decision rule performed with a sensitivity of 93.9% (95% CI 85.0%–98.3%), a specificity of 42.3% (95% CI 31.7%–53.6%), a positive predictive value of 55.5% (95% CI 50.7%–60.2%), and a negative predictive value of 90% (95% CI 77.1%–96.0%). The sensitivity of the clinical decision rule improved with higher ICP cutoffs up to a sensitivity of 100% when intracranial hypertension was defined as ICP > 30 mm Hg. Similar results were found in the North American cohort.
A simple clinical decision rule based on a combination of clinical and imaging findings was found to be highly sensitive in distinguishing patients with severe TBI who would suffer intracranial hypertension. It could be used to identify patients who require ICP monitoring in high-resource settings or start ICP-lowering treatment in environments where resource limitations preclude invasive monitoring.
Clinical trial registration no.: NCT02059941 (clinicaltrials.gov).
Mohamad A. Hussain, Aziz S. Alali, Muhammad Mamdani, Jack V. Tu, Gustavo Saposnik, Konard Salata, Avery B. Nathens, Charles de Mestral, Deepak L. Bhatt, Subodh Verma and Mohammed Al-Omran
Intracranial hemorrhage (ICH) associated with cerebral hyperperfusion syndrome is a rare but major complication of carotid artery revascularization. The objective of this study was to compare the rate of ICH after carotid artery stenting (CAS) with that after endarterectomy (CEA).
The authors performed a retrospective population-based cohort study of patients who underwent carotid artery revascularization in the province of Ontario, Canada, between 2002 and 2015. The primary outcome was the rate of ICH that occurred within 90 days after carotid artery intervention among patients who underwent CAS versus that of those who underwent CEA. The authors used inverse probability of treatment weighting and propensity scores to account for selection bias. In sensitivity analyses, patients who had postprocedure ischemic stroke were excluded, and the following subgroups were examined: patients with symptomatic and asymptomatic carotid artery stenosis, patients treated between 2010 and 2015, and patients aged ≥ 66 years (to account for antiplatelet and anticoagulant use).
A total of 16,688 patients underwent carotid artery revascularization (14% CAS, 86% CEA). Patients with more comorbid illnesses, symptomatic carotid artery stenosis, or cardiac disease and those who were taking antiplatelet agents or warfarin before surgery were more likely to undergo CAS. Among the overall cohort, 80 (0.48%) patients developed ICH within 90 days (0.85% after CAS, 0.42% after CEA). The 180-day mortality rate after ICH in the overall cohort was 2.7%, whereas the 180-day mortality rate among patients who suffered ICH was 42.5% (40% for CAS-treated patients, 43.3% for CEA-treated patients). In the adjusted analysis, patients who underwent CAS were significantly more likely to have ICH than those who underwent CEA (adjusted OR 1.77; 95% CI 1.32–2.36; p < 0.001). These results were consistent after excluding patients who developed postprocedure ischemic stroke (adjusted OR 1.90; 95% CI 1.41–2.56) and consistent among symptomatic (adjusted OR 1.74; 95% CI 1.16–2.63) and asymptomatic (adjusted OR 1.75; 95% CI 1.16–2.63) patients with carotid artery stenosis, among patients treated between 2010 and 2015 (adjusted OR 2.21; 95% CI 1.45–3.38), and among the subgroup of patients aged ≥ 66 years (adjusted OR 1.53; 95% CI 1.05–2.24) after adjusting for medication use.
CAS is associated with a rare but higher risk of ICH relative to CEA. Future research is needed to devise strategies that minimize the risk of this serious complication after carotid artery revascularization.