Primary Objectives: 1. To determine if impaired cerebral autoregulation as measured by NIRS is associated with clinically significant vasospasm in patients with moderate to severe TBI; 2. To determine the sensitivity and specificity of NIRS in detecting clinically significant vasospasm with Transcranial Doppler (TCD) ultrasound followed by CT brain angiography and diffusion-weighted brain MRI as the gold standard . Secondary Objectives: 1. To determine the relationship between impaired cerebral autoregulation and outcomes; 2. To determine the relationship between impaired cerebral autoregulation, clinically significant vasospasm and outcomes
Clinical observations The subject will be continuously monitored with INVOS NIRS system within the first 24 hours after admission up to 7 days while the subject is still in the STC. If decreased cerebral oxygenation is detected by NIRS, TCDs will be offered to the family and considered part of routine clinical care. If vasospasm is detected by TCD, CT brain angiography will be offered to the family for angiographic confirmation and considered part of routine clinical care. If vasospasm is confirmed by CT brain angiography, diffusion-weighted MRI will be offered to the family to evaluate for cerebral ischemia/infarction and considered part of routine clinical care.
Laboratory evaluations All patients will have at least twice daily measurements of serum electrolytes, blood counts, arterial blood gases, and coagulation profile as per our standard of care. Culture results will be recorded. No tests or procedure will be ordered for research purposes only.
Patient Management All enrolled patients will be admitted to the Neurotrauma Critical Care Unit (NTCC) and be jointly managed by the Trauma, Critical Care and Neurosurgical services. All patients will be managed utilizing the STC Institutional Severe Traumatic Brain Injury Management Algorithm which is based on the Brain Trauma Foundation Guidelines for the Management of Severe Traumatic Brain Injury. Other consults will be obtained as clinically indicated.
Questionnaires / Assessment tools Functional outcome using the Extended Glasgow Outcome Scale (GOS-E) will be assessed in the STC Outpatient Clinic as part of their standard of care. An early functional outcome assessment will be obtained if the GOS-E form is completed at the STC Outpatient Clinic within 6 weeks post hospital discharge day. A mid functional outcome assessment will be obtained if the GOS-E form is completed at the STC Outpatient Clinic 6 weeks to 3 months post hospital discharge day. A late functional outcome assessment will be obtained if the GOS-E form is completed at the STC Outpatient Clinic 3 months to 6 months post hospital discharge day. Finally, a very late functional outcome assessment will be obtained if the GOS-E form is completed at the STC Outpatient Clinic more than 6 months post-hospital discharge day.
STATISTICAL CONSIDERATIONS / ANALYSIS OF DATA The goal of this pilot study is to determine if impaired cerebral autoregulation as measured by NIRS is associated with the development of clinically significant vasospasm in patients with moderate to severe TBI. By enrolling 100 patients in the study, it is expected to estimate the correlation to within 0.098 with a probability of at least 95%. In this study, all primary and secondary outcomes may be classified into two categories: binary and continuous. In the first step, quantitative descriptive statistics will be used initially to study the characteristics of patients and the association between clinical outcomes (e.g. vasospasm) and various demographic and clinicopathologic variables such as age, gender and injury severity scores. For binary data, chi-square and Fisher's exact tests will be used to identify differences. For continuous variables, t-tests and analysis of variance (ANOVA) will be used to determine the significant association. These univariate tests will be done at a significance level of 0.05. In addition to constructing 95% confidence interval for the correlation of impaired cerebral autoregulation as measured by NIRS and clinically significant vasospasm, the investigators will also explore potential risk factors associated with impaired cerebral autoregulation and impaired cerebral autoregulation associated with vasospasm. To this end, the correlation will be analyzed using the logistic regression model with various demographic and clinicopathologic variables as independent variables. The stepwise regression procedure will be used for identifying potential risk factors for the incidence of vasospasm. To evaluate the validity of NIRs as an assessment method of vasospasm, the investigators will measure the agreement between TCD and NIRS by using kappa statistics.
