Objectives of the ACT-TBI study:
In patients with severe TBI,
1. To validate admission CTP features of brain death, relative to the clinical examination outcome, for characterizing early in-hospital mortality.
2. To establish the safety and inter-rater reliability of features of brain death on admission CTP.
3. To evaluate the determinants (age, sex, and GCS score) influencing the variability in response of CTP.
4. To establish the usefulness of CTP in facilitating timely organ transplantation, if possible.
Research Design and Method The ACT-TBI study is a prospective, multi-centre, cohort study in patients with severe TBI and will be conducted in 4 different Canadian centres (Winnipeg, Ottawa, Montreal, and Halifax) over the next 4 years.
Those patients meeting eligibility criteria will be identified by a dedicated research nurse with the help of the trauma team at the time of hospital admission, with the ACT-TBI study protocol will be activated at the time of their first diagnostic imaging. A deferral of consent will be obtained like that in the pilot study.
Clinical Examination- The results of initial clinical, laboratory and imaging assessment will be recorded as per the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) core and extended models. The clinical examination will occur during a sedation hold, when possible acknowledging some confounding from effect of residual sedation.
Radiological Examinations Upon hospital admission, at the time of initial diagnostic imaging, besides the standard diagnostic tests of whole-body CT scan, enrolled patients will undergo the whole head imaging protocol with CTP.
Plain computed tomography (CT) of head: As a standard imaging protocol, plain CT of head will be performed for severe TBI patients. These images will be assessed for the presence of various lesions (subarachnoid hemorrhage, sub-dural hemorrhage, epidural hemorrhage, intra-ventricular hemorrhage, cerebral contusions, and edema).
Computed tomography perfusion (CTP): Besides, a standard imaging protocol, CTP imaging protocol for whole head will be performed. Images will be acquired following our previously published protocol. In brief, a total of 40 mL of CT contrast media will be injected at a rate of 5 mL/sec. A set of axial images with a slice thickness of 5 mm for the perfusion analysis will be reconstructed. CTP images will only be acquired. The anonymized images will be transferred and stored in the secured imaging core lab, department of Radiology, University of Manitoba, for processing and interpretation later. CTP will be processed using a semiautomatic deconvolution algorithm on a vendor neutral software package (Oleasphere). CTP will be assessed both quantitatively as well as qualitatively.
* Quantitative assessment: brain death will be defined as Cerebral Blood Flow (CBF) \<5 mL/100g/min and Cerebral Blood Volume (CBV) \<2 mL/100g in the brainstem.
* Qualitative assessment: brain death will be defined as matched decrease of CBF and CBV in the brainstem. The perfusion maps for CBF and CBV will be assessed for binary outcome of 'dead' or 'not-dead', according to our previously published methods.
The perfusion images will be assessed by the two independent neuroradiologists, who are blinded to the clinical status of the patient and also to each other's assessment. In case of disagreement, the expert neuroradiologist opinion will be employed to have a consensus agreement for the final analysis.
Post-perfusion care: Since the prognostic value of CTP has not been established in patients with severe TBI, the outcomes of CTP will not be made available to the clinical team involved in patient care. All patients will receive the standard care.
