Computed tomography (CT) angiography for confirmation of the clinical diagnosis of brain death. 2014

Tim Taylor, and Rob A Dineen, and Dale C Gardiner, and Charmaine H Buss, and Allan Howatson, and Nathan Leon Pace
Department of Imaging, Queens Medical Centre campus, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, UK, NG7 2UH.

BACKGROUND The diagnosis of death using neurological criteria (brain death) has profound social, legal and ethical implications. The diagnosis can be made using standard clinical tests examining for brain function, but in some patient populations and in some countries additional tests may be required. Computed tomography (CT) angiography, which is currently in wide clinical use, has been identified as one such test. OBJECTIVE To assess from the current literature the sensitivity of CT cerebral angiography as an additional confirmatory test for diagnosing death using neurological criteria, following satisfaction of clinical neurological criteria for brain death. METHODS We performed comprehensive literature searches to identify studies that would assess the diagnostic accuracy of CT angiography (the index test) in cohorts of adult patients, using the diagnosis of brain death according to neurological criteria as the target condition. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5) and the following databases from January 1992 to August 2012: MEDLINE; EMBASE; BNI; CINAHL; ISI Web of Science; BioMed Central. We also conducted searches in regional electronic bibliographic databases and subject-specific databases (MEDION; IndMed; African Index Medicus). A search was also conducted in Google Scholar where we reviewed the first 100 results only. We handsearched reference lists and conference proceedings to identify primary studies and review articles. Abstracts were identified by two authors. Methodological assessment of studies using the QUADAS-2 tool and further data extraction for re-analysis were performed by three authors. METHODS We included in this review all large case series and cohort studies that compared the results of CT angiography with the diagnosis of brain death according to neurological criteria. Uniquely, the reference standard was the same as the target condition in this review. METHODS We reviewed all included studies for methodological quality according to the QUADAS-2 criteria. We encountered significant heterogeneity in methods used to interpret CT angiography studies and therefore, where possible, we re-analysed the published data to conform to a standard radiological interpretation model. The majority of studies (with one exception) were not designed to include patients who were not brain dead, and therefore overall specificity was not estimable as part of a meta-analysis. Sensitivity, confidence and prediction intervals were calculated for both as-published data and as re-analysed to a standardized interpretation model. RESULTS Ten studies were found including 366 patients in total. We included eight studies in the as-published data analysis, comprising 337 patients . The methodological quality of the studies was overall satisfactory, however there was potential for introduction of significant bias in several specific areas relating to performance of the index test and to the timing of index versus reference tests. Results demonstrated a sensitivity estimate of 0.84 (95% confidence interval (CI) 0.69 to 0.93). The 95% approximate prediction interval was very wide (0.34 to 0.98). Data in three studies were available as a four-vessel interpretation model and the data could be re-analysed to a four-vessel interpretation model in a further five studies, comprising 314 patient events. Results demonstrated a similar sensitivity estimate of 0.85 (95% CI 0.77 to 0.91) but with an improved 95% approximate prediction interval (0.56 to 0.96). CONCLUSIONS The available evidence cannot support the use of CT angiography as a mandatory test, or as a complete replacement for neurological testing, in the management pathway of patients who are suspected to be clinically brain dead. CT angiography may be useful as a confirmatory or add-on test following a clinical diagnosis of death, assuming that clinicians are aware of the relatively low overall sensitivity. Consensus on a standard radiological interpretation protocol for future published studies would facilitate further meta-analysis.

UI MeSH Term Description Entries
D001926 Brain Death A state of prolonged irreversible cessation of all brain activity, including lower brain stem function with the complete absence of voluntary movements, responses to stimuli, brain stem reflexes, and spontaneous respirations. Reversible conditions which mimic this clinical state (e.g., sedative overdose, hypothermia, etc.) are excluded prior to making the determination of brain death. (From Adams et al., Principles of Neurology, 6th ed, pp348-9) Brain Dead,Coma Depasse,Irreversible Coma,Brain Deads,Coma, Irreversible,Death, Brain
D002533 Cerebral Angiography Radiography of the vascular system of the brain after injection of a contrast medium. Angiography, Cerebral,Angiographies, Cerebral,Cerebral Angiographies
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012680 Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) Specificity,Sensitivity,Specificity and Sensitivity
D014057 Tomography, X-Ray Computed Tomography using x-ray transmission and a computer algorithm to reconstruct the image. CAT Scan, X-Ray,CT Scan, X-Ray,Cine-CT,Computerized Tomography, X-Ray,Electron Beam Computed Tomography,Tomodensitometry,Tomography, Transmission Computed,X-Ray Tomography, Computed,CAT Scan, X Ray,CT X Ray,Computed Tomography, X-Ray,Computed X Ray Tomography,Computerized Tomography, X Ray,Electron Beam Tomography,Tomography, X Ray Computed,Tomography, X-Ray Computer Assisted,Tomography, X-Ray Computerized,Tomography, X-Ray Computerized Axial,Tomography, Xray Computed,X Ray Computerized Tomography,X Ray Tomography, Computed,X-Ray Computer Assisted Tomography,X-Ray Computerized Axial Tomography,Beam Tomography, Electron,CAT Scans, X-Ray,CT Scan, X Ray,CT Scans, X-Ray,CT X Rays,Cine CT,Computed Tomography, Transmission,Computed Tomography, X Ray,Computed Tomography, Xray,Computed X-Ray Tomography,Scan, X-Ray CAT,Scan, X-Ray CT,Scans, X-Ray CAT,Scans, X-Ray CT,Tomographies, Computed X-Ray,Tomography, Computed X-Ray,Tomography, Electron Beam,Tomography, X Ray Computer Assisted,Tomography, X Ray Computerized,Tomography, X Ray Computerized Axial,Transmission Computed Tomography,X Ray Computer Assisted Tomography,X Ray Computerized Axial Tomography,X Ray, CT,X Rays, CT,X-Ray CAT Scan,X-Ray CAT Scans,X-Ray CT Scan,X-Ray CT Scans,X-Ray Computed Tomography,X-Ray Computerized Tomography,Xray Computed Tomography
D015331 Cohort Studies Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. Birth Cohort Studies,Birth Cohort Study,Closed Cohort Studies,Cohort Analysis,Concurrent Studies,Historical Cohort Studies,Incidence Studies,Analysis, Cohort,Cohort Studies, Closed,Cohort Studies, Historical,Studies, Closed Cohort,Studies, Concurrent,Studies, Historical Cohort,Analyses, Cohort,Closed Cohort Study,Cohort Analyses,Cohort Studies, Birth,Cohort Study,Cohort Study, Birth,Cohort Study, Closed,Cohort Study, Historical,Concurrent Study,Historical Cohort Study,Incidence Study,Studies, Birth Cohort,Studies, Cohort,Studies, Incidence,Study, Birth Cohort,Study, Closed Cohort,Study, Cohort,Study, Concurrent,Study, Historical Cohort,Study, Incidence

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