Abstract
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.
Objectives
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.
Search 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.
Selection criteria
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.
Data collection and analysis
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.
Main 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).
Authors’ 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.
Plain language summary
The use of computed tomography angiography (CTA) to confirm the clinical diagnosis of brain death
This Cochrane diagnostic test accuracy review looked at the evidence for the radiology test computed tomography angiography (CTA), which demonstrates blood flow in the main vessels of the brain, to support the results of clinical tests of brain function performed in unconscious patients on mechanical breathing machines who are thought by their doctors to have died.
Establishing a correct diagnosis is very important as the diagnosis confirms the death of the patient, which will have profound legal and societal implications including making organs available for transplantation. The diagnosis of death using neurological criteria, or brain death, is usually made by performing a highly specific set of clinical tests on the patient. However in some cases, for example when patients are anaesthetized or heavily sedated, performing these tests may not be possible and additional tests are required such as CTA. In some countries it is a statutory requirement for doctors to always carry out an additional test and recently some clinicians have called for these additional tests to be mandatory even when there is no statutory requirement. It is important for doctors to know how useful CTA is when compared to, or added to, the usual clinical tests.
Ten studies were found, including 366 patients in total. Most of the studies were performed in intensive care departments but involved only small numbers of patients. In most studies it would be possible for the doctors performing the CTA test to already know the results of the clinical test. This might affect the study results, however this situation would also be the case in normal medical practice. Methods used to report the CTA study also varied from study to study and so the published results were re-analysed to take this into account.
When compared to clinical testing for brain death, the CTA test had a sensitivity of 0.85. This means that in 100 cases of patients satisfying the clinical tests for death, the CTA test will correctly identify 85 of the cases. The data also showed that this might be as few as 77 cases per 100 and as many as 91 cases per 100. Our review was unable to tell us how many patients the CTA might falsely give a diagnosis of death for, when the patient was not dead. Based on these results, it appears that CTA is not good enough to be a compulsory test.
