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Meta-Analysis
. 2014 Mar 31;2014(3):CD009694.
doi: 10.1002/14651858.CD009694.pub2.

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

Tim Taylor  1 , Rob A Dineen, Dale C Gardiner, Charmaine H Buss, Allan Howatson, Nathan Leon Pace
Affiliations
Meta-Analysis

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

Tim Taylor et al. Cochrane Database Syst Rev. .

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.

PubMed Disclaimer

Conflict of interest statement

Tim Taylor and Allan Howatson were fully funded to attend the Cochrane DTA training course in Amsterdam, September 2010. This was paid for by a grant from NHS Blood and Transplant.

Dale Gardiner is the Clinical Lead for Organ Donation, Nottingham University Hospitals NHS Trust and the Midlands Regional Clinical Lead for Organ Donation. Nottingham University Hospitals NHS Trust is reimbursed by NHS Blood and Transplant for his time.

Charmaine Buss is a Specialist Nurse for Organ Donation employed and managed by NHS Blood and Transplant.

Nathan Pace: none known.

Rob Dineen: none known.

Figures

1
1
Example study flow diagram demonstrating typical patient progression through an included study (Frampas E et al).
2
2
Search and analysis flow diagram.
3
3
Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies.
4
4
Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study.
5
5
Forest plot of 8 studies displaying sensitivity (decimal fractions) by the original grading in the studies. The observed effect size (sensitivity) of each study is indicated by a square with corresponding 95% Confidence Interval; larger squares reflect greater precision of the estimate. The diamond is the summary value of sensitivity; the edges of the diamond are the 95% Confidence Interval of the summary sensitivity. Confidence Intervals are asymmetric. Numeric values are shown in the right column. The dotted vertical line is the summary sensitivity value. The dotted horizontal line enclosing the diamond is the 95% Prediction Interval (0.34, 0.98) of the summary sensitivity value. There is a large degree of statistical heterogeneity (I2 = 81%).
6
6
Forest plot of 8 studies displaying sensitivity (decimal fractions) by 4 vessel grading in the studies. The observed effect size (sensitivity) of each study is indicated by a square with corresponding 95% Confidence Interval; larger squares reflect greater precision of the estimate. The diamond is the summary value of sensitivity; the edges of the diamond are the 95% Confidence Interval of the summary sensitivity. Confidence Intervals are asymmetric. Numeric values are shown in the right column. The dotted vertical line is the summary sensitivity value. The dotted horizontal line enclosing the diamond is the 95% Prediction Interval (0.56, 0.96) of the summary sensitivity value. There is a large degree of statistical heterogeneity (I2 = 71%)
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD009694

References

References to studies included in this review

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