Taylor Tim, Dineen Rob A, Gardiner Dale C, Buss Charmaine H, Howatson Allan, Pace Nathan Leon
Department of Imaging, Queens Medical Centre campus, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, UK, NG7 2UH.
Cochrane Database Syst Rev. 2014 Mar 31;2014(3):CD009694. doi: 10.1002/14651858.CD009694.pub2.
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.
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.
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.
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.
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.
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.
使用神经学标准诊断死亡（脑死亡）具有深远的社会、法律和伦理意义。可以通过检查脑功能的标准临床测试来做出诊断，但在某些患者群体和某些国家，可能需要额外的测试。计算机断层扫描（CT）血管造影目前在临床中广泛应用，已被确定为这样一种测试。
根据现有文献，评估在临床神经学脑死亡标准得到满足后，CT脑血管造影作为使用神经学标准诊断死亡的额外确证性测试的敏感性。
我们进行了全面的文献检索，以确定评估CT血管造影（索引测试）在成年患者队列中诊断准确性的研究，将根据神经学标准诊断脑死亡作为目标疾病。我们检索了Cochrane对照试验中心注册库（CENTRAL）（《Cochrane图书馆》2012年第5期）以及1992年1月至2012年8月的以下数据库：MEDLINE；EMBASE；BNI；CINAHL；ISI科学网；BioMed Central。我们还在区域电子书目数据库和特定主题数据库（MEDION；IndMed；非洲医学索引）中进行了检索。还在谷歌学术中进行了检索，我们仅查看了前100个结果。我们手工检索参考文献列表和会议论文集以确定原始研究和综述文章。两位作者识别摘要。三位作者使用QUADAS - 2工具对研究进行方法学评估，并进行进一步的数据提取以便重新分析。
本综述纳入了所有比较CT血管造影结果与根据神经学标准诊断脑死亡的大型病例系列和队列研究。独特的是，本综述中的参考标准与目标疾病相同。
我们根据QUADAS - 2标准评估了所有纳入研究的方法学质量。我们在用于解释CT血管造影研究的方法中遇到了显著的异质性，因此，在可能的情况下，我们重新分析了已发表的数据以符合标准的放射学解释模型。大多数研究（有一项例外）并非设计纳入非脑死亡患者，因此作为荟萃分析的一部分，总体特异性无法估计。对已发表数据和重新分析为标准化解释模型的数据都计算了敏感性、置信区间和预测区间。
共找到10项研究，总计366例患者。我们在已发表数据分析中纳入了8项研究，共337例患者。研究的方法学质量总体令人满意，但在与索引测试的执行以及索引测试与参考测试的时间安排相关的几个特定领域存在引入显著偏差的可能性。结果显示敏感性估计值为0.84（95%置信区间（CI）0.69至0.93）。95%近似预测区间非常宽（0.34至0.98）。三项研究中的数据可作为四血管解释模型获取，另外五项研究（共314例患者事件）的数据可重新分析为四血管解释模型。结果显示类似的敏感性估计值为0.85（95% CI 0.77至0.91），但95%近似预测区间有所改善（0.56至0.96）。
现有证据不支持在疑似临床脑死亡患者的管理流程中，将CT血管造影用作强制性测试或完全替代神经学测试方法。假设临床医生知晓总体敏感性相对较低，CT血管造影在临床诊断死亡后作为确证性或附加测试可能有用。就未来发表研究的标准放射学解释方案达成共识将有助于进一步的荟萃分析。
