Skip to main content
SpringerLink
Log in

Computed Tomography Angiography in the Diagnosis Of Brain Death: A Systematic Review and Meta-Analysis

  • Review Article
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

Physiological instability and confounding factors may interfere with the clinical diagnosis of brain death. Computed tomography angiography (CTA) has been suggested as a potential ancillary test for confirmation of brain death, but its diagnostic accuracy remains unclear.

Methods

We searched MEDLINE, EMBASE, and CENTRAL for studies comparing CTA with other accepted methods of diagnosing brain death (clinical or radiographic). Summary estimates of diagnostic accuracy were computed using random effects models. Subgroup analyses and meta-regression were performed to assess associations between CTA sensitivity and study or patient characteristics.

Results

Twelve studies, involving 541 patients, were included. If the CTA criterion for brain death was complete lack of opacification of intracranial vessels, then the pooled sensitivity was 62 % (50–74 %) for venous phase and 84 % (75–94 %) for arterial phase imaging. The sensitivity of CTA was higher when the criterion for brain death involved absence of opacification of internal cerebral veins, either alone (99 %, 97–100 %) or in combination with lack of flow to the distal middle cerebral artery branches (85 %, 77–93 %). CTA sensitivity was not influenced by different reference standards (clinical vs. radiographic) or predominant diagnostic category (stroke vs. brain trauma). Specificity of CTA could not be adequately determined from the existing data.

Conclusion

Many patients who progress to brain death by accepted clinical or radiographic criteria have persistent opacification of proximal intracranial vessels when CTA is performed. The specificity of CTA in the diagnosis of brain death has not been adequately assessed. Routine use of CTA as an ancillary test in the diagnosis of brain death is therefore not recommended until diagnostic criteria have undergone further refinement and prospective validation. Absence of opacification of the internal cerebral veins appears to be the most promising angiographic criterion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Wijdicks EFM, Varelas PN, Gronseth GS, Greer DM. The Quality Standards Subcommittee of the American Academy of Neurology. Evidence-based guideline update: determining brain death in adults. Neurology. 2010;74:1911.

    Article  PubMed  Google Scholar 

  2. Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ. 2006;174:S1–30.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Academy of Medical Royal Colleges. A code of practice for the diagnosis and confirmation of death. London: Academy of Medical Royal Colleges, 2008. Available at: www.aomrc.org.uk/doc_view/42-a-code-of-practice-for-the-diagnosis-and-confirmation-of-death (Accessed March 2014).

  4. Australian and New Zealand Intensive Care Society (ANZICS): The ANZICS statement on death and organ donation (3rd Ed). Melbourne: ANZICS, 2013. Available at: http://www.anzics.comau/death-and-organ-donation (Accessed March 2014).

  5. Busl KM, Greer DM. Pitfalls in the diagnosis of brain death. Neurocrit Care. 2009;11:276–87.

    Article  PubMed  Google Scholar 

  6. Saposnik G, Basile VS, Young GB. Movements in brain death: a systematic review. Can J Neurol Sci. 2009;36:154–60.

    PubMed  Google Scholar 

  7. Wijdicks EFM, Rabinstein AA, Manno EM, Atkinson JD. Pronouncing brain death: contemporary practice and safety of the apnea test. Neurology. 2008;71:1240–4.

    Article  PubMed  Google Scholar 

  8. Savard M, Turgeon AF, Gariepy JL, et al. Selective 4 vessel angiography in brain death: a retrospective study. Can J Neurol Sci. 2010;37:492–7.

    PubMed  Google Scholar 

  9. Wijdicks EFM. The case against confirmatory tests for determining brain death in adults. Neurology. 2010;75:77–83.

    Article  PubMed  Google Scholar 

  10. Wijdicks EFM. Brain death worldwide: accepted fact but no global consensus in diagnostic criteria. Neurology. 2002;58:20–5.

    Article  PubMed  Google Scholar 

  11. Heran MKS, Heran NS, Shemie SD. A review of ancillary tests in evaluating brain death. Can J Neurol Sci. 2008;35:409–19.

    PubMed  Google Scholar 

  12. Shemie SD, Lee D, Sharpe M, et al. Brain blood flow in the neurological determination of death: Canadian expert report. Can J Neurol Sci. 2008;35:140–5.

    PubMed  Google Scholar 

  13. Swiss Academy of Medical Sciences. The determination of death in the context of organ transplantation: Medical-ethical guidelines. Available at www.samw.ch. Accessed 28 Mar 2014.

  14. Leclere X, Boulin A, Bracard S, et al. CT angiography for the diagnosis of brain death: recommendations of the French Society of Neuroradiology (SFNR). J Neuroradiol. 2007;34:217–9.

    Article  Google Scholar 

  15. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.

    Article  CAS  PubMed  Google Scholar 

  16. Leeflang MMG, Deeks JJ, Gatsonis C, Bossuyt PMM. Systematic reviews of diagnostic test accuracy. Ann Intern Med. 2008;149:889–97.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.

    Article  CAS  PubMed  Google Scholar 

  18. Berlin JA. Does blinding of readers affect the results of meta-analyses? Lancet. 1997;350:185–6.

    Article  CAS  PubMed  Google Scholar 

  19. Whiting PF, Rutjes AWS, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.

    Article  PubMed  Google Scholar 

  20. Dupas B, Gayet-Delacroix M, Villers D, et al. Diagnosis of brain death using two-phase spiral CT. Am J Neuroradiol. 1998;19:641–7.

    CAS  PubMed  Google Scholar 

  21. Frampas E, Videcoq M, de Kerviler E, et al. CT angiography for brain death diagnosis. Am J Neuroradiol. 2009;30:1566–70.

    Article  CAS  PubMed  Google Scholar 

  22. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika. 1934;26:404–13.

    Article  Google Scholar 

  23. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  24. Lipsey MW, Wilson DB. Practical meta-analysis. London: SAGE Publications, Inc; 2000.

    Google Scholar 

  25. Lamb T, Arumaithurai K, Shastri R, Putta S. The case for brain death determination by CTA: where are the results. J Trauma Acute Care Surg. 2012;72:1123.

    PubMed  Google Scholar 

  26. Angstwurm H. CT angiography in the diagnosis of brain death. Dtsch Arztebl Int. 2012;109:623.

    PubMed Central  PubMed  Google Scholar 

  27. Welschehold S, Boor S, Reuland K, et al. CT angiography as a confirmatory test in brain death. Acta Neurochir Suppl. 2012;114:311–6.

    Article  PubMed  Google Scholar 

  28. Welschehold S, Boor S, Reuland K, et al. Technical aids in the diagnosis of brain death: a comparison of SEP, AEP, EEG, TCD and CT angiography. Dtsch Arztebl Int. 2012;109:624.

    PubMed Central  PubMed  Google Scholar 

  29. Welschehold S, Kerz T, Boor S, et al. Detection of intracranial circulatory arrest in brain death using cranial CT angiography. Eur J Neurol. 2013;20:173–9.

    Article  CAS  PubMed  Google Scholar 

  30. Welschehold S, Kerz T, Boor S, et al. Computed tomographic angiography as a useful adjunct in the diagnosis of brain death. J Trauma Acute Care Surg. 2013;74:1279–85.

    Article  PubMed  Google Scholar 

  31. Sawicki M, Bohatyrewicz R, Safranow K, et al. Dynamic evaluation of stasis filling phenomenon with computed tomography in diagnosis of brain death. Neuroradiology. 2013;55:1061–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Bohatyrewicz R, Sawicki M, Walecka A, et al. Computed tomographic angiography and perfusion in the diagnosis of brain death. Transpl Proc. 2010;42:3941–6.

    Article  CAS  Google Scholar 

  33. Orban JC, El-Mahjoub A, Rami L, et al. Transcranial Doppler shortens the time between clinical brain death and angiographic confirmation: a randomized trial. Transplantation. 2012;94:585–8.

    Article  PubMed  Google Scholar 

  34. Lovrencic-Huzjan A, Vukovic V, Gopcevic A, et al. Usefulness of transcranial Doppler in brain death confirmation. Acta Med Croatica. 2009;63:55–60.

    PubMed  Google Scholar 

  35. Quesnel C, Fulgencio JP, Adrie C, et al. Limitations of computed tomographic angiography in the diagnosis of brain death. Intensive Care Med. 2007;33:2129–35.

    Article  PubMed  Google Scholar 

  36. Combes JC, Chomel A, Ricolfi F, et al. Reliability of computed tomographic angiography in the diagnosis of brain death. Transpl Proc. 2007;39:16–20.

    Article  Google Scholar 

  37. Escudero D, Otero J, Marques L, et al. Diagnosing brain death by CT perfusion and multislice CT angiography. Neurocrit Care. 2009;11:261–71.

    Article  PubMed  Google Scholar 

  38. Berenguer C, Davis FE, Howington JU. Brain death confirmation: comparison of computed tomographic angiography with nuclear medicine perfusion scan. J Trauma. 2010;68:553–9.

    Article  PubMed  Google Scholar 

  39. Musacchio M, Meyer A, Manoila I, et al. CT angiography in brain death diagnosis: clinical experience in 184 patients. Neuroradiology. 2010;29:46–7.

    Google Scholar 

  40. Rieke A, Regli B, Mattle HP, et al. Computed tomography angiography (CTA) to prove circulatory arrest for the diagnosis of brain death in the context of organ transplantation. Swiss Med Wkly. 2011;141:w13261.

    CAS  PubMed  Google Scholar 

  41. Shankar JJ, Vandorpe R. CT perfusion for confirmation brain death. Am J Neuroradiol. 2013;34:1175–9.

    Article  CAS  PubMed  Google Scholar 

  42. Leclerc X, Taschner CA, Vidal A, et al. The role of spiral CT for the assessment of the intracranial circulation in suspected brain-death. J Neuroradiol. 2006;33:90–5.

    Article  CAS  PubMed  Google Scholar 

  43. Strozyk D, Schwamm LH. False positive CT angiography in brain death. Neurocrit Care. 2009;11(2):272–5.

    Article  PubMed  Google Scholar 

  44. Braun M, Ducrocq X, Huot JC, et al. Intravenous angiography in brain death: report of 140 patients. Neuroradiology. 1997;39:400–5.

    Article  Google Scholar 

  45. Munari M, Zucchetta P, Carollo C, et al. Confirmatory tests in the diagnosis of brain death: comparison between SPECT and contrast angiography. Crit Care Med. 2005;33:2068–73.

    Article  PubMed  Google Scholar 

  46. Taylor T, Dineen RA, Gardiner DC, et al. Computed tomography (CT) angiography for confirmation of the clinical diagnosis of brain death. Cochrane Database Syst Rev. 2014;3:CD009694.

    PubMed  Google Scholar 

  47. Monteiro LM, Bollen CW, van Huffelen AC, et al. Transcranial Doppler ultrasonography to confirm brain death: a meta-analysis. Intensive Care Med. 2006;32:1937–44.

    Article  PubMed  Google Scholar 

  48. Report of the adhoc committee of the. Harvard medical school to examine the definition of brain death: a definition of irreversible coma. JAMA. 1968;205:337–40.

    Article  Google Scholar 

  49. Wijdicks EF, Pfeifer EA. Neuropathology of brain death in the modern transplant era. Neurology. 2008;70:1234–7.

    Article  PubMed  Google Scholar 

  50. Young GB, Lee D. A critique of ancillary tests for brain death. Neurocrit Care. 2004;1:499–508.

    Article  PubMed  Google Scholar 

  51. Joffe AR, Lequier L, Cave D. Specificity of radionuclide brain blood flow testing in brain death: case report and review. J Intensive Care Med. 2010;25:53–64.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Peter Faris (PhD, University of Calgary) who provided helpful comments regarding the statistical analysis.

Author information

Authors and Affiliations

  1. Departments of Critical Care Medicine & Clinical Neurosciences, Foothills Hospital, University of Calgary, McCaig Tower, 3134 Hospital Drive N.W., Calgary, AB, T2N 2T9, Canada

    Andreas H. Kramer

  2. Departments of Critical Care Medicine, Surgery & Community Health Sciences, University of Calgary, Calgary, AB, Canada

    Andreas H. Kramer & Derek J. Roberts

Authors
  1. Andreas H. Kramer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derek J. Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas H. Kramer.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 22 kb)

Online Appendix 2

Funnel plot showing relationship between the sensitivity of individual studies (x-axis) and the standard error of the sensitivity (y-axis). (PDF 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kramer, A.H., Roberts, D.J. Computed Tomography Angiography in the Diagnosis Of Brain Death: A Systematic Review and Meta-Analysis. Neurocrit Care 21, 539–550 (2014). https://doi.org/10.1007/s12028-014-9997-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-014-9997-4

Keywords

Search

Navigation