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Radiologic Diagnosis of Brain Death
To the Editor: The diagnosis of brain death relies on clinical documentation that the patient is in a coma, has no brain stem reflexes, and is apneic following maximal stimulation of respiratory centers. The American Academy of Neurology calls for at least a 6-hour observation period before a second clinical examination that is consistent with brain death can be used to confirm the diagnosis.1 It may be difficult and time consuming to make an official diagnosis of brain death, however, especially when variables such as sedative drugs, hypothermia, or acute metabolic derangements complicate the patient's status. Therefore the diagnosis is often supported by confirmatory tests including radionuclide brain perfusion imaging, cerebral angiography, electroencephalography, or transcranial doppler.
Such tests, nonetheless, have limitations. Electroencephalography can be inconclusive in patients who have been administered drugs that act on the brain. While angiography can be a useful confirmatory test, it is limited to evaluating the larger vessels, and may damage organs needed for anticipated transplantation (especially the kidneys).
Several reports evaluating radionuclide brain perfusion imaging, however, suggested this technique may be useful in confirming brain death.2-3 Our prior experience with approximately 100 patients has demonstrated no false-positive studies when compared with clinical criteria for brain death, which remains the definitive test.4
Making a timely diagnosis is particularly important for organ procurement, since the requirements of maintaining optimal oxygenation, hemodynamic stability, normothermia, and volume status are complex and expensive. For this reason, we have used radionuclide perfusion imaging to reduce the observation time for clinically diagnosing brain death. No studies, however, have examined whether brain perfusion imaging affects time to diagnosis of death and organ procurement.
Methods
We retrospectively analyzed time to diagnosis and rate of organ donation among 58 adults who were consecutively referred to the nuclear medicine department of the Hospital of the University of Pennsylvania with the clinical diagnosis of brain death. All underwent brain perfusion imaging using 30 mCi of Tc-99m hexamethylpropylene amineoxime. Dynamic blood flow images were obtained in the anterior projection followed by static planar images in the anterior, posterior, and lateral projections. The imaging diagnosis of brain death was made if there was complete absence of flow throughout the brain and the internal carotid arteries.
Results
Thirty-six patients (62 %) were found to have complete cessation of cerebral blood flow and were subsequently declared clinically brain dead a median of 1.75 hours (interquartile range, 0.75-3.25 hours) after the imaging procedure. This result was substantially decreased compared with the time from imaging to death in the 22 patients with evidence of cerebral blood flow (median, 11.8 hours; interquartile range, 9.7-13.7 hours) This latter group excludes 1 patient discharged from the hospital in a persistent vegetative state.
Patients in both groups met all clinical criteria for brain death. Most had had trauma or stroke. Most had no prior significant medical problems, and none were hypothermic. The findings were similar for a subset of patients who had been administered drugs that could influence cerebral function, such as pentobarbital, benzodiazepines, or phenytoin (with a median time from imaging to death of 2.25 hours when imaging revealed no perfusion vs 12 hours when perfusion was present).
We found that 61% of patients who had no cerebral flow underwent organ donation, a significantly greater proportion than the rate of 33% among patients with residual flow (Fisher exact probability = .014), even though all but 1 patient in this latter group actually died, essentially ruling out long-term survival as the cause for the difference.
Comment
Our findings support the use of radionuclide brain perfusion imaging for shortening the time to clinically diagnose brain death and to improve organ procurement rates. A shorter duration of preharvesting management may result in considerable cost savings.5 The improved rate of organ procurement may be attributable to the reduction in time to organ harvesting, which likely results in a greater viability of the organs. Referring physicians have also reported to us that the presentation of imaging studies with visual, objective support for the diagnosis of brain death provides family members a psychological benefit that helps them with the decision to withdraw care.
AUTHOR INFORMATION
Dr Cotter is now affiliated with the Department of Pathology at the University at Buffalo, State University of New York.—ED.
Andrew Newberg, MD;
Abass Alavi, MD;
Salina van Rhijn, MD;
Adolfo Cotter, MD
Division of Nuclear Medicine
Patrick Reilly, MD
Department of Surgery
Hospital of the University of Pennsylvania
Philadelphia
1. The Quality Standards Subcommittee of the American Academy of Neurology. Practice parameters for determining brain death in adults [summary statement]. Neurology. 1995;45:1012-1014.
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2. Wieler H, Marohl K, Kaiser KP, Klawki P, Frossler H. Tc-99m HMPAO cerebral scintigraphy: a reliable, noninvasive method for determination of brain death. Clin Nucl Med. 1993;18:104-109.
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3. Larar GN, Nagel JS. Technetium-99m-HMPAO cerebral perfusion scintigraphy: considerations for timely brain death declaration. J Nucl Med. 1992;33:2209-2211.
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4. Wijdicks E. Current concepts: the diagnosis of brain death. N Engl J Med. 2001;344:1215-1221.
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5. Jenkin DH, Alavi A, Reilly J, et al. The cost effectiveness of cerebral perfusion imaging to diagnose brain death. J Nucl Med. 1997;38:275P.
JAMA. 2002;288:2121-2122.
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