Persistence of Cerebral Blood Flow After Brain Death

W. Mel. Flowers, JR., MD, Bharti R. Patel, MD, Department of Radiology, Division of Nuclear Medicine, University of Mississippi Medical Center, Jackson

South Med J. 2000;93(4) 

In This Article

Abstract and Introduction

Persistent cerebral blood flow occasionally confounds confirmatory tests for brain death and results in the anguish of delayed diagnosis, unnecessary use of expensive resources, and loss of transplant opportunities. We reviewed the literature to examine the reasons, frequency, and meaning of this problem. We found that this phenomenon occurs: (1) before increasing intracranial pressure completely shuts down flow; (2) in infants with pliable skulls; and with (3) decompressing fractures, (4) ventricular shunts, (5) ineffective deep brain flow, (6) reperfusion, (7) brain herniation, (8) jugular reflux, (9) emissary veins, and (10) pressure injection artifacts. Isolated venous sinus visualization is common (occurring in up to 57%) but represents trivial blood flow and confirms brain death. Arterial flow is much less common (2.6% incidence in our series). Normal flow occurs but is rare. Arterial flow does not exclude brain death, but the diagnosis should be confirmed by repeated studies or other means.

We recently reported results of 229 radionuclide studies in 219 patients with suspected brain death.[1] Seven examinations showed some arterial flow in 6 patients who were clinically brain dead. Brain death was confirmed by electroencephalography (EEG) in 2 patients, repeat radionuclide angiography was done in 3, and the remaining patient had cardiac arrest within 24 hours. Six other clinically brain-dead patients had isolated superior sagittal sinus activity. One of them had no sinus activity on a repeat study. Another patient's repeat examination was unchanged. This experience led us to believe that cerebral blood flow (CBF) is not always completely shut down as soon as brain death occurs. We reviewed the literature to find other examples of this phenomenon. Our initial MEDLINE search of titles and online abstracts from 1966 through July 1999 using the key words "brain death" yielded 3,972 references. Examples cited in our review were found through examination of these titles and abstracts and from the text and bibliographies of selected articles.

Although brain death is a clinical diagnosis, confirmation by additional testing is often required by local practice standards or local law. Confirmation is also helpful if there is suspected drug or metabolic intoxication, if there is reason to shorten the observation period, or to present additional evidence to the family that the patient is dead. The diagnosis of brain death can be confirmed in two ways, either by the neurophysiologic demonstration that the brain has been destroyed or by showing that CBF is no longer present.

The authors of the Harvard criteria thought that electrocerebral silence was of great confirmatory value.[2] Thus, the EEG became the first supporting study for the determination of brain death and is still used despite important limitations.[3] Minor transient residual EEG activity can be present in the face of clinical brain death.[4] The EEG is subject to electrical artifacts in the intensive care environment.[3] It has failed to recognize reversibility of coma in patients with drug intoxication.[5,6] More recently, evoked potentials (EPs), the potentials generated by the nervous system in response to sensory stimuli, have been proposed as better tools. Visual EPs, somatosensory EPs, and brain stem auditory EPs (BAEPs) can be used.[7]

Tests for cerebral flow are important confirmatory examinations.[8,9,10] Current established methods include cerebral angiography, radionuclide angiography, planar cerebral perfusion scintigraphy (CPS), and computed CPS.[10,11]

Four-vessel cerebral angiography is the standard of confirmatory tests. It can evaluate both cerebral and posterior fossa blood flow. The study can be done with flush injection of iodinated contrast media into the aortic arch or by direct injection of the cerebral vessels. Normally, the cerebral arteries are patent and are easily seen on angiography. In brain death, flow is obstructed in the internal carotid arteries and vertebral arteries due to increased intracranial pressure. Unfortunately, cerebral angiography is too expensive and too invasive for routine use. It also exposes potential donor organs to toxic contrast material. Cerebral angiography for the confirmation of brain death has had greater popularity in Europe than in the United States.

Radionuclide angiography uses an intravenous bolus of radioactive material to show the presence or absence of blood flow in the cerebral circulation. A scan is compatible with brain death when there is absence of arterial flow on the dynamic study. Venous sinuses are seen ordinarily, but they are not usually seen when there is brain death. An important advantage of radionuclide angiography is the ability to detect blood flow in patients who have coma due to drug intoxication. [2,13] There are occasional technical failures due to inadequate bolus injection of the radiopharmaceutical. The major disadvantage of the procedure is that the posterior fossa circulation is not evaluated.

Planar CPS involves localization of radioactive material in the brain tissue itself and has the advantage of direct visualization of perfusion of the cerebral cortex and brain stem. Since a cohesive bolus of radioactive material is not necessary, a simple intravenous injection is given. This is easier and more reliable than a bolus injection. Normally, static planar imaging with a scintillation camera shows the radioactive agent localized within and throughout the brain. Usually, there is no significant activity within the cranium in a patient with brain death. Cerebral perfusion scintigraphy is advocated by many as a replacement for radionuclide angiography. The most important advantage of this procedure is its ability to directly show the posterior fossa. The major disadvantage is the considerably higher cost when compared with radionuclide angiography.

Tomographic CPS involves the same principles and diagnostic agents as planar CPS. A single photon emission computed tomographic scintillation camera is used to make the images. In brain death, image slices do not show concentration of radioactivity within the brain substance. This procedure is the most expensive of the three radionuclide tests and costs three or four times as much as radionuclide angiography. Although considerable improvement in diagnostic detail is possible with this test, no investigations have been reported to show that tomography offers significant advantages over planar images in the confirmation of brain death.

In 1998, a consensus opinion regarding the use of Doppler sonography was published,[14] stating that Doppler sonography is sufficient to reliably confirm brain death. It is completely noninvasive. Like all blood flow tests, the procedure is of special value when the therapeutic use of sedative drugs renders EEG unreliable. The development of cerebral circulatory arrest is identified by characteristic changes of the velocity wave form of the basal cerebral arteries.

Tests less frequently used, but able to quantify flow, include positron emission tomography (PET) and stable xenon computed tomography (XeCT). These examinations are expensive, complex, and not readily available. In addition to their clinical utility, they are excellent research tools.

The destruction of the lower brain stem causes the loss of capacity to breathe spontaneously, and brain death is observed only in patients supported by respirators. Confirmatory tests measuring or showing CBF are based on the assumption that there is cessation of blood flow with brain death. Although this is usually eventually true, it is not absolute. Persistence of CBF after brain death can result in the anguish of delayed diagnosis, unnecessary use of expensive resources, and loss of transplant opportunities.

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