Confirmatory Tests For Brain Death

Examination for brain death can be frequently completed based on the clinical criteria outlined above without the need for confirmatory testing. In published reports on adult patients diagnosed as brain dead using these criteria there have been no survivors.11 However, in a significant number of patients where these criteria are not met (hypoxic brain injury, chronic obstructive pulmonary disease, young children), there may be an indication to shorten the observation period (hemodynamic instability) or there may be a concern about potentially reversible metabolic conditions. Hence, irreversibility of brain damage can be confirmed and the observation period reduced by the appropriate and timely use of confirmatory tests. In view of the multitude of tests available, it is generally preferred that a single method is adopted by the medical team involved as the study of choice. This will provide consistency and improved accuracy as expertise is developed using that particular study.

Cerebral Blood Flow Studies

Contrast angiography of the cerebral vessels has long been considered the gold standard to determine the absence of cerebral blood flow.3,4 Failure to opacify the intracranial vessels during conventional or digital subtraction angiography is accepted as confirmatory evidence for brain death. Some have expressed concerns that radio-opaque contrast can be artifactually introduced into the intracranial circulation if injected too vigorously during angiography. This worry is remedied with venous digital subtraction imaging or aortic arch injections rather than selective (carotid or innominate artery) injections. Patient transportation to the an-

giography suite, however, remains a potential hazard in unstable and critically ill patients. In addition, this study frequently presents technical challenges in small children, eliminating its role in that setting. Hence, many have favored the use of radionuclide angiography as the first choice study for cerebral blood flow imaging.

Radionuclide angiography has been found to be a reliable, sensitive and safe method in the evaluation of cerebral blood flow in both adults and children.18,23 The test can also be performed at the bedside, making it very practical. For many years, blood pool agents, including Tc-99m pertechnetate, DTPA or gluco-heptonate, have been used for this study. These agents do not cross the blood-brain barrier. They are injected intravenously as a bolus while imaging of the brain is performed over the head with a portable gamma camera for about 15 minutes. Blood pool agents are not reliable indicators of posterior fossa and brainstem perfusion, though in the appropriate clinical setting this information is not typically needed. In the event of poor bolus injection, gamma camera malfunction or imaging interruption, the study cannot be interpreted and repeat imaging is not possible. Cerebral perfusion agents that cross the blood brain barrier, Tc-99m hexamthylpropylene-amine oxime (HMPAO) or I-123 iodoamphetamine (IMP), have been recommended instead of blood pool agents for the confirmation of brain death.3,4 These agents are taken up by perfused and viable gray matter cells after the initial flow phase and held for several hours. An initial image is taken during the flow phase (Fig. 1.1) showing absence of flow. This is followed by delayed images that can be performed in more than one plane (Fig. 1.2). Radionu-clide cerebral perfusion can be coupled with single photon emission computed tomography (SPECT) to provide more precise regional information including blood flow to the posterior fossa. If initial flow imaging is interrupted, delayed images can be obtained without repeat bolus administration.

Transcranial doppler and real time cranial ultrasound have been used to confirm brain death, especially in the newborn and young infant.20,3 Characteristic findings in brain death include oscillating movement of the blood column within cerebral arteries, short systolic spikes and absence of a signal when previously found. This technique has the advantage of being noninvasive, portable, quick and relatively inexpensive. However, it requires considerable practice and skill. Specificity and sensitivity have been reported to be as high as 100% and 91% respectively.20

Stable xenon computerized tomography (XeCT) is another noninvasive method capable of measuring cerebral blood flow (mL/min/100g) in multiple brain regions. XeCT is more sensitive than radionuclide angiography, particularly in children,18 because it yields anatomic and regional quantitative flow information. Minimal (less than 1-5 mL/min/100g) or absent cerebral blood flow is indicative of brain death.20

Electroencephalography and the Confirmation of Brain Death

Electroencephalography has long been used to evaluate coma and brain death.1,2 Electrocerebral silence, defined as no electrocerebral activity over 2 FV, has been used for confirmation of brain death. The President's Commission criteria for

Ceretec Scan
Fig. 1.1. Early flow phase of a Technetium 99m-HMPAO radionuclide brain scan supporting the diagnosis of brain death.

brain death did not include EEG as a requirement. However, EEG has been used as a confirmatory study and diagnostic adjunct for brain death diagnosis in young children.17 Due to multiple technical problems that may be encountered during the test, strict guidelines have been developed by the American Electro-encephalography Society.3 A 16- or 18-channel instrument is used with a minimum of eight scalp electrodes. Electrodes are set at least 10 cm apart and the recording is continued for at least 30 minutes. Many artifacts are possible and may be related to electrical interference, faulty equipment or neuromuscular activity. Hence the test should be performed only by a qualified technician, adhering strictly to the methodology formulated by the American EEG Society. In adults, if the EEG is not indicated and brain death has been declared on clinical grounds, it may be prudent not to perform this examination. Most patients fulfilling the criteria for brain death will have an isoelectric EEG. However, as many as 20% will have residual activity that can last for many hours,12 frequently delaying brain death declaration and allowing for cardiorespiratory failure.

Gamma Scan Brain Planar
Fig. 1.2. Delayed images showing no tracer uptake within the brain confirming the clinical diagnosis of brain death. Peripheral shadows are attributed to scalp circulation.

In infants and children, the EEG is the most widely used laboratory study for determining brain death. Many unique aspects must be considered in this population.18 Most importantly, the test should be performed and interpreted by personnel experienced with pediatric EEGs. In patients with a clinical diagnosis of brain death, electrocerebral silence is confirmatory of brain death. However, the EEG may still demonstrate some activity in some patients with established brain death by clinical examination and cerebral blood flow study.11,18 Some of these patients may progress to have an isoelectric EEG although many will succumb to cardiorespiratory failure with persistent EEG activity. Hence, in children as well as in adults, the EEG may not correlate with the clinical diagnosis of brain death or cerebral blood flow studies.

Brainstem auditory evoked potentials (BAERs) evaluate the function of the auditory pathway from the cochlea to the thalamus. In the usual clinical setting, this study has very limited practical applications. In children, published reports suggest that BAERs should not be used as confirmatory evidence for brain death.18,3


The concept of brain death has evolved significantly over the past decades. Much of the controversy revolved around its significance in relation to survival and potential reversibility. In addition, studies that fueled some of the controversy (EEG as an example) attempted to establish the survival of few intracranial neurons but without much clinical relevance. In adhering to the methodology outlined above, one should rely mostly on clinical criteria to establish death of the "brain as a whole". Confirmatory studies have a role in select situations where clinical criteria are not entirely applicable. With the knowledge we currently have about brain death diagnosis, timely diagnosis and clinical disposition reduces the futile supportive efforts in the intensive care unit and spares the family much prolonged agony over this terminal event. In addition, at a time when organ transplantation has become such a widely applied modality, the need for potentially transplantable organs continues to rise. It is our responsibility to promote the awareness about brain death and support sound clinical practices to assure timely diagnosis and organ donation as a benefit to society.


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