When Are Ancillary Tests Recommended In Brain Death Confirmation

Abstract

It is widely accepted that brain death (BD) is a clinical diagnosis, although ancillary tests are recommended when specific components of the clinical testing cannot reliably be evaluated. The therapeutic use of barbiturates in patients with severe intracranial hypertension or other forms of drug intoxication, hypothermia, and other metabolic disturbances, can prevent determination of BD by clinical criteria. We present a review here about the use of ancillary tests in BD confirmation. Confirmatory tests in BD can be divided in those proving absent cerebral blood flow (CBF) and those that demonstrate loss of bioelectrical activity. We recommend assessing circulatory arrest by transcranial Doppler (TCD), and neuronal function by a neurophysiologic test battery. If TCD fails to validate the absence of CBF, computer tomography angiography can be used to confirm BD diagnosis. It is widely accepted that brain death (BD) is a clinical diagnosis, and it is currently defined as a complete and irreversible loss of brain function. Confirmatory laboratory tests are recommended when specific components of the clinical testing cannot reliably be evaluated 1-3 In certain European, Central and South American, and Asian countries, law requires confirmatory tests. The diagnosis of BD in children and neonates is more complicated and ancillary tests are usually advocated. 6-12 According to Wijdicks, “a confirmatory test is needed for patients in whom specific components of clinical testing cannot be reliably evaluated.” An ideal confirmatory study for BD should be safe, extremely accurate and reliable, available, quick and inexpensive. Heran et al. also affirmed that an ideal confirmatory study for BD should be “readily available, rapid, safe, portable, non-invasive, inexpensive, independently sufficient to establish brain death, not susceptible to external/internal confounding factors”. The therapeutic use of barbiturates in patients with severe intracranial hypertension or other forms of drug intoxication, hypothermia, and other metabolic disturbances, can prevent determination of BD by clinical criteria. Confirmatory tests in BD can be divided in those proving absent cerebral blood flow (CBF) and those that demonstrate loss of bioelectrical activity. In fact, confirmatory tests that are widely accepted are conventional angiography and EEG. We review here when ancillary tests are recommended in BD confirmation. TESTS TO DEMONSTRATE ABSENT CEREBRAL BLOOD FLOW Several authors have defended that the only reliable test to prove irreversibility in BD is showing the complete absence of intracranial circulation. 1,3 During the 1950s and 1960s the phenomenon of 'cerebral circulatory arrest' (or 'blocked cerebral circulation') was repeatedly demonstrated. Bernat recently emphasized that “the most confident way to demonstrate that the global loss of clinical brain functions is irreversible is to show the complete absence of intracranial blood flow.” It is well established that brain neurons are irreversible damaged after a few minutes of complete cessation of CBF, and are globally destroyed when blood flow completely ceases for about 20-30 minutes. Ingvar defended that the permanent cessation of CBF produces the total brain infarction. Although the absence of CBF is deemed as a precise indicator of BD, a patient may be brain-dead regardless CBF preservation. According to Palmer and Bader, there are When Are Ancillary Tests Recommended In Brain Death Confirmation? 2 of 9 two patterns of BD. The most common pattern is characterized by an increase of intracranial pressure (ICP) to a point which goes above the mean arterial pressure (MAP), resulting in no net CBF. Of course, tests proving absent cerebral blood flow (CBF) are appropriate for this pattern. The second pattern is typified by ICP not exceeding MAP, but as there is an inherent pathology which affects brain tissue on a cellular level, BD may occurs. Hence, in this BD pattern CBF is preserved, and ancillary tests relying on its lack would result in false negative. Hence, ancillary tests in this situation should evaluate neuronal function and viability. Several tests have been developed in the last decades that can accurately and validly measure CBF in suspected braindead patients. The first technique used to demonstrate absence of intracranial circulation in BD distal to the intracranial portions of the internal carotid and vertebral arteries was the cerebral angiography. Other techniques used to determine absent CBF have been: Cerebral intravenous digital subtraction angiography, Intravenous radionuclide angiography, single photon emission tomography (SPECT). echoencephalography, measurement of arm to retina circulation time, ophthalmic artery pressure, rheoencephalography, xenon-enhanced computed tomography, MRI angiography, CT angiography and CT perfusion, and transcranial Doppler (TCD). We will concentrate our review on TCD in BD confirmation. To assess CBF in suspected brain-dead patients we recommended the use of transcranial Doppler ultrasonography (TCD). Transcranial Doppler ultrasonography (TCD) is a noninvasive technique that measures local blood flow velocity and direction in the proximal portions of large intracranial arteries. TCD requires training and experience to perform it and interpret results; hence it is typified as operator-dependent. In the ICU setting intensivists or neurologists usually receive training to apply this technique using portable Doppler devices in suspected brain-dead cases. Immediately after Doppler-sonography had been introduced in clinical practice, typical findings for brain circulatory arrest were described. In general, the principal advantages of TCD are: it is noninvasive, it can be carried out at the bedside, it can repeated as needed or in continuous monitoring, it is less expensive than other techniques, and dye contrast agents are not needed. Its main chief disadvantages are: it can only study CBF velocities in certain segments of large intracranial vessels, it is operatordependent requiring training and experience to perform it and interpret results, and, up to 20% of studies may be unsuccessful because some patients have cranial vaults too thick impeding a proper visualization of intracranial arteries. Nonetheless, Conti et al. have recently recommended serial TCD examinations using trancervical and transorbital carotid Insonation for improving TCD sensitivity in BD confirmation. The American Academy of Neurology Therapeutics and Technology Assessment Subcommittee presented a remarkable report on the transcranial Doppler ultrasonography (TCD) clinical applications. The use of TCD to diagnose cerebral circulatory arrest and brain death (BD) was fully analyzed. The Subcommittee reviewed a number of high quality articles that also discuss some caveats with an important impact upon the diagnosis of BD by TCD, concluding with strict criteria, that TCD is highly sensitive and specific for the diagnosis of BD. Oscillating flow and systolic spikes patterns are typical Doppler-sonographic flow signals found in the presence of cerebral circulatory arrest, which if irreversible, results in BD. The pathophysiology to explain these findings is the following. In comatose patients, the earliest sign of an ICP augmentation is an increased pulsatilty followed by progressive decrease in diastolic flow velocities and reduction in mean flow velocities. If the velocity at the end of diastole becomes zero, then the ICP has reached the diastolic blood pressure. Forward flow continues in systole, and hence in this phase it can’t be diagnosed a brain circulatory arrest. When the ICP the ICP equals or exceeds the systolic blood pressure forward and reverse flow are nearly identical, and in this stage a cessation of cerebral perfusion has been reached. It is characterized by a pattern known as oscillating flow, biphasic flow, net zero flow, etc. Equality of forward and reverse flows can be demonstrated calculating the area under the envelope of the positive and negative deflection in the velocity waveforms. As an additional reduction of the blood movement occurs, systolic spikes appear, which very short velocity peaks are. The systolic spike is a distinctly pattern for diagnosing brain circulatory arrest. Finally, when ICP augments further and flow hitch becomes more proximal, no flow signals in the basal cerebral arteries are identified. It is important to stress that a failure to detect flow signals can be due to ultrasonic transmission problems. To face this controversy and confirm diagnosis, it is necessary to perform extracranial bilateral When Are Ancillary Tests Recommended In Brain Death Confirmation? 3 of 9 recording of the common carotid, internal carotid, and vertebral arteries. The Neurosonology Research Group of the World Federation of Neurology created a Task Force Group in order to evaluate the role of Doppler-sonography as a confirmatory test for determining brain death, concluding that “extraand intracranial Doppler-sonography is a useful confirmatory test to establish irreversibility of cerebral circulatory arrest as optional part of a brain death protocol. Moreover, this Task Force Group specially recommended TCD in patients when the therapeutic use of sedative drugs causes to be electroencephalography unreliable. This Group proposed a series of guidelines for the use of Dopplersonography for detecting brain circulatory arrest: Cerebral circulatory arrest can be confirmed if the following extraand intracranial Doppler sonographic findings have been recorded and documented both intra and extracranially and bilaterally on two examinations at an interval of at