JOHN POULARAS, GREGORIOS KOURAKLIS, MICHAEL BLAIVAS and DIMITRIOS KARAKITSOS

“ . . . To die: to sleep; No more; and by a sleep to say we end. . . .”

William Shakespeare, Hamlet

Overview

The role of transcranial color coded Doppler (TCCD) in neurocritical monitoring has been illustrated in previous chapters. We will here focus on its use as a confirmatory test in the diagnosis of brain death (BD). The concept of death in Western civilization has been linked to the cessation of breathing and heart beat, irrespective of cultural and religious variability. Advances in medical technology after the Second World War and the development of critical care integrating the use of mechanical ventilators, as well as the advent of successful transplantation of vital organs, presented new ethical, legal, and medical dilemmas.¹

In 1968, the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of BD concluded that BD is a strictly clinical diagnosis, defined as the irreversible cessation of all hemispheric, cerebellum, and brainstem neurologic functions.^2,3 Analyzing BD is beyond the scope of this chapter; however, readers are referred to the White Paper published by the U.S. President’s Council on Bioethics in 2009, which illustrates controversies in the diagnosis of BD, while introducing the term “total brain failure” and defining the irreversible cessation of whole-brain function.^4,5 Controversies in the diagnosis of BD and the use of the traditional cardiopulmonary standard in the organ procurement practice, known as “controlled donation after cardiac death,” have led to the development of confirmatory tests in BD diagnostic protocols.^4,6 These tests are recommended whenever specific elements of the clinical examination may be unreliable and are rarely implemented by law in certain countries.⁶ Patients with severe brain injury are usually treated with barbiturates; moreover, the presence of various metabolic, thermoregulatory, respiratory, and other disturbances may prevent determination of BD by clinical criteria.⁷ Confirmatory tests are used in children and neonates because clinical diagnosis of BD can be challenging in these cases.^8,9 Confirmatory tests are divided into those diagnosing cerebral circulatory arrest (CCA) (e.g., angiography) and those that demonstrate loss of bioelectrical activity (e.g., electroencephalography).^10,11

Transcranial doppler in the diagnosis of cerebral circulatory arrest

CCA is an element of the destructive pathophysiologic process leading toward BD. Of note, brain neurons are irreversibly damaged after several minutes of CCA, and global brain destruction can be evident within 30 minutes.¹² However, BD may occur regardless of CCA and vice versa because the specific pathophysiology can be different among patients progressing toward BD.^10–14 The common pattern is underlined by an increase in intracranial pressure (ICP) that will eventually lead to brain “tamponade” because ICP rises above mean arterial pressure (MAP), resulting thus in CCA. Another pattern is characterized by ICP increments that may not exceed MAP, although there is pathology affecting the brain on a cellular level, resulting in edema and tissue necrosis.^10,11 Early testing for CCA may lead to false-negative findings, and thus testing for neuronal function and viability may be advocated; however, in cases where brain damage becomes irreversible, CCA could finally emerge.¹⁴ Detecting CCA requires careful timing of the initial and follow-up examinations in patients with severe brain injury progressing toward BD. Several ancillary tests to detect CCA were developed, such as cerebral angiography, intravenous digital subtraction angiography, intravenous radionuclide angiography, single-photon emission computed tomography, echoencephalography, measurement of arm-to-retina circulation time, ophthalmic artery pressure, rheoencephalography, xenon-enhanced computed tomography (CT), magnetic resonance imaging angiography, CT angiography and perfusion, and TCD.¹¹ Invasive angiography remains the gold standard examination in detecting CCA; however, recent developments in CT angiography (e.g., multirow CT, allowing reconstructions of intracranial vessels) is rapidly shifting current practice. This practice change is occurring even though more studies are required to evaluate its efficacy to diagnose CCA. Lack of portability and use of iodinated contrast remain major disadvantages of invasive and CT angiography.^11,14,15 Angiographic patterns indicative of BD are (1) absent filling of intracranial arteries at the skull entry (at the foramen magnum in the posterior circulation and at the petrosal portion of the carotid artery in the anterior circulation) and (2) minimal arterial opacification with absent parenchymal and venous phases.10–14

TCCD was used in the diagnosis of CCA after studies that proved its high agreement with invasive angiography.^11,13–15 The sensitivity and specificity of TCCD for BD confirmation, when compared with angiography, are 88% and 100%, respectively.^11,