Implications of ischemic penumbra for the diagnosis of brain death

Abstract

The data reviewed here suggest the possibility that a global reduction of blood supply to the whole brain or solely to the infratentorial structures down to the range of ischemic penumbra for several hours or a few days may lead to misdiagnosis of irreversible brain or brain stem damage in a subset of deeply comatose patients with cephalic areflexia. The following proposals are advanced: 1) the lack of any set of clinically detectable brain functions does not provide a safe diagnosis of brain or brain stem death; 2) apnea testing may induce irreversible brain damage and should be abandoned; 3) moderate hypothermia, antipyresis, prevention of arterial hypotension, and occasionally intra-arterial thrombolysis may contribute to good recovery of a possibly large subset of cases of brain injury currently regarded as irreversible; 4) confirmatory tests for brain death should not replace or delay the administration of potentially effective therapeutic measures; 5) in order to validate confirmatory tests, further research is needed to relate their results to specific levels of blood supply to the brain. The current criteria for the diagnosis of brain death should be revised. Correspondence

Brain Death and True Patient Care

“…Such a drop in CBF adds to the suppression of neurological functions, but without loss of organic vitality because physiologically, the level of energy required for sustaining the vitality of an organ is much lower than that needed for maintaining its function. Neurological functions, therefore, remain recoverable, provided that CBF is maintained such that "the oxygen extraction fraction continues to be [sufficiently] elevated" (Coimbra 1999(Coimbra , 1480. This is why the penumbra is such a critical timewindow when prompt application of aggressive therapeutic intervention can significantly improve the outcomes of patients with SBI.…”

‘Brain death’: should it be reconsidered?

“…39 Nevertheless, 'since the hypothalamus is supplied with blood from the circle of Willis and the hypothalamic nuclei provide both the releasing hormones for the anterior hypophysis and the hormones to be liberated by the posterior hypophysis, preserved hypothalamic -hypophyseal function in some patients presumed to be brain dead cannot be explained by a hypothetical collateral blood flow to the anterior hypophysis through the inferior hypophyseal arteries arising extradurally from the internal carotid arteries'. 40 Maintaining endocrine activity includes various integrated neuro-endocrinic functionsFfor example, regulation of salt and water balance, as is seen in high percentage of these patients, 11,41 temperature control, increase of the levels of growth hormone after intravenous injection of insulin 42 in which hypothalamus is involved in 'brain-dead' patients.…”

Clinical and ethical perspectives on brain death

“…[34][35][36] "Indeed", Joffe et al wrote, "it is reasonable to suggest that the apnea test itself can result in failing the apnea test, creating a self-fulfilling prophecy". 34 Finally, although eupneic inspiratory efforts are stimulated by hypercarbia in the setting of normal physiology, in the context of the specific pathophysiology of a cascade of rostral-caudal dysfunction in which the lower medulla will be the final anatomic area to be compromised, the appropriate stimulus would be hypoxia (not hypercarbia), because hypoxia stimulates the lower medulla-mediated gasping reflex.…”

“…43 Furthermore, since intracranial circulatory arrest is not entirely complete in all cases, 44 since ICP decreases after its acute trigger resolves, and since the arteries supplying the brain can remain patent, it may be physiologically possible that some areas of neural tissue can remain viable through something like a global ischemic penumbra. 35 As in stroke pathophysiology, the concept of ischemic penumbra refers to a condition in which blood flow diminishes to a degree that is incompatible with clinically detectable functioning but is sufficient to maintain the physiological viability of the tissue for some time. However, there have been no sustained research efforts on this issue, and cardiovascular collapse following the diagnosis of brain death is a self-fulfilling prophecy since the patient will either become an organ donor or mechanical support will be removed; 45 therefore, it is unknown whether this is a realistic possibility or mere speculation.…”