Must Hypothalamic Neurosecretory Function Cease for Brain Death Determination? No

Abstract

The Uniform Determination of Death Act of 1980, 1 which provides the statute of death in the United States, states, 1. [Determination of Death].An individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead.A determination of death must be made in accordance with accepted medical standards.Most of the attention has been placed on the word "entire."The reason is that in other countries, such as the United Kingdom, the entire brain criterion is not required and instead the brainstem criterion is deemed adequate. 2In the United States, the word "entire" has also generated debate, with a small minority arguing that when used to the letter, up to half of brain dead (BD) patients are erroneously diagnosed as dead and, in fact, when heart-beating organ donation follows, these mistakenly diagnosed dead patients may be considered homicide victims. 3I will try to refute this proposition.The rationale behind this serious accusation is that not all BD patients lose pituitary activity.The reason for any residual pituitary activity may be traced to anatomical variances that theoretically could allow some perfusion of these basal brain structures. 4,5For example, central diabetes insipidus (DI) was encountered in 65% of 266 BD patients included in a recent large single-center study. 6In review articles, 50%-60% of adult and 52% of pediatric BD patients were diagnosed with DI. 3,7 The authors of these review articles speculate that hypothalamic and pituitary functions were still present.This argument is problematic for many reasons: First, not every study used rigorous diagnostic criteria for central DI.Polyuria is an easily noticed feature, but not pathognomonic in patients treated with diuretics, such as mannitol.Rising serum sodium is also not indicative of DI when these patients receive osmotic agents that have an uplifting effect on sodium.If hypotension occurs and vasopressin infusion is used, this external hormone will not allow DI to clinically manifest and may be confused with inherent hormone production.Similarly, if the peripheral organ (the kidney) has decreased function because of an acute or chronic process, clinical signs of DI will not be observed.Although this association has not been rigorously assessed, in a small sample of pediatric patients, 8 in the aforementioned study, 6 those patients who did not develop DI had statistically significant higher blood urea nitrogen and creatinine levels (implying kidney dysfunction) than those who did (Varelas, unpublished data).Therefore, it is possible that a higher percentage of posterior pituitary or hypothalamic loss of function could be present because of the "masking" effect on DI.Similar to vasopressin, other hypothalamic hormones may or may not be reduced in BD patients, but because they do not lead to an obvious clinical sign (such as polyuria), they are nor regularly measured nor reported. 3Although there is a paucity of autopsy data on pathologic injury of the hypothalamus/pituitary gland in BD patients, the few studies that exist are revealing.In the National Institute of Neurological and Communicative Disorders and Stroke Collaborative "nonintervention" study, 226 of 459 patients who died had brain autopsies.Although the thalamus/hypothalamus was one of the areas examined, the pituitary gland was not.The diencephalon had damage in 85% of the cases, but the hypothalamic and From the Albany Medical College, NY.Go to Neurology.org/Nfor full disclosures.

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