Hypothalamic–Pituitary Function in Brain Death

Abstract

The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord.

Brain Death in Children: Incidence, Donation Rates, and the Occurrence of Central Diabetes Insipidus

“…The most straightforward explanation for the observation of normouria in patients with BD is that the hypothalamic osmoregulation system continues to function, in at least some patients. The various findings consistent with the preservation of hypothalamic control of the anterior pituitary corroborate this by suggesting preserved blood flow to the area, and suggest some hypothalamic-anterior pituitary function as well, albeit often in the presence of peripheral endocrine insufficiency [6]. Furthermore, anatomical considerations indicate that preserved hypothalamic osmoregulation may be expected in BD.…”

“…In a recent meta-analysis of 32 studies, concerning 1878 patients with BD, ranging in age from 2 months to 89 years, 925 (49%) were reported to have CDI [6]. The five studies that have published exclusively on pediatric patients, collectively indicated that 145 (52%) of 279 patients had CDI [ 3,4,9,16,17].…”

“…For example, electroencephalographic (EEG) activity has been documented in more than 20% of brain death patients [19], cerebral blow has been recorded in more than 5% of brain death patients [20], and it has been stated that CDI does not occur in more than half of brain death patients [6]. The most straightforward explanation for the observation of normouria in patients with BD is that the hypothalamic osmoregulation system continues to function, in at least some patients.…”

“…The incidence of CDI accompanying BD in adults and children varies. In a recent review of 32 studies, of the 1878 patients with BD, ranging in age from 2 months to 89 years, 925 (49%) were reported to have CDI [6]. At least some of thenormouric patients in these studies had some preserved brain function through hypothalamic osmoregulation.…”

Clinical and ethical perspectives on brain death

“…However, patients who meet the accepted diagnostic criteria for brain death can sometimes have some preserved neurological functioning, particularly hypothalamic functions such as the regulation of free water in the bloodstream (osmoregulation). In a recent review of the clinical literature, Nair-Collins et al 32 found evidence suggesting preservation of hypothalamic function in a substantial proportion of patients declared dead by neurologic criteria. Approximately half of the patients reported in the literature showed evidence suggesting osmoregulation via the regulated secretion of vasopressin (anti-diuretic hormone).…”