• G H Van den Berghe.
• Department of Intensive Care Medicine, University Hospital Gasthuisberg, K.U. Leuven.
• Verh. K. Acad. Geneeskd. Belg. 1998 Jan 1; 60 (6): 487-518; discussion 518-20.

AbstractAcute and prolonged critical illness are different metabolic and neuroendocrine paradigms and should perhaps be approached with different therapeutic strategies. The initial endocrine response consists primarily of an activated release of anterior pituitary hormones and peripheral inactivation of anabolic pathways, thought to provide substrates for survival while anabolism is postponed and to activate the immune cascade while the host is being protected against deleterious effects of the latter. There is still no solid basis for hormonal intervention in the acute phase of illness. The development of modern intensive care now enables survival of previously lethal conditions and unmasked previously unknown disorders such as the "wasting syndrome" of chronic intensive care-dependency. In the chronic phase of critical illness, we documented a uniformly impaired pulsatile secretion of anterior pituitary hormones, at least in part of hypothalamic origin, to correlate positively with reduced activity of target tissues. An acute event complicating the chronic phase of illness may evoke mixed acute/prolonged endocrine patterns, which are difficult to interpret and account for some of the apparent paradoxes in the literature. It is unlikely that the reduced neuroendocrine stimulation, distinctively present in the chronic phase of illness, has been selected by evolution and should accordingly be considered as time-honoured and appropriate. The hypothesis of inappropriate neuroendocrine dysfunction can be validated by studying the effects either of combined peripheral hormonal substitution or of hypophysiotropic releasing peptide administration. We demonstrated that selected pituitary-dependent axes can be reactivated in the chronic phase of critical illness, with preserved peripheral responsiveness. Intervening at the hypothalamic-pituitary level appears to be a safer strategy compared to administration of peripheral hormones, as presence of active feed-back inhibition prevents overtreatment on an individual basis at a time when it is difficult--if not impossible--to determine what is a "normal" or "optimal" level of circulating peripheral hormones. Whether this novel endocrine strategy will result in beneficial metabolic effects and, ultimately, will stimulate the recovery process in those patients who need it most, remains to be elucidated.

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