Téblick Arno, Langouche Lies, Van den Berghe Greet
Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Endocr Connect. 2019 Aug 1;8(8):R131-R143. doi: 10.1530/EC-19-0318.
Critical illness is hallmarked by major changes in all hypothalamic-pituitary-peripheral hormonal axes. Extensive animal and human studies have identified a biphasic pattern in circulating pituitary and peripheral hormone levels throughout critical illness by analogy with the fasting state. In the acute phase of critical illness, following a deleterious event, rapid neuroendocrine changes try to direct the human body toward a catabolic state to ensure provision of elementary energy sources, whereas costly anabolic processes are postponed. Thanks to new technologies and improvements in critical care, the majority of patients survive the acute insult and recover within a week. However, an important part of patients admitted to the ICU fail to recover sufficiently, and a prolonged phase of critical illness sets in. This prolonged phase of critical illness is characterized by a uniform suppression of the hypothalamic-pituitary-peripheral hormonal axes. Whereas the alterations in hormonal levels during the first hours and days after the onset of critical illness are evolutionary selected and are likely beneficial for survival, endocrine changes in prolonged critically ill patients could be harmful and may hamper recovery. Most studies investigating the substitution of peripheral hormones or strategies to overcome resistance to anabolic stimuli failed to show benefit for morbidity and mortality. Research on treatment with selected and combined hypothalamic hormones has shown promising results. Well-controlled RCTs to corroborate these findings are needed.
危重病的特征是下丘脑-垂体-外周激素轴的所有主要变化。大量动物和人体研究通过与禁食状态类比,确定了危重病全过程中循环垂体和外周激素水平的双相模式。在危重病的急性期,有害事件发生后,快速的神经内分泌变化试图引导人体进入分解代谢状态,以确保提供基本能量来源,而代价高昂的合成代谢过程则被推迟。由于新技术和危重症护理的改善,大多数患者在急性损伤后存活并在一周内康复。然而,入住重症监护病房(ICU)的患者中有相当一部分未能充分康复,进而进入危重病的延长阶段。危重病的这一延长阶段的特征是下丘脑-垂体-外周激素轴的全面抑制。虽然危重病发作后的最初数小时和数天内激素水平的变化是经过进化选择的,可能有利于生存,但长期危重病患者的内分泌变化可能是有害的,可能会阻碍康复。大多数研究外周激素替代或克服合成代谢刺激抵抗策略的研究未能显示对发病率和死亡率有好处。对选定的下丘脑激素联合治疗的研究已显示出有希望的结果。需要进行严格控制的随机对照试验来证实这些发现。