Marx Christian, Petros Sirak, Bornstein Stefan R, Weise Matthias, Wendt Matthias, Menschikowski Mario, Engelmann Lothar, Höffken Gert
Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Germany.
Crit Care Med. 2003 May;31(5):1382-8. doi: 10.1097/01.CCM.0000063282.83188.3D.
Activation and suppression of immune responses are crucial events during sepsis. Based on substantial new data, a complex picture of differential immune-enhancing and immunosuppressive actions of adrenocortical steroids is emerging. The adrenal androgen dehydroepiandrosterone and its precursor, dehydroepiandrosterone-sulfate, show a considerable decrease with increasing age and serve as functional antagonists to endogenous glucocorticoids. Therefore, we examined time-dependent changes in dehydroepiandrosterone, dehydroepiandrosterone-sulfate, cortisol, adrenocorticotropin, and inflammatory variables in surviving and nonsurviving patients with severe sepsis.
Prospective observational study in consecutive patients.
Medical and interdisciplinary intensive care units in two university hospitals and one city hospital.
Thirty nonsurgical patients (25 men and 5 women) with severe sepsis (American College of Chest Physicians/Society of Critical Care Medicine criteria); 15 survivors (mean age, 54 +/- 14 yrs; Acute Physiology and Chronic Health Evaluation III score, 59 +/- 35) and 15 nonsurvivors (mean age, 63 +/- 15 yrs; Acute Physiology and Chronic Health Evaluation III score, 67 +/- 24) were included. Hormones were compared individually and between survivors/nonsurvivors by sequential blood drawings from early sepsis till time of recovery/death.
None.
During early sepsis, cortisol (nmol/L) was not significantly higher in survivors than nonsurvivors (750 +/- 121 vs. 454 +/- 92, p <.08) and decreased in survivors (p <.01) during late sepsis. During early sepsis, dehydroepiandrosterone-sulfate (percentage of age-matched normal levels) was higher in survivors than nonsurvivors (85 +/- 19 vs. 22 +/- 7, p <.01). Dehydroepiandrosterone-sulfate decreased in survivors (p =.0001) but remained low in nonsurvivors during late sepsis. Dehydroepiandrosterone (percentage of age-matched normal levels) was not significantly elevated in survivors compared to nonsurvivors during early sepsis (282 +/- 42 vs. 214 +/- 63, p <.08). Dehydroepiandrosterone decreased in survivors (p <.01) but not in nonsurvivors during late sepsis. Linear regression for dehydroepiandrosterone levels showed a reconstitution of age dependence only in survivors during recovery. Adrenocorticotropin levels did not change. The dehydroepiandrosterone-sulfate/cortisol ratio decreased significantly in both survivors and nonsurvivors, whereas dehydroepiandrosterone/cortisol ratio only decreased in survivors during course of sepsis.
During sepsis, adrenal androgens and glucocorticoids show a diverse time-dependent course in survivors and nonsurvivors.
免疫反应的激活与抑制是脓毒症病程中的关键事件。基于大量新数据，肾上腺皮质类固醇的免疫增强和免疫抑制作用呈现出复杂的差异情况。肾上腺雄激素脱氢表雄酮及其前体硫酸脱氢表雄酮随年龄增长显著降低，并作为内源性糖皮质激素的功能拮抗剂。因此，我们研究了严重脓毒症存活和非存活患者中脱氢表雄酮、硫酸脱氢表雄酮、皮质醇、促肾上腺皮质激素及炎症变量的时间依赖性变化。
对连续患者进行前瞻性观察研究。
两家大学医院和一家城市医院的内科及多学科重症监护病房。
30例非手术严重脓毒症患者（美国胸科医师学会/危重病医学会标准）（25例男性和5例女性）；纳入15例幸存者（平均年龄54±14岁；急性生理与慢性健康状况评估III评分59±35）和15例非幸存者（平均年龄63±15岁；急性生理与慢性健康状况评估III评分67±24）。通过从脓毒症早期直至恢复/死亡时的序贯采血，对激素进行个体间及幸存者/非幸存者间的比较。
无。
脓毒症早期，幸存者的皮质醇（nmol/L）并不显著高于非幸存者（750±121 vs. 454±92，p<.08），且在脓毒症晚期幸存者中皮质醇水平下降（p<.01）。脓毒症早期，幸存者的硫酸脱氢表雄酮（年龄匹配正常水平的百分比）高于非幸存者（85±19 vs. 22±7，p<.01）。脓毒症晚期，幸存者的硫酸脱氢表雄酮水平下降（p=.0001），而非幸存者仍维持在低水平。脓毒症早期，幸存者的脱氢表雄酮（年龄匹配正常水平的百分比）与非幸存者相比无显著升高（282±42 vs. 214±63，p<.08）。脓毒症晚期，幸存者的脱氢表雄酮水平下降（p<.01），而非幸存者无变化。脱氢表雄酮水平的线性回归显示仅在幸存者恢复过程中呈现年龄依赖性重建。促肾上腺皮质激素水平无变化。幸存者和非幸存者的硫酸脱氢表雄酮/皮质醇比值均显著下降，而在脓毒症病程中仅幸存者的脱氢表雄酮/皮质醇比值下降。
脓毒症期间，肾上腺雄激素和糖皮质激素在幸存者和非幸存者中呈现出不同的时间依赖性变化过程。
