Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock - A double-blind, randomized, placebo-controlled, crossover study
Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock - A double-blind, randomized, placebo-controlled, crossover study
复制标题
DOI：
10.1164/rccm.200205-446oc
复制
发表时间：
2003-02-15
影响因子：
24.7
通讯作者：
Gerlach, H
中科院分区：
文献类型：
--
作者：
Keh, D;Boehnke, T;Gerlach, H
在过去的几年中，越来越多的证据表明感染性休克中相对肾上腺功能不全引起了对氢化可的松治疗的重新评估。为了评估氢化可的松对促炎和抗炎平衡的作用，40例脓毒性休克患者在一项双盲交叉研究中随机分组，接受前100 mg氢化可的松作为负荷剂量，每小时10 mg，直到第3天（n = 20）或安慰剂（n = 20），随后进行相反的药物治疗，直到第6天。氢化可的松输注导致平均动脉压升高，全身血管阻力增加，心率、心脏指数和去甲肾上腺素需求量下降。血浆亚硝酸盐/硝酸盐的减少表明一氧化氮的形成受到抑制，并与血管加压素支持的减少相关。炎症反应（白细胞介素-6和白细胞介素-8）、内皮（可溶性e -选择素）和中性粒细胞活化（cd11b、CD640的表达）和抗炎反应（可溶性肿瘤坏死因子受体I、II和白细胞介素-10）均减弱。在外周血单核细胞中，人白细胞抗原- dr的表达仅轻微下降，而体外吞噬和单核细胞活化细胞因子白细胞介素-12升高。氢化可的松停药引起血流动力学和免疫反弹效应。综上所述，氢化可的松治疗恢复血流动力学稳定性，并以抗炎而非免疫抑制的方式差异调节应激免疫反应。
Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 (n = 20) or placebo (n = 20), followed by the opposite medication until Day 6. Hydrocortisone infusion induced an increase of mean arterial pressure, systemic vascular resistance, and a decline of heart rate, cardiac index, and norepinephrine requirement. A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support. The inflammatory response (interieukin-6 and interieukin-8), endothelial (soluble E-selectin) and neutrophil activation (expression of CD11 b, CD640, and antlinflammatory response (soluble tumor necrosis factor receptors I and II and interieukin-10) were attenuated. In peripheral blood monocytes, human leukocyte antigen-DR expression was only slightly depressed, whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased. Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects. In conclusion, hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression.