Soni A, Pepper G M, Wyrwinski P M, Ramirez N E, Simon R, Pina T, Gruenspan H, Vaca C E
Department of Medicine, Lincoln Medical and Mental Health Center, Bronx, New York.
Am J Med. 1995 Mar;98(3):266-71. doi: 10.1016/S0002-9343(99)80373-8.
In patients with septic shock, to (1) determine the incidence of adrenal insufficiency (AI), (2) observe the effects of glucocorticoid therapy on outcome in those with impaired adrenal function, and (3) investigate a possible correlation between adrenal function and peripheral cytokine levels.
Twenty-one patients admitted to the medical and surgical intensive care unit with septic shock and 11 healthy volunteers were studied. Cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured before and after infusion of low (1 microgram) and standard doses (250 micrograms) of adrenocorticotropic hormone (ACTH) within 24 hours of the diagnosis of septic shock. Patients with subnormal adrenal responses to ACTH were treated with stress doses of steroids. Hormone, cytokine, and survival data in patients with normal response were compared to those with subnormal adrenal function.
Five patients (23.8%) exhibited AI by ACTH stimulation testing. Three of them received steroid supplementation with rapid improvement in hemodynamic parameters. Autopsies of 2 patients with AI revealed intact adrenal cortices. Sixteen patients had adequate adrenal responses (AAR) to the standard-dose ACTH infusion. TNF-alpha levels were inversely correlated with mean arterial pressure (MAP) (r = -.52, P = 0.038) in AAR but not AI. There was no difference in mean peripheral TNF-alpha levels between AAR and AI. There was no correlation between TNF-alpha levels and mortality or adrenal function in those with septic shock. A trend toward lower IL-6 levels in AI suggests a link between reduced IL-6 levels and understimulation of the pituitary-adrenal axis in this group. Mortality in patients with AI was 80% at 4 weeks as compared with 43.8% in the group with normal adrenal response.
Adrenal hyporesponsiveness is a feature of septic shock in some patients. Its etiology is probably complex. Steroid supplementation appeared to improve short-term survival when AI occurred, although these patients' overall mortality was worse than that of patients with septic shock and AAR. The standard-dose (250 micrograms) rapid ACTH infusion test was adequate for detecting AI. Adrenal insufficiency should be suspected in patients with septic shock who do not respond to conventional treatment. Performing the ACTH infusion test and initiating a trial of stress doses of glucocorticoids pending the results is a reasonable strategy in this situation.
对于感染性休克患者，(1) 确定肾上腺功能不全 (AI) 的发生率；(2) 观察糖皮质激素治疗对肾上腺功能受损患者预后的影响；(3) 研究肾上腺功能与外周细胞因子水平之间可能存在的相关性。
对21例因感染性休克入住内科和外科重症监护病房的患者以及11名健康志愿者进行了研究。在感染性休克诊断后24小时内，于输注低剂量（1微克）和标准剂量（250微克）促肾上腺皮质激素 (ACTH) 之前及之后，测量皮质醇、肿瘤坏死因子-α (TNF-α) 和白细胞介素-6 (IL-6) 的水平。对ACTH肾上腺反应低于正常的患者给予应激剂量的类固醇治疗。将肾上腺反应正常患者的激素、细胞因子和生存数据与肾上腺功能低于正常的患者进行比较。
通过ACTH刺激试验，5例患者（23.8%）表现出AI。其中3例接受了类固醇补充治疗，血流动力学参数迅速改善。2例AI患者的尸检显示肾上腺皮质完整。16例患者对标准剂量ACTH输注有充分的肾上腺反应 (AAR)。在AAR患者中，TNF-α 水平与平均动脉压 (MAP) 呈负相关（r = -0.52，P = 0.038），而在AI患者中无此相关性。AAR和AI患者的外周平均TNF-α 水平无差异。在感染性休克患者中，TNF-α 水平与死亡率或肾上腺功能之间无相关性。AI患者中IL-6水平有降低趋势，提示该组IL-6水平降低与垂体-肾上腺轴刺激不足之间存在联系。AI患者4周时的死亡率为80%，而肾上腺反应正常组为43.8%。
肾上腺低反应性是部分感染性休克患者的一个特征。其病因可能很复杂。当发生AI时，补充类固醇似乎可改善短期生存，尽管这些患者的总体死亡率高于感染性休克且有AAR的患者。标准剂量（250微克）快速ACTH输注试验足以检测AI。对于对常规治疗无反应的感染性休克患者，应怀疑存在肾上腺功能不全。在这种情况下，进行ACTH输注试验并在等待结果期间启动应激剂量糖皮质激素试验是一种合理的策略。
