Corticosteroid-binding globulin deficiency independently predicts mortality in septic shock

Context Hydrocortisone administration in septic shock remains controversial. Corticosteroid-binding globulin (CBG) transports cortisol to inflammatory sites and is depleted in septic shock. Objective To determine if severely deficient serum CBG <200 nmol/L (Ref range 269-641 nmol/L) independently predicts septic shock mortality. Methods A prospective observational study in patients with septic shock. Patients were categorised into two groups: mean plasma CBG concentrations <200 nmol/L and ≥200 nmol/L (day 1/2), with additional categorisation by nadir CBG. Primary outcome was ICU mortality. Secondary outcomes were 28- and 90-day mortality, norepinephrine requirements, renal-replacement therapy, and clinician-instituted hydrocortisone. Results 135 patients were included. Mortality rates in ICU were higher in the CBG <200 nmol/L vs the CBG ≥200 nmol/L group: 32.4% vs 13.9%; Odds ratio (OR), 2.97, (95% confidence intervals (CI) 1.19,7.41); P=0.02: 28-days; OR 2.25 (95% CI 0.99,5.11): 90-days; OR 2.21 (95% CI 0.99,4.91). Multivariate analysis revealed 4 factors independently associated with ICU mortality: CBG <200 nmol/L (OR 3.23, 95% CI 1.06,9.88), Acute Physiology and Chronic Health Evaluation II >25 (OR 3.58, 95% CI 1.20,10.68); SOFA liver score (OR 1.98, 95% CI 1.04,3.72); and renal-replacement therapy (OR 6.59, 95% CI 2.17,20.01). Nadir CBG levels were associated with higher SOFA cardiovascular scores, norepinephrine total dose (ug) P<0.01 and duration (days) P<0.01. Plasma cortisol concentrations and hydrocortisone administration did not relate to ICU mortality. Conclusion Septic shock patients with CBG <200 nmol/L had higher norepinephrine requirements and 3.2-fold higher ICU mortality. CBG concentration was the only directly reversible independent mortality risk factor.

背景：脓毒性休克患者使用氢化可的松的治疗方案仍存在争议。皮质类固醇结合球蛋白（Corticosteroid-binding globulin, CBG）可将皮质醇转运至炎症部位，在脓毒性休克患者体内其水平会出现耗竭。
目的：明确血清CBG严重缺乏（<200 nmol/L，参考范围269~641 nmol/L）是否可独立预测脓毒性休克患者的病死率。
方法：本研究为一项针对脓毒性休克患者的前瞻性观察性研究。将患者依据其入院第1、2天的平均血浆CBG浓度分为两组：<200 nmol/L组与≥200 nmol/L组，并进一步按最低CBG水平进行分组。主要结局指标为ICU病死率；次要结局指标包括28天病死率、90天病死率、去甲肾上腺素使用剂量、肾脏替代治疗情况以及临床医师开具的氢化可的松使用方案。
结果：本研究共纳入135例患者。CBG<200 nmol/L组的ICU病死率显著高于≥200 nmol/L组：32.4% vs 13.9%；比值比（Odds ratio, OR）为2.97，95%置信区间（confidence interval, CI）为1.19~7.41，P=0.02；28天病死率的OR为2.25（95%CI 0.99~5.11）；90天病死率的OR为2.21（95%CI 0.99~4.91）。多因素分析显示，共有4项因素与ICU病死率独立相关：CBG<200 nmol/L（OR=3.23，95%CI 1.06~9.88）、急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）>25分（OR=3.58，95%CI 1.20~10.68）、序贯器官衰竭评分（SOFA）肝脏分项得分（OR=1.98，95%CI 1.04~3.72）以及肾脏替代治疗（OR=6.59，95%CI 2.17~20.01）。最低CBG水平与更高的SOFA心血管分项得分、去甲肾上腺素总使用剂量（单位：μg，P<0.01）及使用时长（单位：天，P<0.01）相关。血浆皮质醇浓度与氢化可的松使用情况均与ICU病死率无显著关联。
结论：脓毒性休克患者中，CBG<200 nmol/L者的去甲肾上腺素使用剂量更高，ICU病死率是对照组的3.2倍。CBG浓度是唯一可直接干预的独立病死率危险因素。