小剂量糖皮质激素对皮质醇不足的慢性阻塞性肺病急性加重期患者的影响

Effect of low-dose glucocorticoid on corticosteroid insufficient patients with acute exacerbation of chronic obstructive pulmonary disease

目的探讨小剂量糖皮质激素对慢性阻塞性肺病急性加重期（AECOPD）患者合并危重症疾病相关性皮质醇不足（CIRCI）的治疗效果。方法采用前瞻性随机对照临床试验。收集2010年1月至2012年12月入住湘潭市中心医院重症医学科慢性阻塞性肺病急性加重期患者385例。入住重症医学科12 h内行促肾上腺皮质激素刺激试验，对筛查出合并危重症疾病相关性皮质醇不足的AECOPD患者（63例），采用随机数字法分为治疗组（n=32）和对照组 （n=31），分别予以静脉注射氢化可的松150 mg/d和生理盐水，连续7 d。对比28 d病死率、非休克时间、入住重症监护单元时间以及非机械通气时间等方面的差异，并观察入住时以及治疗7 d后炎症指标C反应蛋白、白介素6、肿瘤坏死因子α和降钙素原的变化。使用SPSS 18.0数据包进行分析，两组间比较使用t检验或非参数检验，两组间率的比较采用χ2检验，生存分析采用Kaplan-Meier检验。结果①共筛查了385例AECOPD患者，合并CIRCI的患病率为16.4%，合并CIRCI的AECOPD患者休克的发生率为23.8%，未合并CIRCI的AECOPD患者休克的患病率为8.7%；②治疗组患者28 d病死率为2/32，明显低于对照组8/31（P〈0.05），并且治疗组28 d非休克时间平均为（25.8±4.1） d，明显长于对照组（18.2±9.5） d（P〈0.05），但是，28d休克发生率、入住重症监护单元时间以及非机械通气时间两组之间差异无统计学意义；③糖皮质激素治疗7 d后，对照组和治疗组炎症指标C反应蛋白分别为（13.2±5.5） mg/L vs.（8.3±3.1） mg/L，（13.5±5.9）mg/L vs.（5.1±2.3） mg/L；肿瘤坏死因子α分别为（26.1±16.2）μg/L vs. （17.5±11.7） μg/L，（25.0±14.8） μg/L vs.（10.4±7.8） μg/L；降钙素原分别为3.88（0.25, 8.5） μg/L vs. 2.03（0.15, 5.1） μg/L，3.77（0.21, 8.0） μg/L vs. 1.26（0.10,3.2） μg/L，均明显下降（P〈0.01），且治疗组下降更明显，其差异具有统计学意义（P〈0.01）。结论AECOPD患者合并CIRCI的患病率较高，对合并CIRCI的AECOPD患者小剂量糖皮质激素能降低病死率和休克时间，以及有利于炎症和感染控制。

Objective To investigate the effect of low-dose glucocorticoid on prognosis of critical illness-related corticosteroid insufficient （ CIRCI ） patients with acute exacerbation of chronic obstructive pulmonary disease （AECOPD）. Methods A total of 385 eligible patients met the criteria of AECOPD were admitted from January 2010 to December 2012. The AECOPD patients co-morbid with CIRCI screened by an adrenal corticotrophic hormone test within 12 hours after admission were randomly divided into treatment group （ n = 32 ） and control group （ n = 31 ） for prospective, randomized （ random number） and controlled clinical study. Hydrocortisons （150mg/d） for treatment group or normal saline instead for control group was injected intravenously for 7 days. The 28-day mortality, shock-free days, length of ICU stay within 28 days and ventilator-free days were evaluated. And the markers of inflammation C-reactive protein, tumor necrosis factor-a, interleukin 6 and procalcitonin were measured before and 7 days after treatment. The variables were analyzed by Student＇ s t-test, non-parametric statistical test, Chi-square test or Kaplan- Meier test with SPSS 18.0 statistic software. P 〈 0.05 was considered statistically significant. Results A cohort of 385 patients with AECOPD was screened, and the prevalence rate of CIRCI was 16. 4%. The shock rate was higher in the AECOPD patients co-morbid with CIRCI than that in the AECOPD patients without CIRCI （23.8% vs 8. 7%, P 〈 0. 01 ）. Compared with the control group, the 28-day mortality was significantly lower in treatment group （2/32 vs 8/31, P 〈 0. 05 ）, and shock-free days within 28 days longer in the treatment group （ 18. 2 ± 9.5 vs 25.8 ± 4. 1, P 〈 0. 05 ）. However, there was no difference in the shock rate, days of ICU stay and ventilator-free days between the two groups. After treatment, the levels of infection markers were decreased and obviously lower than those in control group （P 〈 0. 01 ） , such as C- reactive protein （13.2±5.5 mg/L vs 8.3 ±3. 1 mg/L for control group; 13.5 ±5.9 mg/L vs 5.1 ±2.3 mg/L for treatment group） , tumor necrosis factor-α （26. 1 ± 16. 2μg/L vs 17.5 ± 11.7 ±g/L for control group; 25.0 -± 14. 8 ±g/L vs 10. 4 ±7.8 μg/L for treatment group） and proealcitonin [3.88 （0. 25, 8.5） ±g/L vs 2. 03 （0. 15, 5.1 ） μg/L for control group; 3.77 （0. 21, 8.0） μg/L vs 1.26 （0. 10, 3.2） μg/L for treatment group ] , furthermore, the levels of infection markers were decrease more obviously in the treatment group than those in the control group （ P 〈 0.01 ）. Conclusions There was high prevalence rate of CIRCI in the patients with AECOPD in the department of critical medicine, and low-dose glueocorticoid reduced 28-day mortality, shock days and markers of infection and inflammation.