尼可地尔治疗急性呼吸窘迫综合征患者的疗效观察

Therapeutic effect of nicorandil for treatment of patients with acute respiratory distress syndrome

目的 观察尼可地尔对急性呼吸窘迫综合征（ARDS）患者的临床疗效.方法 采用前瞻性随机对照研究方法,选择2012年10月至2014年10月贵州省人民医院重症医学科收治的ARDS患者40例,按完全随机原则分为观察组和对照组,每组20例.两组入院后均给予西医常规治疗,在此基础上,观察组给予尼可地尔10 mg 胃管注入,对照组给予温开水10 mL胃管内注入;两组均每日3次,连用5 d.观察两组治疗后重症加强治疗病房（ICU）住院时间、机械通气时间,比较两组治疗前后氧合指数（OI）、肺泡动脉氧分压差（PA-aO2）、呼气末正压（PEEP）、急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分、格拉斯哥昏迷评分（GCS）、预期死亡风险（PDR）及28 d病死率的差异.采用二元logistic回归分析影响ARDS患者28 d病死率的预测因子.结果 对照组ICU住院时间、机械通气时间较观察组延长,但差异均无统计学意义〔ICU住院时间（d）：14.55±12.71比9.15±6.00,机械通气时间（d）：13.25±12.27比7.75±5.32,均P〉0.05〕.对照组和观察组治疗后GCS评分均较治疗前升高（分：11.95±3.98比10.75±4.89,12.95±3.67比12.20±4.56）, APACHEⅡ评分、PDR、PEEP均较治疗前降低〔APACHEⅡ（分）：21.05±8.58比24.90±5.63,18.70±11.21比 26.65±7.67;PDR：（47.71±29.49）% 比（61.00±23.29）%,（36.79±18.49）% 比（56.12±18.16）%;PEEP （cmH2O,1 cmH2O=0.098 kPa）：4.40±3.14比5.75±2.59,3.80±2.55比7.55±3.32〕,但两组治疗前后同时间点比较差异无统计学意义（均P〉0.05）.两组治疗后OI均较治疗前明显升高,PA-aO2均较治疗前明显降低,且以观察组的改善程度较对照组更显著〔OI（mmHg,1 mmHg=0.133 kPa）：224.72±85.12比141.37±45.82, PA-aO2（mmHg）：132.60±46.64比204.30±121.2,均P〈0.05〕.观察组28 d病死率较对照组降低,但两组比较差异无统计学意义〔15%（3/20）比25%（5/20）,χ^2=0.156,P〉0.050）.二元logistic回归分析显示,治疗后 PA-aO2〔优势比（OR）=0.958,P=0.013,95%可信区间（95%CI）=0.927～0.991〕、APACHEⅡ评分（OR=0.882, P=0.010,95%CI=0.803～0.970）、GCS评分（OR=1.399,P=0.004,95%CI=1.111～1.761）、PDR（OR=0.907, P=0.002,95%CI=0.853～0.965）是患者28 d病死率的独立预测因子.结论 尼可地尔可以改善ARDS患者的氧合,但不能降低患者的28 d病死率.

Objective To investigate the clinical effect of nicorandil for treatment of patients with acute respiratory distress syndrome （ARDS）.Methods A prospective randomized controlled trial was conducted. A total of 40 cases of patients with ARDS admitted to Department of Critical Care Medicine of Guizhou Provincial People＆#39;s Hospital from October 2012 to October 2014 were enrolled, and they were randomly divided into two groups, 20 cases in each group. The two groups were treated with routine western medicine after admission. On this basis, the observation group was given nicorandil 10 mg, while the control group was given warm boiled water 10 mL, through gastric tubes 3 times a day, the therapeutic course being consecutive 5 days in both groups. The length of stay in intensive care unit （ICU）, duration of mechanical ventilation after treatment, oxygenation index （OI）, alveolo-arterial oxygen partial pressure difference （PA-aO2）, positive end-expiratory pressure （PEEP）, acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ） score, Glasgow coma score （GCS） before and after treatment, the predicted death rate （PDR） and 28-day mortality were compared between the two groups. The predicitive factors for 28-day mortality were screened by binary logistic analysis.Results The length of stay in ICU and duration of mechanical ventilation of control group were longer than those of observation group, but the difference was not statistically significant [ICU length of stay （day）： 14.55±12.71 vs. 9.15±6.00, duration of mechanical ventilation （day）： 13.25±12.27 vs. 7.75±5.32, bothP 〉 0.05]. After treatment, the GCS was higher than that before treatment in control group and observation group （11.95±3.98 vs. 10.75±4.89, 12.95±3.67 vs. 12.20±4.56）, while APACHE Ⅱ score, PDR and PEEP were all lower than those before treatment [APACHE Ⅱ： 21.05±8.58 vs. 24.90±5.63, 18.70±11.21 vs. 26.65±7.67; PDR： （47.71±29.49）% vs. （61.00±23.29）%, （36.79±18.49）% vs. （56.12±18.16）%; PEEP （cmH2O, 1 cmH2O = 0.098 kPa）： 4.40±3.14 vs. 5.75±2.59, 3.80±2.55 vs. 7.55±3.32], but there were no statistically significant differences between the two groups before and after treatment （allP 〉 0.05）. After treatment, the OI was significantly higher and the PA-aO2 was significantly lower than those before treatment in the two groups, and the degrees of improvement of the observation group were more remarkable than those of the control group [OI （mmHg, 1 mmHg = 0.133 kPa）： 224.72±85.12 vs. 141.37±45.82, PA-aO2 （mmHg）： 132.60±46.64 vs. 204.30±121.2, bothP 〈 0.05]. The 28-day mortality of observation group was lower than that of control group, but no statistically significant difference was seen [15% （3/20） vs. 25% （5/20）,χ^2 = 0.156,P 〉 0.05）. Binary logistic regression analyses showed that the PA-aO2 [odds ratio （OR） = 0.958,P = 0.013, 95% confidence interval （95%CI） = 0.927 - 0.991], APACHE Ⅱ score （OR = 0.882,P = 0.010, 95CI = 0.803 - 0.970）, GCS （OR = 1.399, P = 0.004, 95%CI = 1.111 - 1.761） and PDR （OR = 0.907,P = 0.002, 95%CI = 0.853 - 0.965） after treatment were the independent predictors of 28-day mortality.Conclusion Nicorandil can significantly improve oxygenation, but cannot reduce 28-day mortality in patients with ARDS.