乌司他丁在预防急性呼吸窘迫综合征中的作用

摘要

目的：探讨乌司他丁对预防急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）的作用。方法：采用前瞻性随机对照试验，选择2012年1月至2014年12月北京大学第三医院危重医学科、沧州市人民医院、中国中医科学院西苑医院和北京中日友好医院重症医学科的185例患者，随机分为干预组（n ＝77）和对照组（n ＝108）。两组患者均接受常规治疗，干预组患者入重症监护病房（intensive care unit，ICU）后在常规治疗基础上每天加用乌司他丁60万单位，静脉输注，连用5 d；对照组静脉输注等体积生理盐水，连续5 d。于干预的第1、3、7天分别检测静脉血中性粒细胞弹性蛋白酶（human neutrophil elastase，HNE）和中性粒细胞弹性蛋白酶抑制剂（peptidase inhibitor 3，PI3）的水平，计算 HNE ／PI3比值，监测患者急性生理学及慢性健康状况评分（acute physiology and chronic health evaluation scoring Ⅱ，APACHE Ⅱ）、体温、呼吸频率、心率、平均动脉压、白细胞计数、氧合指数（PaO2／FiO2），并记录两组患者 ARDS 发生率、机械通气时间、ICU 治疗时间、住院时间及28 d 生存率。结果：两组患者在性别、年龄、APACHE Ⅱ评分、吸烟情况、基础疾病情况、入院诊断等方面差异无统计学意义。两组患者的3次 HNE 检测值比较（第1、3、7天）差异均无统计学意义，两组患者第1天 PI3检测值比较差异无统计学意义，第3天及第7天 PI3的检测值比较差异均有统计学意义（P ＜0．01）；两组患者第1天 HNE ／PI3比值比较差异无统计学意义，第3天及第7天的 HNE ／PI3比值差异有统计学意义（P ＜0．05）。两组患者在第1、3、7天的体温、呼吸频率、心率、平均动脉压、白细胞计数方面的比较差异均无统计学意义；两组患者第1天的氧合指数比较差异无统计学意义，第3天及第7天的氧合指数比较差异有统计学意义（P ＜0．05）。干预组患者 ARDS 的发生率为15．58％，明显低于对照组的33．33％，差异有统计学意义（P ＜0．05）。在两组进展为 ARDS 的患者中，均以脓毒症、腹部术后及胰腺炎患者为主。干预组患者的机械通气时间、ICU 治疗时间短于对照组，差异有统计学意义（P ＜0．05）。两组患者的住院时间差异无统计学意义，干预组患者的28 d 生存率高于对照组，但两组差异无统计学意义。结论：通过增加外源性HNE 拮抗剂乌司他丁，可以恢复 HNE 与其拮抗剂的平衡，对抗 HNE 对肺组织的破坏作用，降低 ARDS 的发病率。%Objective:To explore the effect of ulinastatin on prevention of acute respiratory distress syn-drome (ARDS).Methods:A prospective multicentral cohort study was conducted.The patients from three intensive care units (ICUs)of grade A tertiary hospitals in Beijing and a ICU of grade A tertiary hospitals in Cangzhou from January 2012 to December 2014,included 77 ARDS at-risk patients with uli-nastatin treatment and 108 ARDS at-risk patients without ulinastatin treatment (control)were eligible. Both groups received normal treatment;additionally,the intervention group received 600 000 units of uli-nastatin via intravenous infusion for 5 days.The control group received the same amount of saline via in-travenous infusion for 5 days.Venous blood human neutrophil elastase (HNE)and peptidase inhibitor 3 (PI3)levels were measured on days 1,3,and 7,respectively.Other outcomes included acute physiolo-gy and chronic health evaluation scoring Ⅱ (APACHE Ⅱ),body temperature,respiratory rate,heart rate,mean arterial pressure,white blood cell counts,PaO2 /FiO2 ,ARDS incident,mechanical ventila-tion time,ICU treatment and hospitalization duration,28 days mortality.Results:The PI3 levels showed no statistical difference on day 1,but significant differences on day 3 and day 7 between the two groups (P <0.01).HNE /PI3 ratio showed no statistical difference on day 1,but significant differences on day 3 and day 7 (P <0.05).PaO2 /FiO2 was significantly higher in ulinastatin group on day 3 and day 7 (P <0.05).The incident rate for ulinastatin group was 15.58%,lower than that for the control group (33.33%),and the difference was statistically significant (P <0.05).The mechanical ventilation time and ICU treatment time in ulinastatin group was shorter than that in the control group,and the difference was statistically significant (P <0.05).There were no significant effects in other factors.Conclusion:Increased dose of ulinastatin can recover the balance of HNE and its antagonist,lower the HNE’s damage to lungs,and further reduce the ARDS incident rate.