北京大学学报(医学版) ›› 2016, Vol. 48 ›› Issue (4): 672-679. doi: 10.3969/j.issn.1671-167X.2016.04.021

• 论著 • 上一篇    下一篇

乌司他丁在预防急性呼吸窘迫综合征中的作用

贾丽静1,2,易亮3,杨志旭3,王书鹏4,李刚4,朱曦1△   

  1. (1. 北京大学第三医院危重医学科,北京100191; 2. 沧州市人民医院重症医学科,河北沧州061000; 3. 中国中医科学院西苑医院重症医学科,北京100091; 4. 中日友好医院重症医学科,北京100029)
  • 出版日期:2016-08-18 发布日期:2016-08-18
  • 通讯作者: 朱曦 E-mail:xizhuccm@163.com
  • 基金资助:

    国家自然科学基金(81372043)、首都医学发展科研基金(20091014)、北京市自然科学基金(7162199)、天普研究基金(01201113)资助

Preventive effects of ulinastatin on acute respiratory distress syndrome

JIA Li-jing1,2, YI Liang3, YANG Zhi-xu3, WANG Shu-peng4, LI Gang4, ZHU Xi1△   

  1. (1. ICU, Peking University Third Hospital, Beijing 100191, China; 2. ICU, Cangzhou People’s Hospital, Cangzhou 061000, Hebei, China; 3. ICU, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China; 4. ICU, China-Japan Friendship Hospital, Beijing 100029, China)
  • Online:2016-08-18 Published:2016-08-18
  • Contact: ZHU Xi E-mail:xizhuccm@163.com
  • Supported by:

    Supported by the National Natural Science Foundation of China (81372043), the Capital Medical Development and Scientific Research Fund (2009-1014), Beijing Natural Science Foundation (7162199), and Techpool Research Fund (01201113)

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。

关键词: 乌司他丁, 呼吸窘迫综合征, 成人, 白细胞弹性蛋白酶

Abstract:

Objective:To explore the effect of ulinastatin on prevention of acute respiratory distress syndrome (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 ulinastatin 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 ulinastatin via intravenous infusion for 5 days. The control group received the same amount of saline via intravenous 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 physiology 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 ventilation 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.

Key words: Ulinastatin, Respiratory distress syndrome, adult, Leukocyte elastase

中图分类号: 

  • R563.8
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