亚低温对急性呼吸窘迫综合征患者肺血管通透性的影响

Effects of mild hypothermia on pulmonary vascular permeability in patients with acute respiratory distress syndrome

目的探讨全身亚低温干预对感染所致急性呼吸窘迫综合征（ARDS）患者早期肺毛细血管通透性的影响。方法采用前瞻性随机对照研究方法，选择2012年5月至2015年11月广西医科大学第一附属医院重症加强治疗病房（ICU）收治的因肺部感染所致ARDS患者，纳入年龄18～70岁且存在人工气道、需机械通气、无明显凝血功能异常者；排除肿瘤、烧伤、心脏疾病、血管相关性疾病及3个月内接受血管手术者。按随机数字表法将人选患者分为非控温组和亚低温组。两组患者均根据治疗原则进行原发病治疗，给予呼吸支持、各器官功能支持及对症治疗等综合处理；亚低温组在此基础上以全身降温方式将患者中心体温（鼻咽温）在1h内快速降至34～35℃。分别监测两组患者治疗或中心体温达标1、24、48、72h的急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分、氧合指数（PaO2／FiO2）、血管外肺水指数（EVLWI）及肺血管通透性指数（PVPI）；用酶联免疫吸附试验（ELISA）检测静脉血中血管内皮生长因子（VEGF）及支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）和肺泡表面活性蛋白A（SP—A）含量，并计数循环内皮细胞（CEC）；记录机械通气时间及7d存活率。结果共人选56例患者，非控温组32例，亚低温组24例，两组患者性别、年龄、APACHEⅡ评分、PaO]FiO，等基线资料均衡。随治疗时间延长，两组APACHEⅡ评分、EVLWI、PVPI、VEGF、CEC、TNF-α逐渐升高，PaO2／FiO2、SP—A逐渐降低。亚低温组治疗24h起APACHEⅡ评分（分：16．34±4．27比19．24±5．95）、EVLWI（mL／kg：12．17±2．26比12．39±4．71）、PVPI（15．40±10．95比16．08±10．24）、VEGF（ng／L：127．92±31．49比159．12±40．67）、CEC（个／pL：4．15±1．79比5．70±2．38）、TNF-α（ng／L：147．18±48．85比257．17±40．84）即较非控温组明显降低（均P〈0．05），Pa02／FiO2[mmHg（1mmHg=O．133kPa）：175．03±12．64比162．53±14．15]、SP—A（μg／L：80．85±16．18比62．06±17．28）明显升高（均P〈0．05），机械通气时间则明显缩短（t=10．38±1．50比15．74±3．06，P〈0．01），7d存活率明显提高（75．0％比46．9％，P〈0．05）。结论亚低温治疗能降低ARDS患者早期肺血管通透性，改善早期肺氧合、缩短机械通气时间、降低短期病死率。

Objective To study the influence of mild hypothermia on pulmonary vascular permeability in patients with acute respiratory distress syndrome （ARDS） induced by infection. Methods A prospective randomized controlled trial was conducted. Patients with ARDS induced by infection satisfied criteria including age 18-70 years, endotracheal intubation and mechanical ventilation （MV）, and without severe coagulation disorder admitted to intensive care unit （ICU） of the First Affiliated Hospital of Guangxi Medical University from May 2012 to November 2015 were enrolled, excluding tumor, burn, cardiac disease, vascular disease, and endovascular surgery within 3 months. The patients enrolled were randomly divided into non-temperature controlled group and mild hypothermia group. The primary diseases in all patients were treated according to the treating principles, including respiratory support, integrated treatment of organ support and symptomatic treatment. Besides, the patients in the mild hypothermia group were administered with systemic hypothermia, and the patients＇ core body temperature （nasopharyngeal temperature） was rapidly decreased to 34-35℃ within 1 hour. Acute physiology and chronic health evaluation I/ （APACHE Ⅱ ） score, oxygenation index （PaO2/FiO2）, extravascular lung water index （EVLWI） and pulmonary vascular permeability index （PVPI） in two groups at 1, 24, 48, and 72 hours after treatment or core temperature up to standards were monitored respectively. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of vascular endothelial growth factor （VEGF） in venous blood as well as tumor necrosis factor-α （TNF-α） and surfactant apoprotein A （SP-A） in bronchoalveolar lavage fluid （BALF）, and circulating endothelial cell （CEC） was counted. The duration of mechanical ventilation and 7-day survival rate were recorded. Results Fifty-six patients were enrolled, with 32 in non-temperature controlled group and 24 in mild hypothermia group. There was no difference in baseline variables including gender, age, APACHE Ⅱ score, PaO2/FiO2 between two groups. APACHE score, EVLWI, PVPI, VEGF, CEC, and TNF-α in both groups were gradually increased with treatment time prolongation, and PaO2/FiO2 and SP-A were gradually decreased. Compared with non-temperature controlled group, APACHE Ⅱ score （16.34±4.27 vs. 19.24±5.95）, EVLWI （mL/kg： 12.17±2.26 vs. 12.39±4.71）, PVPI （15.40± 10.95 vs. 16.08± 10.24）, VEGF （ng/L： 127.92 ± 31.49 vs. 159.12 ±40.67）, CEC （cells/μL： 4.15 ± 1.79 vs. 5.70 ± 2.38）, and TNF- α （ng/L： 147.18 ±48.85 vs. 257.17 ±40.84） in mild hypothermia group were significantly decreased from 24 hours （all P 〈 0.05）, and PaO2/FiO2 [mmHg （1 mmHg = 0.133 kPa）： 175.03 ± 12.64 vs. 162.53 ± 14.15] and SP-A （μg/L： 80.85 ± 16.18 vs. 62.06± 17.28） were significantly increased （both P 〈 0.05）, the duration of meehanieal ventilation was signifieantly shortened （days： 10.38± 1.50 vs. 15.74 ± 3.06, P 〈 0.01）, and 7-day survival rate was significantly increased （75.0% vs. 46.9%, P 〈 0.05）. Conclusion Mild hypothermia can reduce the pulmonary vascular permeability, and improve pulmonary funetion in early phase in patients with ARDS, as well as shorten the duration of mechanieal ventilation, and decrease short-term mortality.