现已认识到免疫反应、转录因子核因子κB( NF-κB) 的激活、细胞因子、中性粒细胞的激活和肺泡渗入、凝血级联反应、肾素-血管紧张素系统等多种因素构成的复杂网络参与急性肺损伤/急性呼吸窘迫综合征( ALI/ARDS) 的发病过程[ 1-5] 。虽然脓毒症、创伤、肺炎等ALI/ARDS诱发因素很常见, 但仅有部分病人发生ALI/ARDS, 并且具有相似临床特征的ALI/ARDS病人可有截然不同的结果, 这种异质性引起研究者对影响ALI/ARDS 易感性和预后的遗传因子进行鉴别的浓厚兴趣[ 6] 。由于数量庞大的表现型变异, 不完全的基因外显率、复杂的基因-环境相互作用及高度可能的基因座不均一性而使ALI 遗传学的研究受到挑战[ 7] 。近年来基因组学技术被应用于ALI/ARDS 发病机制的研究, 加深了人们对ALI/ARDS的认识并有可能发展出新的治疗策略以降低其发病率和病死率。
急性肺损伤( ALI) 及急性呼吸窘迫综合征( ARDS) 是各种肺内外致病因素导致的急性呼吸衰竭, 以进行性呼吸困难和顽固性低氧血症为特征, 常继发于休克、创伤、严重感染以及大面积烧伤等疾病。病理以双肺弥漫性的渗出为特点。病情进展迅速, 预后极差, 具有很高死亡率。治疗时需要纠正缺氧, 以保证组织氧供。传统的常规机械通气( CMV) 在改善氧合、呼吸力学参数以及肺内炎症反应的同时, 导致肺损伤, 即呼吸机相关性肺损伤( VALI) 。近年认为, 采用高频振荡通气( HFOV) 代替CMV 能明显避免产生VALI, 并能改善ALI/ARDS的呼吸系统顺应性和氧合作用, 减轻肺内炎症反应和VALI, 利于急性损伤肺内塌陷和闭塞的小气道和肺泡重新开放。并且有人提出HFOV 与部分液体通气( PLV)联用( HFOV-PLV) 可进一步改善气体交换, 抑制肺组织的炎性反应, 减少肺损伤及氟碳化合物( PFCs) 用量, 稳定全身血液循环, 减少中枢神经系统( CNS) 并发症[ 1] 。
Objective To investigate the effects of high dose ulinastatin with lung protective ventilatory strategies on respiratory function and prognosis in critical disease patients combined with acute lung injury/acute respiratory distress syndrome. Methods Using retrospective analysis, we involved the critical disease patients combined with ALI/ARDS in ICU of The Second Affiliated Hospital of Anhui Medical University. According to whether they were treated with high dose ulinastatin with lung protective ventilatory strategies or not, the patients were divided into the treatment group and the control group. Then pulmonary vascular permeability index (PVPI), extravascular lung water index (EVLWI), oxygenation index, length of SIRS, length of stay in ICU and APACHE Ⅱ score were observed. Statistic analysis was conducted using SPSS 19.0 software. Results A total of 24 patients were included, 13 cases in the treatment group and 11 cases in the control group. After 72 h, PVPI (P=0.016), EVLWI (P=0.045), length of SIRS (P=0.002), length of stay in ICU (P=0.024) and APACHE Ⅱ score (P=0.002) decreased significantly, while oxygenation index (P=0.004) increased significantly in the treatment group compared with the control group. Conclusion High dose ulinastatin with lung protective ventilatory strategies decreased lung capillary permeability, reduced lung blood capillary leakage and extravascular lung water, resulted in the improvement of lung oxygenation function, decreased of length of stay in ICU and the improvement of prognosis in critical disease patients combined with acute lung injury/acute respiratory distress syndrome.