現已認識到免疫反應、轉錄因子核因子κB( NF-κB) 的激活、細胞因子、中性粒細胞的激活和肺泡滲入、凝血級聯反應、腎素-血管緊張素系統等多種因素構成的復雜網絡參與急性肺損傷/急性呼吸窘迫綜合征( ALI/ARDS) 的發病過程[ 1-5] 。雖然膿毒癥、創傷、肺炎等ALI/ARDS誘發因素很常見, 但僅有部分病人發生ALI/ARDS, 并且具有相似臨床特征的ALI/ARDS病人可有截然不同的結果, 這種異質性引起研究者對影響ALI/ARDS 易感性和預后的遺傳因子進行鑒別的濃厚興趣[ 6] 。由于數量龐大的表現型變異, 不完全的基因外顯率、復雜的基因-環境相互作用及高度可能的基因座不均一性而使ALI 遺傳學的研究受到挑戰[ 7] 。近年來基因組學技術被應用于ALI/ARDS 發病機制的研究, 加深了人們對ALI/ARDS的認識并有可能發展出新的治療策略以降低其發病率和病死率。
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.
急性肺損傷( ALI) 及急性呼吸窘迫綜合征( ARDS) 是各種肺內外致病因素導致的急性呼吸衰竭, 以進行性呼吸困難和頑固性低氧血癥為特征, 常繼發于休克、創傷、嚴重感染以及大面積燒傷等疾病。病理以雙肺彌漫性的滲出為特點。病情進展迅速, 預后極差, 具有很高死亡率。治療時需要糾正缺氧, 以保證組織氧供。傳統的常規機械通氣( CMV) 在改善氧合、呼吸力學參數以及肺內炎癥反應的同時, 導致肺損傷, 即呼吸機相關性肺損傷( VALI) 。近年認為, 采用高頻振蕩通氣( HFOV) 代替CMV 能明顯避免產生VALI, 并能改善ALI/ARDS的呼吸系統順應性和氧合作用, 減輕肺內炎癥反應和VALI, 利于急性損傷肺內塌陷和閉塞的小氣道和肺泡重新開放。并且有人提出HFOV 與部分液體通氣( PLV)聯用( HFOV-PLV) 可進一步改善氣體交換, 抑制肺組織的炎性反應, 減少肺損傷及氟碳化合物( PFCs) 用量, 穩定全身血液循環, 減少中樞神經系統( CNS) 并發癥[ 1] 。