低分子肝素治疗脓毒症急性肺损伤/急性呼吸窘迫综合征的临床研究

摘要

Objective To explore the therapeutic effects of low molecular weight heparin (LMWH) on sepsis associated ALI/ARDS. Methods 65 patients were collected in the Second Affiliated Hospital of Nantong University from August 2012 to October 2013. The patients were randomly divided into two groups: routine therapy group (n=32) and LMWH therapy group (n=33). The routine therapy group received broad-spectrum antibiotics, mechanical ventilation and treatment of the primary disease. The supportive care included circulation blood volume supplement, acid suppression, nutrition and maintenance of homeostasis. Mechanical ventilation follow lung protective strategy. The LMWH therapy group, in addition to routine therapy, received LMWH (nadroparin) 4,100 IU subcutaneous injection everyday for seven consecutive days. The 28-day mortality and the days of mechanical ventilation were compared between the two groups. Extra vascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI) and oxygenation index were observed before and during treatment daily. Platelet count, coagulation indicators (PT, APTT) were observed before treatment and 3-days, 7-days after treatment. Results The 28-day mortality of LMWH therapy group was lower than routine therapy group [27.3%(9/33) vs. 37.5%(12/32), P=0.378], but without significant difference. EVLWI, oxygenation index and PVPI of both groups were improved, and the improvement in LMWH therapy group was significantly better than the routine therapy group (6.56±2.24 mL/kg, 254.72±51.88 mmHg, 1.25±0.46 vs. 8.79±3.02 mL/kg, 206.40±64.16 mmHg, 1.71±0.75, all P<0.05). The mechanical ventilation days of LMWH therapy group were shorter than routine therapy group (8.55±3.31 d vs. 10.72±4.44 d, P<0.05). Before treatment and after 3 days, 7 days, platelet count and coagulation indicators (PT, APTT) were no significantly different (P>0.05). There were no bleeding and other adverse reactions in LMWH therapy group. Logistic regression analysis showed that EVLWI and APACHEⅡscores were independent risk factors for sepsis associated ALI/ARDS death. ROC analysis show the area under curve (AUC) of EVLWI is greater than APACHEⅡscore. Conclusion LMWH therapy can significantly reduce extravascular lung water and lung vascular permeability of sepsis ALI/ARDS patients, and can shorten the days of mechanical ventilation. EVLWI and APACHEⅡscore both are independent risk factors for death in sepsis ALI/ARDS patients, and EVLWI has better sensibility and specificity.%目的：研究低分子肝素（LMWH）对脓毒症急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）患者的治疗作用。方法收集脓毒症ALI/ARDS患者65例，随机分为LMWH治疗组及常规治疗组：①常规治疗组32例，均接受广谱抗生素、综合支持治疗及原发病治疗；②LMWH治疗组33例，除常规治疗外，同时使用LMWH 4,100 IU皮下注射，1次/d，连续7 d。比较2组患者28 d病死率及机械通气时间，治疗前及过程中1～7 d血管外肺水指数（EVLWI）、肺血管通透性指数（PVPI）、肺氧合指数，治疗前、治疗后3 d、7d血小板计数、凝血指标的变化。结果①LMWH治疗组EVLWI、氧合指数及PVPI（6.56±2.24 mL/kg、254.72±51.88 mmHg、1.25±0.46）改善优于常规治疗组（8.79±3.02 mL/kg、206.40±64.16 mmHg、1.71±0.75），P均＜0.05。②LMWH治疗组患者机械通气时间（8.55±3.31 d）短于常规治疗组（10.72±4.44 d），P＜0.05。③LMWH治疗组28 d病死率为27.3%（9/33），常规治疗组28 d病死率为37.5%（12/32），P＞0.05。④Logistic回归分析表明，EVLWI与APACHE Ⅱ评分均是脓毒症ALI/ARDS患者死亡的独立危险因素。受试者工作特征（ROC）分析，EVLWI的曲线下面积（AUC）大于APACHE Ⅱ评分。结论临床应用LMWH治疗可显著降低脓毒症ALI/ARDS患者EVLWI及PVPI，改善氧合，缩短机械通气时间，临床应用安全有效。EVLWI、APACHE Ⅱ评分是脓毒症ALI/ARDS患者死亡的独立危险因素，EVLWI敏感性和特异性优于APACHEⅡ评分。