大剂量乌司他丁与低分子肝素对脓毒症患者的早期治疗研究

Early treatment using large dose ulinastatin and low molecular weight heparin for patients with sepsis

目的观察低分子肝素与乌司他丁联合应用早期治疗对脓毒症患者的治疗效果,为脓毒症患者临床早期抗凝和免疫调理治疗提供理论依据。方法25例脓毒症患者随机分为对照组13例和低分子肝素与乌司他丁联合治疗组（以下简称实验组）12例。观察两组患者治疗前后急性生理学与既往健康状况Ⅱ（APACHEⅡ）评分,以及治疗前后肿瘤坏死因子TNF-α,白细胞介素-10 （IL-10）,D-二聚体,凝血功能,血小板计数（PLT）变化。流式细胞仪测定两组患者治疗前后CD14-＋单核细胞HLA-DR。结果（1）D-二聚体在实验组明显下降,并且在治疗5、10、16 d的D-二聚体值分别与对照组比较,差异有统计学意义（P〈0.05）。（2）对照组与实验组TNF-α随着时间延长均呈下降趋势,但实验组下降更为明显,在治疗3 d时分别为（38.1±4.5）pg/ml与（55.1±7.6）pg/ml,5 d时为（30.1±6.3）pg/ml与（49.2±3.9）pg/ml,10 d为（23.3±3.7）pg/ml与（42.4±6.5）pg/ml,16 d为（12.1±4.2）pg/ml与（39.8±7.1）pg/ml四个时间点与对照组相比较,差异有统计学意义（P〈0.05）。（3）对照组与实验组CD14-＋单核细胞HLA-DR表达率随着时间延长均呈升高趋势,但实验组升高更为明显,在治疗3 d时分别为（41.6±5.5）%与（25.3±5.6）%,5 d时为（61.7±3.4）%与（35.7±4.5）%,10 d时为（62.4±4.1）%与（40.6±7.8）%,16 d时为（60.1±2.9）%与（43.3±2.3）%四个时间点与对照组相比较,差异有统计学意义（P〈0.05）。结论低分子肝素与乌司他丁联合应用早期干预,可以改善脓毒症患者恶化的全身炎症反应状态、免疫功能紊乱和血液高凝状态,具有一定的临床应用价值。

Objective This study was to explore the effects of early use of low molecular weight heparin with ulinastatin for the treatment of patients with sepsis. Methods Twenty-five patients with sepsis were randomized into control group （ 13 cases） and experimental group （ 12 cases） with the treatment of low molecular weight heparin and ulinastatin. APACHE Ⅱ score, TNF-α, interleukin-10, D-dimer, blood clotting and thrombocyte count were determined pre-, and posttreatment. Preoperative and postoperative HLA-DR contents in CD14^＋ histoleucocyte was measured with flow cytometry. Results 1. D-dimer decreased obviously in experimental group, and the level on the 5th,10th,and 16th day was statistically different compared with that in control group （P 〈 0. 05 ）. 2. TNF-α decreased dramatically in the experimental group with statistically difference compared to the control group on the four time pionts, on the 3th day was （38. 1 ±4. 5 pg/ml） vs. （55.1 ±7.6 pg/ml） ,the 5th day （30. 1 ±6. 3 pg/ml） vs. （49. 2 ± 3.9pg/ml）,the 10th day （23.3 ±3.7 pg/ml） vs. （42.4 ±6.5 pg/ml）,and the 16th day （12.1 ± 4. 2pg/ml） vs. （39. 8 ± 7. 1 pg/ml）. 3. CD14^＋ monocytes HLA-DR% increased dramaticly in the experimental group with the difference being statistically significant compared to that in control group on the four time points ：on the3th day was （41.6±5.5%） vs. （25.3 ±5.6%）,5th day（61.7 ±3.4%） vs. （35.7±4.5%）,10th day（62.4 ±4. 1%） vs. （40.6 ±7.8%）,16th day （60.1 ±2.9%） vs. （43.3 ± 2. 3% ）. Condusion Early intervention of low molecular weight heparin combined with ulinastatin improved the systemic inflammatory response syndrome in patients with sepsis.