乌司他丁、α1胸腺肽联合治疗严重脓毒症——一种新的免疫调理治疗方法的临床研究

Clinical trial with a new immunomodulatory strategy:treatment of severe sepsis with Ulinastatin and Maipuxin

目的评估联合抗炎和免疫刺激治疗严重脓毒症方法的有效性。方法本研究采用多中心、前瞻、随机、对照方法。共433例患者进入本研究。进入 ICU 内严重脓毒症(Marshall 评分5～20)的患者入选,随机分为对照组:常规治疗;治疗组1(第1阶段):常规治疗+乌司他丁30万 U/日,α1胸腺肽(迈普新)1.6 mg/d,连续7 d;治疗组2(第2阶段):常规治疗+乌司他丁60万 U/日,迈普新3.2 mg/日,连续7 d,进行28 d 和90 d 预后等疗效评估。结果第1阶段91例,治疗组(治疗组1)与对照组28 d 预后等各项疗效评估指标差异均无统计学意义。第2阶段342例,治疗组(治疗组2)与对照组相比(意向治疗分析),28 d 病死率为25.1%vs 38.3%(P=0.0088),90 d 病死率为37.1%vs 52.1%(P=0.0054),28 d APACHEⅡ评分12.7±9.4 vs 14.3±9.2(P=0.0384),28 d 单核细胞 HLA-DR/CD14+(51.7±26.5)%vs(40.1±22.0)%(P=0.0092)。其他疗效评估指标,如 ICU内治疗天数、呼吸机使用天数、抗生素使用时间等,两组差异无统计学意义。结论本研究治疗方案能够明显改善严重脓毒症患者28 d 和90 d 预后,具有积极推广价值;治疗的有效性具有剂量依赖性,最佳剂量有待进一步探讨。

Objective To evaluate the efficacy of treatment of severe sepsis by combining antiinflammatory and immune-enhancing agents. Methods Multiple-center, prospective, randomized, controlled designs. Cases were from surgical or general ICU of 26 university teaching hospitals. Totally, 433 adult patients developing severe sepsis with Marshall score 5-20 were enrolled. Patients received either standard treatment based on SSC direction （ as group control）, or additional Ulinastatin （ urinary trypsin inhibitor） 300 K units per day ＋ thymosin alphal （Maipuxin） 1.6 rag per day for 7 days （as treatment group 1, adopted in the first trial）, or double dosage of the above agents （ as treatment group 2, adopted in the second trial）. The outcome of 28 and 90 days, APACHE Ⅱ and Marshall score, monocyte HLA-DR/ CD14 ＋ at several points until 28 days, and the lengths of ICU stay, antibiotics usage and mechanical ventilation were determinated. Results In the first trial （91 cases）, there was no significant difference in variables between treatment group 1 and control at28 days. In the second trial （342 cases）, the mortality of treatment group 2 decreased from 38.32% to 25.14% （P = 0. 0088） , compared with group control at 28 days, and from 52. 10% to 37.14% （P = 0. 0054） on 90 days. APACHE Ⅱ also decreased from 14.32 to 12.70 （P =0.0384） ＂and monocyte HLA-DR/CD14 ＋ increased from 40. 13% to 51.65% （P =0. 0092） on 28 days in treatment group2. Other variables had no significant differences between two groups. Conclusion Treatment by the combining anti-inflammatory and inmmune enhancing agents can significantly improve the outcome of severe sepsis. The efficacy of this therapy seems to be dose dependent on.