不同剂量低分子肝素治疗感染性休克的临床研究

Therapeutic effects of different doses administration of LMWH in patients with severe sepsis

目的探讨早期应用低分子肝素抗凝对感染性休克患者的治疗效果。方法入住我院重症医学科的感染性休克患者共61例,随机分为低分子肝素干预A组(低分子肝素5 000 IU,皮下注射,q12h,22例)、低分子肝素干预B组(低分子肝素5 000 IU,皮下注射,qd,20例)和生理盐水对照组(19例)。对照组常规治疗早期应用广谱抗生素,补液,保护胃黏膜,纠正水、电解质及酸碱紊乱,营养支持及对症治疗,干预组除常规治疗外,应用低分子肝素,疗程一般为7 d(或用至患者有明显的低凝状态或出血倾向)。记录患者治疗前、治疗后3 d和7 d的急性生理学与慢性健康状况Ⅱ(APACHEⅡ)评分、住ICU时间、28 d病死率、血清降钙素原(PCT)、凝血指标及出血并发症的情况。结果低分子肝素A组治疗后3 d和7 d、低分子肝素B组治疗后3 d与治疗前比较APACHEⅡ评分均显著下降(P<0.05);与同时间的对照组比较,低分子肝素A组治疗后7 d的APACHEⅡ评分及血清降钙素原水平显著下降,差异有统计学意义(P<0.05)。低分子肝素A组和B组的28 d病死率分别为59.1%和70.0%,低于生理盐水对照组的73.7%,但差异无统计学意义(P>0.05)。三组凝血指标(PT、APTT、FIB、D二聚体)及血小板计数治疗前后差异均无统计学意义(P>0.05)。与对照组相比,低分子肝素A组出血并发症的发生率明显增加(P<0.05),最常见为消化道出血;低分子肝素B组虽增加了出血风险,但与对照组比较差异无统计学意义(P>0.05)。结论低分子肝素能改善感染性休克患者的近期预后,但不能明显降低病死率,且有增加出血并发症的可能,寻找合适治疗剂量需进一步研究。

Objective To investigate the therapeutic effect of early administration of low molecular weight heparin （LMWH） in patients with severe sepsis and septic shock. Methods 61 patients with septic shock in intensive care unit （ICU） were randomly divided into LMWH treatment group A （ n = 22 ）, LMWH treatment group B （ n = 20 ） and control group （n = 19 ）. The patients of control group received a serie of remedies, including broad-spectrum antibi- otics in early stage, supplementing of circulation volume, protecting of gastric mucosa, correcting the water, electrolyte and acid-base disturbance, nutritional support and symptomatic treatment. The patients of LMWH treatment group A were treated with LMWH 5 000 IU subcutaneous injection ql2h for 7 days in addition to routine treatment, while LM- WH treatment group B was given once daily when patients left hospital or dead or showed sign of bleeding. The differ- ences in APACHE U score, the length of ICU stay, the 28-day mortality, procalcitonin, coagulation markers and hemor- rhage complication among the three groups were analyzed before and after treatment respectively. Results The A- PACHE Ⅱ score in LMWH group A after treatment for 3,7 d and LMWH group B after treatment for 3 d decreased significantly compared with before treatment （ P 〈 0. 05 ） , compared with the same time of control group, the APACHE Ⅱ score and procalcitonin in LMWH group A after treatment for 7 d decreased significantly, there was significant difference among the two groups （P 〈 0. 05 ）. The 28-day mortality was 59. 1% in LMWH group A and 70. 0% in LMWH group B,they were lower than that in control group （73.7%） ,but no significant difference was fourd （P 〉 0. 05 ）. The difference in coagulation function and PLT was not significant among the three groups. Compared with thecontrol group, the LMWH group A significantly increased the incidence of bleeding complications （ P 〈 0.05 ） , and the most common complication was gastrointestinal bleeding. LMWH group B increased risk of bleeding, but there was no significant difference compared with the control group （ P 〉 0. 05 ）. Conclusion LMWH can improve the short-term prognosis of patients with septic shock, but it can not significantly reduce the mortality, and there is the possibility of in- creasing bleeding complications. Further studies are needed for searching a suitable therapeutic dose of LMWH.