背景:内毒素吸附是一种有前途但有争议的治疗方法,难治性脓毒性休克和矛盾的结果存在有效的能力,可用的装置,以降低循环内毒素和炎症细胞因子水平。
方法:多臂,随机化,两个瑞士重症监护病房的对照试验,1:1:1随机分配患有严重疾病的患者,难治性脓毒性休克伴高水平内毒素血症,定义为内毒素活性≥0.6,血管加压药依赖性指数≥3,至少30ml/kg/24h的容量复苏和至少单器官衰竭,对血液吸附(托雷菌素),增强的吸附血液滤过(oXiris)或控制干预。主要终点是干预后72小时内毒素活性与基线的差异。此外,炎性细胞因子,评估了最初72小时内的血管加压药依赖性指数和SOFA评分动态。
结果:在筛选的437人中,有30人,随机患者(10标准护理,10oXiris,10Toraymyxin),干预开始后72小时的内毒素减少在干预措施之间没有差异(护理标准:12[1-42]%,oXiris:21[10-51]%,Toraymyxin:23[10-36]%,p=0.82)。此外,对于炎性细胞因子水平的降低,两组之间均未观察到差异(p=0.58),也不是血管加压药断奶(p=0.95)或器官损伤逆转(p=0.22)。
结论:在高度内毒素血症中,严重,难治性脓毒性休克人群的Toraymyxin吸附剂和oXiris膜均未显示出循环内毒素或细胞因子水平低于护理标准。审判登记ClinicalTrials.gov.NCT01948778。2013年8月30日注册https://clinicaltrials.gov/study/NCT01948778.
BACKGROUND: Endotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels.
METHODS: Multiarm, randomized, controlled
trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia.
RESULTS: In the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1-42]%, oXiris: 21 [10-51]%, Toraymyxin: 23 [10-36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels (p = 0.58), nor for vasopressor weaning (p = 0.95) or reversal of organ injury (p = 0.22).
CONCLUSIONS: In a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care.
Trial registration ClinicalTrials.gov. NCT01948778. Registered August 30, 2013. https://clinicaltrials.gov/
study/NCT01948778.