多黏菌素 B 血液灌流治疗非极端内毒素血症性脓毒性休克患者：EUPHRATES 试验的事后分析。
Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial.
机构信息
Department of Critical Care, St. Michael's Hospital, University of Toronto, 4-054c Donnelly Wing, Toronto, ON, M5B1W8, Canada.
Spectral Medical Inc, Toronto, Canada.
出版信息
Intensive Care Med. 2018 Dec;44(12):2205-2212. doi: 10.1007/s00134-018-5463-7. Epub 2018 Nov 23.
PURPOSE
The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA ≥ 0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6-0.89.
METHODS
Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA ≥ 0.6-0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline.
RESULTS
At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted for baseline variables, P = 0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P = 0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (- 0.5, 19.5) vs. 4 mmHg (- 4.0, 11) P = 0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P = 0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P = 0.005]. The median EAA change in the population was - 12.9% (range: increase 49.2%-reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P = 0.08.
CONCLUSIONS
These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA ≥ 0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality.
TRIAL REGISTRATION
Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.
目的
EUPHRATES 试验研究了多黏菌素 B 血液灌流（PMX）对败血症性休克和内毒素血症患者死亡率的影响，内毒素血症定义为 EAA≥0.60。28 天全因死亡率无差异。然而，该试验表明，在一些败血症性休克患者中，内毒素活性负担极高（EAA≥0.9）。在事后分析中，我们评估了在 EAA 为 0.6-0.89 之间接受 PMX 治疗的败血症性休克患者的影响。
方法
对 EUPHRATES 试验的 194 名 EAA≥0.6-0.89 的患者进行事后分析，这些患者完成了两次治疗（PMX 或假治疗）。主要终点是调整 APACHE II 评分和基线平均动脉压（MAP）后 28 天的死亡率。其他终点包括 MAP 变化、累积血管加压药指数（CVI）、中位数 EAA 降低、无呼吸机天数（VFD）、无透析天数（DFD）和住院时间。分析的亚组包括感染部位和类型，以及基线时去甲肾上腺素剂量>0.1 mcg/kg/min 的患者。
结果
在 28 天，PMX 组 88 例患者中有 23 例（26.1%）死亡，而假治疗组 106 例患者中有 39 例（36.8%）死亡[风险差异 10.7%，OR 0.52，95%CI（0.27，0.99），P=0.047]。当未调整基线变量时，P=0.11。PMX 组的 28 天生存率长于假治疗组[HR 0.56（95%CI 0.33，0.95），P=0.03]。与假治疗相比，PMX 治疗组 MAP 变化更大[中位数（IQR）8mmHg（-0.5，19.5）vs. 4mmHg（-4.0，11），P=0.04]和 VFD[中位数（IQR）20 天（0.5，23.5）vs. 6 天（0，20），P=0.004]。其他终点无显著差异。在无细菌生长的 PMX 治疗患者中，死亡率有显著差异[PMX，6/30（20%）vs. 假治疗，13/31（41.9%），P=0.005]。人群中 EAA 的中位数变化为-12.9%（范围：增加 49.2%-降低 86.3%）。在上述中位数 EAA 变化组中，PMX 组的死亡率为 6/38（15.7%），假治疗组为 15/49（30.6%），P=0.08。
结论
这些基于 EUPHRATES 试验的探索性事后分析产生的结果表明，在 EAA≥0.6 至 0.89 的败血症性休克患者中，MAP、呼吸机无天数和死亡率的变化可观察到有意义的反应。
试验注册
Clinicaltrials.gov 标识符：NCT01046669。资金来源：Spectral Medical Incorporated。
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