Saito Nobuyuki, Sugiyama Kazuhiro, Ohnuma Testu, Kanemura Takashi, Nasu Michitaka, Yoshidomi Yuya, Tsujimoto Yuta, Adachi Hiroshi, Koami Hiroyuki, Tochiki Aito, Hori Kota, Wagatsuma Yukiko, Matsumoto Hisashi
Shock and Trauma Center, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
Faculty of Medicine, Department of Clinical Trial and Clinical Epidemiology, University of Tsukuba, Ibaraki, Japan.
PLoS One. 2017 Mar 30;12(3):e0173633. doi: 10.1371/journal.pone.0173633. eCollection 2017.
Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB.
University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).
重症监护病房（ICU）中与脓毒性休克相关的死亡率仍然很高，报告的死亡率在30%-50%之间。特别是革兰氏阴性杆菌（GNB），它会引发严重炎症并导致多器官功能衰竭，在40%的严重脓毒症病例中是致病细菌。使用吸附内毒素的多粘菌素B固定纤维（PMX）进行血液灌流，有望减少由GNB引起的炎症性脓毒症级联反应。然而，这种治疗的临床疗效尚未得到证实。在此，我们旨在通过回顾性分析2009年1月至2012年12月期间在日本三级医院的11个ICU中因GNB相关脓毒性休克接受广谱抗菌治疗的413例患者，来验证使用PMX进行内毒素吸附治疗的疗效。在对齐患者的治疗时间阶段后，我们根据患者在ICU入院后24小时内是否接受PMX血液灌流（PMXHP）治疗将患者分为两组（PMXHP组：n = 134，传统组：n = 279）。主要研究终点是ICU入院后28天的死亡率。平均年龄为72.4（标准差：12.6）岁，ICU入院时的平均序贯器官衰竭评估评分是9.9（3.4）。感染部位包括腹腔内（38.0%）、肺部（18.9%）和尿路（32.2%），所有患者中有三分之二患有GNB相关菌血症。值得注意的是，两组患者在ICU入院后28天的死亡率没有差异（PMXHP组：29.1% vs. 传统组：29.0%，P = 0.98），并且在Cox回归分析中未发现PMXHP治疗能改善这一结果（风险比 = 1.16；95%置信区间，0.81 - 1.64，P = 0.407）。我们得出结论，在ICU入院后24小时内基于PMX的内毒素吸附与GNB所致脓毒性休克患者的死亡率无关。
大学医院医学信息网络临床试验注册中心（UMIN - CTR ID：UMIN000012748）。
