title: Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection.
abstract: 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.
  
  
  BACKGROUND
  University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).
authors.affiliation: 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.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Saito
authors.affiliation: Department of Emergency and Critical Care Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Intensive Care Unit, Department of Anesthesiology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Testu
authors.initials: T
authors.lastname: Ohnuma
authors.affiliation: Department of Emergency and Critical Care Medicine, National Disaster Medical Center, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanemura
authors.affiliation: Department of Emergency and Critical Care Medicine, Urasoe General Hospital, Okinawa, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Nasu
authors.affiliation: Department of Emergency Medicine, Saga-Ken Medical Center Koseikan, Saga, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yoshidomi
authors.affiliation: Department of Emergency Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsujimoto
authors.affiliation: Department Intensive Care Medicine, Iizuka Hospital, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Adachi
authors.affiliation: Advanced Emergency Care Center, Saga University Hospital, Saga, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koami
authors.affiliation: Department of Emergency and Critical Care Medicine, Tsukuba Medical Center Hospital, Ibaraki, Japan.
authors.forename: Aito
authors.initials: A
authors.lastname: Tochiki
authors.affiliation: Department of Emergency and Critical Care Medicine, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Hori
authors.affiliation: Faculty of Medicine, Department of Clinical Trial and Clinical Epidemiology, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Wagatsuma
authors.affiliation: Shock and Trauma Center, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004731:Endotoxins / Q000008:administration & dosage; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D006464:Hemoperfusion; D006801:Humans; D007362:Intensive Care Units; D007564:Japan; D008297:Male; D009026:Mortality; D011112:Polymyxin B / Q000008:administration & dosage*; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality
chemical_list: D004731:Endotoxins; D011112:Polymyxin B