Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection

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 case...

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Published inPLOS ONE Vol. 12; no. 3; p. e0173633
Main Authors 我妻 ゆき子, 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
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 30.03.2017
Public Library of Science (PLoS)
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ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0173633

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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. Trial registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).
AbstractList 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.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).TRIAL REGISTRATIONUniversity Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).
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. Trial registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).
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).
Audience Academic
Author Yoshidomi Yuya
Ohnuma Testu
我妻 ゆき子
Kanemura Takashi
Tsujimoto Yuta
Matsumoto Hisashi
Adachi Hiroshi
Hori Kota
Nasu Michitaka
Sugiyama Kazuhiro
Tochiki Aito
Koami Hiroyuki
Wagatsuma Yukiko
Saito Nobuyuki
AuthorAffiliation 8 Department of Emergency Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan
1 Shock and Trauma Center, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
4 Intensive Care Unit, Department of Anesthesiology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
11 Department of Emergency and Critical Care Medicine, Tsukuba Medical Center Hospital, Ibaraki, Japan
10 Advanced Emergency Care Center, Saga University Hospital, Saga, Japan
7 Department of Emergency Medicine, Saga-Ken Medical Center Koseikan, Saga, Japan
9 Department Intensive Care Medicine, Iizuka Hospital, Fukuoka, Japan
12 Department of Emergency and Critical Care Medicine, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan
5 Department of Emergency and Critical Care Medicine, National Disaster Medical Center, Tokyo, Japan
Bambino Gesù Children's Hospital, ITALY
3 Department of Emergency and Critical Care Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
6 Department of Emergency and Crit
AuthorAffiliation_xml – name: 1 Shock and Trauma Center, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
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https://www.ncbi.nlm.nih.gov/pubmed/28358803$$D View this record in MEDLINE/PubMed
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Competing Interests: The authors have declared that no competing interests exist.
Conceptualization: NS KS.Data curation: NS KS.Formal analysis: NS YW.Funding acquisition: NS.Investigation: NS KS TO TK MN YY YT HA AT KH HK.Methodology: NS KS.Project administration: NS YW.Resources: NS KS TO TK MN YY YT HA AT KH HK.Software: NS YW.Supervision: NS YW HM.Validation: YW HM.Visualization: NS KS.Writing – original draft: NS.Writing – review & editing: NS KS TO YW HM.
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Snippet Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30–50%. In particular, Gram-negative bacilli (GNB),...
Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB),...
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SubjectTerms Abdomen
Adsorption
Aged
Aged, 80 and over
Bacilli
Bacteremia
Biology and Life Sciences
Care and treatment
Causes of
Clinical trials
Critical care
Data collection
Diagnosis
Drug resistance
Effectiveness
Emergency medical care
Endotoxins
Endotoxins - administration & dosage
Epidemiology
Female
Gram-negative bacilli
Gram-negative bacteria
Gram-Negative Bacteria - drug effects
Gram-Negative Bacteria - pathogenicity
Gram-Negative Bacterial Infections - drug therapy
Gram-Negative Bacterial Infections - microbiology
Gram-Negative Bacterial Infections - mortality
Health aspects
Health services
Hemoperfusion
Hospitals
Humans
Immobilization
Infections
Inflammation
Intensive care
Intensive Care Units
Japan
Male
Medicine
Medicine and Health Sciences
Mortality
Nosocomial infections
Pathogens
People and Places
Physiological aspects
Polymyxin B
Polymyxin B - administration & dosage
Regression analysis
Respiratory Tract Infections - drug therapy
Respiratory Tract Infections - microbiology
Respiratory Tract Infections - mortality
Sepsis
Septic shock
Shock
Shock, Septic - drug therapy
Shock, Septic - microbiology
Shock, Septic - mortality
Statistical analysis
Therapy
Trauma
Trauma centers
Urinary tract
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Title Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection
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