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 in | PLOS ONE Vol. 12; no. 3; p. e0173633 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Public Library of Science
30.03.2017
Public Library of Science (PLoS) |
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ISSN | 1932-6203 1932-6203 |
DOI | 10.1371/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). |
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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 – name: 5 Department of Emergency and Critical Care Medicine, National Disaster Medical Center, Tokyo, Japan – name: 3 Department of Emergency and Critical Care Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan – name: 12 Department of Emergency and Critical Care Medicine, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan – name: 2 Faculty of Medicine, Department of Clinical Trial and Clinical Epidemiology, University of Tsukuba, Ibaraki, Japan – name: 4 Intensive Care Unit, Department of Anesthesiology, Saitama Medical Center, Jichi Medical University, Saitama, Japan – name: 9 Department Intensive Care Medicine, Iizuka Hospital, Fukuoka, Japan – name: 10 Advanced Emergency Care Center, Saga University Hospital, Saga, Japan – name: 8 Department of Emergency Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan – name: 11 Department of Emergency and Critical Care Medicine, Tsukuba Medical Center Hospital, Ibaraki, Japan – name: 6 Department of Emergency and Critical Care Medicine, Urasoe General Hospital, Okinawa, Japan – name: 7 Department of Emergency Medicine, Saga-Ken Medical Center Koseikan, Saga, Japan – name: Bambino Gesù Children's Hospital, ITALY |
Author_xml | – sequence: 1 fullname: 我妻 ゆき子 – sequence: 2 fullname: Saito Nobuyuki – sequence: 3 fullname: Sugiyama Kazuhiro – sequence: 4 fullname: Ohnuma Testu – sequence: 5 fullname: Kanemura Takashi – sequence: 6 fullname: Nasu Michitaka – sequence: 7 fullname: Yoshidomi Yuya – sequence: 8 fullname: Tsujimoto Yuta – sequence: 9 fullname: Adachi Hiroshi – sequence: 10 fullname: Koami Hiroyuki – sequence: 11 fullname: Tochiki Aito – sequence: 12 fullname: Hori Kota – sequence: 13 fullname: Wagatsuma Yukiko – sequence: 14 fullname: Matsumoto Hisashi |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 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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