title: Polymyxin B-immobilised haemoperfusion and mortality in critically ill patients with sepsis/septic shock: a protocol for a systematic review and meta-analysis.
abstract: Polymyxin-B immobilised haemoperfusion (PMX-HP) is a promising adjuvant strategy for the treatment of sepsis and septic shock. PMX-HP therapy works by clearing circulating endotoxin through binding to polymyxin-immobilised fibres during haemoperfusion. Small clinical trials have shown that PMX-HP therapy is associated with improved haemodynamic profile, oxygenation and survival. However, clear inferences have been largely inconclusive due to limitations in study design (eg, small, unblinded) and generalisability. We therefore propose to perform an up-to-date systematic review and evidence synthesis to describe the efficacy, safety and effectiveness of PMX-HP for adult patients with sepsis or septic shock.
  
  
  
  We will search the following databases from 1946 to 2016 MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library, Health Technology Assessment Database (HTA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and 'Igaku Chuo Zasshi' (ICHUSHI) for randomised controlled trials of PMX-HP in critically ill patients with sepsis or septic shock. There will be no language restrictions in the electronic search for studies. Two reviewers will extract data and appraise the quality of each study independently. The primary outcome will be the pooled risk ratio of 28-day all-cause mortality. Serious adverse events and changes in organ dysfunction scores will also be evaluated. The secondary outcomes will be 90-day all-cause mortality, changes in haemodynamic profile and endotoxin levels, and health services use.
  
  
  
  Our systematic review will synthesise the evidence on use of the PMX-HP as an adjuvant therapy in sepsis/septic shock to improve patient-centred, physiological and health services outcomes. Research ethics is not required for this review. The study will be disseminated by peer-reviewed publication and conference presentation.
  
  
  
  CRD42016038356.
authors.affiliation: Department of Epidemiology and Preventive Service, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Research Fellow of Japan Society for the Promotion of Science.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Surgery, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Riki
authors.initials: R
authors.lastname: Ganeko
authors.affiliation: Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Department of Pediatrics, Alberta Research Center for Health Evidence (ARCHE), University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Robin
authors.initials: R
authors.lastname: Featherstone
authors.affiliation: Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bagshaw
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Toshi A
authors.identifier: 0000-0003-2159-3776
authors.initials: TA
authors.lastname: Furukawa
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016638:Critical Illness; D004731:Endotoxins / Q000097:blood; D006439:Hemodynamics; D006464:Hemoperfusion / Q000379:methods; D006801:Humans; D009026:Mortality; D016017:Odds Ratio; D063305:Organ Dysfunction Scores; D011112:Polymyxin B / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality*; D000078202:Systematic Reviews as Topic; D013997:Time Factors; D015201:Meta-Analysis as Topic
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins; D011112:Polymyxin B
keywords: hemoperfusion; meta-analysis; polymyxin; sepsis; systematic review