title: The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis.
abstract: BACKGROUND
  Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis.
  
  
  METHODS
  We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model.
  
  
  RESULTS
  Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n = 128) and the mean age of children ranged from 0.9 to 18 years (n = 66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma.
  
  
  CONCLUSIONS
  Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.
authors.affiliation: Department of Internal Medicine, University of Manitoba, GC425-820 Sherbrook Street, HSC, Winnipeg, R3A 1R9, Canada. emily.rimmer@cancercare.mb.ca.|Department of Haematology and Medical Oncology, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, R3E 0V9, Canada. emily.rimmer@cancercare.mb.ca.
authors.forename: Emily
authors.initials: E
authors.lastname: Rimmer
authors.affiliation: Faculty of Medicine, University of Manitoba, 250 Brodie Centre, 727 McDermot Ave, Winnipeg, R3E 3P5, Canada. umhoustb@cc.umanitoba.ca.
authors.forename: Brett L
authors.initials: BL
authors.lastname: Houston
authors.affiliation: Department of Internal Medicine, University of Manitoba, GC425-820 Sherbrook Street, HSC, Winnipeg, R3A 1R9, Canada. akumar61@yahoo.com.
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.affiliation: George & Fay Yee Center for Healthcare Innovation, University of Manitoba/Winnipeg Regional Health Authority, GE706-820 Sherbrook Street, HSC, Winnipeg, R3A 1R9, Canada. abousetta_md@hotmail.com.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abou-Setta
authors.affiliation: Neil John Maclean Health Sciences Library, University of Manitoba, Brodie Centre, 727 McDermot Ave, Winnipeg, R3E 3P5, Canada. carol_friesen@umanitoba.ca.
authors.forename: Carol
authors.initials: C
authors.lastname: Friesen
authors.affiliation: Section of Critical Care Medicine, St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada. marshallj@smh.toronto.on.ca.
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.affiliation: Ottawa Hospital, 501 Smyth Road, Ottawa, K1H 8L6, Canada. gailrock1@hotmail.com.
authors.forename: Gail
authors.initials: G
authors.lastname: Rock
authors.affiliation: Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine and Population Health and Optimal Health Practices Unit, CHU de Québec Research Center, Université Laval, 1401-18th Street, Québec, G1J 1Z4, Canada. alexis.turgeon@fmed.ulaval.ca.
authors.forename: Alexis F
authors.initials: AF
authors.lastname: Turgeon
authors.affiliation: Department of Medicine, McMaster University, Hamilton, L8S 4K1, Canada. debcook@mcmaster.ca.|Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street, West, Hamilton, Canada. debcook@mcmaster.ca.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Cook
authors.affiliation: Department of Internal Medicine, University of Manitoba, GC425-820 Sherbrook Street, HSC, Winnipeg, R3A 1R9, Canada. houston@cc.umanitoba.ca.|Department of Haematology and Medical Oncology, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, R3E 0V9, Canada. houston@cc.umanitoba.ca.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Houston
authors.affiliation: Department of Internal Medicine, University of Manitoba, GC425-820 Sherbrook Street, HSC, Winnipeg, R3A 1R9, Canada. rzarychanski@cancercare.mb.ca.|Department of Haematology and Medical Oncology, CancerCare Manitoba, 675 McDermot Ave, Winnipeg, R3E 0V9, Canada. rzarychanski@cancercare.mb.ca.|George & Fay Yee Center for Healthcare Innovation, University of Manitoba/Winnipeg Regional Health Authority, GE706-820 Sherbrook Street, HSC, Winnipeg, R3A 1R9, Canada. rzarychanski@cancercare.mb.ca.
authors.forename: Ryan
authors.initials: R
authors.lastname: Zarychanski
mesh_terms: D006801:Humans; D007362:Intensive Care Units / Q000639:trends; D010951:Plasma Exchange / Q000379:methods* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic / Q000401:mortality / Q000639:trends; D018805:Sepsis / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D012772:Shock, Septic / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D016896:Treatment Outcome