title: A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection.
abstract: Endotoxin is an important pathogenic trigger for sepsis. The polymyxin B-immobilized endotoxin removal hemoperfusion cartridge, Toraymyxin (hereafter PMX), has been shown to remove endotoxin in preclinical and open-label clinical studies. In a multicenter, open-label, pilot, randomized, controlled study conducted in the intensive care unit in six academic medical centers in Europe, 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were randomized to PMX treatment of 2 h (n = 17) or standard therapy (n = 19). PMX was well tolerated and showed no significant side effects. There were no statistically significant differences in the change in endotoxin levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. There was also no significant difference in the change in interleukin (IL)-6 levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. Patients treated with PMX demonstrated significant increases in cardiac index (CI; P = 0.012 and 0.032 at days 1 and 2, respectively), left ventricular stroke work index (LVSWI, P = 0.015 at day 2), and oxygen delivery index (DO2I, P = 0.007 at day 2) compared with the controls. The need for continuous renal replacement therapy (CRRT) after study entry was reduced in the PMX group (P = 0.043). There was no significant difference between the groups in organ dysfunction as assessed by the Sequential Organ Failure Assessment (SOFA) scores from day 0 (baseline) to day 6. Treatment using the PMX cartridge is safe and may improve cardiac and renal dysfunction due to sepsis or septic shock. Further studies are needed to prove this effectiveness.
authors.affiliation: Department of Intensive Care, Erasme Hospital, Free University of Brussels, Brussels, Belgium. jlvincen@ulb.ac.be
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.forename: Hilmar
authors.initials: H
authors.lastname: Burchardi
authors.forename: Hajo
authors.initials: H
authors.lastname: Bruining
authors.forename: Francisco Alvarez
authors.initials: FA
authors.lastname: Lerma
authors.forename: Xavier
authors.initials: X
authors.lastname: Wittebole
authors.forename: Daniel
authors.initials: D
authors.lastname: De Backer
authors.forename: Stephen
authors.initials: S
authors.lastname: Brett
authors.forename: Dolores
authors.initials: D
authors.lastname: Marzo
authors.forename: Haruji
authors.initials: H
authors.lastname: Nakamura
authors.forename: Stephanie
authors.initials: S
authors.lastname: John
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004731:Endotoxins / Q000378:metabolism; D005260:Female; D006464:Hemoperfusion / Q000295:instrumentation*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D010477:Perfusion; D010865:Pilot Projects; D011112:Polymyxin B / Q000737:chemistry / Q000494:pharmacology*; D018805:Sepsis / Q000628:therapy*; D012772:Shock, Septic / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins; D015850:Interleukin-6; D011112:Polymyxin B