Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock: The EUPHAS Randomized Controlled Trial | Critical Care Medicine | JAMA | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.226.234.102. Please contact the publisher to request reinstatement.
1.
Marshall JC, Foster D, Vincent JL,  et al; MEDIC study.  Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study.  J Infect Dis. 2004;190(3):527-53415243928PubMedGoogle ScholarCrossref
2.
Opal SM, Glück T. Endotoxin as a drug target.  Crit Care Med. 2003;31(1):(suppl)  57-6412544978PubMedGoogle ScholarCrossref
3.
Kellum JA. A targeted extracorporeal therapy for endotoxemia: the time has come  Crit Care. 2007;11(3):13717567925PubMedGoogle ScholarCrossref
4.
Shoji H. Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin).  Ther Apher Dial. 2003;7(1):108-11412921125PubMedGoogle ScholarCrossref
5.
Cruz DN, Perazella MA, Bellomo R,  et al.  Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review.  Crit Care. 2007;11(2):R4717448226PubMedGoogle ScholarCrossref
6.
Vincent JL, Laterre PF, Cohen J,  et al.  A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection.  Shock. 2005;23(5):400-40515834304PubMedGoogle ScholarCrossref
7.
Cantaluppi V, Assenzio B, Pasero D,  et al.  Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors.  Intensive Care Med. 2008;34(9):1638-164518463848PubMedGoogle ScholarCrossref
8.
Levy MM, Fink MP, Marshall JC,  et al; SCCM/ ESICM/ACCP/ATS/SIS.  2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.  Crit Care Med. 2003;31(4):1250-125612682500PubMedGoogle ScholarCrossref
9.
Dellinger RP, Carlet JM, Masur H,  et al.  Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.  Intensive Care Med. 2004;30(4):536-55514997291PubMedGoogle ScholarCrossref
10.
Vincent JL, Moreno R, Takala J,  et al.  The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure: on behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.  Intensive Care Med. 1996;22(7):707-7108844239PubMedGoogle ScholarCrossref
11.
Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients.  JAMA. 2001;286(14):1754-175811594901PubMedGoogle ScholarCrossref
12.
Moreno R, Vincent JL, Matos R,  et al.  The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care: results of a prospective, multicentre study: Working Group on Sepsis Related Problems of the ESICM.  Intensive Care Med. 1999;25(7):686-69610470572PubMedGoogle ScholarCrossref
13.
Jones AE, Trzeciak S, Kline JA. The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation.  Crit Care Med. 2009;37(5):1649-165419325482PubMedGoogle ScholarCrossref
14.
Shore S, Nelson DP, Pearl JM,  et al.  Usefulness of corticosteroid therapy in decreasing epinephrine requirements in critically ill infants with congenital heart disease  Am J Cardiol. 2001;88(5):591-59411524081PubMedGoogle ScholarCrossref
15.
Wernovsky G, Wypij D, Jonas RA,  et al.  Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants: a comparison of low-flow cardiopulmonary bypass and circulatory arrest.  Circulation. 1995;92(8):2226-22357554206PubMedGoogle ScholarCrossref
16.
Zuppa AF, Nadkarni V, Davis L,  et al.  The effect of a thyroid hormone infusion on vasopressor support in critically ill children with cessation of neurologic function.  Crit Care Med. 2004;32(11):2318-232215640648PubMedGoogle Scholar
17.
Tsujimoto H, Ono S, Hiraki S,  et al.  Hemoperfusion with polymyxin B-immobilized fibers reduced the number of CD16+CD14+ monocytes in patients with septic shock.  J Endotoxin Res. 2004;10(4):229-23715373966PubMedGoogle Scholar
18.
Rossi C, Bertolini G. Progetto Margherita: Promuovere la ricerca e la valutazione in Terapia Intensiva RAPPORTO 2004 Bergamo: Edizioni Sestante, 2005. http://www.giviti.marionegri.it/Monografie.asp. Accessed May 26, 2009
19.
Esteban A, Frutos-Vivar F, Ferguson ND,  et al.  Noninvasive positive-pressure ventilation for respiratory failure after extubation.  N Engl J Med. 2004;350(24):2452-246015190137PubMedGoogle ScholarCrossref
20.
Lau WY, Leung TW, Ho SK,  et al.  Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial.  Lancet. 1999;353(9155):797-80110459961PubMedGoogle ScholarCrossref
21.
Pocock SJ. Clinical Trials: A Practical Approach. Chichester, England: Wiley; 1983
22.
Nemoto H, Nakamoto H, Okada H,  et al.  Newly developed immobilized polymyxin B fibers improve the survival of patients with sepsis.  Blood Purif. 2001;19(4):361-368, discussion 368-36911574732PubMedGoogle ScholarCrossref
23.
Suzuki H, Nemoto H, Nakamoto H,  et al.  Continuous hemodiafiltration with polymyxin B immobilized fiber is effective in patients with sepsis syndrome and acute renal failure.  Ther Apher. 2002;6(3):234-24012109950PubMedGoogle ScholarCrossref
24.
Nakamura T, Ebihara I, Shoji H, Ushiyama C, Suzuki S, Koide H. Treatment with polymyxin B-immobilized fiber reduces platelet activation in septic shock patients: decrease in plasma levels of soluble P-selectin, platelet factor-4 and betathromboglobulin.  Inflamm Res. 1999;48(4):171-17510344466PubMedGoogle ScholarCrossref
25.
Nakamura T, Ushiyama C, Suzuki Y, Shoji H, Shimada N, Koide H. Hemoperfusion with polymyxin-B immobilized fiber for urinary albumin excretion in septic patients with trauma.  ASAIO J. 2002;48(3):244-24812058997PubMedGoogle ScholarCrossref
26.
Nakamura T, Ushiyama C, Suzuki Y,  et al.  Hemoperfusion with polymyxin B immobilized fiber in septic patients with methicillin-resistant Staphylococcus aureus-associated glomerulonephritis.  Nephron Clin Pract. 2003;94(2):c33-c3912845235PubMedGoogle ScholarCrossref
27.
Nakamura T, Kawagoe Y, Matsuda T, Koide H. Effect of polymyxin B-immobilized fiber on bone resorption in patients with sepsis.  Intensive Care Med. 2004;30(9):1838-184115197430PubMedGoogle ScholarCrossref
28.
Nakamura T, Matsuda T, Suzuki Y, Shoji H, Koide H. Polymyxin B-immobilizied fiber in patient with sepsis.  Dial Transplant. 2003;32:602-607Google Scholar
29.
Perego AF, Morabito S, Graziani G, Casella GP, Parodi O. Polymyxin-B direct hemoperfusion (PMX-DHP) in gram negative sepsis.  G Ital Nefrol. 2006;23:(suppl 36)  S94-S10217068736PubMedGoogle Scholar
30.
Ruberto F, Pugliese F, D'Alio A,  et al.  Clinical effects of direct hemoperfusion using a polymyxin-B immobilized column in solid organ transplanted patients with signs of severe sepsis and septic shock: a pilot study.  Int J Artif Organs. 2007;30(10):915-92217992653PubMedGoogle Scholar
31.
Kushi H, Miki T, Okamaoto K, Nakahara J, Saito T, Tanjoh K. Early hemoperfusion with an immobilized polymyxin B fiber column eliminates humoral mediators and improves pulmonary oxygenation.  Crit Care. 2005;9(6):R653-R66116280061PubMedGoogle ScholarCrossref
32.
Enomoto N, Suda T, Uto T,  et al.  Possible therapeutic effect of direct haemoperfusion with a polymyxin B immobilized fibre column (PMX-DHP) on pulmonary oxygenation in acute exacerbations of interstitial pneumonia.  Respirology. 2008;13(3):452-46018399872PubMedGoogle ScholarCrossref
33.
Noma S, Matsuyama W, Mitsuyama H,  et al.  Two cases of acute exacerbation of interstitial pneumonia treated with polymyxin B-immobilized fiber column hemoperfusion treatment.  Intern Med. 2007;46(17):1447-145417827847PubMedGoogle ScholarCrossref
34.
Nakamura T, Kawagoe Y, Matsuda T, Ueda Y, Koide H. Effects of polymyxin B-immobilized fiber on urinary N-acetyl-B-glucosaminidase in patients with severe sepsis.  ASAIO J. 2004;50(6):563-56715672789PubMedGoogle ScholarCrossref
35.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P.Acute Dialysis Quality Initiative workgroup.  Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.  Crit Care. 2004;8(4):R204-R21215312219PubMedGoogle ScholarCrossref
36.
Nakamura T, Ushiyama C, Suzuki Y,  et al.  Combination therapy with polymyxin B-immobilized fibre haemoperfusion and teicoplanin for sepsis due to methicillin-resistant Staphylococcus aureus.  J Hosp Infect. 2003;53(1):58-6312495686PubMedGoogle ScholarCrossref
37.
Uriu K, Osajima A, Hiroshige K,  et al.  Endotoxin removal by direct hemoperfusion with an adsorbent column using polymyxin B immobilized fiber ameliorates systemic circulatory disturbance in patients with septic shock.  Am J Kidney Dis. 2002;39(5):937-94711979337PubMedGoogle ScholarCrossref
Caring for the Critically Ill Patient
June 17, 2009

Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock: The EUPHAS Randomized Controlled Trial

Author Affiliations

Author Affiliations: Department of Nephrology, Dialysis, and Transplantation, St Bortolo Hospital and International Renal Research Institute Vicenza, Vicenza (Drs Cruz and Ronco); Department of Anesthesiology and Intensive Care, Policlinico Gemelli, Catholic University of Sacred Heart, Rome (Dr Antonelli); Department of Anesthesiology and Intensive Care I, Milano Bicocca University, St Gerardo dei Tintori Hospital, Monza (Dr Fumagalli); Department of Surgery, University of Pisa, Pisa (Drs Foltran and Giunta); Department of Emergency and Organ Transplantation, Anesthesia and Intensive Care Unit, University of Bari, Bari (Drs Brienza and Malcangi); Department of Neuroscience, Anesthesia, and Intensive Care, Polytechnical University of Marche, Ancona (Dr Donati); Department of Anesthesia, Intensive Care, and Emergency, University of Chieti-Pescara, Chieti (Dr Petrini); Department of Anesthesiology and Intensive Care, Policlinico S. Orsola-Malpighi Hospital, Bologna (Dr Volta); Department of Intensive Care, S. Martino University Hospital, Genova (Dr Bobbio Pallavicini); and Department of Anesthesiology and Intensive Care, Riuniti Hospital, Bergamo (Dr Rottoli), Italy.

JAMA. 2009;301(23):2445-2452. doi:10.1001/jama.2009.856
Abstract

Context Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative–induced abdominal sepsis is likely associated with high circulating endotoxin. Reducing circulating endotoxin levels with polymyxin B hemoperfusion could potentially improve patient clinical outcomes.

Objective To determine whether polymyxin B hemoperfusion added to conventional medical therapy improves clinical outcomes (mean arterial pressure [MAP], vasopressor requirement, oxygenation, organ dysfunction) and mortality compared with conventional therapy alone.

Design, Setting, and Patients A prospective, multicenter, randomized controlled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]) conducted at 10 Italian tertiary care intensive care units between December 2004 and December 2007. Sixty-four patients were enrolled with severe sepsis or septic shock who underwent emergency surgery for intra-abdominal infection.

Intervention Patients were randomized to either conventional therapy (n=30) or conventional therapy plus 2 sessions of polymyxin B hemoperfusion (n=34).

Main Outcome Measures Primary outcome was change in MAP and vasopressor requirement, and secondary outcomes were PaO2/FIO2 (fraction of inspired oxygen) ratio, change in organ dysfunction measured using Sequential Organ Failure Assessment (SOFA) scores, and 28-day mortality.

Results MAP increased (76 to 84 mm Hg; P = .001) and vasopressor requirement decreased (inotropic score, 29.9 to 6.8; P < .001) at 72 hours in the polymyxin B group but not in the conventional therapy group (MAP, 74 to 77 mm Hg; P = .37; inotropic score, 28.6 to 22.4; P = .14). The PaO2/FIO2 ratio increased slightly (235 to 264; P = .049) in the polymyxin B group but not in the conventional therapy group (217 to 228; P = .79). SOFA scores improved in the polymyxin B group but not in the conventional therapy group (change in SOFA, −3.4 vs −0.1; P < .001), and 28-day mortality was 32% (11/34 patients) in the polymyxin B group and 53% (16/30 patients) in the conventional therapy group (unadjusted hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20-0.94; adjusted HR, 0.36; 95% CI, 0.16-0.80).

Conclusion In this preliminary study, polymyxin B hemoperfusion added to conventional therapy significantly improved hemodynamics and organ dysfunction and reduced 28-day mortality in a targeted population with severe sepsis and/or septic shock from intra-abdominal gram-negative infections.

Trial Registration clinicaltrials.gov Identifier: NCT00629382

×