Background/Aims: Polymyxin-B (PMX) treatment has been reported to decrease mortality in patients with septic shock and acute kidney injury (AKI). In this study, we aimed to evaluate whether extended sessions of PMX (Ext-PMX) immobilized fiber column hemoperfusion ameliorate clinical outcomes in patients complicated with septic shock and AKI without surgical control. Methods: Twenty-two patients with nonsurgical septic shock and AKI who received PMX were included. They were divided according to the duration of PMX treatment: Ext-PMX and standard PMX (Std-PMX). Results: The mean blood pressure increased and inotrope requirement decreased within 24 h after PMX initiation. The median value of predicted mortality was 52.5%, and the -28-day mortalities in the Ext-PMX and Std-PMX groups were 44.4 and 75% respectively. Renal replacement therapy (RRT) was also initiated in 17 patients, and renal insufficiency was recovered. Conclusion: Ext-PMX combined with RRT improved clinical outcomes in patients with nonsurgical septic shock and AKI.

Keywords:
Septic shock, Acute kidney injury, Polymyxin B, Renal replacement therapy
1.
Tabah A, Koulenti D, Laupland K, Misset B, Valles J, Bruzzi de Carvalho F, Paiva JA, Cakar N, Ma X, Eggimann P, Antonelli M, Bonten MJ, Csomos A, Krueger WA, Mikstacki A, Lipman J, Depuydt P, Vesin A, Garrouste-Orgeas M, Zahar JR, Blot S, Carlet J, Brun-Buisson C, Martin C, Rello J, Dimopoulos G, Timsit JF: Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Med 2012; 38: 1930–1945.
2.
Conde KA, Silva E, Silva CO, Ferreira E, Freitas FG, Castro I, Rea-Neto A, Grion CM, Moura AD, Lobo SM, Azevedo LC, Machado FR: Differences in sepsis treatment and outcomes between public and private hospitals in brazil: a multicenter observational study. PLoS One 2013; 8:e64790.
3.
Rodriguez F, Barrera L, De La Rosa G, Dennis R, Duenas C, Granados M, Londono D, Molina F, Ortiz G, Jaimes F: The epidemiology of sepsis in Colombia: a prospective multicenter cohort study in ten university hospitals. Crit Care Med 2011; 39: 1675–1682.
4.
Cruz DN, Perazella MA, Bellomo R, de Cal M, Polanco N, Corradi V, Lentini P, Nalesso F, Ueno T, Ranieri VM, Ronco C: Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review. Crit Care 2007; 11:R47.
5.
Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, Malcangi V, Petrini F, Volta G, Bobbio Pallavicini FM, Rottoli F, Giunta F, Ronco C: Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA 2009; 301: 2445–2452.
6.
Payen DM, Guilhot J, Launey Y, Lukaszewicz AC, Kaaki M, Veber B, Pottecher J, Joannes-Boyau O, Martin-Lefevre L, Jabaudon M, Mimoz O, Coudroy R, Ferrandiere M, Kipnis E, Vela C, Chevallier S, Mallat J, Robert R; ABDOMIX Group: Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med 2015; 41: 975–984.
7.
Sakamoto Y, Mashiko K, Obata T, Matsumoto H, Hara Y, Kutsukata N, Yokota H: Effectiveness of early start of direct hemoperfusion with polymyxin B-immobilized fiber columns judging from stabilization in circulatory dynamics in surgical treatment patients. Indian J Crit Care Med 2010; 14: 35–39.
8.
Mitaka C, Fujiwara N, Yamamoto M, Toyofuku T, Haraguchi G, Tomita M: Polymyxin B-immobilized fiber column hemoperfusion removes endotoxin throughout a 24-hour treatment period. J Crit Care 2014; 29: 728–732.
9.
Mitaka C, Tsuchida N, Kawada K, Nakajima Y, Imai T, Sasaki S: A longer duration of polymyxin B-immobilized fiber column hemoperfusion improves pulmonary oxygenation in patients with septic shock. Shock 2009; 32: 478–483.
10.
Kono M, Suda T, Enomoto N, Nakamura Y, Kaida Y, Hashimoto D, Inui N, Mizuguchi T, Kato A, Shirai T, Nakamura H, Chida K: Evaluation of different perfusion durations in direct hemoperfusion with polymyxin B-immobilized fiber column therapy for acute exacerbation of interstitial pneumonias. Blood Purif 2011; 32: 75–81.
11.
Iwagami M, Yasunaga H, Noiri E, Horiguchi H, Fushimi K, Matsubara T, Yahagi N, Nangaku M, Doi K: Potential survival benefit of polymyxin B hemoperfusion in septic shock patients on continuous renal replacement therapy: a propensity-matched analysis. Blood Purif 2016; 42: 9–17.
12.
Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA: Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2007; 2: 431–439.
13.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41: 580–637.
14.
Khwaja A: KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012; 120:c179–c184.
15.
Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC; Surviving Sepsis Campaign: The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010; 38: 367–374.
16.
Morrison DC, Jacobs DM: Binding of polymyxin B to the lipid a portion of bacterial lipopolysaccharides. Immunochemistry 1976; 13: 813–818.
17.
Novelli G, Ferretti G, Ruberto F, Morabito V, Pugliese F: Early management of endotoxemia using the endotoxin activity assay and polymyxin B-based hemoperfusion. Contrib Nephrol 2010; 167: 91–101.
18.
Wang Y, Liu Y, Ito Y, Hashiguchi T, Kitajima I, Yamakuchi M, Shimizu H, Matsuo S, Imaizumi H, Maruyama I: Simultaneous measurement of anandamide and 2-arachidonoylglycerol by polymyxin B-selective adsorption and subsequent high-performance liquid chromatography analysis: increase in endogenous cannabinoids in the sera of patients with endotoxic shock. Anal Biochem 2001; 294: 73–82.
19.
Nishibori M, Takahashi HK, Katayama H, Mori S, Saito S, Iwagaki H, Tanaka N, Morita K, Ohtsuka A: Specific removal of monocytes from peripheral blood of septic patients by polymyxin B-immobilized filter column. Acta Med Okayama 2009; 63: 65–69.
20.
Wang Y, Liu Y, Sarker KP, Nakashima M, Serizawa T, Kishida A, Akashi M, Nakata M, Kitajima I, Maruyama I: Polymyxin B binds to anandamide and inhibits its cytotoxic effect. FEBS Lett 2000; 470: 151–155.
21.
Iwagami M, Yasunaga H, Doi K, Horiguchi H, Fushimi K, Matsubara T, Yahagi N, Noiri E: Postoperative polymyxin B hemoperfusion and mortality in patients with abdominal septic shock: a propensity-matched analysis. Crit Care Med 2014; 42: 1187–1193.
22.
Klein DJ, Foster D, Schorr CA, Kazempour K, Walker PM, Dellinger RP: The EUPHRATES trial (evaluating the use of polymyxin B hemoperfusion in a randomized controlled trial of adults treated for endotoxemia and septic shock): study protocol for a randomized controlled trial. Trials 2014; 15: 218.
23.
Nakamura T, Ushiyama C, Suzuki Y, Inoue T, Shoji H, Shimada N, Koide H: Combination therapy with polymyxin b-immobilized fibre haemoperfusion and teicoplanin for sepsis due to methicillin-resistant Staphylococcus aureus. J Hosp Infect 2003; 53: 58–63.
24.
Varga K, Wagner JA, Bridgen DT, Kunos G: Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. FASEB J 1998; 12: 1035–1044.
25.
Timmerman CP, Mattsson E, Martinez-Martinez L, De Graaf L, Van Strijp JA, Verbrugh HA, Verhoef J, Fleer A: Induction of release of tumor necrosis factor from human monocytes by staphylococci and staphylococcal peptidoglycans. Infect Immun 1993; 61: 4167–4172.
26.
Jaber BL, Barrett TW, Cendoroglo Neto M, Sundaram S, King AJ, Pereira BJ: Removal of cytokine inducing substances by polymyxin-B immobilized polystyrene-derivative fibers during in vitro hemoperfusion of 10% human plasma containing Staphylococcus aureus challenge. ASAIO J 1998; 44: 48–53.
27.
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:R653–R661.
28.
Nakamura T, Kawagoe Y, Matsuda T, Shoji H, Ueda Y, Tamura N, Ebihara I, Koide H: Effect of polymyxin B-immobilized fiber on blood metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in acute respiratory distress syndrome patients. Blood Purif 2004; 22: 256–260.
29.
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 beta-thromboglobulin. Inflamm Res 1999; 48: 171–175.
30.
Tani T, Hanasawa K, Kodama M, Imaizumi H, Yonekawa M, Saito M, Ikeda T, Yagi Y, Takayama K, Amano I, Shimaoka H, Ohta M, Okahisa T, Koga N, Fujita N, Yamasa H: Correlation between plasma endotoxin, plasma cytokines, and plasminogen activator inhibitor-1 activities in septic patients. World J Surg 2001; 25: 660–668.
31.
Nakazawa H, Nozaki M, Shimoda K, Kikuchi Y, Honda T, Isago T: Successful management using combination therapy of endotoxin absorption therapy (PMX) and continuous hemodiafiltration (CVVHDF) of a critically ill burn patient suffering from methicillin-resistant Staphylococcus aureus toxic shock syndrome. Burns 2008; 34: 288–291.
32.
Taniguchi T, Sato K, Kurita A, Noda T, Okajima M: Efficacy of endotoxin adsorption therapy (polymyxin B hemoperfusion) for methicillin-resistant Staphylococcus aureus toxic shock syndrome: a case report about five patients. Minerva Anestesiol 2013; 79: 758–761.
33.
Lafrance JP, Miller DR: Acute kidney injury associates with increased long-term mortality. J Am Soc Nephrol 2010; 21: 345–352.
34.
Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294: 813–818.
35.
Jo SK, Cha DR, Cho WY, Kim HK, Chang KH, Yun SY, Won NH: Inflammatory cytokines and lipopolysaccharide induce Fas-mediated apoptosis in renal tubular cells. Nephron 2002; 91: 406–415.
36.
Bordoni V, Bolgan I, Brendolan A, Crepaldi C, Gastaldon F, D'Intini V, Pilotto L, Inguaggiato P, Bonello M, Galloni E, Everard P, Bellomo R, Ronco C: Caspase-3 and -8 activation and cytokine removal with a novel cellulose triacetate super-permeable membrane in an in vitro sepsis model. Int J Artif Organs 2003; 26: 897–905.
37.
Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE: Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 1999; 27: 1230–1251.
38.
Ayala A, Herdon CD, Lehman DL, DeMaso CM, Ayala CA, Chaudry IH: The induction of accelerated thymic programmed cell death during polymicrobial sepsis: control by corticosteroids but not tumor necrosis factor. Shock 1995; 3: 259–267.
39.
Crouser ED, Julian MW, Weinstein DM, Fahy RJ, Bauer JA: Endotoxin-induced ileal mucosal injury and nitric oxide dysregulation are temporally dissociated. Am J Respir Crit Care Med 2000; 161: 1705–1712.
40.
Camussi G, Mariano F, Biancone L, De Martino A, Bussolati B, Montrucchio G, Tobias PS: Lipopolysaccharide binding protein and CD14 modulate the synthesis of platelet-activating factor by human monocytes and mesangial and endothelial cells stimulated with lipopolysaccharide. J Immunol 1995; 155: 316–324.
41.
Imai Y, Parodo J, Kajikawa O, de Perrot M, Fischer S, Edwards V, Cutz E, Liu M, Keshavjee S, Martin TR, Marshall JC, Ranieri VM, Slutsky AS: Injurious mechanical ventilation and end-organ epithelial cell -apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome. JAMA 2003; 289: 2104–2112.
42.
Hotchkiss RS, Karl IE: The pathophysiology and treatment of sepsis. N Engl J Med 2003; 348: 138–150.
43.
Maatman RG, van de Westerlo EM, van Kuppevelt TH, Veerkamp JH: Molecular identification of the liver- and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction. Biochem J 1992; 288(Pt 1):285–290.
44.
Kamijo A, Kimura K, Sugaya T, Yamanouchi M, Hikawa A, Hirano N, Hirata Y, Goto A, Omata M: Urinary fatty acid-binding protein as a new clinical marker of the progression of chronic renal disease. J Lab Clin Med 2004; 143: 23–30.
45.
Nakamura T, Sugaya T, Koide H: Urinary liver-type fatty acid-binding protein in septic shock: effect of polymyxin b-immobilized fiber hemoperfusion. Shock 2009; 31: 454–459.
46.
Cantaluppi V, Assenzio B, Pasero D, Romanazzi GM, Pacitti A, Lanfranco G, Puntorieri V, Martin EL, Mascia L, Monti G, Casella G, Segoloni GP, Camussi G, Ranieri VM: Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors. Intensive Care Med 2008; 34: 1638–1645.
47.
Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS: One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003; 348: 683–693.
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2018
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