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Published in: Journal of Artificial Organs 3/2017

01-09-2017 | Original Article

Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study

Authors: Sigrun Friesecke, Stephanie-Susanne Stecher, Stefan Gross, Stephan B. Felix, Axel Nierhaus

Published in: Journal of Artificial Organs | Issue 3/2017

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Abstract

Sepsis is the most common cause of death in medical intensive care units (ICU). If sepsis progresses to refractory septic shock, mortality may reach 90–100% despite optimum current therapy. Extracorporeal cytokine adsorption in addition to regular therapy was studied prospectively in refractory septic shock patients on a medical ICU. Refractory shock was defined as increasing vasopressor dose required to maintain mean arterial blood pressure above 65 mmHg or increasing lactate levels despite protocol-guided shock therapy for 6 h. We analysed noradrenaline requirements after 6 and 12 h (primary endpoint), lactate clearance after 6 and 12 h, SOFA-scores in the first days and achievement of shock reversal (i.e., normalization of lactate concentrations and sustained discontinuation of vasopressors; secondary endpoints). Twenty consecutive patients with refractory septic shock were included; CytoSorb® treatment was started after 7.8 ± 3.7 h of shock therapy. Following the initiation of adsorption therapy, noradrenaline dose could be significantly reduced after 6 (−0.4 µg/kg/min; p = 0.03) and 12 h (−0.6 µg/kg/min; p = 0.001). Lactate clearance improved significantly. SOFA-scores on day 0, 1 and 2 remained unchanged. Shock reversal was achieved in 13 (65%) patients; 28-day survival was 45%. In severe septic shock unresponsive to standard treatment, haemodynamic stabilization was achieved using cytokine adsorption therapy, resulting in shock reversal in two-thirds of these patients. The study was registered in the German Register for Clinical Trials (DRKS) No. 00005149.
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Literature
1.
go back to reference Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med. 2007;33:606–18.CrossRefPubMed Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med. 2007;33:606–18.CrossRefPubMed
2.
go back to reference Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, et al. Nationwide trends of severe sepsis in the 21st century (2000–2007). Chest. 2011;140:1223–31.CrossRefPubMed Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, et al. Nationwide trends of severe sepsis in the 21st century (2000–2007). Chest. 2011;140:1223–31.CrossRefPubMed
3.
4.
go back to reference Levy MM, Macias WL, Vincent JL, Russell JA, Silva E, Trzaskoma B, et al. Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med. 2005;33:2194–201.CrossRefPubMed Levy MM, Macias WL, Vincent JL, Russell JA, Silva E, Trzaskoma B, et al. Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med. 2005;33:2194–201.CrossRefPubMed
5.
go back to reference Conrad M, Perez P, Thivilier C, Levy B. Early prediction of norepinephrine dependency and refractory septic shock with a multimodal approach of vascular failure. J Crit Care. 2015;30:739–43.CrossRefPubMed Conrad M, Perez P, Thivilier C, Levy B. Early prediction of norepinephrine dependency and refractory septic shock with a multimodal approach of vascular failure. J Crit Care. 2015;30:739–43.CrossRefPubMed
6.
go back to reference Benchekroune S, Karpati PC, Berton C, Nathan C, Mateo J, Chaara M, et al. Diastolic arterial blood pressure: a reliable early predictor of survival in human septic shock. J Trauma. 2008;64:1188–95.CrossRefPubMed Benchekroune S, Karpati PC, Berton C, Nathan C, Mateo J, Chaara M, et al. Diastolic arterial blood pressure: a reliable early predictor of survival in human septic shock. J Trauma. 2008;64:1188–95.CrossRefPubMed
8.
go back to reference Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine. 2005;29:169–75.CrossRefPubMed Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine. 2005;29:169–75.CrossRefPubMed
9.
go back to reference Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167:1655–63.CrossRefPubMedCentral Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167:1655–63.CrossRefPubMedCentral
11.
go back to reference Ronco C, Tetta C, Mariano F, Wratten ML, Bonello M, Bordoni V, et al. Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. Artif Organs. 2003;27:792–801.CrossRefPubMed Ronco C, Tetta C, Mariano F, Wratten ML, Bonello M, Bordoni V, et al. Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. Artif Organs. 2003;27:792–801.CrossRefPubMed
12.
go back to reference Kellum JA, Venkataraman R, Powner D, Elder M, Hergenroeder G, Carter M. Feasibility study of cytokine removal by hemoadsorption in brain-dead humans. Crit Care Med. 2008;36:268–72.CrossRefPubMed Kellum JA, Venkataraman R, Powner D, Elder M, Hergenroeder G, Carter M. Feasibility study of cytokine removal by hemoadsorption in brain-dead humans. Crit Care Med. 2008;36:268–72.CrossRefPubMed
13.
14.
go back to reference Song M, Winchester J, Albright RL, Capponi VJ, Choquette MD, Kellum JA. Cytokine removal with a novel adsorbent polymer. Blood Purif. 2004;22:428–34.CrossRefPubMed Song M, Winchester J, Albright RL, Capponi VJ, Choquette MD, Kellum JA. Cytokine removal with a novel adsorbent polymer. Blood Purif. 2004;22:428–34.CrossRefPubMed
15.
go back to reference Schädler D, Porzelius C, Jörres A, Marx G, Meier-Hellmann A, Putensen C, Quintel M, Spies C, Engel C, Weiler N, Kuhlmann M. A multicenter randomized controlled study of an extracorporeal cytokine hemoadsorption device in septic patients. eposter Crit Care; 2013. Schädler D, Porzelius C, Jörres A, Marx G, Meier-Hellmann A, Putensen C, Quintel M, Spies C, Engel C, Weiler N, Kuhlmann M. A multicenter randomized controlled study of an extracorporeal cytokine hemoadsorption device in septic patients. eposter Crit Care; 2013.
16.
go back to reference Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, et al. Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis. Kidney Int. 2012;81:363–9.CrossRefPubMed Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, et al. Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis. Kidney Int. 2012;81:363–9.CrossRefPubMed
17.
go back to reference Mikhova KM, Don CW, Laflamme M, Kellum JA, Mulligan MS, Verrier ED, et al. Effect of cytokine hemoadsorption on brain death-induced ventricular dysfunction in a porcine model. J Thorac Cardiovasc Surgery. 2013;145:215–23 (discussion 23-4).CrossRef Mikhova KM, Don CW, Laflamme M, Kellum JA, Mulligan MS, Verrier ED, et al. Effect of cytokine hemoadsorption on brain death-induced ventricular dysfunction in a porcine model. J Thorac Cardiovasc Surgery. 2013;145:215–23 (discussion 23-4).CrossRef
18.
go back to reference Hetz H, Berger R, Recknagel P, Steltzer H. Septic shock secondary to beta-hemolytic streptococcus-induced necrotizing fasciitis treated with a novel cytokine adsorption therapy. Int J Artif Organs. 2014;37:422–6.CrossRefPubMed Hetz H, Berger R, Recknagel P, Steltzer H. Septic shock secondary to beta-hemolytic streptococcus-induced necrotizing fasciitis treated with a novel cytokine adsorption therapy. Int J Artif Organs. 2014;37:422–6.CrossRefPubMed
19.
go back to reference Mitzner SR, Gloger M, Henschel J, Koball S. Improvement of hemodynamic and inflammatory parameters by combined hemoadsorption and hemodiafiltration in septic shock: a case report. Blood Purif. 2013;35:314–5.CrossRefPubMed Mitzner SR, Gloger M, Henschel J, Koball S. Improvement of hemodynamic and inflammatory parameters by combined hemoadsorption and hemodiafiltration in septic shock: a case report. Blood Purif. 2013;35:314–5.CrossRefPubMed
20.
go back to reference Hinz B, Jauch O, Noky T, Friesecke S, Abel P, Kaiser R. CytoSorb, a novel therapeutic approach for patients with septic shock: a case report. Int J Artif Organs. 2015;38:461–4.CrossRefPubMed Hinz B, Jauch O, Noky T, Friesecke S, Abel P, Kaiser R. CytoSorb, a novel therapeutic approach for patients with septic shock: a case report. Int J Artif Organs. 2015;38:461–4.CrossRefPubMed
21.
go back to reference Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228.CrossRefPubMed Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228.CrossRefPubMed
22.
go back to reference Reiter K, Bordoni V, Dall’Olio G, Ricatti MG, Soli M, Ruperti S, et al. In vitro removal of therapeutic drugs with a novel adsorbent system. Blood Purif. 2002;20:380–8.CrossRefPubMed Reiter K, Bordoni V, Dall’Olio G, Ricatti MG, Soli M, Ruperti S, et al. In vitro removal of therapeutic drugs with a novel adsorbent system. Blood Purif. 2002;20:380–8.CrossRefPubMed
23.
go back to reference Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009;301:2445–52.CrossRefPubMed Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009;301:2445–52.CrossRefPubMed
24.
go back to reference Bayer O, Reinhart K, Kohl M, Kabisch B, Marshall J, Sakr Y, et al. Effects of fluid resuscitation with synthetic colloids or crystalloids alone on shock reversal, fluid balance, and patient outcomes in patients with severe sepsis: a prospective sequential analysis. Crit Care Med. 2012;40:2543–51.CrossRefPubMed Bayer O, Reinhart K, Kohl M, Kabisch B, Marshall J, Sakr Y, et al. Effects of fluid resuscitation with synthetic colloids or crystalloids alone on shock reversal, fluid balance, and patient outcomes in patients with severe sepsis: a prospective sequential analysis. Crit Care Med. 2012;40:2543–51.CrossRefPubMed
25.
go back to reference Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26:1793–800.CrossRefPubMed Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26:1793–800.CrossRefPubMed
26.
go back to reference Haas SA, Lange T, Saugel B, Petzoldt M, Fuhrmann V, Metschke M, et al. Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intensive Care Med. 2016;42:202–10.CrossRefPubMed Haas SA, Lange T, Saugel B, Petzoldt M, Fuhrmann V, Metschke M, et al. Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intensive Care Med. 2016;42:202–10.CrossRefPubMed
27.
go back to reference Nguyen HB, Loomba M, Yang JJ, Jacobsen G, Shah K, Otero RM, et al. Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock. J Inflamm. 2010;7:6.CrossRef Nguyen HB, Loomba M, Yang JJ, Jacobsen G, Shah K, Otero RM, et al. Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock. J Inflamm. 2010;7:6.CrossRef
28.
go back to reference Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004;32:1637–42.CrossRefPubMed Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004;32:1637–42.CrossRefPubMed
29.
go back to reference Marty P, Roquilly A, Vallee F, Luzi A, Ferre F, Fourcade O, et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in Intensive Care Unit: an observational study. Ann Intensive Care. 2013;3:3.CrossRefPubMedPubMedCentral Marty P, Roquilly A, Vallee F, Luzi A, Ferre F, Fourcade O, et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in Intensive Care Unit: an observational study. Ann Intensive Care. 2013;3:3.CrossRefPubMedPubMedCentral
30.
go back to reference Turnbull IR, Javadi P, Buchman TG, Hotchkiss RS, Karl IE, Coopersmith CM. Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels. Shock. 2004;21:121–5.CrossRefPubMed Turnbull IR, Javadi P, Buchman TG, Hotchkiss RS, Karl IE, Coopersmith CM. Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels. Shock. 2004;21:121–5.CrossRefPubMed
31.
go back to reference Levy B, Collin S, Sennoun N, Ducrocq N, Kimmoun A, Asfar P, et al. Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. Intensive Care Med. 2010;36:2019–29.CrossRefPubMed Levy B, Collin S, Sennoun N, Ducrocq N, Kimmoun A, Asfar P, et al. Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. Intensive Care Med. 2010;36:2019–29.CrossRefPubMed
32.
go back to reference Shiga H, Hirasawa H, Nishida O, Oda S, Nakamura M, Mashiko K, et al. Continuous hemodiafiltration with a cytokine-adsorbing hemofilter in patients with septic shock: a preliminary report. Blood Purif. 2014;38:211–8.CrossRefPubMed Shiga H, Hirasawa H, Nishida O, Oda S, Nakamura M, Mashiko K, et al. Continuous hemodiafiltration with a cytokine-adsorbing hemofilter in patients with septic shock: a preliminary report. Blood Purif. 2014;38:211–8.CrossRefPubMed
33.
go back to reference Peng Z, Singbartl K, Simon P, Rimmele T, Bishop J, Clermont G, et al. Blood purification in sepsis: a new paradigm. Contrib Nephrol. 2010;165:322–8.CrossRefPubMed Peng Z, Singbartl K, Simon P, Rimmele T, Bishop J, Clermont G, et al. Blood purification in sepsis: a new paradigm. Contrib Nephrol. 2010;165:322–8.CrossRefPubMed
34.
go back to reference Peng ZY, Bishop JV, Wen XY, Elder MM, Zhou F, Chuasuwan A, et al. Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model. Crit Care. 2014;18:R141.CrossRefPubMedPubMedCentral Peng ZY, Bishop JV, Wen XY, Elder MM, Zhou F, Chuasuwan A, et al. Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model. Crit Care. 2014;18:R141.CrossRefPubMedPubMedCentral
35.
go back to reference Bello G, Di Muzio F, Maviglia R, Antonelli M. New membranes for extracorporeal blood purification in septic conditions. Minerva Anestesiol. 2012;78:1265–81.PubMed Bello G, Di Muzio F, Maviglia R, Antonelli M. New membranes for extracorporeal blood purification in septic conditions. Minerva Anestesiol. 2012;78:1265–81.PubMed
37.
go back to reference Zhou F, Peng Z, Murugan R, Kellum JA. Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med. 2013;41:2209–20.CrossRefPubMedPubMedCentral Zhou F, Peng Z, Murugan R, Kellum JA. Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med. 2013;41:2209–20.CrossRefPubMedPubMedCentral
38.
go back to reference Antonelli M, Cutuli SL, Ronco C. Polymyxin B hemoperfusion in septic shock: just look at the evidence! Intensive Care Med. 2015;41:1731–2.CrossRefPubMed Antonelli M, Cutuli SL, Ronco C. Polymyxin B hemoperfusion in septic shock: just look at the evidence! Intensive Care Med. 2015;41:1731–2.CrossRefPubMed
39.
go back to reference Trager K, Fritzler D, Fischer G, Schroder J, Skrabal C, Liebold A, et al. Treatment of post-cardiopulmonary bypass SIRS by hemoadsorption: a case series. Int J Artif Organs. 2016;39:141–6.CrossRefPubMed Trager K, Fritzler D, Fischer G, Schroder J, Skrabal C, Liebold A, et al. Treatment of post-cardiopulmonary bypass SIRS by hemoadsorption: a case series. Int J Artif Organs. 2016;39:141–6.CrossRefPubMed
40.
go back to reference Cornejo R, Downey P, Castro R, Romero C, Regueira T, Vega J, et al. High-volume hemofiltration as salvage therapy in severe hyperdynamic septic shock. Intensive Care Med. 2006;32:713–22.CrossRefPubMed Cornejo R, Downey P, Castro R, Romero C, Regueira T, Vega J, et al. High-volume hemofiltration as salvage therapy in severe hyperdynamic septic shock. Intensive Care Med. 2006;32:713–22.CrossRefPubMed
41.
go back to reference Vieillard-Baron A, Caille V, Charron C, Belliard G, Aegerter P, Page B, et al. Reversal of refractory septic shock with drotrecogin alpha (activated). Intensive Care Med. 2009;35:1204–9.CrossRefPubMed Vieillard-Baron A, Caille V, Charron C, Belliard G, Aegerter P, Page B, et al. Reversal of refractory septic shock with drotrecogin alpha (activated). Intensive Care Med. 2009;35:1204–9.CrossRefPubMed
42.
go back to reference Donati A, Domizi R, Damiani E, Adrario E, Pelaia P, Ince C. From macrohemodynamic to the microcirculation. Crit Care Res Pract. 2013;2013:892710.PubMedPubMedCentral Donati A, Domizi R, Damiani E, Adrario E, Pelaia P, Ince C. From macrohemodynamic to the microcirculation. Crit Care Res Pract. 2013;2013:892710.PubMedPubMedCentral
Metadata
Title
Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study
Authors
Sigrun Friesecke
Stephanie-Susanne Stecher
Stefan Gross
Stephan B. Felix
Axel Nierhaus
Publication date
01-09-2017
Publisher
Springer Japan
Published in
Journal of Artificial Organs / Issue 3/2017
Print ISSN: 1434-7229
Electronic ISSN: 1619-0904
DOI
https://doi.org/10.1007/s10047-017-0967-4

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