Background: Extracorporeal blood purification therapies have been proposed as a strategy to remove inflammatory mediators during sepsis, thus improving outcome. Objectives: We aimed to evaluate changes in cytokines, haemodynamics and microcirculation during blood purification with Cytosorb adsorber in septic patients. Methods: Prospective observational study on critically ill adult patients with sepsis/septic shock underwent renal replacement therapy (RRT) for acute renal failure and haemoadsorption with Cytosorb as adjunctive therapy for 24 h. Measurements were taken at baseline, after 6 and 24 h: haemodynamic parameters, arterial and central venous blood gases, plasma levels of tumour necrosis factor alpha, interleukin (IL) 1-beta, IL-6, IL-8 and IL-10. The sublingual microcirculation was assessed with sidestream dark field videomicroscopy to evaluate the perfused vessel density (PVD) and microvascular flow quality. Tissue oxygenation and microvascular reactivity were assessed with thenar near infrared spectroscopy (NIRS) with a vascular occlusion test. Results: Nine patients; plasma levels of IL-8 decreased at 24 h (p < 0.05 versus 6 h); no significant variation was found for other cytokines. Haemodynamic remained stable throughout the observation. Microvascular perfusion improved over time, with an increase in PVDs at 6 and 24 h (from 13.9 [13.3–16.4] to 15.7 [15–17.3] and 17 [14.8–18.6] mm/mm2 respectively, p = 0.003) and total vessel densities at 24 h (14.9 [13.9–16.9] vs. 17.9 [15.3–20], p = 0.0015). No significant variation was detected in NIRS-derived parameters. The Sequential Organ Failure Assessment score decreased from 12 ± 3 to 10 ± 1 at 24 h (p = 0.039). Conclusions: In septic patients undergoing RRT, haemoadsorption with Cytosorb seems to determine a decreasing in plasma levels of IL-8, although levels of other cytokines did not vary significantly, and an improvement of microcirculation despite no significant variation in macro-haemodynamics.

1.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA
. 2016 Feb;315(8):801–10.
2.
Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, et al.; GenIMS Investigators. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study.
Arch Intern Med
. 2007 Aug;167(15):1655–63.
3.
Ince C. The microcirculation is the motor of sepsis.
Crit Care
. 2005;9 Suppl 4:S13–9.
4.
Donati A, Domizi R, Damiani E, Adrario E, Pelaia P, Ince C. From macrohemodynamic to the microcirculation.
Crit Care Res Pract
. 2013;2013:892710.
5.
Donati A, Damiani E, Domizi R, Romano R, Adrario E, Pelaia P, et al. Alteration of the sublingual microvascular glycocalyx in critically ill patients.
Microvasc Res
. 2013 Nov;90:86–9.
6.
Rimmelé T, Kellum JA. Clinical review: blood purification for sepsis.
Crit Care
. 2011;15(1):205.
7.
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 Jun;301(23):2445–52.
8.
Kellum JA, Song M, Venkataraman R. Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia.
Crit Care Med
. 2004 Mar;32(3):801–5.
9.
Peng ZY, Carter MJ, Kellum JA. Effects of hemoadsorption on cytokine removal and short-term survival in septic rats.
Crit Care Med
. 2008 May;36(5):1573–7.
10.
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016.
Intensive Care Med
. 2017 Mar;43(3):304–77.
11.
Goedhart PT, Khalilzada M, Bezemer R, Merza J, Ince C. Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation.
Opt Express
. 2007 Nov;15(23):15101–14.
12.
Ince C, Boerma EC, Cecconi M, De Backer D, Shapiro NI, Duranteau J, et al.; Cardiovascular Dynamics Section of the ESICM. Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine.
Intensive Care Med
. 2018 Mar;44(3):281–99.
13.
Gómez H, Mesquida J, Simon P, Kim HK, Puyana JC, Ince C, et al. Characterization of tissue oxygen saturation and the vascular occlusion test: influence of measurement sites, probe sizes and deflation thresholds.
Crit Care
. 2009;13 Suppl 5:S3.
14.
Donati A, Damiani E, Domizi R, Scorcella C, Carsetti A, Tondi S, et al. Near-infrared spectroscopy for assessing tissue oxygenation and microvascular reactivity in critically ill patients: a prospective observational study.
Crit Care
. 2016 Oct;20(1):311.
15.
Peng Z, Singbartl K, Simon P, Rimmelé T, Bishop J, Clermont G, et al. Blood purification in sepsis: a new paradigm.
Contrib Nephrol
. 2010;165:322–8.
16.
Tomescu DR, Olimpia Dima S, Ungureanu D, Popescu M, Tulbure D, Popescu I. First report of cytokine removal using CytoSorb® in severe noninfectious inflammatory syndrome after liver transplantation.
Int J Artif Organs
. 2016 May;39(3):136–40.
17.
Träger K, Schütz C, Fischer G, Schröder J, Skrabal C, Liebold A, et al. Cytokine reduction in the setting of an ARDS-associated inflammatory response with multiple organ failure.
Case Rep Crit Care
. 2016;2016:9852073.
18.
Bernardi MH, Rinoesl H, Dragosits K, Ristl R, Hoffelner F, Opfermann P, et al. Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent.
Crit Care
. 2016 Apr;20(1):96.
19.
Träger K, Fritzler D, Fischer G, Schröder J, Skrabal C, Liebold A, et al. Treatment of post-cardiopulmonary bypass SIRS by hemoadsorption: a case series.
Int J Artif Organs
. 2016 May;39(3):141–6.
20.
Träger K, Skrabal C, Fischer G, Datzmann T, Schroeder J, Fritzler D, et al. Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass - a case series.
Int J Artif Organs
. 2017 May;40(5):240–9.
21.
Friesecke S, Träger K, Schittek GA, Molnar Z, Bach F, Kogelmann K, et al. International registry on the use of the CytoSorb® adsorber in ICU patients : study protocol and preliminary results.
Med Klin Intensivmed Notfmed
. 2017, Epub ahead of print.
22.
Steltzer H, Grieb A, Mostafa K, Berger R. Use of CytoSorb in traumatic amputation of the forearm and severe septic shock.
Case Rep Crit Care
. 2017;2017:8747616.
23.
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 Aug;38(8):461–4.
24.
Kogelmann K, Jarczak D, Scheller M, Drüner M. Hemoadsorption by CytoSorb in septic patients: a case series.
Crit Care
. 2017 Mar;21(1):74.
25.
Friesecke S, Stecher SS, Gross S, Felix SB, Nierhaus A. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study.
J Artif Organs
. 2017 Sep;20(3):252–9.
26.
Schädler D, Pausch C, Heise D, Meier-Hellmann A, Brederlau J, Weiler N, et al. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial.
PLoS One
. 2017 Oct;12(10):e0187015.
27.
Honoré PM, Matson JR. Extracorporeal removal for sepsis: acting at the tissue level—the beginning of a new era for this treatment modality in septic shock.
Crit Care Med
. 2004 Mar;32(3):896–7.
28.
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 Feb;81(4):363–9.
29.
Damiani E, Adrario E, Luchetti MM, Scorcella C, Carsetti A, Mininno N, et al. Plasma Free Hemoglobin and Microcirculatory Response to Fresh or Old Blood Transfusions in Sepsis.
PLoS One
. 2015 May;10(5):e0122655.
30.
Vellinga NA, Boerma EC, Koopmans M, Donati A, Dubin A, Shapiro NI, et al.; microSOAP Study Group. International study on microcirculatory shock occurrence in acutely ill patients.
Crit Care Med
. 2015 Jan;43(1):48–56.
31.
Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation.
Crit Care
. 2015;19 Suppl 3:S8.
32.
David S, Thamm K, Schmidt BM, Falk CS, Kielstein JT. Effect of extracorporeal cytokine removal on vascular barrier function in a septic shock patient.
J Intensive Care
. 2017 Jan;5(1):12.
33.
Hosgood SA, Moore T, Kleverlaan T, Adams T, Nicholson ML. Haemoadsorption reduces the inflammatory response and improves blood flow during ex vivo renal perfusion in an experimental model.
J Transl Med
. 2017 Oct;15(1):216.
34.
Qian J, Yang Z, Cahoon J, Xu J, Zhu C, Yang M, et al. Post-resuscitation intestinal microcirculation: its relationship with sublingual microcirculation and the severity of post-resuscitation syndrome.
Resuscitation
. 2014 Jun;85(6):833–9.
35.
Boerma EC, van der Voort PH, Spronk PE, Ince C. Relationship between sublingual and intestinal microcirculatory perfusion in patients with abdominal sepsis.
Crit Care Med
. 2007 Apr;35(4):1055–60.
36.
Edul VS, Ince C, Navarro N, Previgliano L, Risso-Vazquez A, Rubatto PN, et al. Dissociation between sublingual and gut microcirculation in the response to a fluid challenge in postoperative patients with abdominal sepsis.
Ann Intensive Care
. 2014 Dec;4(1):39.
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