Effects of Bioreactor-Oxygenation During Extracorporeal Granulocytes Treatment in Septic Patients
Corresponding Author
Martin Sauer
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Address correspondence and reprint requests to Dr Martin Sauer, Department of Anesthesiology and Intensive Care Medicine, University Hospital Rostock, Schillingallee 35, 18055 Rostock, Germany. Email: [email protected]Search for more papers by this authorGeorg Richter
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorThomas Wild
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorFanny Doß
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorThomas Mencke
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorJohannes Ehler
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorSandra Doß
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorStephanie Koch
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorAnton Schubert
Department of Surgery, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorGabriele Nöldge-Schomburg
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorSteffen R Mitzner
Department of Medicine (Division of Nephrology), University Hospital of Rostock, Rostock, Germany
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorCorresponding Author
Martin Sauer
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Address correspondence and reprint requests to Dr Martin Sauer, Department of Anesthesiology and Intensive Care Medicine, University Hospital Rostock, Schillingallee 35, 18055 Rostock, Germany. Email: [email protected]Search for more papers by this authorGeorg Richter
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorThomas Wild
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorFanny Doß
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorThomas Mencke
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorJohannes Ehler
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorSandra Doß
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorStephanie Koch
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorAnton Schubert
Department of Surgery, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorGabriele Nöldge-Schomburg
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock, Rostock, Germany
Search for more papers by this authorSteffen R Mitzner
Department of Medicine (Division of Nephrology), University Hospital of Rostock, Rostock, Germany
Fraunhofer Institute for Cell Therapy and Immunology, Rostock, Germany
Search for more papers by this authorAbstract
A granulocyte bioreactor for the extracorporeal treatment was developed to enhance the immune cell function in patients with severe sepsis. The influence of oxygenation on the used cells was tested in a prospective clinical study. Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The used cells were screened for functionality; values of blood gases, glucose and lactate were obtained from the recirculating bioreactor circuit. Five patients were treated with an oxygenator setup (Oxy group), five without oxygenator (Non-Oxy group). The overall in-hospital mortality was 50%. Significantly lower values of oxygen saturation, partial oxygen pressure, lactate, oxyburst and phagocytosis were seen in the Non-Oxy group compared with the Oxy group in the bioreactor circuit. Further studies with this approach are encouraged and should focus on the influence of oxygenation on production of reactive oxygen species and cytokines of used cells.
REFERENCES
- 1Rimmelee T, Kellum JA. Clinical review: blood purification for sepsis. Crit Care 2011; 15: 205.
- 2Zhou F, Peng Z, Murugan R, Kellum JA. Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med 2013; 41: 2209–22203.
- 3McCunn M, Reed AJ. Critical care organ support: a focus on extracorporal systems. Crit Care 2009; 15: 554–9.
- 4Ellis AJ, Hughes RD, Wendon JA et al. Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology 1996; 24: 1446–51.
- 5Leckie P, Davenport A, Jalan R. Extracorporeal liver support. Blood Purif 2012; 34: 158–63.
- 6Song JH, Humes HD. The bioartificial kidney in the treatment of acute kidney injury. Curr Drug Targets 2009; 10: 1227–34.
- 7Humes HD, Buffington DA, Lou L et al. Cell therapy with a tissue-engineered kidney reduces the multiple-organ consequences of septic shock. Crit Care Med 2003; 31: 2421–8.
- 8Humes HD, Weitzel WF, Bartlett RH, Swaniker FC, Paganini EP. Renal cell therapy is associated with dynamic and individualized responses in patients with acute renal failure. Blood Purif 2003; 21: 64–71.
- 9Tumlin J, Wali R, Williams W et al. Efficacy and safety of renal tubule cell therapy for acute renal failure. J Am Soc Nephrol 2008; 19: 1034–40.
- 10Hay PD, Veitch AR, Smith MD, Cousins RB, Gaylor JDS. Oxygen transfer in a diffusion-limited hollow fiber Bioartifical liver. Artif Organs 2000; 24: 278–88.
- 11Hay PD, Veitch AR, Gaylor JDS. Oxygen transfer in a convection-enhanced hollow fiber bioartificial liver. Artif Organs 2001; 25: 119–30.
- 12Sauer M, Altrichter J, Kreutzer HJ et al. Extracorporeal cell therapy with granulocytes in a pig–model of Gram-positive sepsis. Crit Care Med 2009; 37: 606–13.
- 13Sauer M, Altrichter J, Kreutzer HJ et al. Safety evaluation for a cell-based immune support system in an ex vivo rat model of gram-negative sepsis. Ther Apher Dial 2009; 13: 444–50.
- 14Altrichter J, Sauer M, Kaftan K et al. Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study. Crit Care 2011; 15: R82.
- 15Sauer M, Altrichter J, Haubner C et al. Bioartificial therapy of sepsis: changes of norepinephrine-dosage in patients and influence on dynamic and cell based liver tests during extracorporeal treatments. Biomed Res Int 2016; 2016 ID: 7056492.
- 16Boomer JS, To K, Chang KC et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 2011; 306: 2594–605.
- 17Caille V, Chiche JD, Nciri N et al. Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock. Shock 2004; 22: 521–6.
- 18Kaufmann I, Hoelzl A, Schliephake F et al. Polymorphonuclear leukocyte dysfunction syndrome in patients with increasing sepsis severity. Shock 2006; 26: 254–61.
- 19Pachot A, Monneret G, Brion A et al. Messenger RNA expression of major histocompatibility complex class II genes in whole blood from septic shock patients. Crit Care Med 2005; 33: 31–8.
- 20Tavares-Murta BM, Zaparoli M, Ferreira RB et al. Failure of neutrophil chemotactic function in septic patients. Crit Care Med 2002; 30: 1056–61.
- 21Lehmann LE, Novender U, Schroeder S et al. Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis. Intensive Care Med 2001; 27: 1412–5.
- 22American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20: 864–74.
- 23Bernard GR, Vincent JL, Laterre PF et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699–709.
- 24Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29: 1303–10.
- 25Engel C, Brunkhorst FM, Bone HG et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med 2007; 33: 606–18.
- 26Bermejo-Martin JF, Ojeda DA, Almansa R et al. Defining immunological dysfunction in sepsis: a requisite tool for precision medicine. J Infect 2016; 72: 525–36.
- 27Rimmele T, Payen D, Cantaluppi V et al. Immune cell phenotype and function in sepsis. Shock 2016; 45: 282–91.
- 28Arena ET, Tinevez JY, Nigro G et al. The infectious hypoxia: occurrence and causes during Shigella infection. Microbes Infect 2016 mininf.2016.10.011.
- 29Wilde AD, Snyder DJ, Putnam NE et al. Bacterial hypoxic response revealed as critical determinants of the host-pathogen outcome by TnSeq analysis of Staphylococcus Aureus invasive infection. PLoS Pathog 2015; 11: e1005341.
- 30Laurenzi GA, Guarney JJ, Endriga RB, JP C. Clearance of bacteria by the lower respiratory tract. Science 1963; 142: 1572–3.
- 31van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol 2017; 17: 407–20.
- 32Foy BD, Lee J, Morgan J, Toner M, Tompkins RG, Yarmush ML. Optimization of hepatocytes attachment to microcarriers: importance of oxygen. Biotechnol Bioeng 1993; 42: 579–88.
- 33Rotem A, Toner M, Bhatia S, Foy BD, Tompkins RG, Yarmush ML. Oxygen is a factor determining in vitro tissue Asembly: effects on attachment and spreading of hepatocytes. Biotechnol Bioeng 1994; 43: 654–60.
- 34Foy BD, Rotem A, Toner M, Tompkins RG, Yarmush ML. A device to measure the oxygen uptake rate of attached cells: importance in bioartifical organ design. Cell Transplant 1994; 3: 515–27.