title: Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments.
abstract: Purpose. Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients. Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results. The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.
authors.affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Martin
authors.identifier: 0000-0001-6221-9081
authors.initials: M
authors.lastname: Sauer
authors.affiliation: Departments of Medicine, Division of Nephrology, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Altrichter
authors.affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Cristof
authors.initials: C
authors.lastname: Haubner
authors.affiliation: Departments of Surgery, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Pertschy
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wild
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.
authors.forename: Fanny
authors.initials: F
authors.lastname: Doß
authors.affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Thomas
authors.identifier: 0000-0002-9179-4437
authors.initials: T
authors.lastname: Mencke
authors.affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Thomsen
authors.affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ehler
authors.affiliation: Departments of Medicine, Division of Nephrology, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Henschel
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Doß
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Koch
authors.affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Richter
authors.affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.
authors.forename: Gabriele
authors.identifier: 0000-0002-0041-3580
authors.initials: G
authors.lastname: Nöldge-Schomburg
authors.affiliation: Departments of Medicine, Division of Nephrology, Medical Faculty of the University of Rostock, 18057 Rostock, Germany; Fraunhofer Institute for Cell Therapy and Immunology, 04103 Leipzig, Germany.
authors.forename: Steffen R
authors.initials: SR
authors.lastname: Mitzner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D015331:Cohort Studies; D019388:Cytochrome P-450 CYP1A2; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005112:Extracorporeal Circulation / Q000379:methods*; D006439:Hemodynamics; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000473:pathology*; D008111:Liver Function Tests; D019164:Liver, Artificial; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000627:therapeutic use*; D018805:Sepsis / Q000473:pathology* / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007770:L-Lactate Dehydrogenase; D019388:Cytochrome P-450 CYP1A2; D009638:Norepinephrine