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Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments.

Sauer M, Altrichter J, Haubner C, Pertschy A, Wild T, Doß F, Mencke T, Thomsen M, Ehler J, Henschel J, Doß S, Koch S, Richter G, Nöldge-Schomburg G, Mitzner SR - Biomed Res Int (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic drawing of the extracorporeal plasma separation and cell perfusion model.
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fig1: Schematic drawing of the extracorporeal plasma separation and cell perfusion model.

Mentions: After inclusion of a patient, a healthy blood donor for obtaining an ABO-compatible granulocyte concentrate was identified and stimulated with corticosteroids (each 8 mg p.o. methylprednisolone, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany) and lenograstim (Granocyte, each 1.5 μg/kg s.c., Chugai Pharma Deutschland, Frankfurt, Germany) 16 h before donation. Granulocytes were collected by extracorporeal density gradient centrifugation using hydroxyethyl starch (HES 200/0.5 6%, Fresenius Kabi AG, Bad Homburg, Germany) and citrate in a cell separator (COBE Spectra, Gambro BCT, Planegg-Martinsried, Germany) according to standard procedures. Prior to the treatment, the inclusion criteria were reconfirmed and the patients were treated for up to six hours with an extracorporeal bioreactor (Figure 1) consisting of plasma separation and plasma perfusion through the cell compartment containing the donor cells. Blood access was venovenous via a Shaldon catheter. Plasma separation was carried out by a dialysis monitor (BM25, Edwards Lifesciences GmbH, Unterschleissheim, Germany) using a 0.5 μm pore-size plasma filter (PF 1000N, Gambro Hospal GmbH, Planegg-Martinsried, Germany). The plasma was infused into a continuously recirculating donor cell compartment that was prefilled with hemofiltration solution HF-BIC 35-410 (Fresenius Medical Care, Bad Homburg, Germany). Plasma reflux to the patient was done through a second PF 1000N plasma filter to withhold the donor cells from being infused into the patient. Total extracorporeal volume was 400 mL. The blood flow rate was 110–150 mL/minute with a plasma separation rate of 16.7–33.3 mL plasma/minute using the BM 25 monitor. The MARS-Monitor 1 TC (Gambro Rostock GmbH, Rostock, Germany) was used for the recirculating bioreactor circuit at a rate of 200 mL/minute and to maintain the temperature in the cell compartment at 37°C. Unfractionated heparin (40 IU/kg, Roche, Grenzach-Wyhlen, Germany) was given at the beginning of the extracorporeal treatment followed by a continuous infusion into the circuit. Heparin administration was adjusted to maintain activated clotting time (ACT) within 180–200 seconds. Following safety assessment of the first treatment, all patients were treated a second time 48 hours after the first treatment, again for up to six hours with granulocytes from the same donor.


Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments.

Sauer M, Altrichter J, Haubner C, Pertschy A, Wild T, Doß F, Mencke T, Thomsen M, Ehler J, Henschel J, Doß S, Koch S, Richter G, Nöldge-Schomburg G, Mitzner SR - Biomed Res Int (2016)

Schematic drawing of the extracorporeal plasma separation and cell perfusion model.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940519&req=5

fig1: Schematic drawing of the extracorporeal plasma separation and cell perfusion model.
Mentions: After inclusion of a patient, a healthy blood donor for obtaining an ABO-compatible granulocyte concentrate was identified and stimulated with corticosteroids (each 8 mg p.o. methylprednisolone, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany) and lenograstim (Granocyte, each 1.5 μg/kg s.c., Chugai Pharma Deutschland, Frankfurt, Germany) 16 h before donation. Granulocytes were collected by extracorporeal density gradient centrifugation using hydroxyethyl starch (HES 200/0.5 6%, Fresenius Kabi AG, Bad Homburg, Germany) and citrate in a cell separator (COBE Spectra, Gambro BCT, Planegg-Martinsried, Germany) according to standard procedures. Prior to the treatment, the inclusion criteria were reconfirmed and the patients were treated for up to six hours with an extracorporeal bioreactor (Figure 1) consisting of plasma separation and plasma perfusion through the cell compartment containing the donor cells. Blood access was venovenous via a Shaldon catheter. Plasma separation was carried out by a dialysis monitor (BM25, Edwards Lifesciences GmbH, Unterschleissheim, Germany) using a 0.5 μm pore-size plasma filter (PF 1000N, Gambro Hospal GmbH, Planegg-Martinsried, Germany). The plasma was infused into a continuously recirculating donor cell compartment that was prefilled with hemofiltration solution HF-BIC 35-410 (Fresenius Medical Care, Bad Homburg, Germany). Plasma reflux to the patient was done through a second PF 1000N plasma filter to withhold the donor cells from being infused into the patient. Total extracorporeal volume was 400 mL. The blood flow rate was 110–150 mL/minute with a plasma separation rate of 16.7–33.3 mL plasma/minute using the BM 25 monitor. The MARS-Monitor 1 TC (Gambro Rostock GmbH, Rostock, Germany) was used for the recirculating bioreactor circuit at a rate of 200 mL/minute and to maintain the temperature in the cell compartment at 37°C. Unfractionated heparin (40 IU/kg, Roche, Grenzach-Wyhlen, Germany) was given at the beginning of the extracorporeal treatment followed by a continuous infusion into the circuit. Heparin administration was adjusted to maintain activated clotting time (ACT) within 180–200 seconds. Following safety assessment of the first treatment, all patients were treated a second time 48 hours after the first treatment, again for up to six hours with granulocytes from the same donor.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, 18057 Rostock, Germany.

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.

No MeSH data available.


Related in: MedlinePlus