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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

Activity of cytochrome 1A2 (metabolism of ethoxyresorufin to resorufin) and the XTT-test (dehydrogenases activity in the mitochondria) of HepG2/C3A cells (biosensor-test) incubated with plasma from septic patients before extracorporeal treatments compared to plasma from patients after extracorporeal granulocyte treatments (Mann-Whitney U test; n = 10; median/0.25–0.75 quartile). ∗Whisker.
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fig5: Activity of cytochrome 1A2 (metabolism of ethoxyresorufin to resorufin) and the XTT-test (dehydrogenases activity in the mitochondria) of HepG2/C3A cells (biosensor-test) incubated with plasma from septic patients before extracorporeal treatments compared to plasma from patients after extracorporeal granulocyte treatments (Mann-Whitney U test; n = 10; median/0.25–0.75 quartile). ∗Whisker.

Mentions: In the cell based analysis of hepatotoxicity (biosensor), the HepG2/C3A cells were incubated with plasma of the patients before and after each extracorporeal granulocyte treatment. The cell-count and vitality (Figure 3), the synthesis of microalbumin (Figure 4), and the activities of cytochrome 1A2 and mitochondrial dehydrogenases (XTT-test, Figure 5) increased significantly during extracorporeal treatment. In addition, the values of lactatedehydrogenase (LDH) were significantly lower after extracorporeal treatment than the values of LDH before extracorporeal treatment (Figure 4). Only in survivors were significant increases of all biosensor parameters observed between day 1 (before extracorporeal treatment) and day 3 after extracorporeal granulocyte treatment (p < 0.05, data not shown), with the exception of LDH (significant decrease in survivors).


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)

Activity of cytochrome 1A2 (metabolism of ethoxyresorufin to resorufin) and the XTT-test (dehydrogenases activity in the mitochondria) of HepG2/C3A cells (biosensor-test) incubated with plasma from septic patients before extracorporeal treatments compared to plasma from patients after extracorporeal granulocyte treatments (Mann-Whitney U test; n = 10; median/0.25–0.75 quartile). ∗Whisker.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Activity of cytochrome 1A2 (metabolism of ethoxyresorufin to resorufin) and the XTT-test (dehydrogenases activity in the mitochondria) of HepG2/C3A cells (biosensor-test) incubated with plasma from septic patients before extracorporeal treatments compared to plasma from patients after extracorporeal granulocyte treatments (Mann-Whitney U test; n = 10; median/0.25–0.75 quartile). ∗Whisker.
Mentions: In the cell based analysis of hepatotoxicity (biosensor), the HepG2/C3A cells were incubated with plasma of the patients before and after each extracorporeal granulocyte treatment. The cell-count and vitality (Figure 3), the synthesis of microalbumin (Figure 4), and the activities of cytochrome 1A2 and mitochondrial dehydrogenases (XTT-test, Figure 5) increased significantly during extracorporeal treatment. In addition, the values of lactatedehydrogenase (LDH) were significantly lower after extracorporeal treatment than the values of LDH before extracorporeal treatment (Figure 4). Only in survivors were significant increases of all biosensor parameters observed between day 1 (before extracorporeal treatment) and day 3 after extracorporeal granulocyte treatment (p < 0.05, data not shown), with the exception of LDH (significant decrease in survivors).

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