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Low-dose polymyxin: an option for therapy of Gram-negative sepsis.

Harm S, Gabor F, Hartmann J - Innate Immun (2016)

Bottom Line: The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion.Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model.Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure.

View Article: PubMed Central - PubMed

Affiliation: Department for Health Sciences and Biomedicine, Danube University Krems, Krems, Austria Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria stephan.harm@donau-uni.ac.at.

No MeSH data available.


Related in: MedlinePlus

Setup for determination of PMB clearance during hemodialysis using the multiFiltrate. The experiment was performed with (A) 1500 ml plasma, (B) a blood pump with (QB) flow rates between 50 and 200 ml and (C) the dialyzer AV1000 S (Fresenius Medical Care). Samples were taken pre- (Cin) and post- (Cout) filter after 5, 10, 15, 20, 25 and 30 min.
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fig2-1753425916639120: Setup for determination of PMB clearance during hemodialysis using the multiFiltrate. The experiment was performed with (A) 1500 ml plasma, (B) a blood pump with (QB) flow rates between 50 and 200 ml and (C) the dialyzer AV1000 S (Fresenius Medical Care). Samples were taken pre- (Cin) and post- (Cout) filter after 5, 10, 15, 20, 25 and 30 min.

Mentions: Since sepsis patients with acute kidney injury are treated with renal replacement therapy, a dialysis experiment was performed to estimate the clearance of PMB during a treatment. As intensive care treatment sessions usually take several hours, it can be assumed that most of the non-protein-bound fraction of PMB is removed during treatment. In order to avoid that the inflammatory activity of LPS is restored by PMB removal, PMB monitoring would be useful. To check the PMB clearance by a conventional dialysis filter, 1500 ml plasma spiked with 5 µg/ml PMB was circulated through a dialyzer (AV1000S, FMC, Bad Homburg, Germany) using the multiFiltrate device from Fresenius Medical Care (Bad Homburg, Germany). The schematic setup of this experiment is shown in Figure 2. The plasma flow rate (Qb) was 100 ml/min and dialysate (QD) flow rates of 2000 ml/h and 4800 ml/h were chosen. Samples for PMB quantification were collected pre- and postfilter after 5, 10, 15, 20, 25 and 30 min. The experiment was performed three times with different plasma and dialyzers and the PMB clearance was calculated according to the following formula:Cl(PMB)=cin(PMB)-cout(PMB)cin(PMB)×QbFigure 2.


Low-dose polymyxin: an option for therapy of Gram-negative sepsis.

Harm S, Gabor F, Hartmann J - Innate Immun (2016)

Setup for determination of PMB clearance during hemodialysis using the multiFiltrate. The experiment was performed with (A) 1500 ml plasma, (B) a blood pump with (QB) flow rates between 50 and 200 ml and (C) the dialyzer AV1000 S (Fresenius Medical Care). Samples were taken pre- (Cin) and post- (Cout) filter after 5, 10, 15, 20, 25 and 30 min.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4834512&req=5

fig2-1753425916639120: Setup for determination of PMB clearance during hemodialysis using the multiFiltrate. The experiment was performed with (A) 1500 ml plasma, (B) a blood pump with (QB) flow rates between 50 and 200 ml and (C) the dialyzer AV1000 S (Fresenius Medical Care). Samples were taken pre- (Cin) and post- (Cout) filter after 5, 10, 15, 20, 25 and 30 min.
Mentions: Since sepsis patients with acute kidney injury are treated with renal replacement therapy, a dialysis experiment was performed to estimate the clearance of PMB during a treatment. As intensive care treatment sessions usually take several hours, it can be assumed that most of the non-protein-bound fraction of PMB is removed during treatment. In order to avoid that the inflammatory activity of LPS is restored by PMB removal, PMB monitoring would be useful. To check the PMB clearance by a conventional dialysis filter, 1500 ml plasma spiked with 5 µg/ml PMB was circulated through a dialyzer (AV1000S, FMC, Bad Homburg, Germany) using the multiFiltrate device from Fresenius Medical Care (Bad Homburg, Germany). The schematic setup of this experiment is shown in Figure 2. The plasma flow rate (Qb) was 100 ml/min and dialysate (QD) flow rates of 2000 ml/h and 4800 ml/h were chosen. Samples for PMB quantification were collected pre- and postfilter after 5, 10, 15, 20, 25 and 30 min. The experiment was performed three times with different plasma and dialyzers and the PMB clearance was calculated according to the following formula:Cl(PMB)=cin(PMB)-cout(PMB)cin(PMB)×QbFigure 2.

Bottom Line: The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion.Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model.Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure.

View Article: PubMed Central - PubMed

Affiliation: Department for Health Sciences and Biomedicine, Danube University Krems, Krems, Austria Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria stephan.harm@donau-uni.ac.at.

No MeSH data available.


Related in: MedlinePlus