A Prediction and Simulation Model for Target-Oriented Regional Citrate-Calcium Anticoagulation in Extracorporeal Blood Purification

2016 ◽  
Vol 39 (10) ◽  
pp. 497-501
Author(s):  
Martin Brandl ◽  
Karlheinz Kellner
Keyword(s):  
Simulation Model ◽  
Blood Purification ◽  
Extracorporeal Blood ◽  
Extracorporeal Blood Purification ◽  
Prediction And Simulation

Heparin-based blood purification attenuates organ injury in baboons with S. pneumoniae pneumonia

2021 ◽  
Author(s):  
Lingye Chen ◽  
Bryan D Kraft ◽  
Victor L Roggli ◽  
Zachary R Healy ◽  
Christopher W Woods ◽  
...  
Keyword(s):  
Septic Shock ◽  
Pneumococcal Pneumonia ◽  
Kidney Injury ◽  
Blood Purification ◽  
Dose Finding ◽  
Organ Injury ◽  
Inflammasome Activation ◽  
Post Inoculation ◽  
Extracorporeal Blood ◽  
Extracorporeal Blood Purification

Background: Bacterial pneumonia is a major cause of morbidity and mortality worldwide despite the use of antibiotics, and novel therapies are urgently needed. Building on previous work, we aimed to 1) develop a baboon model of severe pneumococcal pneumonia and sepsis with organ dysfunction; and 2) test the safety and efficacy of a novel extracorporeal blood filter to remove pro-inflammatory molecules and improve organ function. Methods: After a dose-finding pilot study, twelve animals were inoculated with S. pneumoniae (5x109 CFU), given ceftriaxone at 24 hours post-inoculation, and randomized to extracorporeal blood purification using a filter coated with surface-immobilized heparin sulfate (n=6) or sham treatment (n=6) for 4 hours at 30 hours post-inoculation. For safety analysis, four uninfected animals also underwent purification. At 48 hours, necropsy was performed. Results: Inoculated animals developed severe pneumonia and septic shock. Compared with sham animals, septic animals treated with purification displayed significantly less kidney injury, metabolic acidosis, hypoglycemia, and shock (P<0.05). Purification blocked the rise in peripheral blood S. pneumoniae DNA, attenuated BAL CCL4, CCL2, and IL-18 levels, and reduced renal oxidative injury and classical NLRP3-inflammasome activation. Purification was safe in both uninfected and infected animals and produced no adverse effects. Conclusions: We demonstrate that heparin-based blood purification significantly attenuates levels of circulating S. pneumoniae DNA and BAL cytokines, and is renal-protective in baboons with severe pneumococcal pneumonia and septic shock. Purification was associated with less severe acute kidney injury, metabolic derangements, and shock. These results support future clinical studies in critically ill septic patients.

Evaluation of plasma levels of meropenem in septic patients during extracorporeal blood purification

2021 ◽  
Vol 20 (4) ◽  
pp. 81-94
Author(s):  
Artem V. Marukhov ◽  
Elena V. Murzina ◽  
Mikhail V. Zakharov ◽  
Genrikh A. Sofronov ◽  
Lyudmila V. Buryakova ◽  
...  
Keyword(s):  
Septic Shock ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Selective Adsorption ◽  
Plasma Concentrations ◽  
Blood Purification ◽  
Continuous Hemodiafiltration ◽  
Extracorporeal Blood ◽  
Extracorporeal Blood Purification ◽  
Extracorporeal Support

The relevance. Meropenem is a broad-spectrum carbapenem antibiotic widely used to treat patients with sepsis / septic shock. Critically ill patients are usually supported with one of the forms extracorporeal blood purification. However, data on the effect of various extracorporeal support techniques on the pharmacokinetics and pharmacodynamics of meropenem are insufficient or contradictory. Aim: To evaluate the effectiveness of meropenem dosage regimens in the treatment of septic patients during extracorporeal blood purification. Materials and methods. Plasma concentrations of meropenem were monitored in three critically ill patients with sepsis or septic shock. Patients were treated using various extracorporeal support techniques. Meropenem was used as empirical antibacterial mono- or complex therapy (1 g every 8 or 12 hours). Meropenem concentrations in plasma were determined by validated assay methods on Acquity ultraefficient liquid chromatography (UPLC) H-Class system. Results. It is shown that the meropenem plasma concentration in critically ill patients changes significantly. It was found that the standard meropenem dosing regimens in patients with sepsis / septic shock during continuous hemodiafiltration do not ensure the achievement of the PK/PD target of 100% TMIC for sensitive strains (MIC2 mg/L) and for intermediate resistance pathogens (2MIC8 mg/L). Continuous hemofiltration and selective adsorption of lipopolysaccharide have a less pronounced effect on the clearance of meropenem. Conclusion. To increase the effectiveness of antibacterial therapy, it is necessary to conduct research aimed at developing protocols for dosing antibacterial drugs for the treatment of sepsis during extracorporeal blood purification.

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