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@ARTICLE{AlChalabi:164245,
author = {Al-Chalabi, Ahmed and Matevossian, Edouard and von Thaden,
Anne and Schreiber, Catherine and Radermacher, Peter and
Huber, Wolfgang and Perez Ruiz de Garibay, Aritz and
Kreymann, Bernhard},
title = {{E}valuation of an {ADV}anced {O}rgan {S}upport ({ADVOS})
system in a two-hit porcine model of liver failure plus
endotoxemia.},
journal = {Intensive Care Medicine Experimental},
volume = {5},
number = {1},
issn = {2197-425X},
address = {Heidelberg},
publisher = {Springer Open},
reportid = {DZNE-2022-00901},
pages = {31},
year = {2017},
abstract = {Novel extracorporeal procedures are constantly being
developed and evaluated for use in patients with sepsis.
Preclinical evaluation of such procedures usually requires
testing in large animal models. In the present work, the
safety and efficacy of a recently developed ADVanced Organ
Support (ADVOS) system in a newly developed large animal
two-hit model of liver failure combined with endotoxemia
were tested.After establishing the model in more than 50
animals, a randomized study was performed. An inflammatory
cholestatic liver injury was initially provoked in pigs.
Three days after surgery, endotoxin was gradually
administered during 7½ h. Animals were randomized to
receive standard medical treatment either with (ADVOS group,
n = 5) or without ADVOS (control group, n = 5). The ADVOS
treatment was started 2½ h after endotoxemia and continued
for 7 h. Survival, cardiovascular, respiratory, renal,
liver, coagulation, and cerebral parameters were
analyzed.Three days after surgery, cholestatic injury
resulted in hyperbilirubinemia [5.0 mg/dl (IQR 4.3-5.9
mg/dl)], hyperammonemia [292 μg/dl (IQR 291-296 μg/dl)],
leukocytosis [20.2 103/μl (IQR 17.7-21.8 103/μl)], and
hyperfibrinogenemia [713 mg/dl (IQR 654-803 mg/dl)]. After
endotoxemia, the ADVOS procedure stabilized cardiovascular,
respiratory, and renal parameters and eliminated surrogate
markers as bilirubin [2.3 (IQR 2.3-3.0) vs. 5.5 (IQR
4.6-5.6) mg/dl, p = 0.001] and creatinine [1.4 (IQR 1.1-1.7)
vs. 2.3 (IQR 2.1-3.1) mg/dl, p = 0.01]. Mortality: All
animals in the ADVOS group survived, while all animals in
the control group expired during the 10-h observation period
(p = 0.002). No adverse events related to the procedure were
observed.The ADVOS procedure showed a promising safety and
efficacy profile and improved survival in a sepsis-like
animal model with dysfunction of multiple organs. An
amelioration of major organ functions (heart and lung)
combined with removal of markers for kidney and liver
function was observed.},
keywords = {Albumin dialysis (Other) / Animal model (Other) /
Cholestasis (Other) / Endotoxemia (Other) / Extracorporeal
organ support (Other) / Liver failure (Other) / Multiple
organ failure (Other) / Sepsis (Other) / Survival (Other) /
Swine (Other)},
cin = {Animal Facility (Mouse) München},
ddc = {610},
cid = {I:(DE-2719)1140012},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28677045},
pmc = {pmc:PMC5496922},
doi = {10.1186/s40635-017-0144-3},
url = {https://pub.dzne.de/record/164245},
}