Abstract
BackgroundNovel 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.MethodsAfter 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.ResultsThree 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.ConclusionsThe 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.
Highlights
Novel extracorporeal procedures are constantly being developed and evaluated for use in patients with sepsis
We evaluated the safety and efficacy of the ADVanced Organ Support (ADVOS) system in an animal model with multiple organ involvement and with a high mortality rate when treated with the standard medical treatment
Kidneys play a major role in ammonia clearance [28], and renal involvement worsens liver failure in 30–50% of the patients [29], which is associated with a poor prognosis once renal failure develops [30]
Summary
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. MOF results from an “altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention” [8]. Bearing this in mind, interrupting this vicious cycle appears to be an essential concept in the treatment of e.g. liver and kidney dysfunction and, sepsis. The newly introduced ADVanced Organ Support (ADVOS) system (previously known as the Hepa Wash procedure), combining liver and renal support, based on albumin dialysis, has been shown to improve dysfunction of the liver and kidney and the circulatory system and survival in an animal model of acute liver failure [10]
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