Survival improvement in pigs with liver failure and superimposed sepsis by a new liver support system (Hepa Wash^®)

Introduction

Liver failure is often complicated by sepsis. Available liver support systems (LSS) failed to show survival benefits. Hepa Wash^® (HW) is a newly developed LSS based on use of recycled albumin dialysate. The study aim is to evaluate its safety and efficacy in an animal model that combines liver failure with sepsis.

Methods

Female German Landrace pigs (~60 kg) were randomly allocated to HW (n = 5) and control (n = 5) groups. On day 0 ischemic and cholestatic liver injury was induced by functional end-to-side portacaval shunt and bile duct ligation. Animals were returned then to the stall for observation. On day 3 the second phase of the experiment was started. Endotoxin was administered intravenously at an initial dose of 4 μg/kg/hour with a stepwise twofold increment every hour and stopped after 7.5 hours. HW was started 2.5 hours after endotoxemia and continued for 7 hours.

Results

On day 3, animals (n = 10) had hyperbilirubinemia (5.2 ± 0.3 mg/dl; mean ± SEM) and hyperammonemia (264 ± 38 μg/dl). Endotoxemia in control animals resulted in severe multisystem organ failure and death (after 6.4 ± 0.3 hours) although they received only one-third of the total endotoxin dose on average. HW improved cardiovascular (Figure 1), cerebral, respiratory and renal parameters and eliminated surrogate parameters as bilirubin (2.8 ± 0.5 vs 5.2 ± 0.3 mg/dl P < 0.05) and ammonia (189 ± 38 vs 1,108 ± 455 μg/dl, P < 0.05). All animals in the HW group survived the 10-hour observation period (P < 0.05). We did not notice any adverse effects during treatment.

Figure 1

Hepa Wash^® stabilizes mean arterial pressure in liver failure and sepsis.

Conclusions

Hepa Wash^® was safe and effective at improving survival in a swine model of liver failure and sepsis due to amelioration of the major organ functions and removal of protein-bound and water-soluble toxins.