A simple dummy liver assist device prolongs anhepatic survival in a porcine model of total hepatectomy by slight hypothermia

Abstract

Background: Advances in intensive care support such as therapeutic hypothermia or new liver assist devices have been the mainstay of treatment attempting to bridge the gap from acute liver failure to liver transplantation, but the efficacy of the available devices in reducing mortality has been questioned. To address this issue, the present animal study was aimed to analyze the pure clinical effects of a simple extracorporeal dummy device in an anhepatic porcine model of acute liver failure.

Methods: Total hepatectomy was performed in ten female pigs followed by standardized intensive care support until death. Five animals (dummy group, n = 5) underwent additional cyclic connection to an extracorporeal dummy device which consisted of a plasma separation unit. The separated undetoxified plasma was completely returned to the pigs circulation without any plasma substitution or exchange in contrast to animals receiving intensive care support alone (control group, n = 5). All physiological parameters such as vital and ventilation parameters were monitored electronically; laboratory values and endotoxin levels were measured every 8 hours.

Results: Survival of the dummy device group was 74 ± 6 hours in contrast to 53 ± 5 hours of the control group which was statistically significant (p < 0.05). Body temperature 24 hours after hepatectomy was significantly lower (36.5 ± 0.5°C vs. 38.2 ± 0.7°C) in the dummy device group. Significant lower values were measured for blood lactate (1.9 ± 0.2 vs. 2.5 ± 0.5 mM/L) from 16 hours, creatinine (1.5 ± 0.2 vs. 2.0 ± 0.3 mg/dL) from 40 hours and ammonia (273 ± 122 vs. 1345 ± 700 μg/dL) from 48 hours after hepatectomy until death. A significant rise of endotoxin levels indicated the onset of sepsis at time of death in 60% (3/5) of the dummy device group animals surviving beyond 60 hours from hepatectomy.

Conclusions: Episodes of slight hypothermia induced by cyclic connection to the extracorporeal dummy device produced a significant survival benefit of more than 20 hours through organ protection and hemodynamic stabilisation. Animal studies which focus on a survival benefit generated by liver assist devices should especially address the aspect of slight transient hypothermia by extracorporeal cooling.

Figure 1

Kaplan-Meier survival plot for control and dummy device group. The control group as demonstrated by the grey line survived 53 ± 5 hours in contrast to the significant longer survival (p < 0.05) of the dummy device group (74 ± 6 hours) as demonstrated by the black line in relation to time after hepatectomy (in hours).

Figure 2

Profile of body temperature, MAP, norepinephrine concentration and ICP in control and dummy device group. Chart A demonstrates the clinical course of body temperature (C°) of the control (grey line) and dummy device group (black line). A cyclic decline could be observed in correlation to the connection cycles. Body temperature, 24 hours after hepatectomy, differ statistically significant (p < 0.05) between the groups. Furthermore chart B and C demonstrate more hemodynamic stability of the dummy device (black line) versus the control group (grey line) presented by the nearly identical course of MAP but the lower amount of vasopressor support. ICP values are presented in chart D. Values did not differ statistically significant between the groups over the observed survival. All values are given as mean ± SEM in relation to time after hepatectomy (in hours). Bold marks indicate connection cycles to the dummy device.

Figure 3

Profile of creatinine, ammonia, lactate and endotoxin in control and dummy device group. The chart demonstrates the course of the selected laboratory values creatinine, A, ammonia, B, lactate, C and endotoxin, D of the control (grey line) and dummy device group (black line) animals. A statistical significance (p < 0.05) could be detected for blood lactate starting from 16 hours, serum creatinine from 40 hours and arterial ammonia from 48 hours after hepatectomy. At time of death no differences were noticed for creatinine, ammonia and lactate, but a statistically significant (p < 0.05) rise of endotoxin serum levels indicated severe sepsis in 60% of the animals surviving beyond 60 hours from hepatectomy. Values are given as mean ± SEM in relation to time after hepatectomy (in hours). Bold marks indicate connection cycles to the dummy device.