Detoxifying capacity and kinetics of prometheus--a new extracorporeal system for the treatment of liver failure.
OBJECTIVE
Extracorporeal liver support therapies have been used for several decades as a bridging therapy prior to liver transplantation or as an addendum to standard medical therapy. The Prometheus system represents a cell-free, extracorporeal, liver assist method for the removal of both albumin-bound and water-soluble endogenous toxins. The aim of the present study was to evaluate the removal capacity and selectivity of the different inbuilt dialyzers and adsorption columns during a single 6-hour treatment.


METHODS
Nine patients with acute on chronic liver failure were included (6 females, age 49+/- 4 years). Levels of endogenous toxins (urea nitrogen [UN, mg/dl], creatinine [Cr, mg/dl], total bilirubin [tB, mg/dl], and bile acids [BA, mumol/l]) and albumin [Alb, g/l] were monitored in blood sampled at different sites (arterial line, venous line and between the absorbers and the high-flux dialyzer) and at various time points (time 0, 30, 60, 120, 240, and 360 min).


RESULTS
A significant decrease of the serum level of all toxins was observed (UN 108.7+/- 23.2 vs. 38.1+/- 14.9, Cr 2.4+/- 0.7 vs. 1.2+/- 0.3, tB 31.1+/- 4.1 vs. 17.0+/- 1.6, BA 155.7+/- 32.5 vs. 66.0+/- 15.4; mean+/- SEM, time 0 vs. time 360, signed rank rest, all p< 0.005). The reduction rate of UN, Cr, tB and BA amounted to 68.1+/- 5.1, 45.9+/- 6.2, 41.2+/- 5.1, and 58.2+/- 5.0%, respectively. Blood clearances [Cl, ml/min] of all, but especially of the protein-bound toxins declined over time (Cl UN 171.5+/- 4.3 vs. 142.9+/- 16.8; Cl Cr 135.7+/- 10.0 vs. 111.8+/- 9.1; Cl tB 29.3+/- 5.1 vs. 13.7+/- 3.7; Cl BA 84.9+/- 4.8 vs. 45.1+/- 13.3; time 30 vs. time 360; linear mixed models, all p< 0.005). Serum albumin levels decreased by 2.9+/- 0.9 g/l (signed rank test, p=0.055). Not unexpectedly, tB was almost uniquely cleared by the adsorbers (UN 0.2+/-1.1, Cr 6.9+/- 5.7, tB 92.3+/- 4.2, BA 62.9+/- 3.9% of total Cl).


CONCLUSIONS
Both albumin-bound and water-soluble toxins are adequately removed by the Prometheus system. Our data suggest that the rate and efficacy of removal of albumin-bound toxins is related to both the strength of the albumin binding and the saturation of the adsorption columns. Limited losses of albumin occur during treatment with the Prometheus system.
Evenepoel
Pieter
P
Department of Medicine, University Hospital Leuven, Leuven, Belgium. Pieter.Evenepoel@uz.kuleuven.ac.be
Laleman
Wim
W
Wilmer
Alexander
A
Claes
Kathleen
K
Maes
Bart
B
Kuypers
Dirk
D
Bammens
Bert
B
Nevens
Frederik
F
Vanrenterghem
Yves
Y
D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D003404:Creatinine / Q000097:blood; D005112:Extracorporeal Circulation; D005260:Female; D006801:Humans; D007700:Kinetics; D017093:Liver Failure / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism; D012995:Solubility; D016060:Sorption Detoxification / Q000295:instrumentation* / Q000592:standards; D014118:Toxins, Biological / Q000097:blood; D014508:Urea / Q000097:blood
D001647:Bile Acids and Salts; D012709:Serum Albumin; D014118:Toxins, Biological; D014508:Urea; D003404:Creatinine; D001663:Bilirubin