Major liver resection results in a changed plasma amino acid pattern as reflected by a decreased Fischer ratio which improves by bactericidal/permeability increasing protein.
OBJECTIVE
Major liver resection results in a high morbidity and mortality, and endotoxin plays a role in post-resection hepatic failure. Severe hepatic failure as seen in hepatitis and cirrhosis may be accompanied by hepatic encephalopathy and is characterized by a typical plasma amino acid pattern reflected by a decreased Fischer ratio. This study was performed to evaluate the plasma amino acid pattern in patients undergoing major liver surgery receiving placebo or the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21).


METHODS
Forty-eight patients were randomized in this phase II, dose escalation, multicenter trial. Plasma amino acid profiles were determined preoperatively, and on the first (day 1) and third (day 3) postoperative day.


RESULTS
In the placebo group the Fischer ratio decreased significantly on both postoperative days. Administration of rBPI21 also resulted in a decreased Fischer ratio on day 1, but not on day 3. Highly elevated alanine plasma levels were observed on day 1 in placebo-treated patients, whereas rBPI21 prevented this elevation. Plasma alanine levels on day 1 correlated with the duration of post-resection hepatic failure.


CONCLUSIONS
Major liver resection results in a decreased Fischer ratio and a rise in plasma alanine levels. Plasma levels of alanine on the first postoperative day correlated with the duration of the post-resection hepatic failure. rBPI21 improved the Fischer ratio and prevented the rise of plasma alanine levels.
Nijveldt
R J
RJ
Department of Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. rj.nijveldt@azvu.nl
Wiezer
M J
MJ
Meijer
C
C
Prins
H A
HA
Statius Muller
M G
MG
Gouma
D J
DJ
Teerlink
T
T
van Gulik
T M
TM
Borel Rinkes
I H
IH
Tilanus
H W
HW
van de Velde
C J
CJ
Wiggers
T
T
Zoetmulder
F A
FA
Scotté
M
M
Cuesta
M A
MA
Meijer
S
S
van Leeuwen
P A
PA
D000328:Adult; D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000097:blood*; D000598:Amino Acids, Cyclic / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004731:Endotoxins / Q000008:administration & dosage*; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects* / Q000401:mortality; D006501:Hepatic Encephalopathy / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage*; D008875:Middle Aged; D016896:Treatment Outcome
D000597:Amino Acids, Branched-Chain; D000598:Amino Acids, Cyclic; D004731:Endotoxins; D008565:Membrane Proteins; C025357:endotoxin binding proteins