A reproducible porcine model of acute liver failure induced by intrajejunal acetaminophen administration.
OBJECTIVE
Severe intoxication following acetaminophen overdose is the most common cause of acute liver failure (ALF) in many Western European and North American countries. A reproducible large animal model of acetaminophen intoxication has not been successfully evaluated previously.


METHODS
Eight male pigs underwent acetaminophen intoxication receiving an initial enteric bolus of 250 mg/kg body weight acetaminophen followed by an acetaminophen plasma level (300-450 mg/l) adapted enteric maintenance dose of 1,000-3,000 mg/h to the onset of ALF (prothrombin time value <30%). Vital and ventilation parameters were continuously recorded until death. Saline, hydroxyethyl starch, fresh frozen plasma and erythrocyte units were used for volume substitution, and norepinephrine to prevent severe hypotension.


RESULTS
All animals developed ALF after 25 ± 3 h, which was confirmed by laboratory values, the clinical course and histological examinations. All animals died due to ALF after a further 21 ± 5 h, precipitated by cerebral edema.


CONCLUSIONS
Using an initial enteric acetaminophen bolus, followed by body weight-adapted acetaminophen plasma level intoxication, it was possible to establish a reproducible, clinically relevant porcine model which may be used for the investigation of novel therapeutic approaches in this life-threatening condition.
Department of General, Visceral and Transplant Surgery, Tübingen University Hospital, Tübingen, Germany.
C
C
Thiel
K
K
Thiel
A
A
Etspueler
M H
MH
Morgalla
S
S
Rubitschek
S
S
Schmid
W
W
Steurer
A
A
Königsrainer
M
M
Schenk
D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics; D006801:Humans; D007427:Intracranial Pressure / Q000187:drug effects; D007583:Jejunum; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D034421:Sus scrofa
D000082:Acetaminophen