Background and Aims: 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.

Keywords:
Intrajejunal administration, Acetaminophen intoxication, Acetaminophen plasma levels, Acute liver failure, Pig model
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2011
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