Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure.
OBJECTIVE
To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose.


METHODS
Eight pigs underwent a midline laparotomy following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study. Portal blood flow, hemodynamic and ventilation parameters were continuously recorded. Laboratory parameters were analysed every eight hours. Liver biopsies were sampled every 24 h following intoxication and upon autopsy.


RESULTS
Acute liver failure (ALF) occurred after 28 ± 5 h resulted in multiple organ failure and death despite maximal support after further 21 ± 1 h (study end). Portal blood flow (baseline 1100 ± 156 mL/min) increased to a maximum flow of 1873 ± 175 mL/min at manifestation of ALF, which was significantly elevated (P< 0.01). Immediately after peaking, portal flow declined rapidly to 283 ± 135 mL/min at study end. Thrombocyte values (baseline 307 × 103/µL ± 34 × 103/µL) of intoxicated animals declined slowly to values of 145 × 103/µL ± 46 × 103/µL when liver failure occurred. Subsequent appearance of severe thrombocytopenia in liver failure resulted in values of 11 × 103/µL ± 3 × 103/µL preceding fatality within few hours which was significant (P> 0.01).


CONCLUSIONS
Declining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model.
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Karolin
K
Thiel
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Wilfried
W
Klingert
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Kathrin
K
Klingert
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Matthias H
MH
Morgalla
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Martin U
MU
Schuhmann
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Pamela
P
Leckie
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Yalda
Y
Sharifi
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Nathan A
NA
Davies
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Rajiv
R
Jalan
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Andreas
A
Peter
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Christian
C
Grasshoff
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Alfred
A
Königsrainer
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Martin
M
Schenk
Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.
Christian
C
Thiel
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D001706:Biopsy; D001783:Blood Flow Velocity / Q000187:drug effects; D062787:Drug Overdose; D005260:Female; D006439:Hemodynamics; D006440:Hemofiltration; D007583:Jejunum / Q000187:drug effects*; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects*; D017114:Liver Failure, Acute / Q000139:chemically induced*; D011169:Portal Vein; D013552:Swine; D013921:Thrombocytopenia / Q000139:chemically induced / Q000209:etiology; D018608:Ultrasonography, Doppler
D000082:Acetaminophen
Acetaminophen intoxication; Acute liver failure; Animal model; Porcine model; Portal blood flow; Thrombocytopenia