Standardized intensive care unit management in an anhepatic pig model: new standards for analyzing liver support systems

Thiel, Christian; Thiel, Karolin; Etspueler, A; Schenk, Thomas; Morgalla, Matthias; Koenigsrainer, Alfred; Schenk, Martin

doi:10.1186/cc9196

Cited by 11 publications

(13 citation statements)

References 25 publications

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“…At the end of experiments, hemodynamic instability was observed with requirements of maximal PEEP support and increasing airway pressures. Renal failure is an additional factor contributing to demise 21, 22. Removal of the “toxic” liver stabilized this patient and temporarily reduced requirements for supportive measures.…”

Section: Discussionmentioning

confidence: 93%

Long-term survival after 67 hours of anhepatic state due to primary liver allograft nonfunction

et al. 2010

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Primary liver allograft nonfunction immediately after transplantation poses a life-threatening situation for the recipient. Emergency retransplantation may not be immediately possible due to organ unavailability. Total hepatectomy with temporary portacaval shunt has been described as a bridge to retransplantation when the presence of the graft appears to be harming the recipient. Case reports of retransplantation after total hepatectomy with anhepatic times greater than 48 hours routinely describe poor outcomes. We present a case with excellent patient outcome after 95 hours of clinical anhepatic state, including 67 hours of anatomical anhepatic time, because of primary liver allograft nonfunction. This case report documents the longest anhepatic time with subsequent successful transplant

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Section: Discussionmentioning

confidence: 93%

Long-term survival after 67 hours of anhepatic state due to primary liver allograft nonfunction

et al. 2010

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“…The advantage of standardized intensive care therapy in an anhepatic pig model has recently been shown [24]. To optimize the care of the ALF animals, the ‘standard of care’ given was to treat the animals as intensive care ‘patients’, maintained under general anesthesia.…”

Section: Discussionmentioning

confidence: 99%

A Reproducible Porcine Model of Acute Liver Failure Induced by Intrajejunal Acetaminophen Administration

Thiel

Thiel²,

Etspueler³

et al. 2011

Eur Surg Res

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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.

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“…The study was performed in eight female German landrace pigs weighing 38 ± 2 kg. Premedication, anaesthesia, intensive care medication and algorithms for standardized intensive care management have been previously reported in detail[ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure

Thiel¹,

Klingert²,

Klingert³

et al. 2017

WJG

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AIMTo investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose.METHODSEight 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.RESULTSAcute 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).CONCLUSIONDeclining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model.

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Standardized intensive care unit management in an anhepatic pig model: new standards for analyzing liver support systems

Cited by 11 publications

References 25 publications

Long-term survival after 67 hours of anhepatic state due to primary liver allograft nonfunction

Long-term survival after 67 hours of anhepatic state due to primary liver allograft nonfunction

A Reproducible Porcine Model of Acute Liver Failure Induced by Intrajejunal Acetaminophen Administration

Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure

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