Early bedside detection of ischemia and rejection in liver transplants by microdialysis

Authors

  • Håkon Haugaa,

    1. Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway
    2. Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Ebbe B. Thorgersen,

    1. Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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  • Anne Pharo,

    1. Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
    2. Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Kirsten M. Boberg,

    1. Section for Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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  • Aksel Foss,

    1. Section for Transplant Surgery, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
    2. Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Pål Dag Line,

    1. Section for Transplant Surgery, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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  • Truls Sanengen,

    1. Department of Pediatrics, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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  • Runar Almaas,

    1. Department of Pediatrics, Oslo University Hospital, Rikshospitalet, Oslo, Norway
    2. Department of Pediatric Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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  • Guro Grindheim,

    1. Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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  • Soeren Erik Pischke,

    1. Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway
    2. Intervention Center, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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  • Tom Eirik Mollnes,

    1. Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
    2. Faculty of Medicine, University of Oslo, Oslo, Norway
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  • Tor Inge Tønnessen

    Corresponding author
    1. Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway
    2. Faculty of Medicine, University of Oslo, Oslo, Norway
    • Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Box 4950 Nydalen, 0424 Oslo, Norway
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    • Telephone: +47-23070000; FAX: +47-23073684;


  • The study was financially supported by grants 2009007 and 2008104 from the South-Eastern Norwegian Health Authority.

Abstract

This study was performed to explore whether lactate, pyruvate, glucose, and glycerol levels sampled via microdialysis catheters in the transplanted liver could be used to detect ischemia and/or rejection. The metabolites were measured at the bedside every 1 to 2 hours after the operation for a median of 10 days. Twelve grafts with biopsy-proven rejection and 9 grafts with ischemia were compared to a reference group of 39 grafts with uneventful courses. The median lactate level was significantly higher in both the ischemia group [5.8 mM (interquartile range = 4.0-11.1 mM)] and the rejection group [2.1 mM (interquartile range = 1.9-2.4 mM)] versus the reference group [1.5 mM (interquartile range = 1.1-1.9 mM), P < 0.001 for both]. The median pyruvate level was significantly increased only in the rejection group [185 μM (interquartile range = 155-206 μM)] versus the reference group [124 μM (interquartile range = 102-150 μM), P < 0.001], whereas the median lactate/pyruvate ratio and the median glycerol level were increased only in the ischemia group [66.1 (interquartile range = 23.9-156.7) and 138 μM (interquartile range = 26-260 μM)] versus the reference group [11.8 (interquartile range = 10.6-13.6), P < 0.001, and 9 μM (interquartile range = 9-24 μM), P = 0.002]. Ischemia was detected with 100% sensitivity and greater than 90% specificity when a positive test was repeated after 1 hour. In 3 cases of hepatic artery thrombosis, ischemia was detected despite normal blood lactate levels. Consecutive pathological measurements for 6 hours were used to diagnose rejection with greater than 80% sensitivity and specificity at a median of 4 days before the activity of alanine aminotransferase, the concentration of bilirubin in serum, or both increased. In conclusion, bedside measurements of intrahepatic lactate and pyruvate levels were used to detect ischemia and rejection earlier than current standard methods could. Discrimination from an uneventful patient course was achieved. Consequently, intrahepatic graft monitoring with microdialysis may lead to the earlier initiation of graft-saving treatment. Liver Transpl, 2012. © 2012 AASLD.

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