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

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 ¼ 4.0-11.1 mM)] and the rejection group [2.1 mM (interquartile range ¼ 1.9-2.4 mM)] versus the reference group [1.5 mM (interquartile range ¼ 1.1-1.9 mM), P < 0.001 for both]. The median pyruvate level was significantly increased only in the rejection group [185 lM (interquartile range ¼ 155-206 lM)] versus the reference group [124 lM (interquartile range ¼ 102-150 lM), 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 ¼ 23.9-156.7) and 138 lM (interquartile range ¼ 26-260 lM)] versus the reference group [11.8 (interquartile range ¼ 10.6-13.6), P < 0.001, and 9 lM (interquartile range ¼ 9-24 lM), P ¼ 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 18: 839-849, 2012. V C 2012 AASLD. Received December 9, 2011 accepted February 29, 2012.As many as 20% of transplanted liver grafts are lost within the first year despite considerable therapeutic improvements in treatment during the last decades.1 Most grafts are lost within the first week or weeks. As a result, attempts to improve overall graft survival rates should include the early detection and adequate treatment of complications such as acute rejection 2 and vascular occlusion with subsequent ischemia.3 The latter is an especially major contributor to the loss of grafts. Biliary complications and infections are other organ-threatening complications. [4][5][6]

Clinical experience with microdialysis catheters in pediatric liver transplants

“…In contrast to the anaerobic metabolism with increases in the lactate level and lactate/pyruvate ratio detected with ischemia, ACR was detected as simultaneously increased lactate and pyruvate levels with a stable lactate/pyruvate ratio. This phenomenon is physiologically consistent with hypermetabolism due to increased aerobic glycolysis by activated lymphocytes . In comparison with the current standard of care, according to which biopsy is performed after an elevation of liver enzymes and/or bilirubin, microdialysis might represent an opportunity to perform biopsy according to a justified indication and at an earlier time .…”

“…With respect to the intrahepatic metabolism as measured by microdialysis, we used the optimal cutoff values determined in our previous study . Ischemia was thus defined as a lactate level > 3.0 mM and a lactate/pyruvate ratio > 20, and rejection was defined as a lactate level > 2.0 mM and a lactate/pyruvate ratio < 20.…”

Role of microdialysis catheters in clinical decision making: Bench to bedside?

“…These results have been reported in a series of 3 articles published in Liver Transplantation . They have demonstrated that dialysate analysis can distinguish acute rejection from ischemia.…”

Continuous measurement of enzymatic kinetics in droplet flow for point-of-care monitoring

“…3,6,7 Using this method several different analytes (including glucose, 3 lactate, 8 pyruvate, 9 glutamate, 10 and potassium 3,8 ) have been accurately monitored in vivo. Recently, Gao and co-workers developed a non-invasive wearable sensor to measure glucose, lactate, potassium and sodium in the perspiration of human subjects.…”