Microdialysis : potentials and limitations

Despite improvements in operating technique and post-operative management, many patients undergoing liver transplantation still suffer post-operative complications, which may lead to graft loss or patient death. Patients are monitored closely post-operatively using blood chemistry, diagnostic imaging and liver biopsies to detect these complications including rejection and arterial- and portal vein thrombosis. However, signs and symptoms of these complications may be subtle and nonspecific leading to a delay in diagnosis and intervention. Microdialysis is a sampling technique, which allows for continuous monitoring of metabolites in the tissue in which it is placed. The aim of this thesis was to study intaorgan metabolism using microdialysis early after liver transplantation as well as in tissue subject to compression, to identify metabolic patterns signaling distress so that major complications may be detected before they are reflected in clinical exam or blood chemistry.

In paper I the impact of compression and possible hypoperfusion on tissue metabolism was studied using microdialysis in kidney during pneumoperitoneum in a pig model. A significant increase in glycerol in the renal medulla after desufflation was shown. In paper II a pig liver transplantation model was used to study the impact of short and long cold ischemia time on the restoration of glucose metabolism. An increase in intrahepatic glucose following portal reperfusion was seen in both groups and was significantly higher in the group with long cold ischemia. An increase in intrahepatic lactate/pyruvate ratio was also seen in both groups but was significantly higher and prolonged in the group with long cold ischemia time. In paper III a clinical study showed no correlation between episodes of increased intrahepatic lactate/pyruvate and development of ischemic complications after liver transplantation. In paper IV an increase in the lactate/pyruvate ratio in the liver during the initial 12 hours post-transplant was found to be correlated to development of post-transplant rejection in a clinical study. Paper V investigated whether a microdialysis catheter placed in the middle hepatic vein is comparable to intrahepatic microdialysis for monitoring liver metabolism during clamping of the hepatic artery using a pig model. It was not.

In conclusion, the microdialysis technique has proven to be a promising tool for continuous monitoring of tissue metabolism and pharmacological studies. However, despite encouraging results from animal experiments and a wide range of clinical studies over the past two decades, microdialysis has not gained a foothold in standard clinical practice. It seems that microdialysis is useful for the detection of primary metabolic changes. However, a better understanding of the recovery of metabolic processes after the ischemia reperfusion injury occurring during the transplantation process is needed to use microdialysis for monitoring of secondary events following liver transplantation.

List of scientific papers

I. Microdialysis monitoring for evaluation of the influence exerted by pneumoperitoneum on the kidney: an experimental study. Surgical Endoscopy. 2008 Apr;22(4):938-42.
https://doi.org/10.1007/s00464-007-9525-0

II. Effect of extended cold ischemia time on glucose metabolism in liver grafts: experimental study in pigs. Journal of Hepatobiliary Pancreatic Surgery. 2007;14(2):183-8.
https://doi.org/10.1007/s00534-006-1127-z

III. Evaluation of intrahepatic lactate/pyruvate ratio as a marker for ischemic complications early after liver transplantation – a clinical study. Transplantation Direct. 5(12):e505, December 2019.
https://doi.org/10.1097/TXD.0000000000000952

IV. Intrahepatic microdialysis for monitoring of metabolic markers to detect rejection early after liver transplantation. [Submitted]

V. Hepatic vein microdialysis is not equivalent to intrahepatic microdialysis monitoring for the detection of metabolic changes induced by arterial ischemia in a pig liver model. [Submitted]