Metabolic monitoring in patients undergoing cardiac surgery using intravascular microdialysis

Sammanfattning: Critically ill patients and patients undergoing cardiac surgery often experience hyperglycemia, hypoglycemia and glycemic variability (fluctuating blood glucose concentrations), all of which have been associated with adverse outcomes. Glycemic control aimed at avoiding both hyper- and hypoglycemia as well as at minimizing glycemic variability has been shown to be beneficial in these patients. In order to enable glycemic control, a safe and reliable glucose monitoring system is required. Additionally, monitoring of lactate is beneficial since an elevated lactate level may serve as a warning signal, and the knowledge of lactate concentration is necessary to guide lactate-reducing treatment, which has been shown to improve outcome in critically ill patients. Intravascular microdialysis is a technique that can monitor small molecules like glucose and lactate in the bloodstream without the need for blood sampling. This thesis aimed at developing intravascular microdialysis into a verified and accepted clinical method for continuous monitoring of glucose and lactate in patients undergoing cardiac surgery requiring postoperative treatment in the intensive care unit. Furthermore, another aim was to incorporate this technology into a standard procedure. The intravascular microdialysis method is based on a new and innovative technology, which involves a small compartment located between a catheter body and a covering microdialysis membrane. By perfusing this compartment, a dialysate fluid is produced wherein the concentrations of glucose and lactate are theoretically equal to those in the surrounding tissue, i.e. the bloodstream as the catheter is placed in a central vein. In Study I, the intravascular microdialysis concept was applied to a single- lumen catheter. The dialysate fluid was collected and intermittently analyzed in a separate dialysate analyzer for glucose and lactate concentrations and compared to blood samples. This study verified the microdialysis concept as an efficient clinical method for measuring blood glucose and lactate levels. In Study II, the outlet of the compartment of the microdialysis catheter was directly connected to a recently developed sensor, continuously analyzing glucose and lactate concentrations of the dialysate fluid. The continuous microdialysis catheter-sensor system was shown to be very accurate in monitoring blood glucose, with a lag time of only a few minutes in the clinical setting. The technique was improved in Study III, in which the microdialysis membrane was integrated in a standard central venous catheter, which is routinely applied in patients subjected to cardiac surgery. The results further demonstrated the accuracy and reliability of the microdialysis system. The data on lactate from Studies II and III were processed in Study IV, which demonstrated that the microdialysis system was also accurate and efficient in monitoring blood lactate. In Study V, the accuracy and responsiveness of the microdialysis system were confirmed in an animal model during extreme hypoglycemic conditions and rapid blood glucose oscillations, as well as during infusion of a solution with a high glucose concentration via the catheter. Finally in Study VI, the microdialysis system was compared to a certified and clinically verified continuous glucose monitoring system placed subcutaneously. The microdialysis system was found to be superior in terms of accuracy and met the clinical standards in terms of safety in the intensive care unit, while the subcutaneous system failed in this respect. This thesis demonstrates that intravascular microdialysis is a safe and accurate method for continuous monitoring of glucose and lactate in patients undergoing cardiac surgery, and is superior to a subcutaneous system in this specific setting. Based on the results of the included studies, a safe, reliable and certified standard procedure was developed for use in critically ill patients for the pertinent control of blood glucose and lactate for early detection of metabolic derangement.