Mark Wefers Bettink

Chapter 10 184 Summary In this thesis we described the development of the CE-marked COMET monitor to a bedsidemonitor of mitochondrial oxygenation and oxygen consumption. Earlier methods to measure mitochondrial function and cellular oxygenation at the bedside were invasive and difficult to perform. Measuring mitochondrial function in sepsis may prove to be fundamental for fully understanding the pathophysiology of sepsis. Proving the stability of the COMET monitor in sepsis like models in animals and healthy volunteers is a necessary step towards the clinical implementation of this monitoring technique. In chapter 2 we described mitochondrial function and its adaptation to the pathophysiology of critical illnesses. Adenosine triphosphate (ATP) production through the process of oxidative phosphorylation is the primary and best known function of mitochondria. Oxidative phosphorylation has a high affinity for oxygen and thus works under low levels of oxygen. Downregulation of mitochondrial function as a consequence of sustained low levels of oxygen is called oxygen conformance, and may last well past the initial exposure to low oxygen concentrations. Oxygen conformance, mitochondrial damage and mitochondrial hits may all work together to a state called cytopathic hypoxia. This is a state in which the delivery of oxygen to the cells is sufficient but cellular or mitochondrial metabolism is hampered. We believe that in the complex pathophysiology of critically ill patients a multilevel approach is required. The interaction between macro- circulation, micro-circulation, and parenchymal cells in critically ill patients is complex. Measuring mitochondrial function may provide fundamental insights into the complex pathophysiology of these patients. We described the COMET monitor and its output in chapter 3 . We observed a decline in cellular oxygen in this first use of the COMET monitor on a patient, which wasn’t observed on the O2C monitor (the current standard method for observing tissue oxygenation). These results suggest the promising potential of the COMET monitor in detecting cellular hypo-oxygenation in critically-ill patients at the bedside. We validated the earlier calibration of the COMET monitor in human skin in chapter 4 . For the oxygen consumption kinetics we compared the COMET measurement with the LEA O2C, SenTec OxiVenT and Medtronic INVOS parameters during a vascular occlusion test. For the dynamic consumption measurement used in the COMET monitor not only vascular occlusion but also direct pressure on the site displacing oxygen carrying erythrocytes out of the microcirculation is of great importance. The COMET monitor’s method to determine mitochondrial oxygen consumption differs in technique and