Mark Wefers Bettink

Chapter 3 56 While COMET is the first clinical device for measuring mitochondrial oxygen and oxygen consumption, the used technology has some limitations. Currently the typical application time of the ALA on the skin is 4 hours. This makes the measurement technique not yet applicable in acute situations. Furthermore, the combination of topical ALA administration and the green excitation light cause a very shallow measurement depth. While this does enable the oxygen consumption measurements, the oxygen measurements become more sensitive to tissue heterogeneity and background light. Till now the feasibility of measuring mitoPO 2 and mitoVO 2 with PpIX-TSLT was tested in healthy volunteers [29] and is currently further evaluated with COMET in the perioperative setting. However, the original main development idea of COMET was the in vivo determination of aspects of mitochondrial (dys)function in critical illness. Indeed, in the laboratory setting the effectiveness of this technique in determining mitochondrial function under septic circumstances could be demonstrated [16]. Furthermore, mitochondrial oxygen measurements could potentially provide a new physiological transfusion trigger for decision-making in transfusion medicine. In a very recent animal study we have shown that mitoPO 2 can be used as an early detector of reaching the individual limit of hemodilution before changes in systemic oxygen consumption and lactate levels occur [27]. If this concept can be translated into the anemic human situation, it is indeed potentially an individual physiological parameter to guide blood transfusions. The technique used in COMET is not limited to measurements in skin, since ALA can be administered systemically [32, 33]. Therefore, endoscopic or intraoperative measurement of mitoPO 2 is technically feasible but such attempts should always take into account extensive safety considerations related to potential photodynamic toxicity. 4. Conclusion This report provides a description of the novel COMET measurement system. The enhanced protoporphyrin IX concentration in the skin is used as endogenous oxygen- sensitive probe. The method gives the possibility to measure cellular oxygen availability and the oxygen disappearance rate at the bedside on a mitochondrial level. In the future the COMET could play a role in clinical practice to assess tissue viability, tomanage oxygen transport, and to recognize and possibly to treat mitochondrial inhibition in critically ill patients. Furthermore it potentially can be used as an individual blood transfusion trigger and may enable testing mitochondrial effects of pharmaceutical substances research.