Mark Wefers Bettink

Monitoring of mitochondrial oxygen tension in the operating theatre 8 147 Introduction Safeguarding an adequate tissue oxygenation to ensure aerobic metabolism is an important task of an anesthesiologist during general anesthesia. After inhalation of air, oxygen enters the lungs, where it passes through the alveoli into the circulating blood where it binds to hemoglobin. Oxygen is then delivered to tissue cells via macro- and microcirculatory flow and finally by the diffusion of molecular oxygen. Eventually the oxygen molecule reaches its ultimate destination, the mitochondria. Here oxygen is used in the oxidative phosphorylation to produce adenosine triphosphate (ATP) that acts as the main energy source for many cellular processes. Current clinical management of maintaining adequate tissue oxygenation is mainly focusing on the normalization of systemic hemodynamic parameters such as blood pressure, hemoglobin levels, peripheral oxygen saturation, cardiac output and venous saturation. But insight into oxygenation where it matters the most, inside the mitochondria, was not available for clinical use until recently. So far, our knowledge about mitochondrial physiology and oxygenation is obtained from ex vivo measurements on isolated mitochondria and cells, mainly derived from muscle biopsies. Repeated sampling and continued monitoring of mitochondrial parameters in humans is not possible because of ethical and technical restraints 1 . The protoporphyrin IX triple state lifetime technique (PPIX-TSLT), based on delayed fluorescence of protoporphyrin IX can overcome these limitations 2,3 . It enables non-invasive mitochondrial oxygen tension (mitoPO 2 ) measurements in humans 4-6 . The positive results of a feasibility study in healthy human volunteers 7,8 resulted in the development of the clinical measuring device “COMET ® ”, an acronym for Cellular Oxygen METabolism 5 . The introduction of COMET ® paved the way for the next step in the development of a monitoring technique, which measures mitochondrial oxygenation during surgery. In this longitudinal observational study we studied the usability and performance of the COMET ® under real-life circumstances during surgery. We focused especially on the behavior of the new parameter mitoPO 2 during stable hemodynamic circumstances, and hypothesized that mitoPO 2 would be stable over time under such conditions. To investigate the stability of the mitoPO 2 measurements we chose to perform the measurements in patients undergoing neurosurgical procedures. We made this choice because of the relatively healthy patient population, stable operation conditions and the relatively long operation duration. As contrast to the behavior of mitoPO 2 under the study circumstances, we present a number of cases from another ongoing study, in which we

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