Mark Wefers Bettink

Chapter 9 174 efficacy study, the power calculation/sample size will be focused on validating mitoPO 2 measurements in neonates and analyzing the ideal priming time of the neonatal skin. This will create insight in the reaction of the skin to the application of ALA in term and preterm neonates. For this study two major non-cardiac congenital anomalies were included: congenital diaphragmatic hernia (CDH) and esophageal atresia (EA). These congenital anomalies were chosen to be eligible because major surgery is required within the first days of life and postoperative brain injury are reported in children with these congenital anomaly (4)(7). CDH neonates suffer from lung hypoplasia and abnormal morphology of the pulmonary vasculature which results in respiratory insufficiency and severe (therapy- resistant) pulmonary hypertension (29)(30). CDH neonates are a challenge for clinicians to manage due this altered physiology. In EA neonates, the physiology is less affected by the congenital anomaly itself, but requires complex surgery with major intrathoracic manipulation which highly affects the neonatal physiology (31). In these children, our preliminary results suggest that monitoring mitochondrial oxygenation might register changes in neonatal physiology which could not have been observed using standard monitoring devices. Clearly, further research into the clinical usability of COMET is warranted but seems justified based on this pilot. Although this was only a feasibility and safety study, these results confirm that mitochondrial hypoxia may occur without clear signs of central hypoxia and are in line with previous research in animals and humans (32–35). A piglets study demonstrated cutaneous mitoPO 2 changed earlier than MABP and lactate during ongoing hemodilution (32). In a sepsis rat model as well as in rats with induced right ventricular failure due to pulmonary arterial hypertension, mitoPO 2 proved an additional parameter monitoring physiological changes (33,34). The clinical prototype of the COMET was tested in healthy volunteers and showed measuring mitochondrial oxygenation and oxygen consumption in humans (13). Previous reports demonstrated the intraoperative use of COMET in adults (15) and also demonstrated that mitoPO 2 measurements are not limited to the skin (35). The first study using COMET during upper gastro-intestinal endoscopy showed it is technically feasible and safe (35). Adequate oxygen supply to tissues is of pivotal importance to sustain mammalian life. Aerobic metabolism is maintained through inhalation of air in the lungs and subsequent transport of the absorbed oxygen to tissues via the circulation. The flow of hemoglobin- bound oxygen through themacro- andmicrocirculation and diffusion of molecular oxygen into the tissue cells brings oxygen to themitochondria. In themitochondria, oxygen is used in oxidative phosphorylation in order to efficiently produce adenosine triphosphate (ATP)