Mark Wefers Bettink

Interim analysis; Feasibility study of measurement of mitochondrial function in patients with sepsis 7 141 not necessary leading to a median measurement time of the O2C monitor of shorter than 30 minutes. Since this methods use is aimed at measuring changes in a patient over time we think the short measurement time does not lead to reliable data. Using the O2C for the rest of the protocol will not give any advantage in the current setup and therefore our advice is to abandon the O2C measurements when only measuring for short periods of time. Measuring changes of mitochondrial function in platelets is possible, however thrombopenia limited the use of this technique. When interested in the pathophysiological changes of mitochondrial function in the different phases of sepsis, measurement of these changes in vivo and ex vivo will give a more complete picture of the changes affecting the patient. In a more longitudinal assessment of these pathophysiological changes a reliable measurement of mitochondrial change to compare to the changes measured with the new monitor is essential. A problem with the ex vivo measurements is the targeted time, with a maximum of 1 hour, between measurement and blood sampling, and therefore this method is only possible when the measurements take place in the same hospital. mtDNAmeasurements out of serumplasma is technically advanced but can be performed centrally and grouped in a dedicated session and therefore might be the easiest way to measure mitochondrial damage when performing a multi-centre study, this might be of an advantage when the in vivo measurements are linked to mitochondrial damage and as a marker for mitochondrial damage mtDNA levels are used. In short, our advice is when a researcher is interested in the pathophysiological changes of mitochondrial function in sepsis a more longitudinal approach will probably be advantageous, possible with multiple measurements over the first days. Using the advanced monitoring the ICU ward in our tertiary university hospital provides in combination with an assessment tool of microvascular flow. Ex vivo assessment of mitochondrial function in blood cells (white blood cells or platelets) would be of additional value in such an protocol. When interested in the distribution of the in vivo parameters of mitoPO 2 and mitoVO 2 during sepsis or an ICU admittance a multi-centre approach or a primary centre other than the Erasmus Medical Centre provides another casemix, a higher patient turnover and therefor a shorter protocol time. mtDNA measurements in this protocol would be efficient and easy to implement and is strongly linked to survival in earlier studies. Ex vivo mitochondrial function assessment is limited in this design due to the limited time available to asses these changes in the Oroboros. In this protocol short use of the O2C gives insufficient additional value in our view.