Mark Wefers Bettink

Interim analysis; Feasibility study of measurement of mitochondrial function in patients with sepsis 7 139 DISCUSSION We demonstrate the feasibility of the COMET monitor to measure mitochondrial oxygenation parameters in a very dynamic situation during the first day of admittance on the ICUward. Of all the available patients, one out of 18measurements failedwith COMET, two out of 18 measurements failed in the ex vivo platelet respiration measurements. The average time of the first measurement after ICU admittance is close to 20 hours. Stabilization of patients with sepsis usually starts on the admitting ward and continues during the first hours of ICU admittance. We were interested in the onset of sepsis and its effect on mitoPO 2 and mitoVO 2 measurements, but we must conclude that the window of measurement in this dynamic period was probably missed. The study was conducted over a period of more than two years, but we were able to include only 11 patients whom were eligible for data analysis. An in depth analysis of the failure to reach the initial interim analysis numbers follows. In short, a combination of unavailability of a dedicated researcher and a low frequency of sepsis patients on our ICU ward in a tertiary university hospital seemed to be the most pressing issues. The initial target of 10 patients in both groups, required to perform an interim analysis, was not achieved, and given the small sample size, further analysis as stipulated in the secondary research goals were not deemed feasible. We would like to further analyze the working of this study and the methods used to give advice for support when interested in studying the initiation phase of sepsis in ICU patients. Lessons learned Inclusion of sufficient numbers of eligible patients is a critical step in an observational study like this. In our ICU, researchers receive fulltime support for including candidates in their studies, however in a setting with multiple active protocols competing for the same subjects, and specific inclusion criteria such as the ones in this study limiting the number of eligible subjects, there is a real risk of not achieving sufficient eligible patient inflow. One way to mitigate this challenge is to include a dedicated researcher in the screening flow for the study of candidates. Another challenge relating to recruiting sufficient subjects in this study is related to the organization of ICU care within the hospital and the region. Our ICU is a third level ICU, which implies that it serves, asides from being a primary ICU, as a second-opinion hospital for neighboring ICU’s. As a consequence, a number of patients coming into the ICU with severe health challenges, such as difficult ventilation patients, were not eligible