Mark Wefers Bettink

Chapter 7 140 for enrollment in our study, given that they had already passed the initiation phase of sepsis. Additionally, third-level ICU’s serve a relatively complex patient population. Hematologic oncology patients for example, whom suffer from bone marrow depletion during their treatments. A relatively simple infection in this group could have disastrous consequences These subjects fulfill the criteria of sepsis, however oncology-targeted therapies are likely to affect mitochondrial function as well and as a consequence these patients cannot be included in the study. Furthermore, during oncology treatment, bone marrow depletion is a common side effect and the accompanying thrombopenia limits the ex vivo platelet respiration experiments. Lastly, the challenges around the limited screening window resulted in a number of eligible subjects not included in our study. Intensive care is by its definition a 24/7 facility, however limited availability of the research nurse or the dedicated researcher, both of whom are critical for performing the informed consent procedure and preparing the COMET measurements, meant that not all eligible patients were admitted into this study. Evaluation of methods The informed consent method was well thought of in advance with expert help of the research unit of the ICU and the expert opinion of our ethicist Dr. Kompanje. However the 4 possible ways of receiving informed consent in a study with a relative low frequency of inclusion were not efficient. The follow up of patients after ICU admittance for final informed consent of the primary subject, if the patient was outplaced to another hospital follow up was difficult and not enough attention for follow up and receiving informed consent lead to exclusion of 5 patients. The design of this study was centered around the in vivo measurement of mitochondrial function in the initiation phase of sepsis. But due to the organization of the study protocol study participants were only available after admittance to the ICU and since these patients were in a critical phase of ICU care direct application of the ALA plasters was not always possible during this essential phase of treatment. Furthermore 5 – 7 hours of ALA application necessary to induce sufficient levels of PpIX further lengthened the time before the first measurement. A possible solution would be to make the ALA plasters part of the admittance protocol for the ICU or even better finding a different plaster technique which shortens the application time of the plaster significantly. The O2C measurement of microvascular flow and oxygenation has been used due to the ease of application and short onset time of this method seemed perfect as screening for microvascular anomalies. In our study protocol lengthy assessment of the patient was