Study protocol and pilot results of an observational cohort study evaluating effect of red blood cell transfusion on oxygenation and mitochondrial oxygen tension in critically ill patients with anaemia: The INsufficient Oxygenation in the Intensive Care Unit (INOX ICU-2) study

Introduction The recently developed protoporphyrin IX-triple state lifetime technique measures mitochondrial oxygenation tension (mitoPO 2) in vivo at the bedside. MitoPO 2 might be an early indicator of oxygen disbalance in cells of critically ill patients and therefore may support clinical decisions regarding red blood cell (RBC) transfusion. We aim to investigate the effect of RBC transfusion and the associated changes in haemoglobin concentration on mitoPO 2 and other physiological measures of tissue oxygenation and oxygen balance in critically ill patients with anaemia. We present the protocol and pilot results for this study. Methods and analysis We perform a prospective multicentre observational study in three mixed intensive care units in the Netherlands with critically ill patients with anaemia in whom an RBC transfusion is planned. The skin of the anterior chest wall of the patients is primed with a 5-aminolevulinic acid patch for 4 hours for induction of mitochondrial protoporphyrin-IX to enable measurements of mitoPO 2, which is done with the COMET monitoring device. At multiple predefined moments, before and after RBC transfusion, we assess mitoPO 2 and other physiological parameters of oxygen balance and tissue oxygenation. Descriptive statistics will be used to describe the data. A linear mixed-effect model will be used to study the association between RBC transfusion and mitoPO 2 and other traditional parameters of oxygenation, oxygen delivery and oxygen balance. Missing data will be imputed using multiple imputation methods. Ethics and dissemination The institutional ethics committee of each participating centre approved the study (reference P16.303), which will be conducted according to the 1964 Helsinki declaration and its later amendments. The results will be submitted for publication in peer-reviewed journals and presented at scientific conferences. Trial registration number NCT03092297