Hyperoxia in critically ill children A brief translation of toxicity

Supplemental oxygen has been used for over a century in daily clinical practice and is a cornerstone therapy in intensive care medicine. While this therapy has undoubtedly saved countless of lives, its overzealous use has been linked to harm in preterm neonates and critically ill adults. Increased availability of oxygen, or hyperoxia, enhances production of reactive oxygen species, which leads to oxidative stress. The following hyperoxia-induced injury is also termed oxygen toxicity and may have an equally relevant impact on critically ill children other than preterm neonates, but important gaps in knowledge currently remain. As a result, titration of oxygen is mainly based on expert opinion. This thesis aims to shed light on the delicate oxygen balance in critically ill children. The first part of this thesis focuses on the burden of oxygen toxicity in critically ill children. It describes the overall oxygen exposure in a cohort of bronchiolitis patients and reports on the acute and long-term effects of hyperoxia in different populations. The second part of this thesis addresses the contribution of hyperoxia-induced lung injury and ventilator-induced lung injury to the overall injury that is associated with invasive ventilation, since patients often receive high dose oxygen and positive pressure ventilation simultaneously. The third part of this thesis describes multiple studies that evaluate the potential value of analyzing exhaled breath to monitor oxidative stress by identification of specific volatile organic compounds in critically ill patients. Lastly, the broader implications of the combined findings and future perspectives are discussed.