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

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

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

Generation of Aerosols by Noninvasive Respiratory Support Modalities:A Systematic Review and Meta-Analysis

Importance: Infection control guidelines have historically classified high-flow nasal oxygen and noninvasive ventilation as aerosol-generating procedures that require specialized infection prevention and control measures. Objective: To evaluate the current evidence that high-flow nasal oxygen and noninvasive ventilation are associated with pathogen-laden aerosols and aerosol generation. Data Sources: A systematic search of EMBASE and PubMed/MEDLINE up to March 15, 2023, and CINAHL and ClinicalTrials.gov up to August 1, 2023, was performed. Study Selection: Observational and (quasi-)experimental studies of patients or healthy volunteers supported with high-flow nasal oxygen or noninvasive ventilation were selected. Data Extraction and Synthesis: Three reviewers were involved in independent study screening, assessment of risk of bias, and data extraction. Data from observational studies were pooled using a random-effects model at both sample and patient levels. Sensitivity analyses were performed to assess the influence of model choice. Main Outcomes and Measures: The main outcomes were the detection of pathogens in air samples and the quantity of aerosol particles. Results: Twenty-four studies were included, of which 12 involved measurements in patients and 15 in healthy volunteers. Five observational studies on SARS-CoV-2 detection in a total of 212 air samples during high-flow nasal oxygen in 152 patients with COVID-19 were pooled for meta-analysis. There was no association between high-flow nasal oxygen and pathogen-laden aerosols (odds ratios for positive samples, 0.73 [95% CI, 0.15-3.55] at the sample level and 0.80 [95% CI, 0.14-4.59] at the patient level). Two studies assessed SARS-CoV-2 detection during noninvasive ventilation (84 air samples from 72 patients). There was no association between noninvasive ventilation and pathogen-laden aerosols (odds ratios for positive samples, 0.38 [95% CI, 0.03-4.63] at the sample level and 0.43 [95% CI, 0.01-27.12] at the patient level). None of the studies in healthy volunteers reported clinically relevant increases in aerosol particle production by high-flow nasal oxygen or noninvasive ventilation. Conclusions and Relevance: This systematic review and meta-analysis found no association between high-flow nasal oxygen or noninvasive ventilation and increased airborne pathogen detection or aerosol generation. These findings argue against classifying high-flow nasal oxygen or noninvasive ventilation as aerosol-generating procedures or differentiating infection prevention and control practices for patients receiving these modalities..</p

Validation of volatile metabolites of pulmonary oxidative injury: a bench to bedside study

Background Changes in exhaled volatile organic compounds (VOCs) can be used to discriminate between respiratory diseases, and increased concentrations of hydrocarbons are commonly linked to oxidative stress. However, the VOCs identified are inconsistent between studies, and translational studies are lacking. Methods In this bench to bedside study, we captured VOCs in the headspace of A549 epithelial cells after exposure to hydrogen peroxide (H2O2), to induce oxidative stress, using high-capacity polydimethylsiloxane sorbent fibres. Exposed and unexposed cells were compared using targeted and untargeted analysis. Breath samples of invasively ventilated intensive care unit patients (n=489) were collected on sorbent tubes and associated with the inspiratory oxygen fraction (FIO2) to reflect pulmonary oxidative stress. Headspace samples and breath samples were analysed using gas chromatography and mass spectrometry. Results In the cell, headspace octane concentration was decreased after oxidative stress ( p=0.0013), while the other VOCs were not affected. 2-ethyl-1-hexanol showed an increased concentration in the headspace of cells undergoing oxidative stress in untargeted analysis ( p=0.00014). None of the VOCs that were linked to oxidative stress showed a significant correlation with FIO 2 (Rs range: -0.015 to -0.065) or discriminated between patients with FIO 2.0.6 or below (area under the curve range: 0.48 to 0.55). Conclusion Despite a comprehensive translational approach, validation of known and novel volatile biomarkers of oxidative stress was not possible in patients at risk of pulmonary oxidative injury. The inconsistencies observed highlight the difficulties faced in VOC biomarker validation, and that caution is warranted in the interpretation of the pathophysiological origin of discovered exhaled breath biomarkers