Acute toxicity threshold of normobaric oxygen therapy: Systematic review

Abstract

Although there is clear dose-dependence of pulmonary toxicity caused by inhalation of normobaric oxygen in animal studies, the threshold of toxicity in humans remains largely unknown. The aim of this systematic review of published clinical studies was to establish threshold in terms of total oxygen dose administered under normal pressure by inhalation that causes first clinical signs of toxicity. MEDLINE, EBSCO, The Cochrane Central Register of Controlled Trials (Central), SCIndeks, Scopus, Google Scholar, and ClinicalTrials.gov were searched from their foundation to April 2022. The systematic review was performed according to the pre-registered protocol at PROSPERO. The studies were included if describing toxic effects of normobaric oxygen therapy in humans. In total 11 human studies of poor quality were found, with either experimental or observational design. In none of the analyzed studies did oxygen therapy cause toxic effects on the respiratory tract if the concentration of oxygen in the inhaled air was below 50%, regardless of the rate of administration. The toxic consequences of inhaling oxygen at a concentration of more than 50% occurred only after oxygen was administered for more than 6 hours, at a rate of more than 7 L/min, and were mainly reflected in inflammation of the tracheobronchial mucosa, with epithelial erosions. Normobaric oxygen therapy can have toxic effects in humans if the oxygen concentration in the inhaled air is higher than 50%, if the administration rate is above 7 L/min, and if the application lasts at least 6 hours.