Using extracorporeal ozone to treat experimental gram-negative sepsis: an exploratory study

Abstract Background Sepsis is the third leading cause of death worldwide, yet there is a significant gap in the development of novel therapeutic approaches. Extracorporeal ozone has recently demonstrated beneficial effects in gram-negative sepsis (bactericidal and anti-inflammatory). We therefore evaluated extracorporeal ozone treatment in an experimental model of acute gram-negative sepsis to explore whether it improves clinically relevant outcomes. Methods Male and female pigs ( n = 9, 31 ± 2 kg) were used. Sepsis was induced by a 30-minute intravenous infusion of Pseudomonas aeruginosa , followed by an additional 30 min for sepsis development. Organ failure was classified according to SOFA score. The pigs were then assigned to either the untreated group ( n = 5) or the ozone-treated group ( n = 4). Treatment continued for 1 h (SangAsept™ system, O 2 /O 3 ratio 98:2%, 50 mL/min, 40 g/m 3 ). After treatment, the pigs were followed for an additional 2 h (endpoint). Mann-Whitney U test, Spearman’s rank correlation, and Fisher’s exact test were used for statistical analysis. Results The ozone-treated pigs had lower SOFA score than untreated pigs. The ozone-treated pigs maintained a normal mean arterial pressure without vasopressor support, whereas 80% of untreated pigs required vasopressor support. Hemoglobin levels remained within the normal range in the treated group but increased in the untreated group. Bilirubin levels were twofold higher in untreated pigs than in ozone-treated pigs. There was a significant positive correlation at endpoint between IL-6 and hemoglobin. Discussion In conclusion, this exploratory cohort of acute experimental gram-negative sepsis showed promising clinical outcomes after 1 h of extracorporeal ozone treatment, suggesting that this approach may represent a novel therapeutic strategy for sepsis.