Morten Hedetoft1, Peter Garred2, Martin Bruun Madsen3, Ole Hyldegaard1. 1. Department of Anaesthesia, Hyperbaric Unit, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 2. Laboratory of Molecular Medicine, Department of Clinical Immunology Section 7631, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 3. Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Abstract
BACKGROUND: The pathophysiological understanding of the inflammatory response in necrotizing soft-tissue infection (NSTI) and its impact on clinical progression and outcomes are not resolved. Hyperbaric oxygen (HBO2 ) treatment serves as an adjunctive treatment; however, its immunomodulatory effects in the treatment of NSTI remains unknown. Accordingly, we evaluated fluctuations in inflammatory markers during courses of HBO2 treatment and assessed the overall inflammatory response during the first 3 days after admission. METHODS: In 242 patients with NSTI, we measured plasma TNF-α, IL-1β, IL-6, IL-10, and granulocyte colony-stimulating factor (G-CSF) upon admission and daily for three days, and before/after HBO2 in the 209 patients recieving HBO2 . We assessed the severity of disease by Simplified Acute Physiology Score (SAPS) II, SOFA score, and blood lactate. RESULTS: In paired analyses, HBO2 treatment was associated with a decrease in IL-6 in patients with Group A-Streptococcus NSTI (first HBO2 treatment, median difference -29.5 pg/ml; second HBO2 treatment, median difference -7.6 pg/ml), and overall a decrease in G-CSF (first HBO2 treatment, median difference -22.5 pg/ml; 2- HBO2 treatment, median difference -20.4 pg/ml). Patients presenting with shock had significantly higher baseline cytokines values compared to non-shock patients (TNF-α: 51.9 vs. 23.6, IL-1β: 1.39 vs 0.61, IL-6: 542.9 vs. 57.5, IL-10: 21.7 vs. 3.3 and G-CSF: 246.3 vs. 11.8 pg/ml; all p < 0.001). Longitudinal analyses demonstrated higher concentrations in septic shock patients and those receiving renal-replacement therapy. All cytokines were significantly correlated to SAPS II, SOFA score, and blood lactate. In adjusted analysis, high baseline G-CSF was associated with 30-day mortality (OR 2.83, 95% CI: 1.01-8.00, p = 0.047). CONCLUSION: In patients with NSTI, HBO2 treatment may induce immunomodulatory effects by decreasing plasma G-CSF and IL-6. High levels of inflammatory markers were associated with disease severity, whereas high baseline G-CSF was associated with increased 30-day mortality.
BACKGROUND: The pathophysiological understanding of the inflammatory response in necrotizing soft-tissue infection (NSTI) and its impact on clinical progression and outcomes are not resolved. Hyperbaric oxygen (HBO2 ) treatment serves as an adjunctive treatment; however, its immunomodulatory effects in the treatment of NSTI remains unknown. Accordingly, we evaluated fluctuations in inflammatory markers during courses of HBO2 treatment and assessed the overall inflammatory response during the first 3 days after admission. METHODS: In 242 patients with NSTI, we measured plasma TNF-α, IL-1β, IL-6, IL-10, and granulocyte colony-stimulating factor (G-CSF) upon admission and daily for three days, and before/after HBO2 in the 209 patients recieving HBO2 . We assessed the severity of disease by Simplified Acute Physiology Score (SAPS) II, SOFA score, and blood lactate. RESULTS: In paired analyses, HBO2 treatment was associated with a decrease in IL-6 in patients with Group A-Streptococcus NSTI (first HBO2 treatment, median difference -29.5 pg/ml; second HBO2 treatment, median difference -7.6 pg/ml), and overall a decrease in G-CSF (first HBO2 treatment, median difference -22.5 pg/ml; 2- HBO2 treatment, median difference -20.4 pg/ml). Patients presenting with shock had significantly higher baseline cytokines values compared to non-shock patients (TNF-α: 51.9 vs. 23.6, IL-1β: 1.39 vs 0.61, IL-6: 542.9 vs. 57.5, IL-10: 21.7 vs. 3.3 and G-CSF: 246.3 vs. 11.8 pg/ml; all p < 0.001). Longitudinal analyses demonstrated higher concentrations in septic shock patients and those receiving renal-replacement therapy. All cytokines were significantly correlated to SAPS II, SOFA score, and blood lactate. In adjusted analysis, high baseline G-CSF was associated with 30-day mortality (OR 2.83, 95% CI: 1.01-8.00, p = 0.047). CONCLUSION: In patients with NSTI, HBO2 treatment may induce immunomodulatory effects by decreasing plasma G-CSF and IL-6. High levels of inflammatory markers were associated with disease severity, whereas high baseline G-CSF was associated with increased 30-day mortality.
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