TY - JOUR

T1 - Hyperbaric oxygen treatment is associated with a decrease in cytokine levels in patients with necrotizing soft-tissue infection

AU - Hedetoft, Morten

AU - Garred, Peter

AU - Madsen, Martin Bruun

AU - Hyldegaard, Ole

N1 - Funding Information: This work was funded by Copenhagen University Hospital (Rigshospitalet) Research Grant (grant number R167‐A7352‐B3897), which included a research fellowship for MH. Moreover, the study was supported by Wedellsborgs Fund and the projects of PERMIT (grant number 8113‐00009B) funded by Innovation Fund Denmark and EU Horizon 2020 under the frame of ERA PerMed (project 2018‐151) and PERAID (grant number 8114‐00005B) funded by Innovation Fund Denmark and Nordforsk (project no. 90456). The research leading to these results has received funding from the European Union Seventh Framework Programme: (FP7/2007‐2013) under the grant agreement 305340 (INFECT project). Publisher Copyright: © 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

KW - anaerobic infection

KW - cytokine

KW - group A-Streptococcus

KW - hyperbaric oxygen treatment

KW - necrotizing soft-tissue infection

KW - outcome

KW - survival

U2 - 10.14814/phy2.14757

DO - 10.14814/phy2.14757

M3 - Journal article

C2 - 33719215

AN - SCOPUS:85102912698

VL - 9

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 6

M1 - e14757

ER -