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Open Access

Hyperbaric oxygen treatment impacts oxidative stress markers in patients with necrotizing soft-tissue infection

Morten Hedetoft, Peter Østrup Jensen, Claus Moser, Julie Vinkel, Ole Hyldegaard
DOI: 10.1136/jim-2021-001837 Published 27 September 2021
Morten Hedetoft
1 Department of Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Peter Østrup Jensen
2 Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
3 Costerton Biofilm Center, Institute of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Claus Moser
2 Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Julie Vinkel
1 Department of Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Ole Hyldegaard
1 Department of Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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    Figure 1

    Baseline MPO, SOD, HO-1 and nitrite +nitrate levels according to; septic shock vs non-shock, amputation vs no amputation and RRT vs no RRT. Medians with interquartile ranges are illustrated. HO-1, heme oxygenase-1; MPO, myeloperoxidase; RRT, renal-replacement therapy; SOD, superoxide dismutase.

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  • Table 1

    Patients’ characteristics

    CharacteristicsNSTI, n=80
    Age (years)61 (52—68)
    Sex, male52 (65)
    BMI (kg/m2)26 (24—31)
    Comorbidities
     Cardiovascular disease35 (44)
     Chronic kidney disease5 (6)
     COPD6 (8)
     Diabetes21 (26)
     Immune deficiency2 (3)
     Liver cirrhosis1 (1)
     Malignancy7 (9)
     Peripheral vascular disease11 (14)
     Rheumatoid disease4 (5)
    Polyicrobial versus monomicrobial
     Monomicrobial infections30 (37)
     Polymicrobial infections42 (53)
     Negative findings8 (10)
    Biochemistry
     Leukocyte count (109/L)15 (10–22)
     C reactive protein (mg/L)221 (148–324)
     Creatinine (µmol/L)109 (78–181)
     Lactate (mmol/L)2.3 (1.3–3.3)
    Other
     SOFA score*8 (6–10)
     SAPS II†44 (35–51)
     LRINEC‡8 (7–10)
     Septic shock on admission§39 (49)
     Amputation within 7 days13 (16)
     RRT within 7 days12 (15)
     Mortality, day 9012 (15)
    • Continuous data are presented as medians (IQR) and categorical data as absolute numbers (percentage, %).

    • *SOFA score, day 1; data were missing for three (4%) patients.

    • †Data were missing for three (4%) patients.

    • ‡Data were missing for eight (10%) patients.

    • §Septic shock defined as lactate>2 mmol/L and use of vasopressor or inotrope.

    • BMI, Body Mass Index; COPD, chronic obstructive pulmonary disease; LRINEC, Laboratory Risk Indicator for Necrotizing Fasciitis Score; NSTI, necrotizing soft-tissue infection; RRT, renal-replacement therapy; SAPS II, Simplified Acute Physiology Score II; SOFA, Sequential Organ Failure Assessment.

  • Table 2

    Effects of HbO2 treatment on ROS and RNS

    Plasma ROS/RNSMedian difference
    Immediately before to after HBO2 After HBO2 to follow-up sample
    AllSeptic shockNon-shock sepsisAllSeptic shockNon-shock sepsis
    MPO (ng/mL)3.4* ↑ 4.63.4* ↑ −11.0* ↓ −14.2* ↓ 1.6
    SOD (ng/mL)8.8* ↑ −1.914.4−19.1** ↓ −24.4* ↓ −10.1* ↓
    HO-1 (pg/mL)17.9301.3* ↑ −172.3−11.6−513.565.6
    Nitrite+nitrate (µM)0.050.160.01−0.190.01−0.20
    • Data are compared immediately before and after the first HbO2 treatment session (left), as well as after the first HbO2 treatment session and following day (right). Differences are presented as median differences across the overall cohort (n=80), patients admitted in septic shock (n=39) and patients without septic shock (n=41). Superscripts indicate level of statistical significance performed by Wilcoxon signed-rank test. A positive value indicates significant upregulation (↑); a negative value indicates significant downregulation (↓).

    • **P<0.05, **P<0.01.

    • HBO2, hyperbaric oxygen; HO-1, heme oxygenase-1; MPO, myeloperoxidase; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase.

  • Table 3

    Spearman rank correlation between severity of disease and baseline ROS and RNS levels

    SAPS IISOFALactate
    RhoP valueRhoP valueRhoP value
    MPO0.160.150.40<0.0010.330.003
    SOD0.55<0.0010.70<0.0010.59<0.001
    HO-10.350.0030.68<0.0010.39<0.001
    Nitrite+nitrate0.270.020.250.030.150.19
    • HO-1, heme oxygenase-1; MPO, myeloperoxidase; RNS, reactive nitrogen species; ROS, reactive oxygen species; SAPS II, Simplified Acute Physiology Score II; SOD, superoxide dismutase; SOFA, Sequential Organ Failure Assessment.

  • Table 4

    Univariate and multivariate logistic regression analyses of 90-day mortality based on low versus high baseline ROS and RNS levels according to the optimal cut-off values

    UnadjustedAdjusted analysis: age and sexAdjusted analysis: age, sex and SOFA Score
    OR95% CI P OR95% CIP valueOR95% CIP value
    MPO
     Low
     <320.4
    1 Ref.1 Ref.1 Ref.
     High
     ≥320.4
    1.870.37 to 7.620.411.510.28 to 6.550.590.380.04 to 2.260.31
    SOD
     Low
     <114.9
    1 Ref.1 Ref.1 Ref.
     High
     ≥114.9
    12.12.16 to 226.920.029.911.67 to 190.410.044.240.52 to 92.970.23
    HO-1
     Low
     <7891
    1 Ref.1 Ref.1 Ref.
     High
     ≥7891
    4.881.11 to 33.950.063.660.75 to 26.740.141.140.13 to 11.220.90
    Nitrite+nitrate
     Low
     <18.62
    1 Ref.1 Ref.1 Ref.
     High
     ≥18.62
    1.480.20 to 7.020.651.730.23 to 8.990.540.940.11 to 5.410.95
    • HO-1, heme oxygenase-1; MPO, myeloperoxidase; Ref., reference; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase; SOFA, Sequential Organ Failure Assessment.

  • Table 5

    Accuracy of high baseline biomarker (defined by being above the optimal cut-off point) level in predicting 90-day mortality

    MPOSODHO-1Nitrite+nitrate
    Sensitivity0.25
    (0.05–0.57)
    0.92
    (0.62–1.00)
    0.80
    (0.44–0.97)
    0.17
    (0.02–0.48)
    Specificity0.85
    (0.74–0.92)
    0.52
    (0.40–0.65)
    0.55
    (0.42–0.68)
    0.88
    (0.78–0.95)
    PPV0.23
    (0.05–0.54)
    0.26
    (0.14–0.42)
    0.22
    (0.10–0.39)
    0.20
    (0.03–0.56)
    NPV0.85
    (0.74–0.92)
    0.97
    (0.85–1.00)
    0.94
    (0.81–0.99)
    0.86
    (0.75–0.93)
    AUC-ROC0.48
    (0.31–0.66)
    0.69
    (0.51–0.87)
    0.69
    (0.49–0.88)
    0.61
    (0.43–0.79)
    • Data are presented as fractions (95% CI).

    • AUC-ROC, area under the receiver operating characteristic curve; HO-1, heme oxygenase-1; MPO, myeloperoxidase; NPV, negative predictive value; PPV, positive predictive value; SOD, superoxide dismutase.

Supplementary Materials

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    [jim-2021-001837supp001.pdf]

Additional Files

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  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    • Data supplement 1
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Hyperbaric oxygen treatment impacts oxidative stress markers in patients with necrotizing soft-tissue infection
Morten Hedetoft, Peter Østrup Jensen, Claus Moser, Julie Vinkel, Ole Hyldegaard
Journal of Investigative Medicine Oct 2021, 69 (7) 1330-1338; DOI: 10.1136/jim-2021-001837

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Hyperbaric oxygen treatment impacts oxidative stress markers in patients with necrotizing soft-tissue infection
Morten Hedetoft, Peter Østrup Jensen, Claus Moser, Julie Vinkel, Ole Hyldegaard
Journal of Investigative Medicine Oct 2021, 69 (7) 1330-1338; DOI: 10.1136/jim-2021-001837
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Hyperbaric oxygen treatment impacts oxidative stress markers in patients with necrotizing soft-tissue infection
Morten Hedetoft, Peter Østrup Jensen, Claus Moser, Julie Vinkel, Ole Hyldegaard
Journal of Investigative Medicine Oct 2021, 69 (7) 1330-1338; DOI: 10.1136/jim-2021-001837
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