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. 2025 Aug;14(8):1715-1738.
doi: 10.1007/s40121-025-01184-5. Epub 2025 Jul 4.

Use of Hyperbaric Oxygen in Patients with Necrotizing Soft Tissue Infections: A Scandinavian Multicenter, Prospective, Observational Cohort

Ole Hyldegaard  1   2 , Michael Nekludov  3 , Per Arnell  4 , Torbjørn Nedrebø  5 , Ylva Karlsson  6 , Martin Bruun Madsen  7   8 , Steinar Skrede  9   10 , Vitor Martins Dos Santos  11 , Mattias Svensson  12 , Anders Perner  13   7 , Julie Vinkel  14 , Anders Kjellberg  3   15 , Anders Rosén  4 , Johan Douglas  6 , Trond Bruun  9   10 , Christopher Hardt  11 , Anna Norrby-Teglund  12 , Morten Hedetoft  14
Affiliations

Use of Hyperbaric Oxygen in Patients with Necrotizing Soft Tissue Infections: A Scandinavian Multicenter, Prospective, Observational Cohort

Ole Hyldegaard et al. Infect Dis Ther. 2025 Aug.

Abstract

Introduction: Hyperbaric oxygen (HBO2) treatment is regularly used as adjuvant treatment in patients with necrotizing soft tissue infections (NSTI). Several observational studies have suggested an association between hyperbaric oxygen (HBO2) treatment and improved survival in patients with necrotizing soft tissue infections (NSTIs); however, the evidence remains inconclusive. Most patients with NSTI are severely ill, having sepsis or septic shock, and requiring mechanical ventilation and inotropic support in an intensive care unit (ICU). Although recent data suggest that the beneficial effect of HBO2 may be largest in the most severely ill, not all patients may receive it due to hemodynamic instability, pressure chamber capabilities, and availability, thereby potentially introducing selection bias.

Methods: From January 2013 until June 2017, we conducted a multicenter, prospective, consecutive, observational study (The INFECT study, ClinicalTrials.gov number; NCT01790698) enrolling NSTI patients at five clinical centers delivering HBO2 to NSTI patients in an ICU setting in Denmark, Norway, and Sweden.

Results: A total of 409 consecutive patients with necrotizing soft tissue infections were prospectively enrolled in the study, of whom 402 (98.3%) were admitted to the ICU. A total of 329 NSTI patients received HBO2, and 80 patients did not. Median time from arrival at a specialized hospital to first HBO2 was 4.3 h (IQR 2.5-7.7). Patients receiving HBO2 had less often chronic liver disease, penetrating trauma within 4 weeks before NSTI, lower extremity NSTI involvement, and acute kidney injury and lower severity scores (Simplified Acute Physiology Score; SAPS-2 and Sequential Organ Failure Assessment score; SOFA score) than patients not treated with HBO2. Patients receiving HBO2 were more frequently on mechanical ventilation. All-cause 30- and 90-day mortality for the HBO2-treated patients was 22/325 (7%) and 36/325 (11%) and for non-HBO2-treated patients 34/80 (43%) and 37/80 (46%). In exploratory analyses, HBO2 was associated with lower all-cause 30-day mortality in unadjusted and in that adjusted for sex, lactate, SAPS-2, and baseline norepinephrine infusion rate.

Conclusions: Patients receiving HBO2 in this cohort were less acutely ill than those not receiving HBO2 likely influencing physicians' decisions thereby introducing selection bias. In exploratory analyses, the use of HBO2 was associated with a reduced 30-day all-cause mortality. A randomized trial of HBO2 treatment seems warranted in patients with NSTI.

Trial registration: ClinicalTrials.gov number NCT01790698.

Keywords: Biofilm; Fournier’s gangrene; Gas gangrene; Intensive care; Ischemia; Necrotizing soft tissue infection; Oxygen; Sepsis; Septic shock; Tissue hypoxia.

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Conflict of interest statement

Declarations. Conflict of Interest: No conflicts of interest, financial or otherwise, are declared by the authors Ole Hyldegaard, Michael Nekludov, Per Arnell, Torbjørn Nedrebø, Ylva Karlsson, Martin Bruun Madsen, Steinar Skrede, Vitor Martins Dos Santos, Mattias Svensson, Anders Perner, Julie Vinkel, Anders Kjellberg, Anders Rosén, Johan Douglas, Trond Bruun, Christopher Hardt, Anna Norrby-Teglund, Morten Hedetoft to this report. Ethical Approval: All participating clinical study centers were granted study approvals from their national- or regional ethics committees as well as approvals from their respective data protection agencies [17]. Written informed consent, including the consent to publish the study results, was obtained from all patients or their legal surrogate as soon as possible and during the acute phase of the treatment period, according to national legislation. Subsequently, for patients where immediate consent was not possible, we obtained consent from the patient when possible [17]. The study was conducted in accordance with the World Medical Association’s Code of Ethics (Declaration of Helsinki 1964 and its later amendments). The INFECT study was approved at all involved study centers under the governance of the Regionala etikprövningsnämnden i Göteborg – Västra Götalandsregionen Dnr 930–12, Den Nationale Videnskabs Etiske Kommitte (DNVK – sag nr. 1211709, dok.nr. 1151739) and the REK – Regionale Komiteer for medisinsk og helsefaglig forskningsetikk, ref. 2012/2227/REK vest.

Figures

Fig. 1
Fig. 1
A typical treatment protocol showing the 5-min compression profile and oxygen breathing partial pressures during a 90-min hyperbaric oxygen treatment session going to 2.8 ATA (284 kPa) and decompression phase to back to atmospheric pressure in 15 min. Giving at total pressure chamber run-time of 110 min of which 90 min is spend at 284 kPa. msw meters of seawater, ATA atmospheres at absolute pressure
Fig. 2
Fig. 2
A, B: A1 Hyperbaric multiplace chamber at the Karolinska Institute, University Hospital of Stockholm, Sweden. The pictures show a large main treatment compartment allowing for intensive care use, access to the patient and treatment of the patient in a hospital bed. Photo: Michael Nekludov. A2 A rectangular access to the pressure chamber accommodating an ICU bed. Photo: Anders Kjellberg. B Hyperbaric multiplace chamber at the Rigshospitalet, University Hospital of Copenhagen, Denmark. The picture shows the main treatment compartment with a patient on a specialized stretcher designed for entering through the door to the main treatment compartment. The patient will need to be on- and off-loaded from the stretcher for each hyperbaric treatment session. Photo: Bjørn Arenkiel
Fig. 3
Fig. 3
A,  B Mean (± SD) accumulated oxygen dosage in minutes at 284 kPa. For a definition of high and low doses of HBO2 and calculation of oxygen dosage, see supplementary material Table S1. The Copenhagen treatment center is significantly different from the treatment centers in Stockholm, Karlskrona, and Bergen. Stockholm dosage is significantly different from Gothenburg. Gothenburg is significantly different from Karlskrona. B Treatment centers divided into low or high dosage, oxygen dosage is significantly different between low (median: 270 min, N = 261) and high dosage (median 429 min, N = 68) centers (P < 0.01). See also supplementary material Tables S1 and S11. HBO2 hyperbaric oxygen
See this image and copyright information in PMC

References

    1. Bakker DJ. Clostridial Myonecrosis (gas gangrene). In: Weaver LK, editor. Hyperbaric oxygen therapy indications. 13th ed. North Palm Beach: Best Publishing Company; 2014. p. 114–25.
    1. Jacoby I. Necrotizing soft tissue infections. In: Weaver LK, editor. Hyperbaric oxygen therapy indications. 13th ed. North Palm Beach: Best Publishing Company; 2014. p. 159–77.
    1. Shaw JJ, Psoinos C, Emhoff Timothy A, Shah Shimul A, Santry HP. Not just full of hot air: hyperbaric oxygen therapy increases survival in cases of necrotizing soft tissue infections. Surg Infect. 2014;15(3):328–35. - PMC - PubMed
    1. Soh CR, Pietrobon R, Freiberger JJ, et al. Hyperbaric oxygen therapy in necrotising soft tissue infections: a study of patients in the United States Nationwide inpatient sample. Intensive Care Med. 2012;38(7):1143–51. - PubMed
    1. Hedetoft M, Madsen MB, Madsen LB, Hyldegaard O. Incidence, comorbidity and mortality in patients with necrotising soft-tissue infections, 2005–2018: a Danish nationwide register-based cohort study. BMJ Open. 2020;10(10): e041302. - PMC - PubMed

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