Modulation of Biomarkers in Patients With Flesh-eating Bacterial Infections After With Hyperbaric Oxygen Treatment

Necrotizing soft tissue infections (NSTI) is a complex, multi-factorial disease and the bacteria show a diverse microbial etiology. The exentisive inflammatory response caused by these bacteria is thought to be a main course of death. In Denmark, most NSTI patients are treated with hyperic oxygen therapy (HBOT). However, the effects of HBOT have never been investigated in NSTI patients.

Location: Copenhagen University Hospital, Rigshospitalet, Denmark.

Design: Observational cohort study.

Cohort: NSTI patients in Denmark treated with HBOT.

Biomarkers: Cytokines, acute-phase proteins, vasoactive biomarkers and other inflammatory biomarkers.

Sample size calculation: The investigators expect a mean IL-6 concentration before HBOT of 3500 pg/ml (standard deviation 1500 pg/ml) and consider a reduction of 800 pg/ml to be clinically relevant. With an alpha = 0.05 and a power of 80%, 112 patients will be required.

Data: The Danish Data Protection Agency has approved the processing of personal data for the NSTI patients (J. no. 30-0900).

Ethics: The trial will adhere to the Helsinki Declaration and the Danish law. The National Ethics Committee and the Regional Scientific Ethics Committee of Copenhagen have approved the study (CVK-1211709 and H-2-2014-071).

Analysis: Biomarker analyses will be performed once the recruitment of patients has ended.

Primary outcomes

• IL-6 as a marker of treatment effects after HBOT [Change from baseline in IL-6 concentration after first HBOT administered during the first 24 hours of admission]

Secondary outcomes

• Inflammatory biomarkers as indicators of treatment effects after HBOT [The first 5 days of admission]
• Vasoactive biomarkers as indicators of treatment effects after HBOT [The first 5 days of admission]
• Mortality [30, 90, 180 days]
• Amputation rate [During the first 7 days of ICU admission]
• SAPS II assessment [During the first 24 hours of ICU admission]
• APACHE II assessment [During the first 7 days of ICU admission]
• SOFA score assessment [During the first 7 days of ICU admission]
• Anaya score assessment [During the first 7 days of ICU admission]
• LRINEC score assessment [During the first 7 days of ICU admission]
• Multiple organ failure assessed by the MODS score [During the first 7 days of ICU admission]
• Number of debridements [During the first 7 days of ICU admission]
• Microbial etiology results from blood and tissue samples [During the first 7 days of ICU admission]

Sex: All, ages: 18 Years to any

Inclusion criteria:

* Necrotizing soft tissue infection based on surgical findings
* Admitted to/planned to be admitted to the ICU at Rigshospitalet and/or operated for NSTI at Rigshospitalet
* Receving a minimum of 1 HBOT

Exclusion criteria:

* Patients who at the operating theatre were categorized as a non-NSTI patient

• Ole Hyldegaard, MD, PhD, Study director, Department of Anaesthesiology, Center of Hyperbaric Treatment, sect. 4092, Copenhagen University Hospital, Denmark
• Marco Bo Hansen, MD, Principal investigator, Department of Anaesthesiology, Center of Hyperbaric Treatment, sect. 4092, Copenhagen University Hospital, Denmark