WHS Grants ‘Level I’ Recommendation to Topical Oxygen Therapy

Wound Healing Society (WHS) Guidelines update: Diabetic Foot Ulcer treatment guidelines – December 2023

The Wound Healing Society (WHS) has recently increased topical oxygen therapy to ‘Level 1’ Evidence in its updated DFU treatment guidelines, signifying a significant leap in the field.

The WHS publishes guidance for clinicians with the goal of improving patient care. The new guidelines for diabetic foot ulcer (DFU) treatment have been updated since its 2016 publication to reflect new, higher-quality evidence. Highlighted in the new guidelines were two Meta-analyses, which include NATROX® O₂ cTOT RCT data

Notably, the guidance states: 

  • Clinical Validation: The Wound Healing Society recognizes the efficacy of topical oxygen therapy in its latest guidelines.
  • Level 1 Evidence: The WHS designates ‘Level 1’ evidence as “Meta-analysis or at least two RCTs supporting the intervention of the guideline.”
  • Game-Changing Potential: Explore how topical oxygen therapy is reshaping wound care practices and achieving lasting healing results.
  1. Lawrence A. Lavery, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  2. Mehmet A. Suludere, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  3. Peter A. Crisologo, Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  4. Chris E. Attinger, Department of Plastic Surgery MedStar Hospital System, Washington D.C. USA
  5. Matthew Malone, Infectious Diseases and Microbiology, School of Medicine, Western Sydney University, Australia
  6. Gu Eon Kang, Department of Bioengineering, University of Texas at Dallas, Richardson, Texas, USA
  7. Edgar J. Peters, Department of Internal Medicine, Section of Infectious Diseases, Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands, and Amsterdam Institute for Infection and Immunity and Amsterdam Movement Sciences, Amsterdam, the Netherlands
  8. Lee. C. Rogers, Department of Orthopaedic Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Update to 2006 and 2016 WHS published guidance providing information for clinicians with a goal to improve patient care, reflecting the new, higher quality evidence.

  • Updated literature search including human and disease specific data of key databases for new reports on DFU treatments
    • Unlike previous WHS guideline editions (2006/ 2016), this update is limited to meta-analyses, systematic reviews, RCTs, retrospective series reviews, clinical case series, and expert panel recommendations
  • Guidelines categorised in appropriate sections relevant to different DFU treatment aspects
  • Each separate guideline has undergone a Delphi consensus among the panel members and the level of evidence supporting it is clearly stated.

42 guidelines split into 8 care categories, including:

  • Diagnosis of lower extremity diabetic ulcers (3 guidelines)
  • Offloading treatment for diabetic ulcers (1 guideline)
  • Infection control and treatment in the management of diabetic ulcers (8 guidelines)
  • Wound bed preparation in diabetic ulcers (8 guidelines)
  • Wound care dressings or therapies in the treatment of diabetic ulcers (2 guidelines)
  • Surgery in the treatment of diabetic ulcers (5 guidelines)
  • Adjunctive agents and topical devices in the treatment of diabetic ulcers (12 guidelines)
  • Prevention of recurrence of diabetic foot ulcers (3 Guidelines)

The authors suggest that percent change in wound area of DFUs over four weeks of treatment is a good predictor of the effectiveness of therapy and likelihood of healing and supports other guidance and consensus documents with when to consider changes to more advanced treatments.

Under category 7, “Adjunctive agents and topical devices in the treatment of diabetic ulcers”: Topical Oxygen Therapy is specifically recognised in new guidance and is supported by the highest level of evidence (Level 1).

The guidance spotlights two high-quality Meta-analysis that include NATROX® O₂ cTOT RCT data Carter et al. (2023)2 and Connaghan et al. (2021).3

The authors point out the key benefits of TOT to eliminate hypoxia and stimulate growth factors that contribute to angiogenesis and progress healing.

Also in category 7, the authors further recognise Oxygen’s clinical importance by highlighting the role of Hyperbaric Oxygen Therapy in wound healing supported by three new systematic reviews and one Health Technology assessment.

Other key points include ensuring proper assessment of sensory neuropathy and diagnosis and  treatment for PAD.  Using clinical signs to diagnose infection and also highlight the increasing awareness of the role of biofilm in these wounds with guidance on the use of topical antimicrobial and antiseptic therapies that may improve wound healing by affecting microorganisms in the wound bed, however prophylactic antibiotics are not recommended.

Holistic assessments and management are stipulated with nutrition balance, glucose control and smoking cessation called out specifically.  In addition, good wound bed preparation practice is emphasised with guidance on debridement and cleansing. Furthermore dressings that support good moisture balance and are cost effective are recommended.

The hierarchical effectiveness of different offloading therapies is suggested to maximise healing potential along with highlighting the importance of preventative measures such as orthotic footwear foot inspections and prevention programs.

  • These guidelines support evidence-based practice to optimise outcomes in patients with diabetic ulcers. 
  • Advanced adjuncts, such as TOT, supported by the highest level of evidence (level 1) should be considered in non-healing wounds due to increased incidence of healing and decreased time to heal following TOT treatment in these wounds.
  • This article builds on evidence from the American Diabetes Association (ADA) which maintains topical oxygen therapy as “Grade A evidence”⁴ in its Standards of Care in Diabetes 2024 and Standards of Care in Diabetes 2023. It also adds to the International Working Group for the Diabetic Foot (IWGDF) 2023 Guidelines for DFUs recommend using “topical oxygen therapy as an adjunct to standard of care for wound healing.”
  1. Lavery, L. A. et al. WHS (Wound Healing Society) guidelines update: Diabetic foot ulcer treatment guidelines. Wound Repair and Regeneration (2023) doi:10.1111/wrr.13133.
  2. Carter, M. J. et al. Efficacy of Topical Wound Oxygen Therapy in Healing Chronic Diabetic Foot Ulcers: Systematic Review and Meta-Analysis. Adv Wound Care (New Rochelle) 12, 177–186 (2023).
  3. Connaghan, F., Avsar, P., Patton, D., O’Connor, T. & Moore, Z. Impact of topical oxygen therapy on diabetic foot ulcer healing rates: a systematic review. J Wound Care 30, 823–829 (2021).
  4. El Sayed, N. A. et al. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2023. Diabetes Care 46, S203–S215 (2023)
  5. IWGDF, 2023. Wound healing interventions guideline (2023 update). Available at: https://bit/ly/nwc-iwgdf-guidelines2023