Is hyperbaric oxygenation and ozonation a treatment choice for Peripheral Arterial Occlusive Disease (PAOD)?

Hyperbaric Oxygen and Ozone Therapy for Peripheral Arterial Occlusive Disease

Hyperbaric oxygen therapy may be considered as an adjunctive therapy to revascularization for wound healing in patients with chronic limb-threatening ischemia (CLTI), but it is not a standalone treatment choice for peripheral arterial occlusive disease, and ozone therapy lacks sufficient evidence to recommend its use. 1

Hyperbaric Oxygen Therapy: Current Evidence and Recommendations

Primary Guideline Position

The most recent 2024 ACC/AHA guidelines acknowledge that hyperbaric oxygen therapy (HBOT) may be considered as an adjunctive therapy specifically in the context of CLTI with diabetic foot ulcers, but only after revascularization has been performed. 1 The 2017 AHA/ACC guidelines were more cautious, stating that the effectiveness of HBOT for wound healing in CLI remains unknown (Class IIb, Level C-LD). 1

Evidence Quality and Limitations

The evidence base for HBOT in PAOD is characterized by significant variability in methodology, wound types, and degree of ischemia across studies. 1 Most research has focused on diabetic foot ulcers without severe PAD, limiting applicability to true peripheral arterial disease. 1

Key study findings:

• One small RCT in patients with foot ulcers and confirmed PAD (ABI <0.80 or TBI <0.70) who were not candidates for revascularization showed a significant decrease in ulcer area at 6 weeks, but no significant differences in ulcer size at 6 months, complete ulcer healing, or major/minor amputations. 1

• A slightly larger study of 70 patients with severely ischemic foot ulcers reported amputation rates of 9% in the HBOT group versus 33% in controls. 1

• However, a larger longitudinal study of diabetic foot ulcers found no improvement in wound healing with HBOT. 1

• A recent systematic review and meta-analysis reported reduction in major amputation with HBOT for diabetic foot ulcers, though no reduction in minor amputation or overall mortality. 1

Critical Context: HBOT is NOT a Primary Treatment

HBOT should never be used as a standalone treatment for PAOD. 2 The American College of Cardiology explicitly states that the effectiveness of HBOT for wound healing in critical limb ischemia is unknown. 2 More importantly, there are no published studies evaluating HBOT for patients with nonreconstructible PAD. 1

When HBOT Might Be Considered

HBOT may be considered only in the following specific scenario:

• After successful revascularization has been performed 1
• In patients with CLTI and diabetic foot ulcers 1
• As an adjunctive therapy to comprehensive wound care 1
• When standard wound healing measures have been optimized 1

Safety and Practical Limitations

HBOT carries physiological risks that may compromise critically ill patients, including barotrauma, seizures, claustrophobia, hypotension, cardiac arrhythmias, and pneumonia. 2 Additionally, high cost and poor availability are significant limitations. 2, 3

Ozone Therapy: Insufficient Evidence

Lack of Guideline Support

Ozone therapy is not mentioned in any major clinical practice guidelines for PAOD management. 1 The absence of ozone therapy from the 2024 ACC/AHA guidelines, 2017 AHA/ACC guidelines, and all other major cardiovascular society recommendations is notable and significant.

Limited Research Evidence

The available research on ozone therapy for PAOD is extremely limited and of low quality:

• A 1995 study suggested oxygen-ozone therapy increased erythrocyte filterability and decreased blood viscosity in PAOD patients, but this was a small study with only hemorrheologic endpoints, not clinical outcomes. 4

• A 2015 review article claimed ozone therapy could be beneficial for PAOD but provided no high-quality clinical trial data to support this assertion. 5

These studies do not meet the threshold for clinical recommendation given the absence of randomized controlled trials demonstrating improvement in patient-centered outcomes such as amputation-free survival, wound healing, or quality of life.

Recommended Treatment Algorithm for PAOD

Instead of hyperbaric oxygen or ozone therapy, the evidence-based approach for PAOD should follow this hierarchy:

1. Medical optimization: Smoking cessation, glycemic control, antiplatelet therapy, statin therapy 1

2. Revascularization evaluation: All patients with CLTI should be evaluated by a multidisciplinary team for revascularization options 1

3. Comprehensive wound care (if CLTI present): Debridement, infection management, pressure offloading, appropriate dressings 1

4. Consider adjunctive therapies only after revascularization:

   • Negative pressure wound therapy for post-amputation wounds 1
   • HBOT may be considered for diabetic foot ulcers in CLTI after revascularization 1
   • Intermittent pneumatic compression devices for patients without revascularization options 1

Common Pitfalls to Avoid

• Do not delay revascularization to pursue HBOT or ozone therapy 1
• Do not use HBOT as monotherapy for PAOD or CLTI 1, 2
• Do not confuse air embolism stroke (where HBOT is indicated) with routine ischemic complications of PAOD 1, 6
• Do not pursue ozone therapy based on limited research studies when guideline-supported treatments are available 1