Hyperbaric Oxygen for Diabetic Foot Ulcer: Useless or Useful?

Marlene Busko

July 13, 2015

Whether systemic hyperbaric-oxygen therapy is effective for diabetic patients with foot ulcers that are resistant to other treatments remains controversial, due to a dearth of solid, consistent evidence, even though this procedure has been used for this indication for 35 years.

At the recent American Diabetes Association (ADA) 2015 Scientific Sessions, in a debate entitled "Is hyperbaric-oxygen therapy effective in treating diabetic foot ulcers?" two adversaries tried to sway the audience to their point of view but in the end both agreed that there is a need for more and better data.

Fortunately, the largest-ever trial to address this concept, DAMOCLES, is about to begin enrollment, and this will also examine the cost-effectiveness of hyperbaric-oxygen therapy.

Arguing for the "pro" side, Magnus Löndahl, MD, from the department of endocrinology at Skane University Hospital and Lund University in Sweden, pointed out that "we do have two high-quality randomized controlled trials supporting the use of hyperbaric-oxygen therapy in treating chronic diabetic foot ulcers."

He was principal investigator on one of these trials, the Hyperbaric Oxygen Therapy as Adjunctive Treatment of Chronic Diabetic Foot Ulcers (HODFU), which examined this treatment in 90 patients; the other trial, by Abidia et al, looked at 16 patients (Eur J Vasc Endovasc Surg. 2003;25:513-518).

But speaking for the "con" side, Ludwik Fedorko, MD, associate professor of anesthesiology and pain management at the University of Toronto, Ontario, noted that the control patients in these studies (the only randomized controlled trials to investigate this) did not receive an innocuous treatment.

During the 90-minute sham therapy, they were exposed to air (as opposed to 100% oxygen, in the treatment group) delivered at roughly 2.5 atmospheres absolute [ATA].

To Medscape Medical News, Dr Fedorko also stressed that hyperbaric oxygen treatment is both time-consuming — typically 40 sessions of 90 minutes/day — and extremely costly. "Why do we bother with a $9000/patient treatment, if I can buy for this $9000 all the advanced dressings…and doctor visits, etc?" he asked.

"Weak/Moderate" Recommendation for Systemic Hyperbaric Oxygen

Dr Löndahl said the HODFU trial results showed that in patients with chronic (>3 month) diabetic foot ulcers, 52% of those who received hyperbaric-oxygen therapy vs 29% of those who received hyperbaric air had complete wound healing at 1 year (P = .03).

Importantly, healing started at 2 months after initiation of therapy and increased until 1 year. "It takes time to see the full effect," he stressed.

The treatment did not lead to any changes in visual acuity or retinopathy; transcutaneous oxygen tension (TcpO2) around the ulcer, rather than ankle-brachial index or toe blood pressure, was a good predictor of healing, he noted.

He agreed that hyperbaric-oxygen therapy — which involves patients lying in a single-person chamber or sitting in a chamber with other people — is not cheap, costing about $200 to $1250 per treatment session. However, he pointed out that the study by Abidia et al reported that, after a year of treatment, there was a net cost saving of £2960 (roughly $4500, in today's dollars) per patient, largely due to decreased costs for medical visits to receive wound dressings.

"Previously a lot more medical conditions were treated [with hyperbaric oxygen] without any scientific evidence at all, [which] has given the treatment a bad reputation," Dr Löndahl acknowledged.

In fact, at the 2008 ADA meeting, "when Dr Anthony R Berendt [of Nuffield Orthopaedic Centre NHS Trust, Oxford, United Kingdom] said, 'Say no to hyperbaric-oxygen therapy' for foot ulcers…I agreed," he continued.

But 2 years later, in an editorial that accompanied the HODFU study, Dr Berendt (and Dr Lipsky of VA Puget Sound, Seattle, Washington) wrote: "For chronic diabetic foot wounds that are not responding to months of appropriate therapy (cleansing, debridement, off-loading, antimicrobials, as needed), the present study, together with most of those previously published, suggests that [hyperbaric oxygen therapy] improves long-term healing" (Diabetes Care. 2010;33:1143-1145).

"At the end of the day, we do have a theoretical framework supporting hyperbaric oxygen treatment…[and] we have evidence that hyperbaric-oxygen treatment improves quality of life," Dr Löndahl noted.

On the other hand, "we need more randomized controlled trials confirming the outcome; we need more data about health economics; and we need better predictors of success," he conceded.

In the meantime, in May 2015, the International Working Group on the Diabetic Foot (IWGDF) issued a "weak/moderate" recommendation to "consider the use of systemic hyperbaric-oxygen therapy [for chronic diabetic foot ulcers], even though further blinded and randomized trials are required to confirm its cost-effectiveness as well as to identify the population most likely benefit from its use."

And this is the same level of recommendation that the IWGDF gave for topical negative-pressure wound therapy, "which is used all over the world," he stressed.

Moreover, the HODFU study showed that patients who had undergone hyperbaric-oxygen therapy were significantly more likely to survive at 3 years, he noted, adding that he will be presenting the 6-year HODFU results at the upcoming European Association for the Study of Diabetes meeting in Stockholm in September.

Negative Findings, Potential Study Flaws

Meanwhile, Dr Fedorko was lead investigator of the Hyperbaric Oxygen Therapy for Chronic Diabetic Lower Limb Ulcers trial, which has not yet been published but was negative.

Patients in the control group breathed air that was 1.3 ATA. At 12 weeks, 22% of patients in the control group vs 20% of patients in the hyperbaric oxygen treatment group had healed foot ulcers, he said.

Moreover, in other trials of hyperbaric-oxygen therapy, patients in the control arms had surprisingly low rates of healing, he pointed out.

"We can safely estimate that from 20% to 49% of chronic diabetic foot ulcers are healed within 12 to 16 weeks, with appropriate, comprehensive wound care, in established wound-care centers," Dr Fedorko said.

But the rates of healing in the Löndahl and Abidia trials and in a randomized open-label study by Duzgun et al (J Foot Ankle Surg. 2008;47:515-519) were much lower. In the latter study, none of the foot ulcers in 50 patients in the control group had healed at 92 weeks.

Importantly, in contrast to the randomized trials, an observational study by Margolis et al, which matched 793 diabetic patients with foot ulcers who underwent hyperbaric-oxygen therapy with similar patients who did not have this adjunctive therapy, found no improvements in wound healing or amputation rates (Diabetes Care. 2013;36:1961-1966), Dr Fedorko observed.

"I like hyperbaric-oxygen therapy…but in my opinion, there is not a shred of evidence that it's actually effective" to heal chronic foot ulcers and decrease the risk of amputation in diabetic patients, he told Medscape Medical News.

Waiting for DAMOCLES

DAMOCLES will be the largest study ever in this field, enrolling close to 300 patients in the Netherlands, and the primary outcome measures are freedom from major amputation after 12 months and achievement of and time to complete wound healing.

Secondary end points include freedom from minor amputations, ulcer recurrence, TcpO2, quality of life, and safety. In addition, the cost-effectiveness of hyperbaric-oxygen therapy with be examined for this indication.

This trial should help establish once and for all "whether hyperbaric-oxygen therapy should be used in diabetic patients or not," Dr Löndahl concluded.

American Diabetes Association 2015 Scientific Sessions; June 7, 2015; Boston, Massachusetts.


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