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Recovery

Wound and tissue healing

This is the longest-established use of hyperbaric oxygen. The research looks at how raised oxygen levels affect slow-healing tissue, post-surgical recovery and the growth of new blood vessels, with the strongest evidence in diabetic foot ulcers.

Evidence so far
Moderate
Reading timeAbout 12 minutes

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Why this is being studied

Chronic wounds, most commonly diabetic foot ulcers and leg ulcers, fail to heal because damaged circulation, swelling and infection leave the wound bed short of oxygen, and every stage of repair from fighting bacteria to building collagen and new capillaries depends on it. Hyperbaric oxygen is one of the few established medical uses of pressurised oxygen: by dissolving large amounts of oxygen into plasma it can temporarily restore oxygen levels in tissue that normal blood flow cannot reach. The evidence is strongest for selected diabetic foot ulcers and remains thinner for other wound types.

Where the evidence stands

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The mechanism

What is going on, and why this might help

What is going on in the body

Wounds that fail to heal, whether diabetic foot ulcers, pressure sores, surgical wounds or skin grafts under threat, almost always share one feature: the tissue is hypoxic. Damaged or diseased small vessels cannot deliver enough oxygen, swelling increases the distance oxygen has to diffuse, and infection consumes what oxygen there is. Below a certain tissue oxygen tension, fibroblasts cannot make collagen, new capillaries cannot form, white cells cannot kill bacteria effectively and the epithelium cannot migrate across the wound bed. The wound becomes stuck in a chronic inflammatory state.

Where oxygen comes in

This is the condition in which the mechanisms are most directly relevant. Breathing oxygen at 2 to 2.5 atmospheres raises dissolved plasma oxygen roughly ten- to fifteen-fold and tissue oxygen tension in the wound margin several-fold, restoring the oxygen gradient that drives healing. Fibroblast proliferation, collagen synthesis and cross-linking are oxygen-dependent. Neutrophils need oxygen to generate the reactive species that kill bacteria, and hyperbaric oxygen is directly toxic to anaerobes. Intermittent hyperoxia up-regulates VEGF and HIF-1α-mediated angiogenesis, and the resulting new capillaries persist after treatment ends. Thom and colleagues showed in 2006 that a single session mobilises bone-marrow stem and progenitor cells into the circulation, and that these home to wounds. Vasoconstriction reduces oedema while delivering more oxygen, and antioxidant defences are up-regulated over a course.

How solid is this

Established. The oxygen-dependence of wound healing has been demonstrated in laboratory, animal and human studies over fifty years, and hyperbaric oxygen for diabetic foot ulcers and compromised grafts and flaps is an accepted indication with randomised trial and Cochrane support, though the size of the clinical effect varies between trials. Key references: Thom 2006 (stem-cell mobilisation); Thom 2011 (mechanisms of action review).

Explainer illustration

The studies

Every study is laid out the same way: what the researchers wanted to find out, who took part, what they actually did, what they found, why it might work and where the limits are. No jargon, and a link to the original if you want to read it yourself.

Each study is laid out the same way: what the researchers asked, who took part, what they did, what they found, why it might work, and where the limits are. The clinician layer at the end of each one carries the numbers.

Paper 1

Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes

Löndahl et al. · Diabetes Care · 2010 · randomised, double-blind, placebo-controlled trial, n=94

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What they asked

Chronic foot ulcers in people with diabetes are slow to heal because nerve damage, poor circulation and infection combine to keep the wound starved of oxygen. Löndahl and colleagues in Sweden asked whether adding a course of hyperbaric oxygen to standard wound care would increase the proportion of ulcers that healed completely within a year, using a properly blinded, sham-controlled design.

Who took part

Ninety-four adults with diabetes were randomised in a single specialist diabetic foot clinic. All had a foot ulcer that had been present for more than three months, graded Wagner 2, 3 or 4 (from deep ulcer through to local gangrene), and all had already been treated for at least two months in the multidisciplinary clinic without healing. Most were in their late 60s.

What they did

This was a randomised, double-blind, placebo-controlled trial. Participants entered a multiplace chamber for 95-minute sessions, breathing at pressure for 85 minutes, five days a week for eight weeks, giving 40 sessions. The treatment group breathed 100 per cent oxygen at 2.5 ATA; the control group breathed ordinary air at the same pressure, so neither they nor the wound-clinic staff assessing them knew who was in which group. Both groups continued full standard foot care. Ulcers were followed for one year.

What they found

At one year, 25 of 48 ulcers (52 per cent) in the oxygen group had healed completely, compared with 12 of 42 (29 per cent) in the air group. Among people who completed at least 35 of the 40 sessions the difference was larger: 61 per cent versus 27 per cent. Major amputation rates did not differ significantly between groups. Side effects were uncommon.

Why it might work

Wound healing needs oxygen for collagen formation, new blood vessel growth and the bacteria-killing activity of white cells. In a diabetic foot the tissue oxygen level is often too low for these processes to proceed. At 2.5 ATA the plasma alone carries enough oxygen to supply tissue that capillaries cannot reach well, and repeated exposure appears to stimulate growth factors and the recruitment of repair cells from the bone marrow. The effect builds over weeks rather than after a single session.

Limits

This was a single-centre trial of fewer than 100 people, and the primary result was significant but not overwhelming. Around a fifth of participants did not complete the full course, which is why the intention-to-treat and per-protocol figures differ. The study was not large enough to say anything reliable about amputation. It was academically funded. It applies to carefully selected patients in a specialist clinic, not to wounds in general.

Paper 2

Hyperbaric oxygen therapy for chronic wounds

Kranke et al. · Cochrane Database of Systematic Reviews · 2015 · systematic review of 12 trials

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What they asked

Cochrane reviews are the most conservative form of evidence summary in medicine. Kranke and colleagues asked whether hyperbaric oxygen, added to usual wound care, helps chronic wounds heal and reduces amputation, considering diabetic foot ulcers, venous leg ulcers, arterial ulcers and pressure sores separately.

Who took part

Twelve randomised trials with 577 participants met the criteria, searched up to February 2015. Ten trials (531 people) involved diabetic foot ulcers, one small trial (16 people) venous ulcers, and one (30 people) mixed ulcer types. No trials of arterial or pressure ulcers were found.

What they did

The reviewers pooled results where trials measured the same outcome at similar times. Protocols in the included trials varied but typically involved 2.0 to 2.5 ATA for 60 to 120 minutes, daily or on most weekdays, for anywhere from a few sessions to 40 or more. Only some trials used a sham chamber; several compared HBOT with usual care alone, which weakens blinding. Outcomes were complete ulcer healing at set time points, amputation, and change in ulcer area.

What they found

For diabetic foot ulcers, HBOT roughly doubled the chance of complete healing at six weeks (five trials, 205 people). At one year the pooled result no longer reached statistical significance, although the estimate still favoured HBOT with very wide uncertainty. Major amputation was less frequent with HBOT but the difference was not statistically significant (five trials, 312 people). For venous ulcers, a single trial showed greater reduction in ulcer area at six weeks only. The mixed-ulcer trial showed a large reduction in area at 30 days.

Why it might work

The review accepts the standard physiological account: chronic wounds are hypoxic, and oxygen is required for collagen synthesis, capillary growth, white-cell killing of bacteria and the signalling that moves a wound from a stuck inflammatory state into repair. Hyperbaric oxygen raises tissue oxygen enough, temporarily, to support those processes.

Limits

Most included trials were small and several had design flaws, including lack of blinding, unclear randomisation and incomplete follow-up, so the authors rated their confidence as low. The one-year result is dominated by a few trials with different results, giving a very imprecise estimate. Long-term outcomes such as ulcer recurrence and quality of life were rarely reported. The venous ulcer conclusion rests on 16 people. The search is now over a decade old.