Part 2 of 4 currently 14 indications for HBO2

Patient selection criteria for HBO2 treatment of specific indications: Part 2 of 4

Currently 14 indications for HBO2 are recognized by the UHMS, with recommendations for treatment. What follows is an abbreviated description of each.

NOTE: While these are effectively ‘snapshots’ of each indication we strongly recommend a thorough reading of each chapter in the UHMS Indications book to appreciate the full view for HBO2 treatment of these conditions.

Because the indication of arterial insufficiencies has a large subgroup of nine different illnesses it is presented first, followed by the closely related indications compromised grafts and flaps, and acute traumatic ischemias. The remaining indications appear separately as Parts 2 and 3.


Several types of problem wounds have been identified where HBO2 has been used with varying degrees of success. An important issue, however, is obtaining reimbursement for those indications. It is a losing proposition to treat all patients on this list without considering the reimbursement equation. With that in mind, the goal of this section is to allow a provider to answer guiding questions on the decision to use HBO2. Once these questions have been considered and indicate that HBO2 is a viable option it is incumbent on the provider to present this analysis to the payer in hopes of getting approval to use HBO2.

  • Is tissue hypoxia a final common factor for why this wound is not healing?
  • Have all interventions to improve wound healing been entertained?
  • Is there enough evidence that HBO2 does improve wound healing?
  • If HBO2 is used, for how long should it be used?
  • Is there a means of objectively measuring a clinical response to HBO2?

Collect and share the data: It is preferable to collect outcomes data when treating these patients so that it can be used to contribute to furthering our understanding of the benefits of HBO2 in healing wounds. Since it is difficult to accumulate large numbers of these patients in any single center, participation in a clinical registry will provide the best opportunity to pool enough patients to prove the efficacy of HBO2 for these conditions.


The most obvious role of HBO2 in wound healing is its ability to provide oxygen to ischemic wounds. The use of HBO2 for the treatment of selected problem wounds has focused almost entirely on the diabetic foot ulcer (DFU) in recent years.

Diabetic foot ulcer:

The diabetic foot ulcer, caused by a functional ischemia due to diabetes mellitus, is problematic. Some patients with DFUs will heal without HBO2; other patients do not heal even with the addition of HBO2; yet other patients may heal if HBO2 is added to their comprehensive treatment.

A fundamental tenet of this treatment plan is that HBO2 is an adjunct to best practices that include vascular assessment and intervention, offloading of neuropathic ulcers, infection control, diabetes control, improved nutrition, corrected hyperglycemia, and surgical debridement of devitalized tissue. Without these additional strategies HBO2 cannot be expected to be successful.

However, HBO2 should not be delayed if there is rapid, ongoing tissue loss. The timing of HBO2 is critical in its ability to effect a change. Tissue that has already succumbed to ischemia cannot be saved, so HBO2 must be utilized when there is still a chance to ameliorate the effects of hypoxia in the ischemic penumbra.

Arterial insufficiency ulcers:

Peripheral arterial disease (PAD) affects 8-12 million people over the age of 40 years in the United States. PAD can result in tissue ischemia due to atherosclerosis of the aorta, iliac and lower-extremity arteries. Many patients with arterial insufficiency (AI) develop arterial insufficiency ulcers (AIU).

HBO2 is one adjunctive therapy to consider in patients with a non-healing AIU despite standard care that includes revascularization or in patients who have been evaluated by vascular surgery and are not a candidate for revascularization. The delivery of oxygen at higher-than-atmospheric-pressure results in increased arterial oxygen tensions and higher concentrations of oxygen in the plasma, thus driving oxygen into otherwise hypoxic injured tissue.

Calciphylaxis: A rare and potentially life-threatening syndrome, calciphylaxis, or calcific uremic arteriolopathy, causes small-vessel calcification, subsequent painful skin lesions, chronic non-healing ulcers and gangrene. It is seen patients suffering from end-stage renal disease and who are on dialysis. Its prevalence is 1-4%, with the incidence reported as increasing. It has a high mortality – 60-80% – with most patient deaths as a result of complications of infection of the calciphylaxis wounds and sepsis.

Patients with calciphylaxis may be considered for HBO2. Biopsy-confirmed diagnosis is recommended, but multidisciplinary consensus of clinical diagnosis is acceptable. It is recommended that patients also receive thiosulfate while undergoing HBO2 to maximize benefit and chances for a successful outcome.

Graft versus host disease:

Allogeneic stem cell transplantation, used in the treatment of hematopoietic and lymphatic malignancies, can result in graft-versus-host disease (GvHD). Its most common findings are cutaneous manifestations, ranging from pruritus, to rash, to chronic wound development. Although the process of GvHD is mediated by the donor T cells, chronic GvHD appears pathologically related to autoimmune disorders, often accompanied by non-specific autoantibodies. Locally the process leads to dermal/subcutaneous endothelial damage and microangiopathy which results in local tissue ischemia and fibrosis.

A GvHD patient with a non-healing ulcer may be considered for HBO2 if their wound has failed to heal despite standard wound care. A room air normobaric transcutaneous oxygen pressure (TcPO2) measurement is the yardstick for determining baseline level of ongoing ischemia: A TcPO2 of lower than 40mmHg indicates impaired healing; after HBO2 the patient should have an in-chamber TcPO2 greater than 200mmHg – indicating likely response to HBO2 – to continue. If levels are lower than 200mmHg at 2.0 ATA the chamber pressure may be increased to 2.4/2.5 ATA. If the TcPO2 remains lower than 200mmHg further treatments are not recommended. HBO2 treatments are delivered at 2.0-2.5 ATA for 90 to 120 minutes once or twice daily for five to seven days a week.

Pyoderma gangrenosum:

Pyoderma gangrenosum (PG) is a rare yet destructive neutrophilic dermatosis that affects the skin and subcutaneous tissues. The disease appears in all ages, races and sexes, often presenting with either solitary lesions or multiples or clusters of lesions. PG occurs as an independent entity in 50% of cases, with the other 50% associated with another underlying pathology such as ulcerative colitis. The incidence of pyoderma gangrenosum along with other diseases is anywhere from 15-80% with ulcerative colitis; up to 16.3% with Crohn’s disease; 30% with seropositive or seronegative arthritis; 10-23.8% with gammopathy; and 30% with Takayasu’s arteritis.

PG often presents as a deep ulcer with a well-defined border of a violaceous or blue color. While most commonly seen on the legs, it can occur on any skin surface. Lesions can be quite painful. Ulcers typically extend to the dermis, but they can penetrate underlying fascia. The most defining aspect of pyoderma gangrenosum is evidence of pathergy – disease initiating from previous trauma or surgical intervention or debridement – which can create new lesions or reactivate old ones.

Conventional remedies for PG include oral, intramuscular or parenteral steroids, immune-modulating therapies, various topical dressings and applications, negative-pressure wound therapy, and other systemic and topical drug therapies or regimens. However, PG can cause select problem wounds that are often refractory to conventional therapy. In these cases HBO2 is a viable treatment option. Most data and/or protocols show HBO2 being administered in the 2.0-2.5 ATA range for anywhere from 30-120 minutes. A reasonable protocol would be to treat these patients at 2.4 ATA for 90 minutes with 100% oxygen for a total of 30 treatments.


Systemic scleroderma

(SSc), also referred to as systemic sclerosis or diffuse scleroderma, is an autoimmune disease of the connective tissue of the human body that involves the hands and face with late involvement of the internal organs. It is a direct result of an abnormal thickening of skin that is caused by the accumulation of collagen and subsequent damage to smaller arteries. It can be divided into two categories: localized and systemic. Localized SSc affects the skin of the face, hands and feet. Diffuse or systemic scleroderma affects the visceral organs as well, specifically the heart, lungs, kidneys and GI tract.

The pathophysiology of scleroderma is an underlying overproduction of collagen due to autoimmune dysfunction. Its deposition in subcutaneous tissues and various other parts of the body creates a physiologically hypoxic environment by restricting blood flow to the skin, which impairs wound healing and causes wounds that eventually become infected, which further reduces oxygen delivery to the periphery of tissues.

Multiple case reports suggest potential benefit in using HBO2 to treat SSc. HBO2 has both local and systemic effects resulting in neovascularization and collagen deposition at the site of hypoxic tissue. Because SSc is an autoimmune disease, HBO2 may play a role in immune modulation by minimizing the proliferation of damaging lymphocytes and modulating the biology of cytokines and inflammatory mediators.

There are no randomized controlled studies that demonstrate HBO2 to be a validated treatment for SSc, so any potential research and/or use should be weighed with the relative risks/benefits of therapy. Approval for HBO2 should be obtained prior to initiating treatment. Typical treatment pressures range from 2.0-2.5 ATA for up to 30 sessions.

Sickle cell ulcers:

Sickle cell disease (SCD) is a genetic disorder characterized by the inheritance of sickle-cell hemoglobin (HbS), which causes red blood cells (erythrocytes) to deform and take a sickled shape. This sickled shape impairs binding of oxygen to the heme group, which compromises circulation, produces ischemia, and may cause permanent damage or hemolysis of the red blood cells, causing a resultant anemia. In a large study of 2,075 patients with SCD, it was shown that there is an approximate prevalence of 2.5% for lower-extremity ulcers. However there is a scarcity of literature examining the treatment of wounds or skin ulcers caused by sickle cell disease. In addition to skin ulcers, SCD causes other manifestations of ischemic disease (e.g., pain crisis) that have been treated using HBO2.

There is evidence that the treatment of SCD patients with HBO2 has helped to raise partial pressure of oxygen in the affected tissue, reducing the potential for sickling of red blood cells, especially when conventional therapies have shown little effect. There are no randomized, controlled studies that demonstrate HBO2 as a validated treatment for SCD or wounds related to SCD. Approval for HBO2 should be obtained prior to initiating treatment. Typical treatment pressures range from 2.0-2.5 ATA for up to 30 sessions.

Venous stasis ulcers:

Venous ulcer disease, or venostasis ulcers, dominate the differential diagnosis for lower-extremity ulcers, accounting for up to 90% of all chronic wounds of the lower extremities. They are chronic non-healing ulcers that occur as a direct result of edema, often seen in older patients. Sources of edema include venous incompetency, heart failure, renal failure or liver failure. Certain medications can cause peripheral or lower-extremity edema as well: calcium channel blockers, non-steroidal anti-inflammatory drugs, and cyclooxygenase 2 inhibitors.

Despite two trials showing increased percent area reduction, there was no difference in overall wound healing with HBO2. There is insufficient evidence to recommend HBO2 for the treatment of venous ulcers at this time.


Central retinal artery occlusion (CRAO) is form of arterial insufficiency. CRAO, which appears as sudden painless loss of vision in the range of light perception to counting fingers, requires emergent HBO2. All patients presenting with suspected CRAO within 24 hours of symptom onset should be considered for HBO2. While there are a few case reports of patients presenting after this time interval who have experienced positive results when treated with HBO2, the majority of cases do not respond beyond this point.

In centers where CRAO is treated by the stroke service, neurology should be consulted. Ideally, patients with suspected CRAO should be admitted to the hospital under the stroke protocol with combined management from both ophthalmology and neurology. Intraocular pressure should be measured and treated if elevated. Ocular massage has been anecdotally reported to dislodge clots on occasion.


Hyperbaric oxygen therapy is neither necessary nor recommended for the support of normal, uncompromised grafts or flaps. However, in tissue compromised by irradiation or in other cases where there is decreased perfusion or hypoxia – as in traumatic amputations and degloving injuries – HBO2 has been shown to be very useful in flap salvage. HBO2 can help maximize the viability of the compromised tissue, thereby reducing the need for regrafting or repeat flap procedures.

Proper patient selection criteria begins by recognizing the underlying cause. While compromised skin grafts and composite grafts are often classified with compromised flaps, these entities are distinctly different from a physiologic standpoint. All flaps, by definition, have an inherent blood supply, whereas grafts are avascular tissues that rely on the quality of the recipient bed for survival and revascularization. Because of this dependence the diagnosis of a compromised graft begins with proper assessment of the recipient wound bed.

Grafts: The most effective solution for the compromised graft is prevention. By ensuring an appropriate recipient bed for a given graft size, a compromised graft can be avoided altogether. There are instances, however, when a questionable recipient bed goes unrecognized or when the size of the harvested graft exceeds the dimensions that can be sustained by the recipient bed. These compromised grafts become hypoxic and may be salvaged with prompt HBO2. Hyperbaric oxygen can help maximize the viability of the compromised graft while revascularization takes place, thereby reducing the need for repeat grafting procedures, which incur further operations and increased donor site morbidity.

Flaps: Flap compromise has many etiologies, ranging from random ischemia, to venous congestion/occlusion, to arterial occlusion, even after meticulous harvest and inset. Similarly, traumatic accidents can result in significant avulsion of soft tissues, extensive degloving injuries, and open fractures with poorly perfused skin flaps.

Free tissue transfers, flaps in which the arterial and venous blood supply is divided and reattached to another location by microsurgical anastomosis, can have their own special problems. Free flaps can be exposed to both ischemia-reperfusion injury and secondary ischemic insults, which can compromise the viability of the flap.

In many cases, surgical re-exploration will identify and treat the etiology of flap compromise. However, in some instances there is no correctable mechanical cause of decreased flap perfusion. In these cases, HBO2 can play an important role in flap salvage. Prompt application of HBO2 can help maximize tissue viability while perfusion is restored. Similar to its use in compromised grafts, HBO2 therapy can reduce the need for repeat flap procedures, thus decreasing overall patient morbidity.


Acute traumatic ischemias are an array of disorders that range from crush injuries to compartment syndromes, from burns to frostbite and from threatened flaps to compromised reimplantations. Two unifying components common to these conditions are a history of trauma – physical, thermal or surgical – and ischemia in the traumatized tissues. Their severity represents a spectrum from mild conditions to tissue death.

Crush injuries of the extremities involve multiple tissue levels, ranging from skin and subcutaneous tissues, to muscle and tendons, to bone and joints, and often include nerves and arteries. Early application of HBO2, preferably within four to six hours of the injury, is recommended. Treatment schedules for crush injuries should be tailored to mitigate the suspected pathophysiology; for example, three or more treatments in the first 24-hour period for critical ischemias; twice a day for threatened flaps; and once a day for dealing with infections, remodeling or resorption of calcified tissues. For the isolated reperfusion injury after revascularization or thrombectomy of an extremity that has sustained minimal physical trauma, a single hyperbaric oxygen treatment is probably adequate. Treatment pressures range from 2.0 ATA in monoplace chambers, with oxygen breathing periods of 90 minutes for two or more treatments a day, to 120 minutes for single daily treatments.

Skeletal muscle-compartment syndrome (SMCS) is another consequence of trauma, but the target tissues are muscles and nerves. Edema and/or bleeding within the fascial envelope increase the pressure in the skeletal muscle-compartment. When the tissue fluid pressure exceeds the capillary perfusion pressure to the muscles and nerves in the compartment, these tissues become ischemic and manifest the signs and symptoms of SMCS.

For the impending stage of the SMCS, HBO2 should be applied twice a day for 24 to 36 hours, the time that the self-perpetuating edema-ischemia cycle would be expected to end. Symptoms and signs of pain reduction, absence of neurological abnormalities, and less tautness in the compartment should be used in deciding when to stop treatments.

For residual complications after fasciotomy, HBO2 treatments should be conducted twice a day for a seven- to 10-day period or when the problems have stabilized enough that no additional improvement is observed from the treatments. Treatment durations and pressures are the same for crush injuries: that is, 90- to 120-minute durations at 2.0 to 2.4 ATA.

Taken from:

Moon RE. Hyperbaric treatment of air or gas embolism: current recommendations. In: Moon RE, ed. Hyperbaric Oxygen Therapy Indications, 14 ed. North Palm Beach: Best Publishing, 2019.

Adapted by Renée Duncan, Communications, UHMS