UHMS position statement: topical oxygen for chronic wounds.

A small body of literature has been published reporting the application of topical oxygen for chronic non-healing wounds . Frequently, and erroneously, this form of oxygen administration has been referred to as "topical hyperbaric oxygen therapy" or even more erroneously "hyperbaric oxygen therapy." The advocates of topical oxygen claim several advantages over systemic hyperbaric oxygen including decreased cost, increased safety, decreased complications and putative physiologic effects including decreased free radical formation and more efficient delivery of oxygen to the wound surface. With topical oxygen an airtight chamber or polyethylene bag is sealed around a limb or the trunk by either a constriction/tourniquet device or by tape and high flow (usually 10 liters per minute) oxygen is introduced into the bag and over the wound. Pressures just over 1.0 atmospheres absolute (atm abs) (typically 1.004 to 1.013 atm abs) are recommended because higher pressures could decrease arterial/capillary inflow. The premise for topical oxygen, the diffusion of oxygen into the wound adequate to enhance healing, is attractive (though not proven) and its delivery is certainly less complex and expensive than hyperbaric oxygen. When discussing the physiology of topical oxygen, its proponents frequently reference studies of systemic hyperbaric oxygen suggesting that mechanisms are equally applicable to both topical and systemic high pressure oxygen delivery. In fact, however, the two are very different. To date, mechanisms of action whereby topical oxygen might be effective have not been defined or substantiated. Conversely, cellular toxicities due to extended courses of topical oxygen have been reported, although, again these data are not conclusive, and no mechanism for toxicity has been examined scientifically. Generally, collagen production and fibroblast proliferation are considered evidence of improved healing, and these are both enhanced by hyperbaric oxygen therapy. Paradoxically, claims of decreased collagen production and fibroblast inhibition in wounds subjected to topical oxygen have been reported in studies of topical oxygen as a benefit of topical oxygen therapy. The literature on topical oxygen is mostly small case series or small controlled but not randomized trials. Moreover, the studies generally are not aimed at specific ulcer types, but rather at "chronic wounds." This non-specific approach is recognized as a major design flaw in any study of therapies designed to improve impaired wound healing. The only randomized trial for topical oxygen in diabetic foot ulcers actually showed a tendency toward impaired wound healing in the topical oxygen group. Contentions that topical oxygen is superior to hyperbaric oxygen are not proven. There are potentially plausible mechanisms that support both possibly beneficial and detrimental effects of topical oxygen therapy, and thus well designed and executed basic science research and clinical trials are clearly needed. There is some ongoing research in regard to the role of topical oxygen at established wound laboratories. Neither CMS nor other third party payors recognize or reimburse for topical oxygen. Therefore, the policy of the Undersea and Hyperbaric Medical Society in regard to topical oxygen is stated as follows: 1. Topical oxygen should not be termed hyperbaric oxygen since doing so either intentionally or unintentionally suggests that topical oxygen treatment is equivalent or even identical to hyperbaric oxygen. Published documents reporting experience with topical oxygen should clearly state that topical oxygen not hyperbaric oxygen is being employed. 2. Mechanisms of action or clinical study results for hyperbaric oxygen cannot and should not be co-opted to support topical oxygen since hyperbaric oxygen therapy and topical oxygen have different routes and probably efficiencies of entry into the wound and their physiology and biochemistry are necessarily different. 3. The application of topical oxygen cannot be recommended outside of a clinical trial at this time based on the volume and quality of scientific supporting evidence available, nor does the Society recommend third party payor reimbursement. 4. Before topical oxygen can be recommended as therapy for non-healing wounds, its application should be subjected to the same intense scientific scrutiny to which systemic hyperbaric oxygen has been held.

Hyperbaric oxygen for delayed radiation injuries.

Hyperbaric oxygen has shown consistent benefit in treating patients with delayed radiation injury. It has also had success in preventing radiation injury in some instances. Additional study in identifying patients at risk for injury and delivering hyperbaric oxygen with prophylactic intent to prevent these injuries appears to be promising. Additional approaches to applying hyperbaric oxygen as a radiosensitizer also deserve further study. No convincing evidence exists to support concerns that hyperbaric oxygen enhances or stimulates malignant growth.

A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: an evidence based approach.

The treatment of delayed radiation injuries (soft tissue and bony radiation necrosis) is one of thirteen conditions approved by the Hyperbaric Oxygen Therapy Committee of the Undersea and Hyperbaric Medical Society as appropriate indications for hyperbaric oxygen (HBO2). This paper provides a systematic review of the literature reporting the results of HBO2 therapy in the treatment and/or prophylaxis of delayed radiation injury. Since the introduction of the concept of evidence based medicine, the medical community in general has set out to apply more critical and stringent standards in evaluating published support for therapeutic interventions. Evidence based medicine is designed to discover the best evidence available and apply it in daily practice for treatment of the individual patient. The preferred level of evidence is the randomized controlled trial, however, other evidence has merit as well. In this review, seventy-four publications are represented reporting results of applying HBO2 in the treatment or prevention of radiation injuries. These are appraised in an evidence-based fashion by applying three established systems of evaluation. All but seven of these publications report a positive result when HBO2 is delivered as treatment for or prevention of delayed radiation injury. These results are particularly impressive in the context of alternative interventions. Without HBO2, treatment often requires radical surgical intervention, which is likely to result in complications. Other alternatives including drug therapies are rarely reported, and for the most part have not been the subject of randomized controlled trials. Based on this review, HBO2 is recommended for delayed radiation injuries for soft tissue and bony injuries of most sites. Of note, an increasing body of evidence supports HBO2 for radiation-induced necrosis of the brain. For other radiation-induced neurological injuries, additional study is required before recommendations for routine hyperbaric therapy can be made.

Salvage external beam radiotherapy for clinical failure after cryosurgery for prostate cancer.

PURPOSE: To investigate the role of external beam radiotherapy (EBRT) as salvage treatment of prostate cancer after cryosurgery failure. METHODS AND MATERIALS: Between 1993 and 1998, 6 patients underwent EBRT with curative intent for local recurrence of prostate cancer after cryosurgery. All 6 patients had biopsy-proven recurrence and palpable disease on digital rectal examination at the time of EBRT. The median follow-up was 34 months (range 8-46). The median prostate-specific antigen level was 2.3 ng/mL (range 0.8-4.1). No patient had evidence of metastatic disease. Two patients received hormonal therapy before beginning EBRT. No patient received hormonal therapy after EBRT completion. The median elapsed time between cryosurgery and EBRT was 3 years (range 1.5-4). The median delivered dose was 66 Gy (range 62-70.2) using a 10-MeV photon beam. An in-house-developed three-dimensional treatment planning system was used to plan delivery of the prescribed dose with conformal radiotherapy techniques. RESULTS: After EBRT, all patients had complete resolution of palpable disease. Four patients (66%) were disease free at the time of the last follow-up. Two patients developed biochemical failure as defined by the American Society for Therapeutic Radiology and Oncology consensus definition. One of these patients had a prostate-specific antigen level of 97 ng/mL before cryosurgery. No patient developed distant metastasis during follow-up. Two patients (33%) developed proctitis; 1 case resolved with Rowasa suppositories and 1 required blood transfusion. CONCLUSIONS: Our preliminary results suggest that EBRT can render a significant number of patients biochemically free of disease and can cause complete resolution of clinically palpable disease after initial cryosurgery. The results also showed that EBRT can be given without excessive morbidity. EBRT should be considered as a treatment option in these potentially curable cases.

Hyperbaric oxygen therapy for late sequelae in women receiving radiation after breast-conserving surgery.

PURPOSE: Persisting symptomatology after breast-conserving surgery and radiation is frequently reported. In most cases, symptoms in the breast resolve without further treatment. In some instances, however, pain, erythema, and edema can persist for years and can impact the patient's quality of life. Hyperbaric oxygen therapy was shown to be effective as treatment for late radiation sequelae. The objective of this study was to assess the efficacy of hyperbaric oxygen therapy in symptomatic patients after breast cancer treatment. PATIENTS AND METHODS: Forty-four patients with persisting symptomatology after breast-conservation therapy were prospectively observed. Thirty-two women received hyperbaric oxygen therapy in a multiplace chamber for a median of 25 sessions (range, 7-60). One hundred percent oxygen was delivered at 240 kPa for 90-min sessions, 5 times per week. Twelve control patients received no further treatment. Changes throughout the irradiated breast tissue were scored prior to and after hyperbaric oxygen therapy using modified LENT-SOMA criteria. RESULTS: Hyperbaric oxygen therapy patients showed a significant reduction of pain, edema, and erythema scores as compared to untreated controls (p < 0.001). Fibrosis and telangiectasia, however, were not significantly affected by hyperbaric oxygen therapy. Seven of 32 women were free of symptoms after hyperbaric oxygen therapy, whereas all 12 patients in the control group had persisting complaints. CONCLUSIONS: Hyperbaric oxygen therapy should be considered as a treatment option for patients with persisting symptomatology following breast-conserving therapy.

Hyperbaric oxygen in the treatment of delayed radiation injuries of the extremities.

Hyperbaric oxygen (HBO2) is used as an adjunct in the treatment of radiation injury at many sites, including the mandible, larynx, chest wall, bladder, and rectum. In these disorders, HBO2 is effective in stimulating neovascularization and reducing fibrosis. No previous publications report the application of HBO2 to radiation injuries of the extremities. From 1979 until 1997, 17 patients were treated at the Southwest Texas Methodist and Nix Hospitals for nonhealing necrotic wounds of the extremities within previously irradiated fields. All but one wound involved a lower extremity. Most of the patients had been irradiated for soft tissue sarcomas or skin cancers. The rest were irradiated for a variety of malignancies. HBO2 was delivered in a multiplace chamber at 2.4 atm abs daily for 90 min of 100% oxygen at pressure. This report is a retrospective, uncontrolled review of these patients. Eleven patients (65%) healed completely whereas five (29%) failed to heal and one (6%) was lost to follow-up. Three (60%) of those who failed were found to have local or distant recurrence of their tumor early in their course of hyperbaric treatment and were discontinued from therapy at that time. When last seen in the clinic, the wound of the patient who was lost to follow-up was improved but not completely healed. Four of those who failed (including the two with local tumor recurrence) required amputation. If we exclude those with active cancer and the patient lost to follow-up, the success rate was 11 of 13 or 85%. HBO2 was applied successfully with complete wound healing and the avoidance of amputation in a majority of these patients. The consequences of failure in patients suffering from radiation necrosis of the extremities (some complicated by the presence of tumor) are significant, with 80% of the five failures requiring amputation. In radiation injuries of the extremities as in delayed radiation injury at other sites, HBO2 is a useful adjunct and should be part of the overall management.

Histologic morphometry confirms a prophylactic effect for hyperbaric oxygen in the prevention of delayed radiation enteropathy.

In a previous publication (Feldmeier et al., Radiother Oncol 1995; 35:138-144) we reported our success in preventing delayed radiation enteropathy in a murine model by the application of hyperbaric oxygen (HBO2). In this study we introduce a histologic morphometric technique for assessing fibrosis in the submucosa of these same animal specimens and relate this assay to the previous results. The histologic morphometry, like the previous gross morphometry and compliance assays, demonstrates a significant protective effect for HBO2. The present assay is related to the previous assays in a statistically significant fashion. The predictive value for the histologic morphometric assay demonstrates a sensitivity of 75% and a specificity of 62.5%. The applicability of this assay to other organ systems and its potential superiority to the compliance assay are discussed.

Dose perturbations due to in vivo dosimetry with diodes.

In vivo dosimetry performed with semiconductor detectors is a reliable method for patient dose control. The purpose of this study is to evaluate the perturbations introduced in the patient's absorbed dose distribution by three types of commercially available diodes (Isorad, Sun Nuclear Corp.; model 114200, 114300 and 114400) from the same company and to present possible solutions for minimizing this side-effect.

Hyperbaric oxygen an adjunctive treatment for delayed radiation injuries of the abdomen and pelvis.

Radiation therapy is often utilized as adjunctive or primary treatment for malignancies of the abdomen and pelvis. Radiation complications are infrequent, but can be life threatening or significantly diminish the quality of life. Radiation necrosis is an approved indication for hyperbaric oxygen (HBO2). Previous publications have reported results in treating delayed radiation injuries involving many sites. This paper reports the experience of a single physician group in treating delayed injuries of the abdomen and/or pelvis. Forty-four such patients have been treated since 1979. Of the 41 patients available for follow up, 26 have healed; 6 failed to heal; and 9 patients had an inadequate course of therapy (fewer than 20 treatments). Especially encouraging was the resolution of fistulae in six of eight patients with only three requiring surgery for closure. Overall, the success rate in patients receiving at least 20 HBO2 treatments was 81%. Hyperbaric oxygen is a useful adjunct in treatment of delayed radiation injuries of the pelvis and abdomen.

Hyperbaric oxygen as an adjunctive treatment for delayed radiation injury of the chest wall: a retrospective review of twenty-three cases.

Since 1979, 23 cases of radiation-induced chest wall necrosis have been treated in the Hyperbaric Medicine Departments of Southwest Texas Methodist Hospital and the Nix Hospital, San Antonio, Texas. Eight cases involved soft tissue only. Six of eight (75%) patients with soft tissue involvement healed without requiring surgical debridement, although four patients (50%) did have flaps or grafts. Fifteen patients had bony and soft tissue necrosis. Eight of these patients (53%) resolved with adjunctive hyperbaric oxygen (HBO), but all required aggressive surgical debridement including skeletal resection. Four (27%) had reconstructive flaps as well. Six patients (40%) with bony necrosis who had either no or incomplete debridement failed to heal. Three patients (13%)(two soft tissue and one bony) were found to have residual tumor during HBO and were discontinued from treatment. HBO is an effective adjunctive therapy for soft tissue chest-wall, radiation-induced necrosis, but must be coupled with appropriate debridement to include surgical removal of all necrotic bone to ensure a successful outcome of bony plus soft tissue necrosis.

Hyperbaric oxygen as a prophylaxis for radiation-induced delayed enteropathy.

This trial was accomplished in C3H mice to determine whether hyperbaric oxygen (HBO) could be administered to prevent delayed radiation enteropathy. Fifty mice randomized into two equal groups received 30 Gy abdominopelvic irradiation in 10 fractions. The study group received a course of 30 HBO treatments beginning 7 weeks after the radiation exposure. The control group received only housing and nutritional support after irradiation. A third group of three animals had no radiation or HBO. All animals were sacrificed 7 months after radiation. Animals were inspected grossly for signs of enteropathy. In addition, a special stretch apparatus was used to quantify narrowing and rigidity of ileum just proximal to the ileocecal junction. Those animals who received HBO had fewer gross signs of enteropathy and had less narrowing and less rigidity in their harvested bowel segments. These differences were highly statistically significant. Treatment with HBO drastically reduces signs of radiation enteropathy. Further study including clinical trials are recommended.

Does hyperbaric oxygen have a cancer-causing or -promoting effect? A review of the pertinent literature.

We reviewed all known published reports or studies related to a possible cancer-causing or growth-enhancing effect by hyperbaric oxygen. Published articles were retrieved using Medline searches for the period 1960-1993. Additional references were obtained from bibliographies included in those articles discovered in the computer search. Also, hyperbaric medicine text books and the published proceedings of international hyperbaric conferences were visually searched. Studies and reports discovered in this fashion and related to the topic were included in the review. Twenty-four references were found: 12 were clinical reports, 11 were animal studies, and 1 reported both an animal study and a clinical report. Three clinical reports suggested a positive cancer growth enhancement, whereas 10 clinical reports showed no cancer growth enhancement. Two animal studies suggested a positive cancer-enhancing effect, and 10 animal studies showed no such effect. (The report that included both animals and humans is counted in both groups). The vast majority of published reports show no cancer growth enhancement by HBO exposure. Those studies that do show growth enhancement are refuted by larger subsequent studies, are mixed studies, or are highly anecdotal. A review of published information fails to support a cancer-causing or growth-enhancing effect by HBO.

Hyperbaric oxygen as an adjunctive treatment for severe laryngeal necrosis: a report of nine consecutive cases.

Laryngeal necrosis is a rare complication of therapeutic radiation, but when it does occur there is no established, definitive treatment and laryngectomy is frequently required. This report is a retrospective review of all patients referred for hyperbaric oxygen (HBO) therapy to a single hyperbaric medicine unit for treatment of their laryngeal necrosis between 1980 and 1985. Nine patients were in this series. One patient had had a vertical hemilaryngectomy and another a supraglottic laryngectomy before referral. Eight of the nine patients had a Chandler grade IV necrosis and the ninth had a Chandler grade III necrosis. All nine patients were able to maintain their voice until death or last follow up. Seven of the nine patients maintained good voice quality while two exhibited some hoarseness. All patients with tracheostomies were able to be decannulated, and all patients with fistulae had these closed. No untoward reactions to HBO occurred. Based on this review, HBO is recommended as a therapeutic option whenever laryngeal necrosis occurs and there is a chance to save the larynx.

Hyperbaric oxygen and the cancer patient: a survey of practice patterns.

A questionnaire was sent to 179 clinical hyperbaric medicine facilities to survey treatment policies and referral patterns for patients with a history of malignancy. Eighty-five surveys were returned. Most respondents indicated that they would accept patients with a history of malignancy for either adjuvant or emergent hyperbaric oxygen (HBO). Depending on specific circumstances, from about one third to one half of respondents believed that such patients should be informed of a theoretical potential for tumor acceleration or reactivation. An overwhelming majority had not personally attended nor had they been told by colleagues of cases of patients whose malignancy had been activated or accelerated by HBO. A large majority felt that referring physicians did not believe that HBO was carcinogenic, and that referrals were not prevented by such concerns. Seven percent believed that HBO is potentially carcinogenic. Forty-two percent of respondents felt that they might be at risk for malpractice litigation if a patient had reactivation or acceleration of a malignancy. Among respondents to the questionnaire, there is a consensus that HBO does not have cancer-promoting or accelerating properties.

Hyperbaric oxygen as prophylaxis or treatment for radiation myelitis.

This animal study was designed to investigate HBO as a treatment or prophylaxis for radiation myelitis. All animals received identical spinal cord radiation doses of 69 Gy in 10 daily fractions. Group I received no HBO; group II began HBO at the onset of signs of myelitis; group III received HBO with prophylactic intent beginning 6 wk after irradiation; and group IV received both modalities on the same day, but radiation always preceded HBO by at least 4 h. HBO consisted of 90 min oxygen at 2.4 atm abs for 20 daily treatments. Animals were objectively assessed for the loss of certain neurologic reflexes indicative of four levels of myelitis. Although all animals progressed to severe myelitis, group III animals had group-averaged levels of myelitis consistently less than control. The differences were statistically significant for several weeks. Group IV animals progressed to severe myelitis much more rapidly than any other group. Additional study is justified by this trial. Key questions to be answered include the optimal timing of HBO to produce a beneficial rather than detrimental effect.

Radiotherapy of pseudotumors of bone in hemophiliacs with circulating inhibitors to factor VIII.

Pseudotumors of bone in two hemophiliacs with severe factor VIII deficiency and a high level of circulating inhibitors are reported. Both had favorable response to radiation therapy after unsuccessful treatment with factor concentrates and remain free of recurrence at 18-62 months. A review of the literature of cases in which radiotherapy has been used is presented. Radiotherapy in the treatment of pseudotumors of bone in hemophiliacs should be strongly considered, particularly if coagulation factor inhibitors are present.