Systemic hyperbaric oxygen therapy: lower-extremity wound healing and the diabetic foot.

ROBERT P. WUNDERLICH 0 1 DPM EDGAR J.G. PETERS 0 1 LAWRENCE A. LAVERY 0 1 DPM 0 1 0 From the Diabetex Foot Care Center (R. P.W., L.A.L.), San Antonio, Texas; and the Vrieje University (E.J.G.P.), Amsterdam , the Netherlands. N. Main St., Suite 100, San Antonio, TX 78212 1 Wunderlich , Peters, and Lavery OBJECTIVE - To document peer-reviewed medical publications that have reported on hyperbaric oxygen (HBO) therapy as an adjunct to standard lower-extremity wound care, focusing on publications dealing with the diabetic foot. RESEARCH DESIGN AND METHODS - A review of the medical literature was conducted using MEDLINE. Research articles involving HBO treatment and the diabetic foot were critiqued to identify factors that may have been a source of bias. RESULTS - Of the published reports on human studies, seven involved diabetes-related foot pathology. Five of these studies, two of which were randomized, included a control group that did not receive HBO therapy. The controlled diabetic foot studies included an average of 28 subjects in the HBO therapy group (range 10-62) and an average of 16.2 subjects in the non-HBO control group (range 5-33). Most of the published reports have several potential sources of bias, including, but not limited to, inadequate evaluation of comorbid conditions relevant to wound healing, small sample size, and poor documentation of wound size or severity. Four of the seven reports involving the diabetic foot were published by a group of researchers at the University of Milan between 1987 and 1996. CONCLUSIONS - Additional randomized placebo-controlled clinical trials in large diabetic populations would further lend credence to the presumption that HBO therapy improves clinical outcomes. Given the relatively high cost of this treatment modality, perhaps a more acute awareness of the medical literature would reduce the economic burden that HBO therapy imposes on care providers that are financially at risk. - Abaric medicine dates back to the 17th lthough the clinical history of hypercentury, reports of the beneficial effects of increased oxygen pressure on wound healing and infection did not appear in the medical literature until the 1960s. The most recent report by the Hyperbaric Oxygen Therapy Committee of the Undersea and Hyperbaric Medical Society (1) lists several indications for hyperbaric oxygen (HBO) therapy that are directly applicable to lower-extremity pathology. These include clostridial myonecrosis, acute traumatic ischemia, enhancement of healing in problem wounds, necrotizing soft tissue infections, refractory osteomyelitis, compromised skin grafts and flaps, and thermal burns. Interestingly, there are relatively few controlled clinical trials in human subjects involving HBO for the treatment of these conditions. In fact, the majority of published reports on this topic consists of review articles, case reports, uncontrolled studies, and animal or in vitro studies. Based on our experiences, we believe that many clinicians routinely incorporate RESEARCH DESIGN AND METHODS A review of the medical literature was conducted using PubMed, the National Library of Medicines World Wide Webbased MEDLINE search engine. The following key phrases were entered in the search engine to identify relevant articles: hyperbaric oxygen, wound healing, diabetic foot, gas gangrene, chronic osteomyelitis, necrotizing fasciitis, and thermal burns. In addition, the references cited in the articles collected through the MEDLINE search were reviewed to identify other relevant publications. Inclusion criteria for articles were as follows: articles published in English, articles from journals listed in Index Medicus, articles describing scientific research of systemic HBO as adjuvant therapy for either wound healing or infection, review articles describing the use of systemic HBO as adjuvant therapy for either wound healing or infection, and case reports describing the use of systemic HBO for either wound healing or infection. Articles were excluded if they were not published in English or if they were not directly applicable to lowerextremity pathology. Articles meeting the inclusion and exclusion criteria were reviewed and placed into one of three categories: reviews and case reports, experimental animal or in vitro studies, or human studies. A table was constructed for the latter category to list relevant data from each article. Furthermore, research articles involving HBO treatment and the diabetic foot were critiqued to identify factors that may have been a source of bias. These factors included, but were not limited to, lack of a control group, inadequate sample size, insufficient evaluation of comorbid conditions, and poorly defined methods of retrospective analysis. RESULTS A total of 76 articles were identified that met the inclusion and exclusion criteria. There were 21 studies involving human subjects (222) (Table 1), 27 animal or in vitro studies (2349), and 28 reviews and/or case reports (5077). Of the studies involving human subjects, 62% (13 of 21 articles) included a control group. Of the published reports of human studies, seven involved diabetes-related foot pathology. Five of these studies, two of which were randomized, included a control group that did not receive HBO therapy. The controlled diabetic foot studies included an average of 28 subjects in the HBO therapy group (range 1062) and 16.2 subjects in the non-HBO control group (range 533). Interestingly, four of the seven reports involving the diabetic foot were published by the same group of researchers at the University of Milan between 1987 and 1996 (8,9,13,14). CONCLUSIONS Although HBO therapy has gained popularity as an adjunctive treatment for diabetic foot wounds, there are surprisingly few published reports that support its efficacy. Furthermore, there seem to be no objective measures to assist clinicians in appropriately selecting patients for HBO therapy. Our literature search revealed only two reports of randomized controlled clinical trials that evaluated HBO therapy in the diabetic foot. Given the substantial cost associated with these treatments, a more thorough analysis of human studies dealing with HBO therapy for the diabetic foot is not only justified but necessary. As previously indicated, more than half of the published research reports dealing with HBO therapy for diabetic foot disease originated from a group of researchers at the Center of Diabetology and Metabolic Diseases, Niguarda Hospital, and the Department of Anesthesia and Hyperbaric Medicine, Galeassi Institute, Milan, Italy (8,9,13,14). The first report published by this group appeared in Diabetes Care in 1987 (9). This nonrandomized study included 18 hospitalized diabetic subjects and 10 diabetic control subjects. Of the 28 study subjects, 23 had gangrene of the foot and 5 had neuropathic ulcers. Both groups were treated with strict metabolic control and daily wound debridement. The HBO gro (...truncated)