It is estimated that Medicare spends $1.5 billion annually to treat diabetic foot ulcers (DFU).1 The debate continues on the cost effectiveness of immediate amputation in comparison with “conservative treatment” using a variety of modalities.
The cost of healing a DFU is related to its severity but detailed “cost to heal” data stratified by Wagner grade are sparse. Primary amputation is costly not so much because of the expense of the surgical procedure itself but because of the consequences of amputation (e.g. rehabilitation and institutional care).
Couch et al., found that following a major amputation, only 76 percent of unilateral above-knee amputees could be rehabilitated. Furthermore, the surgical mortality of major leg amputation is 11 to 13 percent.2 The post-amputation five-year survival rates of 30.9 percent among patients with diabetes without renal failure and 14.4 percent among patients with diabetes and renal failure are similar to an aggressive cancer.3
“Limb salvage” usually requires revascularization and, regardless of whether the method is surgical or endovascular, secondary revascularization is likely to be necessary in three to five years. This is a substantial cost factor. The fact is that primary amputation can save costs and improve rehabilitation in patients who are likely to fail limb salvage interventions. Accordingly, ensuring proper patient selection is critical to the discussion of cost effectiveness. Hopf and Fife recently addressed whether HBOT has a role in limb salvage.4
What You Should Know About Hypoxia And Revascularization
Patients with purely neuropathic diabetic foot ulcers are not candidates for HBOT and one can usually manage such ulcers with aggressive offloading. Even so, diabetic foot ulcers are hard to heal. Margolis, et al., demonstrated that even with adequate arterial inflow, diabetic foot ulcers have only a 24 percent closure rate at 12 weeks and a 31 percent closure rate at 20 weeks.5
However, diabetes is a major risk factor for vascular disease leading to tissue hypoxia. Cutaneous perfusion is the critical physiological determinant of diabetic ulcer healing. Pecoraro, et al., showed there was a 39-fold increased risk of early healing failure when the average periwound TcPO2 is less than 20 mmHg.6
The appropriate treatment for hypoxia due to vascular disease is revascularization whenever possible but results of revascularization are disappointing. Among chronic limb ischemia (CLI) patients undergoing bypass for ischemic tissue loss, 63 percent required more than three months for complete healing with the mean time to healing being 86 days. More than 7 percent of these patients never healed.7
It seems that revascularization is not the final answer. In other words, tissue hypoxia, which prevents healing, persists even after revascularization, assuming it is possible and successful.
What Randomized Controlled Trials Reveal About HBOT
In an upcoming paper, we reviewed all randomized, controlled trials in the area of wound healing over a 10-year period from 1996 to 2006.8 All the trials excluded patients with significant vascular disease except those involving HBOT. After reviewing more than 1,000 papers, we found that only the HBOT studies tackled ischemic diabetic foot ulcers and/or DFUs with Wagner grades higher than II. While HBOT studies have been criticized for being small, they nevertheless stand alone in the literature.
In 1987, Baroni et al., demonstrated the efficacy of HBOT in reducing the incidence of major amputation in patients with diabetic gangrene (11 percent in the HBOT group versus 40 percent in controls).9 In 1990, Oriani, et al., reported a major amputation rate of 5 percent in patients who received HBOT in comparison to 33 percent in similar patients who either refused or had contraindications to HBOT therapy.10
Faglia et al., reported impressive results in a prospective, randomized trial of HBOT in diabetic foot ulcers. In this study, researchers showed an 8.6 percent major amputation rate (below knee or higher) in the HBOT patients in comparison to 33.3 percent for the controls.11 Most interestingly, Faglia and colleagues were also able to show that a course of HBOT improved baseline transcutaneous values to a statistically significant degree, inferring an improvement in the vascular supply to the area.
From 1987 to 1996, six studies involved 435 patients who underwent HBOT with an 80 percent success rate. A retrospective study of the outcome of 1,144 diabetic foot ulcer patients receiving HBOT showed a 76 percent overall success rate, including a 42 percent benefit rate among patients with foot gangrene.12
Remember that patients with foot gangrene have been excluded from all prospective pharmaceutical trials since 1996. Although there are ongoing clinical trials of stem cells for revascularization, HBOT is the only modality that can improve tissue oxygen levels of DFUs, according to the currently published research.
Does The Data Support The Cost-Effectiveness Of HBOT?
In a review of HBOT and DFU, the Cochrane collaboration evaluated three randomized controlled trials, including a total of 118 patients, for whom the relative risk for major amputation was 0.31. The study concluded it is necessary to treat four patients with DFUs with HBOT in order to avert one major amputation.13
Guo et al., subsequently performed a study to evaluate the cost benefit of HBOT.14 The study population was a hypothetical cohort of 1,000 patients who were 60 years of age and had severe DFUs. Researchers constructed a decision tree model to estimate the cost effectiveness of HBOT in the treatment of diabetic foot ulcers at one, five and 12 years.
In this theoretical cohort, the HBOT group had 45 more minor amputations. However, 155 major lower extremity amputations would be averted and these patients gained approximately 50, 265 and 608 quality-adjusted life years (QALY) at one, five and 12 years respectively. This exercise suggests the benefits of HBOT accrue over time in part due to savings from averted major amputations.
Apelquist et al., analyzed the three-year follow-up costs for patients with diabetic foot ulcers from the time of healing (with or without amputation).15 Total average costs for patients who achieved primary healing and did not have critical ischemia were $16,000 (in 1995) in comparison to $63,000 for patients who had required major amputation. This suggests that a course of HBOT in appropriately selected patients is cost-effective.
As a result of the data to support its benefit, hyperbaric oxygen therapy has garnered recommendations from seven independent evidence-based reviews: Blue Cross Blue Shield (1999), the American Diabetic Association Foot Council (1999), the Wound Healing Society (2006), the British Journal of Medicine (2001-2002), the Agency for Healthcare Research and Quality (AHRQ) Report to CMS (2001) and the Medical Services Advisory Committee of Australia (2000).
The Centers For Medicare and Medicaid Services (CMS) issued a Coverage Decision for HBOT in Diabetic Foot Wounds in 2002. The CMS maintains that HBOT is reasonable and necessary in the treatment of limb-threatening diabetic wounds of the lower extremity if the ulcer is a Wagner grade III or worse with no measurable signs of healing for at least 30 days despite standard wound therapy.
Keys To Gauging Proper Patient Selection
The cost effectiveness of HBOT is dependent on ensuring that patients who would heal anyway do not undergo HBOT, and patients who cannot benefit from HBOT are similarly excluded.
Transcutaneous oximetry has been suggested as one way of enhancing patient selection. An evidence-based approach to the use of transcutaneous oximetry is in press.16 The first step is to assess whether wounds are likely to heal spontaneously by using baseline TcPO2.17After vascular status has been optimized, repeat transcutaneous oximetry can assist in determining whether healing is likely.
It may be possible to determine the benefit of HBOT using in-chamber TcPO2. In-chamber values of 200 mmHg or better among patients with diabetes are associated with a high likelihood of benefit from HBOT. However, a trial of HBOT may still be appropriate even in patients with low in-chamber values since the predictive value of TcPO2 is less than 70 percent.12 Retrospective data suggest that among patients who benefited from HBOT, the average number of treatments was 36. One should discontinue treatments as soon as continued healing seems likely.
Data confirm that many wounds remain hypoxic even after revascularization. Healing will not occur unless one corrects the hypoxia. Among all modalities tested over the past 10 years, the currently available research has demonstrated that only HBOT corrects tissue hypoxia.
Studies confirm that HBOT reduces the rate of major amputation and increases quality of life years when one ensures proper patient selection. Given the low likelihood of rehabilitation after a major amputation and the high morbidity and mortality, it is not difficult to demonstrate the cost-effectiveness of HBOT in appropriately selected patients.
In Britain, the National Institute for Health and Clinical Excellence (NICE) has concluded that $45,000 is the maximum amount they will pay to increase a life by one “quality-adjusted” year.
The U.S. government has recently embraced creation of similar “comparative effectiveness” research, carving out $1.1 billion from H.R. 598, the $825 billion economic stimulus bill. Accompanying report language says “more expensive” medical products “will no longer be prescribed.” The bill will create a “federal health board” to rate medical products and create central controls on access. Where shall we set the bar on the cost of quality-adjusted life years?
Dr. Fife is an Associate Professor in the Department of Medicine within the Division of Cardiology at the University of Texas Health Science Center in Houston. She is the Director of Clinical Research at the Memorial Hermann Center for Wound Healing and Hyperbaric Medicine.
Dr. Steinberg is an Assistant Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C. Dr. Steinberg is a Fellow of the American College of Foot and Ankle Surgeons
For further reading, see “Is There A Role For HBO In Limb Salvage?” in the August 2008 issue of Podiatry Today, “A Guide To Hyperbaric Oxygen Therapy For Diabetic Foot Wounds” in the December 2007 issue or “What You Should Know About Using HBO In Diabetic Wounds” in the May 2003 issue.
To access the archives or get information on reprints, visit www.podiatrytoday.com .
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14. Guo S, et al. Cost-effectiveness of adjunctive hyperbaric oxygen in the treatment of diabetic ulcers. Int J Technol Assess Health 19(4):731-737, 2003.
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17. Hanna GP, Fujise K, Kjellgren O, et al. Infrapopliteal transcatheter interventions for limb salvage in diabetic patients: importance of aggressive interventional approach and role of transcutaneous oximetry. J Am Coll Cardiol 1997;30(3):664-669.