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Ont Health Technol Assess Ser. 2005; 5(11): 1–28.
Published online Sep 1, 2005.
PMCID: PMC3382405
Hyperbaric Oxygen Therapy for Non-Healing Ulcers in Diabetes Mellitus
An Evidence-Based Analysis
Health Quality Ontario
Objective
To examine the effectiveness and cost-effectiveness of hyperbaric oxygen therapy (HBOT) to treat people with diabetes mellitus (DM) and non-healing ulcers. This policy appraisal systematically reviews the published literature in the above patient population, and applies the results and conclusions of the review to current health care practices in Ontario, Canada.
Although HBOT is an insured service in Ontario, the costs for the technical provision of this technology are not covered publicly outside the hospital setting. Moreover, access to this treatment is limited, because many hospitals do not offer it, or are not expanding capacity to meet the demand.
Clinical Need
Diabetes mellitus is a chronic disease characterized by an increase in blood sugar that can lead to many severe conditions such as vision, cardiac, and vascular disorders. The prevalence of DM is difficult to estimate, because some people who have the condition are undiagnosed or may not be captured through data that reflect access to the health care system. The Canadian Diabetic Association estimates there are about 2 million people in Canada with diabetes (almost 7% of the population). According to recent data, the prevalence of DM increased from 4.72% of the population aged 20 years and over in 1995, to 6.19% of the population aged 20 years and over in 1999, or about 680,900 people in 1999. Prevalence estimates expanded to 700,000 in 2003.
About 10% to 15% of people with DM develop a foot wound in their lifetimes because of underlying peripheral neuropathy and peripheral vascular disease. This equals between 70,000 and 105,000 people in Ontario, based on the DM prevalence estimate of 700,000 people. Without early treatment, a foot ulcer may fester until it becomes infected and chronic. Chronic wounds are difficult to heal, despite medical and nursing care, and may lead to impaired quality of life and functioning, amputation, or even death.
The Technology
Hyperbaric oxygen therapy has been in use for about 40 years. It is thought to aid wound healing by supplying oxygen to the wound. According to the Hyperbaric Oxygen Therapy Association, HBOT acts as a bactericidal, stops toxin production, and promotes tissue growth to heal difficult wounds.
During the procedure, a patient is placed in a compression chamber with increased pressure between 2.0 and 2.5 atmospheres absolute for 60 to 120 minutes, once or twice daily. In the chamber, the patient inhales 100% oxygen. Treatment usually runs for 15 to 20 sessions.
Noted complications are rare but may include claustrophobia; ear, sinus, or lung damage due to pressure; temporary worsening of short sightedness; and oxygen poisoning. Careful monitoring during the treatment sessions and follow-up by a trained health care provider is recommended.
Review Strategy
The aims of this health technology policy appraisal were to assess the effectiveness, safety, and cost-effectiveness of HBOT, either alone, or as an adjunct, compared with the standard treatments for non-healing foot or leg ulcers in patients with DM. The following questions were asked:
  • Alone or as an adjunct therapy, is HBOT more effective than other therapies for non-healing foot or leg ulcers in patients with DM?
  • If HBOT is effective, what is the incremental benefit over and above currently used strategies?
  • When is the best time in a wound treatment strategy to use HBOT?
  • What is the best treatment algorithm with HBOT?
The Medical Advisory Secretariat searched for health technology assessments in the published and grey literature. The search yielded 4 reports, which were published from 2000 to 2005. The most recent from the Cochrane Collaboration had a literature review and analysis of randomized control trials to 2003.
As an update to this review, as per the standard Medical Advisory Secretariat systematic review strategy, the abstracts of peer-reviewed publications were identified using Ovid MEDLINE, EMBASE, MEDLINE in-process and not-yet-indexed citations, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, and INAHTA using key words and searching from January 1, 2003 to 2004.
The criteria for inclusion were as follows:
  • Patients with diabetes
  • Live human study
  • English-language study
  • HBOT as adjunctive therapy or alone
  • Randomized control trial
The number of excluded studies included the following:
  • 2 animal studies
  • 13 focus on condition other than DM
  • 8 review/protocol for HBOT use
  • 3 HBOT not focus of report
  • 2 health technology assessments (2)
  • 1 non-RCT
Outcomes of interest were wound healing and prevention of amputation.
The search yielded 29 articles published between 2003 and 2004. All 29 of these were excluded, as shown beside the exclusion criteria above. Therefore, this health technology policy assessment focused exclusively on the most recently published health technology assessments and systematic reviews.
Summary of Findings
Four health technology assessments and reviews were found. Cochrane Collaboration researchers published the most recent review in 2005. They included only randomized controlled trials and conducted a meta-analysis to examine wound healing and amputation outcomes. They found that, based on findings from 118 patients in 3 studies, HBOT may help to prevent major amputation (relative risk, 0.31; 95% confidence interval [CI], 0.13–0.71) with a number needed to treat (NNT) of 4 (95% CI, 3–11). They noted, however, that the point estimates derived from trials were not well reported, and had varying populations with respect to wound severity, HBOT regimens, and outcome measures. These noted limitations rendered the comparison of results from the trials difficult. Further, they suggested that the evidence was not strong enough to suggest a benefit for wound healing in general or for prevention of minor amputations.
The Medical Advisory Secretariat also evaluated the studies that the Cochrane Collaboration used in their analysis, and agreed with their evaluation that the quality of the evidence was low for major and minor amputations, but low to moderate for wound healing, suggesting that the results from new and well-conducted studies would likely change the estimates calculated by Cochrane and others.
Conclusions
In 2003, the Ontario Health Technology Advisory Committee recommended a more coordinated strategy for wound care in Ontario to the Ministry of Health and Long-term Care. This strategy has begun at the community care and long-term care institution levels, but is pending in other areas of the health care system.
There are about 700,000 people in Ontario with diabetes; of these, 10% to 15% may have a foot ulcer sometime in their lifetimes. Foot ulcers are treatable, however, when they are identified, diagnosed and treated early according to best practice guidelines. Routine follow-up for people with diabetes who may be at risk for neuropathy and/or peripheral vascular disease may prevent subsequent foot ulcers. There are 4 chambers that provide HBOT in Ontario. Fewer than 20 people with DM received HBOT in 2003.
The quality of the evidence assessing the effectiveness of HBOT as an adjunct to standard therapy for people with non-healing diabetic foot ulcers is low, and the results are inconsistent. The results of a recent meta-analysis that found benefit of HBOT to prevent amputation are therefore uncertain. Future well-conducted studies may change the currently published estimates of effectiveness for wound healing and prevention of amputation using HBOT in the treatment of non-healing diabetic foot ulcers.
Although HBOT is an insured service in Ontario, a well conducted, randomized controlled trial that has wound healing and amputation as the primary end-points is needed before this technology is used widely among patients with foot wounds due to diabetes.
Objective
To examine the effectiveness and cost-effectiveness of hyperbaric oxygen therapy (HBOT) to treat people with diabetes mellitus (DM) and non-healing ulcers. This policy appraisal systematically reviews the published literature in the above patient population, and applies the results and conclusions of the review to current health care practices in Ontario, Canada.
Although HBOT is an insured service in Ontario, costs for the technical provision of this technology is not covered publicly outside the hospital setting. Moreover, access to this treatment is limited, because many hospitals do not offer it, or are not expanding capacity to meet the demand.
Clinical Need: Target Population and Condition
Diabetes mellitus is a chronic disease characterized by an increase in blood sugar that can lead to many severe conditions such as vision, cardiac, and vascular disorders. The prevalence of DM is difficult to estimate, because some people who have the condition are undiagnosed or may not be captured through data that reflect access to the health care system. According to the Canadian Diabetes Association, (www.diabetes.ca/Section_About/feet.asp; accessed May 26, 2005) there are about 2 million people in Canada with diabetes (almost 7% of the population). According to a specialized dataset created by researchers at the Institute for Clinical Evaluative Sciences (ICES) in Toronto, Ontario, (1) the prevalence of DM increased from 4.72% of the population aged 20 years and over in 1995, to 6.19% of the population aged 20 years and over in 1999, or about 680,900 people in 1999. Prevalence estimates expanded to 700,000 in 2003 (Personal communication, 2005). The researchers suggested that the increase in the overall number of cases over time was because people are living longer with DM (prevalence), rather than because more people were acquiring the condition each year (incidence).
Non-Healing Wounds and Diabetes Mellitus
People with DM are prone to foot ulcers, owing to loss of sensation in their feet due to peripheral neuropathy, which can occur if blood sugar levels are not controlled. Because of the neuropathy, a foot injury and subsequent infection cannot be felt. Without treatment, such a foot ulcer may fester until it becomes infected and chronic. Peripheral vascular disease has also been implicated in the development of foot ulcers in people with DM.
Many chronic wounds are difficult to heal, despite medical and nursing care. Chronic wounds may lead to impaired quality of life and functioning, amputation, or even death. Of those with DM, it is estimated that about 10% to 15% will develop foot ulcers sometime in their lifetimes. This translates to about 105,000 people in Ontario (www.diabetes.ca/Section_About/feet.asp; accessed May 26, 2005), based on an Ontario prevalence of 700,000 people with DM.
According to the ICES report cited above, the rate of inpatient hospitalization for skin and soft tissue infections among people with diabetes decreased by about 25% from 807 per 100,000 people aged 20 years and over in 1995, to 602 per 100,000 people aged 20 years and over in 1999. (2) Although these data could not discern the specific cause of the infections, the authors speculated that most of these hospitalizations were due to foot ulcers. They suggested that the decrease might have been due to an active awareness campaign on diabetic foot care among Ontario physicians during this time.
Similarly, as reported in the ICES report, the rate of minor amputations for people with DM dropped by 29% from 1995 to 1999 (158 to 112 per 100,000 people with DM). (2) However, people with DM were 24-fold more likely to have a minor amputation than were people without DM, after adjusting for the age and sex distribution in the populations. The rate of major amputations in the diabetic population also dropped over the study period, but not as drastically as that for minor amputations (202 per 100,000 people with DM in 1995 to 179 per 100,000 in 1999). Despite this drop, people with DM had a 14-fold-higher likelihood of major amputation than did people without DM, after adjusting for age and sex. (2)
According to Ontario hospital discharge abstracts, 1,065 people were admitted primarily for a foot ulcer due to DM (152 per 100,000 people with DM). A further 1,305 (186 per 100,000 people with DM) were admitted to hospital with a foot ulcer as a secondary diagnosis, complication, or comorbid condition in 2003. There were 67 minor amputations of the toe or toe/phalanx in patients identified as having DM reported in the hospital discharge abstract (9.57 per 100,000 people with DM) and 357 major amputations at the foot, ankle, or leg (51 per 100,000 people with DM) in 2003. The 1999 data reported by ICES and the 2003 data cited above cannot be compared because of changes in the administrative data coding systems for both diagnoses and procedures.
Various diagnostic grading systems are routinely used to stratify the severity of foot ulcers. The Wagner system, published in 1981, (3) is widely used to assess the degree and severity of ulcers in people with DM. Many clinical and treatment management guidelines and study protocols use this system to stratify patients with foot ulcers. The system is as follows:
  • Grade 1: partial or full thickness ulcer
  • Grade 2: probing tendon or capsule
  • Grade 3: deep ulcer with osteitis
  • Grade 4: partial foot gangrene
  • Grade 5: whole foot gangrene
Treatment of Chronic Ulcers in Diabetes
Little is known about the wound-healing process, and this makes treating chronic wounds challenging. Usually, a DM foot ulcer takes between 12 and 20 weeks to heal. (4) Many therapies exist for treating wounds in persons with DM, such as: (4)
  • Identification and correction of the etiological cause of the wound (e.g., ensuring good nutrition and maintaining normal blood glucose)
  • Current best practices for the treatment of chronic wounds including debridement and infection control
  • Preventive and therapeutic strategies such as orthopedic shoes/devices and shoe fitting to resist blisters and wounds, and off-loading to relieve pressure on the foot.
  • Amputation in very severe cases.
Hyperbaric oxygen therapy has been in use for about 40 years. It is thought to aid healing by supplying oxygen to the wound. The Hyperbaric Oxygen Therapy Association (www.hotaweb.org/HBOT.asp) notes that HBOT acts as a bactericidal, stops toxin production, and promotes tissue growth.
During the procedure, a patient is placed in a compression chamber with increased pressure between 2.0 and 2.5 atmospheres absolute (ATA) for 60 to 120 minutes, once or twice daily. In the chamber, the patient inhales 100% oxygen. Each treatment cycle consists of 15 to 20 treatment sessions.
Noted complications of HBOT may include ear, sinus, and lung damage; temporary worsening of shortsightedness; claustrophobia; and oxygen poisoning. (5;6) The incidence of aural barotraumas is the most frequently sited complication. (7) The complications are reportedly rare. Careful monitoring during the treatment sessions and follow-up by a trained health care provider are recommended.
Regulatory Status
Health Canada lists 2 manufacturers who are licensed to sell hyperbaric oxygen chambers in Canada:
  • Sechrist Industries, Inc. (Anaheim, California)
    • Monoplace hyperbaric chamber (licence 440, Class 3)
  • Perry Baromedical Corp. (Rivera Beach, Florida)
    • Sigma 34 monoplace hyperbaric system (licence 26990; Class 3)
    • Sigma plus series hyperbaric chamber (licence 27313; Class 3)
    • Sigma II series hyperbaric chamber (licence 28094; Class 3)
    • Sigma MP series hyperbaric chamber (licence 28304; Class 3)
Insurance Coverage
Hyperbaric oxygen therapy has been an insured service in Ontario since 1992 under the Health Insurance Act (codes G800–G806 in the Ontario schedule of benefits for physician services). (http://www.health.gov.on.ca/english/providers/program/ohip/sob/physserv/J_diagth.pdf).
It may be used under special circumstances for these indications (Personal communication, 2004):
  • Air or gas embolism
  • Carbon monoxide complicated by cyanide poisoning, carbon monoxide poisoning, or smoke inhalation
  • Clostridial myonecrosis (gas gangrene)
  • Crush injury, compartment syndrome, and other acute traumatic ischemia
  • Decompression sickness
  • Enhancement of healing in selected problem wounds, including diabetic wounds
  • Exceptional blood loss (e.g., due to anemia)
  • Intracranial abcess
  • Necrotizing soft tissue infections (e.g., of the subcutaneous tissue, muscle, or fascia)
  • Treatment-resistant osteomyelitis (i.e., an acute or chronic bone infection)
  • Radiation tissue damage and osteoradionecrosis (i.e., the death of bone tissue due to radiation)
  • Skin grafts and flaps (compromised)
  • Thermal burns
Other Canadian provinces and territories offer HBOT either as a general insured service or by special provision.
In the United States, reimbursement for HBOT has been covered by the Centers for Medicaid & Medicare Services since 2003 for diabetic wounds. It is covered if a patient has type 1 or 2 diabetes, a Wagner grade III or higher (please see above explanation), and if traditional wound treatment has failed. (8) If the wound does not show signs of healing after 30 days of HBOT, coverage is discontinued. (8) The Centers for Medicaid & Medicare Services (https://www.cms.hhs.gov/) is doing a full review of wound care to determine the burden of illness, to outline and review the knowledge base for chronic wound treatment, and to develop and promote the use of standard outcomes and measures in order to bolster the quality of clinical research initiatives in this area. Specific products and timelines for this initiative have yet to be defined.
Objective
To assess the effectiveness, safety, and cost-effectiveness of HBOT, either alone, or as an adjunct, compared with the standard treatments for non-healing foot or leg ulcers in patients with DM.
Questions Asked
  • Alone or as an adjunct therapy, is HBOT more effective than other therapies for non-healing foot or leg ulcers in patients with DM?
  • If so, what is the incremental benefit over and above currently used strategies?
  • When is the best time in a treatment strategy to use HBOT?
  • What is the best treatment algorithm with HBOT?
Methods
The Medical Advisory Secretariat searched for health technology assessments in the published and grey literature. The search yielded 4 reports, which were published from 2000 to 2005. The most recent report from the Cochrane Collaboration had a literature review and analysis of randomized control trials (RCTs) to 2003.
As an update to this review, and as per the Medical Advisory Secretariat’s standard review strategy, the abstracts of peer-reviewed publications were identified through Ovid MEDLINE, EMBASE, MEDLINE in-process and not-yet-indexed citations, the Cochrane Database of Systematic Reviews, Cochrane CENTRAL, and INAHTA using the following key words from January 1, 2003 to 2004.
  • hyperbaric oxygenation, oxygen
  • HBOT
  • wound healing
  • diabetic foot
  • osteomyelitis or diabetic chronic osteomyelitis
  • gas gangrene or diabetic gas gangrene
  • fasciitis, necrotizing/or diabetic necrotizing fasciitis
  • diabetic thermal burn
  • skin ulcer or exp decubitus ulcer or exp leg ulcer or exp foot ulcer or varicose ulcer
  • wounds and injuries or chronic wound.
The criteria for inclusion were as follows:
  • Patient population comprising people with diabetes
  • Live human study
  • English-language study
  • HBOT as adjunctive therapy or alone
  • RCT
The number of excluded studies were as follows:
  • 2 animal studies
  • 13 focus on condition other than DM
  • 8 review/protocol for HBOT use
  • 3 HBOT not focus of report
  • 2 Health technology assessments
  • 1 Non-RCT
The outcomes of interest were wound healing and prevention of amputation.
The search yielded 29 citations of papers published between 2003 and 2004. All 29 of these articles were excluded, as shown beside the criteria above. Therefore, this health technology policy appraisal focused exclusively on the most recently published health technology assessments and systematic reviews.
Summary of Health Technology Reports
The Medical Advisory Secretariat retrieved 4 recent health technology assessments or systematic reviews that examined the effectiveness of HBOT to treat ulcers due to diabetes compared with other therapies (Table 1).
Table 1:
Table 1:
Summary of Health Technology Assessments and Systematic Reviews on Hyperbaric Oxygen Therapy for People With Diabetes*
The most recent systematic review, (7) which was published in 2005 by German and Australian researchers in the Cochrane Collaboration, extended a previous Cochrane Collaboration health technology assessment (5) that was published in 2005. The extended review aimed to elucidate the best evidence on the impact of HBOT to manage diabetic, venous, arterial, and pressure ulcers, because the available evidence was “sparse and difficult to interpret.” This systematic review followed the Cochrane method to search and assess the literature. Their inclusion criteria were as follows:
  • Comparison of effect of HBOT (adjunctive) with no HBOT or sham therapy
  • Diabetic, venous, arterial, and pressure ulcers
  • RCT with random allocation
  • Chronic wounds that had not responded to other therapy
The exclusion criteria were as follows:
  • Animal studies
  • Topical HBOT
The literature search spanned 1966 to 2003 using the standard medical search databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) and DORCTHIM (a specialized hyperbaric medicine database); results were cross-referenced to the Cochrane Wounds Group Special Trials register. Six studies with 191 patients were included. Out of 6 RCTs included in the review, 5 focused on HBOT for non-healing wounds due to diabetes, and 4 focused on the outcomes of interest for the Medical Advisory Secretariat’s health technology policy assessment.
The methods used in this assessment were rigorous. The Jadad score (9) for RCT quality was used to assess each study, and homogeneity was assessed for pooled analyses across stratified outcome measures (wound healing, minor or major amputation, transcutaneous oxygen tension measurements). These RCTs are discussed in more detail further in this report.
The conclusions from this extended health technology assessment and from the previous Cochrane report were that there was no evidence of the effectiveness of HBOT for wound healing in general, or for prevention of minor amputation (Table 1). However, their analysis found that HBOT might decrease the risk of major amputation compared with a control treatment (relative risk [RR], 0.31; 95% confidence interval [CI], 0.13–0.71). The calculated number needed to treat (NNT) to prevent 1 amputation was 4 (95% CI, 3–11). Further, the transcutaneous oxygen tensions monitored before and after treatment in some of these studies may have provided support for this finding. Caveats to these conclusions were stated as inconsistent study quality, inclusion and exclusion criteria, and HBOT treatment regimens; and small sample sizes. The RCTs from this health technology assessment are discussed in more detail further in this report.
In 2003, the Alberta Heritage Foundation (10) and Agency for Healthcare Research and Quality (AHRQ) (11) published reviews of the use of HBOT to heal wounds in diabetes. Neither did an analytic synthesis of the data. The Alberta Heritage Foundation suggested that there might be some benefit, but that the benefit had yet to be established in the published literature. AHRQ suggested that more research is needed to determine how and where HBOT fits in wound care for diabetes.
In 2000, the Medical Services Advisory Committee (MSAC) (6) in Australia reviewed the effectiveness of HBOT for many indications, including the following:
  • Thermal burns
  • Diabetic and other chronic wounds
  • Necrotizing soft tissue infections and necrotizing fasciitis (a rare bacterial infection also called flesh-eating disease)
  • Fournier’s gangrene (a bacterial skin infection that affects the genitals and perineum)
  • Osteomyelitis
  • Osteoradionecrosis
  • Skin grafting
The MSAC found that HBOT was effective at healing wounds based on a pooled analysis of 38 patients across 2 comparative studies (odds ratio [OR], 39.39; 95% CI, 5.54–280.32; P < .0001) with no apparent heterogeneity (P = .462). The confidence in this result is, however, questionable, because the confidence intervals are wide.
Based on a pooled 251 patients from 2 RCTs and 2 comparative studies (no apparent heterogeneity [x2df=3, 0.87; P = .833]), the MSAC found that HBOT was effective at preventing major amputations (OR, 0.25 (95% CI, 0.13–0.50; P < .0001). Their analysis of minor amputations was not statistically significant.
The authors also analyzed the cost of treating diabetic wounds. They found a cost savings of $63,100 (AU) or less per amputation avoided with the use of HBOT based on 15 to 40 sessions that cost $6,941 (AU). A caveat about these estimates, however, is that the conclusion of the effectiveness of HBOT was based on limited evidence.
The MSAC accepted recommendations for public funding of HBOT to treat chronic wounds due to diabetes, necrotizing soft tissue infection, decompression illness, gas gangrene, and air or gas embolism, despite the limitations of the studies reviewed and the scant evidence of effectiveness. They did not develop standards for the therapy, but they encouraged Standards Australia to do so.
Studies Included in the Recently Published Cochrane Review
Tables 2 and and33 (on the next 2 pages) show summaries of the designs and quality of the studies included in the Cochrane pooled analyses on HBOT. (7) There were 4 studies (12-15) that focused on the outcomes of interest to the Medical Advisory Secretariat. All of the studies compared HBOT as an adjunct to standard treatment with the control arm as standard treatment. The studies included in the pooled analysis were not well described, with the exception of one high-quality study (12) that was given a Jadad score (9) of 5 by the Cochrane authors. However, the sample size of this high-quality study was small (8 people in each arm) and therefore, the results might be subject to a type II error where a negative result was found. Moreover, the method of the sample size calculation for this study was not explicit.
Table 2:
Table 2:
Summary of Randomized Controlled Trials in the 2005 Cochrane Systematic Review (7)
Table 3:
Table 3:
The Medical Advisory Secretariat’s Assessment of the Quality of RCTs* in the 2005 Cochrane Systematic Review (7)
Despite an analysis of heterogeneity performed by Cochrane, the studies reviewed were comprised of patients with varying degrees of wound severity, HBOT protocols and control interventions, follow-up durations, and outcome measures. As a result, the validity of the obtained results of the Cochrane pooled analysis may be uncertain.
Summary of Literature Review
The Cochrane health technology assessment focused only on RCTs, whereas the MSAC assessment included all study designs. The MSAC assessment pooled all study designs and treatment protocols; thus, the uncertainty around their estimates is high.
The pooled results from the Cochrane assessment suggests that HBOT plus adjunct treatment might prevent amputation compared with adjunctive treatment alone in people who have DM and non-healing wounds (RR, 0.31; 95% CI, 0.13–0.71). They also found an NNT of 4 (95% CI, 3–11). The effect of HBOT plus adjunctive therapies compared to adjunctive therapy alone is not known for wound healing in general, or for minor amputation, according to the Cochrane review.
The Medical Advisory Secretariat examined the quality of the studies that were included in the Cochrane review, using the recently published GRADE Assessment, (18) a tool designed by international study design experts. GRADE provides a systematic approach to judge the certainty or confidence of results, based on the quality of the available evidence, and provides advice on recommendations surrounding a body of literature. According to this rubric, the overall certainty of the outcomes gleaned from the HBOT literature is low to moderate for the outcome of wound healing, and low for the outcomes of major and minor amputation. (See Table 4.)
Table 4:
Table 4:
GRADE (18) Analysis of Studies in the 2005 Cochrane Systematic Review (7)
According to the GRADE criteria, (18) the judgement of low to moderate quality evidence suggests that further research will likely have an important impact on the confidence in the estimate of effect and may, in fact, change the estimate.
There are many guidelines from various organizations on the treatment of DM foot ulcers:
  • American Diabetes Association
  • International Working Group on the Diabetic Foot
  • Canadian Diabetes Association
  • Canadian Association of Wound Care
  • American College of Foot and Ankle Surgeons
  • Wound Healing Society
Recently, Frykberg (4) summarized these guidelines and concluded that the assessment and treatment of foot ulcers in DM should include the following:
  • Taking a detailed patient history: trauma to foot, neuropathy, previous ulcer, infection, hypoxia, and protein glycosylation
  • Assessing the wound and cause of wound cause: kidney function, depth, location, area, odour, neurological exam, vascular exam, infection
  • Classifying the wound: no universally accepted system
  • Addressing treatment: correct causal etiology, treatment of comorbidities, debridement, total contrast cast for ‘off-loading,’ topical cream, gel, antimicrobials, dressings, etc.
  • Focusing on prevention: provider/patient education, protective/therapeutic footwear, appropriately fitted shoes, prophylactic surgery Adopting a multidisciplinary approach.
The Canadian Diabetes Association’s guidelines (www.diabetes.ca) suggest 10 steps to prevent foot ulcers for people with DM, as follows:
  • Check feet regularly, either with a caregiver or using hand mirror. Any change in the skin should be examined by a health care provider.
  • Keep feet clean.
  • Apply moisturizer or medicated ointment to damaged skin.
  • Avoid heat, like heating pad or hot water bottle.
  • Follow directions from health care providers.
  • Wear loose clothing.
  • Be careful with sharp instruments, such as nail clippers or scissors.
  • Maintain a healthy weight.
  • Don’t walk barefoot.
  • Quit smoking.
  • Visit a health care professional regularly.
Disclaimer: This economic analysis represents an estimate only, based on assumptions and costing methodologies that have been explicitly stated. These estimates will change if different assumptions and costing methodologies are applied for the purpose of developing implementation plans for the technology.
A literature review was conducted to examine the costs and cost-effectiveness of HBOT plus standard treatment for lower-limb diabetic wounds. The MSAC (6) assessment analyzed cost, as did 1 RCT (12) that was included in the recent Cochrane review, and one stand-alone article by Guo. (19) The MSAC assessment and the Guo article emphasized that the costing analyses were based on uncertain estimates of effectiveness.
Table 5:
Table 5:
Costs and Cost-Effectiveness of Hyperbaric Oxygen Therapy
Ontario Context
According to estimates, (1) there are about 700,000 people with diabetes in Ontario; of these, from 70,000 to 100,00 may have a foot ulcer in their lifetime (10–15% of prevalent cases). According to current Ontario hospital discharge abstracts, in 2003, 1,065 cases were admitted primarily for a foot ulcer due to DM (152 per 100,000 people with DM), and a further 1,305 (186 per 100,000 people with DM) were admitted to hospital with a diagnosed foot ulcer as a secondary diagnosis, complication, or comorbid condition. There were a reported 67 minor amputations of the toe or toe/phalanx in patients identified as having DM from the hospital discharge abstracts (9.57 per 100,000 people with DM), and 357 major amputations at the foot, ankle, or leg (51 per 100,000 people with DM) in 2003. The Ontario codes used are in Appendix 1.
There are 6 hyperbaric oxygen chambers in Ontario, which are located in the Greater Toronto area, Ottawa, and Hamilton. The abstracting of HBOT by Ontario hospital health records coders is not mandatory; therefore, the use as indicated in the provincial hospital discharge abstracts may underestimate the true use. Nonetheless, the data suggest that only 17 patients identified as having DM received HBOT in 2003.
Direct Costs of Hyperbaric Oxygen Therapy and Chronic Wounds
All costs are in Canadian currency. The cost to lease a hyperbaric oxygen chamber is about $275,000 plus $315,000 in variable and fixed costs annually (e.g., maintenance, staff resources, medical supplies, etc.). The cost of HBOT per treatment cycle for a patient that has DM and an ulcer is estimated at $5,200 based on 100 patients treated each year with 1 chamber (Personal communication, 2005), plus amortization of the cost of the machine (about $1,000). Thus, the total cost per patient is about $6,200.
It is estimated that the hospital cost for a patient that has DM and an ulcer, and that does not require amputation, is $58,500 (based on 78 days in the hospital at $750 per day). The estimated system cost for an amputation is $60,000 per patient (Personal communication, 2005). To determine the possible cost avoidance of HBOT, the following analysis was done:
  • Cost avoidance for 1 amputation: $ 60,000 (cost amputation) - $6,200 (HBOT) = $53,800
  • Cost avoidance in Ontario:
Low estimate: One-third of amputations avoided with HBOT (Cochrane estimate)
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Object name is ohtas-05-23-e001.jpg
High estimate: All amputations avoided with HBOT
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Thus, between $5.8 million and $19.6 million in costs could be avoided based on current estimates if HBOT was deemed effective at preventing amputations in patients who have DM and foot ulcers.
Demographics
  • About 700,000 people may have diabetes in Ontario.
  • About 10% to 15% of these people may have a foot wound in their lifetime.
  • At least 67 minor and 357 major amputations were done in people with diabetes in 2003 in Ontario.
  • Fewer then 20 patients with DM were treated with HBOT in 2003, according to Ontario hospital discharge abstracts.
Patient Outcomes – Medical, Clinical
  • Pooled data found a potential benefit of HBOT for preventing major amputation but not for prevention of minor amputation or for wound healing overall.
  • Theses pooled estimates reported in a previously published health technology assessment are uncertain, because there is a dearth of good quality studies.
  • The Medical Advisory Secretariat’s synthesis of the quality of the studies included in the pooled data found that more research of higher quality likely would change the current estimates and certainty around the estimates.
Cost
All costs are in Canadian currency:
  • In Ontario, a hyperbaric oxygen chamber costs about $275,000 plus $315,000 in variable and fixed costs.
  • The cost per patient with DM treated with HBOT is $6,200 in Ontario.
  • The system cost of an amputation is estimated at $60,000.
  • The cost per amputation avoided using HBOT may be estimated as $5.8 million to $19.6 million if HBOT was deemed effective at avoiding amputation in patients who have DM and foot ulcers.
Stakeholder Analysis
  • Significant patient burden is associated with diabetic foot ulcers.
  • A registered hyperbaric technician should operate the chamber.
System Pressures
  • A previous Medical Advisory Secretariat health technology policy assessment on wound care highlighted the need for a coordinated wound care effort across providers in Ontario.
There are 6 HBOT chambers in 3 sites in Ontario, with limited access for wound treatment.
The quality of the evidence assessing the effectiveness of HBOT as an adjunct to standard therapy for people with non-healing diabetic foot ulcers is low, and the results are inconsistent. The results of a recent meta-analysis that found benefit of HBOT to prevent amputation are therefore uncertain. Future well-conducted studies may change the currently published estimates of effectiveness for wound healing and prevention of amputation for HBOT in the treatment of non-healing diabetic foot ulcers. This health technology policy assessment could not determine when the best time to provide HBOT in the treatment cycle or what the best algorithm for effective treatment would be.
Based on the level of evidence, a well-conducted study may change the currently published estimates of effectiveness for wound healing and prevention of amputation for HBOT in the treatment of non-healing diabetic foot ulcers.
There are about 700,000 people in Ontario with diabetes, and 10% to 15% of these people may have a foot ulcer sometime in their lives. Foot ulcers are treatable when they are identified, diagnosed, and treated early, according to best-practice guidelines. Routine follow-up for people with diabetes who may be at risk for neuropathy and/or peripheral vascular disease may prevent subsequent foot ulcers.
HBOT is an insured service in Ontario; however, fewer than 20 people with DM were treated with this therapy in 2003, according to hospital discharge abstracts. There are 3 centres housing 6 hyperbaric oxygen chambers in Ontario.
In 2003, the Ontario Health Technology Advisory Committee recommended a more coordinated strategy for wound care in Ontario to the Ministry of Health and Long-term Care. This strategy has begun at the community care and long-term care institution levels, but is pending in other areas of the health care system.
Appendices
Appendix 1: Codes Extracted From Ontario Hospital Discharge Abstracts at the Ontario Ministry of Health and Long-term Care 2005
ICD-10 CA Diagnosis CodesCanadian Classification of Interventions
Diabetic foot ulcerE10700-10709
E11700-E11709
E13700-E13709
E14700-E14709
Unspecified skin condition -diabetesE10610-E10619
E11610-E11619
E13610-E13619
E14610-E14619
Oxygenation wound therapy:
Monoplace hyperbaric chamber (or chamber NOS)

Multiplace hyperbaric chamber
1.YZ.12.JA-MS

1.YZ.12.JA-MT
Amputation of toe/phalanx1.WL.93
Amputation of toe at joint1.WM.93
Amputation of tarsometatarsal, metatarsal bones and metatarsophalangeal joints1.WJ.93
Amputation at ankle1.WA.93
Amputation of femur1.VC.93
Amputation through knee joint1.VG.93
Amputation through tibula-fibula1.VQ.93
Amputation through mid-foot1.WE.93
Notes
Suggested Citation
This report should be cited as follows:
Medical Advisory Secretariat. Hyperbaric oxygen therapy for non-healing ulcers in diabetes mellitus: an evidence-based analysis. Ontario Health Technology Assessment Series 2005; 5(11)
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About the Medical Advisory Secretariat
The Medical Advisory Secretariat is part of the Ontario Ministry of Health and Long-Term Care. The mandate of the Medical Advisory Secretariat is to provide evidence-based policy advice on the coordinated uptake of health services and new health technologies in Ontario to the Ministry of Health and Long-Term Care and to the healthcare system. The aim is to ensure that residents of Ontario have access to the best available new health technologies that will improve patient outcomes.
The Medical Advisory Secretariat also provides a secretariat function and evidence-based health technology policy analysis for review by the Ontario Health Technology Advisory Committee (OHTAC).
The Medical Advisory Secretariat conducts systematic reviews of scientific evidence and consultations with experts in the health care services community to produce the Ontario Health Technology Assessment Series.
About the Ontario Health Technology Assessment Series
To conduct its comprehensive analyses, the Medical Advisory Secretariat systematically reviews available scientific literature, collaborates with partners across relevant government branches, and consults with clinical and other external experts and manufacturers, and solicits any necessary advice to gather information. The Medical Advisory Secretariat makes every effort to ensure that all relevant research, nationally and internationally, is included in the systematic literature reviews conducted.
The information gathered is the foundation of the evidence to determine if a technology is effective and safe for use in a particular clinical population or setting. Information is collected to understand how a new technology fits within current practice and treatment alternatives. Details of the technology’s diffusion into current practice and information from practicing medical experts and industry, adds important information to the review of the provision and delivery of the health technology in Ontario. Information concerning the health benefits; economic and human resources; and ethical, regulatory, social and legal issues relating to the technology assist policy makers to make timely and relevant decisions to maximize patient outcomes.
If you are aware of any current additional evidence to inform an existing Evidence-Based Analysis, please contact the Medical Advisory Secretariat: MASInfo/at/moh.gov.on.ca. The public consultation process is also available to individuals wishing to comment on an analysis prior to publication. For more information, please visit http://www.health.gov.on.ca/english/providers/program/ohtac/public_engage_overview.html.
Disclaimer
This evidence-based analysis was prepared by the Medical Advisory Secretariat, Ontario Ministry of Health and Long-Term Care, for the Ontario Health Technology Advisory Committee and developed from analysis, interpretation and comparison of scientific research and/or technology assessments conducted by other organizations. It also incorporates, when available, Ontario data, and information provided by experts and applicants to the Medical Advisory Secretariat to inform the analysis. While every effort has been made to do so, this document may not fully reflect all scientific research available. Additionally, other relevant scientific findings may have been reported since completion of the review. This evidence-based analysis is current to the date of publication. This analysis may be superceded by an updated publication on the same topic. Please check the Medical Advisory Secretariat Website for a list of all evidence-based analyses: http://www.health.gov.on.ca/ohtas.
Abbreviations
AHRQAgency for Healthcare Research and Quality
CIConfidence interval
DMDiabetes mellitus
HBOTHyperbaric oxygen therapy
ICESInstitute for Clinical Evaluative Sciences
MSACMedical Services Advisory Committee
NNTNumber needed to treat
OROdds ratio
QUALYQuality adjusted life year
RCTRandomized controlled trial
RRRelative risk
SDStandard deviation

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