WoundReference improves clinical decisions
 Choose the role that best describes you
WoundReference logo

Diabetic Foot Ulcer - Hyperbaric Oxygen Therapy

Diabetic Foot Ulcer - Hyperbaric Oxygen Therapy

Diabetic Foot Ulcer - Hyperbaric Oxygen Therapy

INTRODUCTION

Treatment Protocol Guidelines

This hyperbaric oxygen therapy (HBO) treatment protocol is based upon the recommendations of the Hyperbaric Oxygen Committee of the Undersea and Hyperbaric Medical Society (UHMS).[1] Clinical protocols and/or practice guidelines are systematically developed statements that help physicians, other practitioners, case managers and clients make decisions about appropriate health care for specific clinical circumstances. The UHMS has published a clinical practice guideline for the use of HBO in DFU.[2]  


Protocols and practice guidelines allow health providers to offer evidence-based, appropriate, standardized diagnostic treatment and care services. This section will discuss diabetic foot ulcers (DFU).  Evidenced-based medicine offers clinicians a way to achieve improved quality, improved patient satisfaction, and reduced health care costs.  Utilization Review should be initiated when clinical decisions result in deviation from, or modification of, treatment protocols.  This includes any course of treatment at or above the recognized threshold limits. Evidence and recommendations for treatment initiation, therapy, and utilization review is found in the UHMS Indications Manual, 13th edition.[1]

Medical Necessity

Medicare.gov defines “medically necessary” as “health-care services or supplies needed to prevent, diagnose, or treat an illness, injury, condition, disease, or its symptoms and that meet accepted standards of medicine.” 

The following condition meets coverage indications per the National Coverage Determination (NCD) 20.29.[3] Continued HBO therapy without documented evidence of effectiveness does not meet the Medicare definition of medically necessary treatment. A thorough re-evaluation of the patient's clinical response should be made at least every 30 days in order to document the appropriate application of therapy. 

TREATMENT PROTOCOL



Background
  • Patients with diabetes are at high risk of developing foot ulcers (DFU). The incidence of DFU in the United States is stable at approximately 6% of patients with diabetes. Nearly 60% of non-traumatic lower extremity amputations are the result of diabetes mellitus. DFU is a result of complex peripheral neuropathy, peripheral arterial occlusive disease, impaired white blood cell response to infection, and cellular dysfunction. There is a component of repetitive stress injury in all DFU. In spite of standard wound care, DFU can progress with complications such as cellulitis, deep tissue infection, abscess formation, osteitis, and osteomyelitis can arise. [4]
  • Deep plantar diabetic foot ulcers (DFU) with abscess, osteomyelitis, or joint sepsis are characterized as Wagner Grade 3. Among other requirements listed on Medicare local coverage determinations (LCD), a DFU must be classified as Wagner 3 or higher in order to justify adjunctive treatment with HBO2. For more information on Wagner and other DFU classifications see "Diabetic Foot Ulcers - Classification Systems". The key point to remember in treating DFU patients is the quality of wound care management significantly impacts the outcome of the DFU. Hyperbaric oxygen therapy (HBOT) is adjunctive and must stand on the shoulders of superb wound care management in order to have a positive outcome.
  • We note that grading DFU can be confusing at times. When a patient presents to the clinic, and a Wagner Grade 2 ulcer is diagnosed, the characteristics of the DFU may change during treatment and the DFU grade advances to a Grade 3 or Grade 4. However, reverse grading must never happen. Once a Wagner Grade 3 ulcer is diagnosed, it remains a Wagner Grade 3 ulcer, even if the signs/symptoms of infection are eradicated. Technically, we would refer to this as a 'healing Wagner Grade 3' DFU. 
  • The primary goal of wound care and HBOT for DFU is to have the patient with intact lower extremities. We also expect that these patients will remain ambulatory. Mortality for limb-threatening DFU treated with aggressive limb salvage and HBOT is approximately 35%, while patients who have a major lower extremity amputation have death rates approaching 50%. [5]
Goals of HBOT
To restore the following oxygen-dependent processes that are necessary for wound healing:
  • Inflammatory and repair functions of neutrophils, fibroblasts, macrophages and osteoclasts
  • Collagen deposition
  • Angiogenesis
  • Resistance to infection
  • Intracellular leukocyte bacterial killing
Diagnosis
Patient with diabetes with lower extremity ulcer of neuropathic, neuroischemic or ischemic etiology [6]  
Hyperbaric Criteria
  • The patient has Type 1 or 2 diabetes and a lower extremity ulcer due to diabetes AND 
  • The ulcer is a Wagner grade 3 or higher AND
  • The patient has failed a 30-day course of standard wound care. The phrase "standard wound care" is important. We do not set the definition for standard wound care; the payer, fiscal intermediary, or state/local agency sets the requirements. We take this definition directly from the Noridian HBOT LCD: "Standard wound care in patients with diabetic wounds includes: assessment of a patient’s vascular status and correction of any vascular problems in the affected limb if possible, optimization of nutritional status, optimization of glucose control, debridement by any means to remove devitalized tissue, maintenance of a clean, moist bed of granulation tissue with appropriate moist dressings, appropriate off-loading, and necessary treatment to resolve any infection that might be present. " In our HBOT consultation, we must address each of the standard wound care criteria as part of the 30-day requirement. Otherwise, during a pre-determination or a post-treatment audit, reimbursement for HBOT will be denied.
  • Transcutaneous Oximetry (TCOM) may reveal evidence of reversible local tissue hypoxia. TCOM is a valuable tool to guide the management of hypoxia wounds or ulcers. It should never be used as a regulatory statute or requirement.
  • Careful analysis of each case is based on the criteria above 
Evaluation
  • Comprehensive history
    • length of time patient has been treated for DM and state DM Type 1 or 2
    • at least an estimate of time with foot neuropathy
    • history of any previous DFU
    • date of onset for current DFU
    • any record of prior physician evaluation, and whether or not this treatment met 'standard wound care' criteria
    • any history consistent with peripheral vascular disease and/or evaluation for vascular disease
    • any history of other vascular disease (coronary artery disease, kidney dysfunction, retinal changes, etc.)
  • Physical Exam:
    • Foot anatomy (obvious deformities, previous amputations, and/or evidence of prior DFU)
    • Neurologic (monofilament testing, vibration, pinprick sensation)
    • Vascular (pulse palpation, Doppler pulses with signal quality, Ankle Brachial Index (ABI), skin perfusion pressure (SPP), fluorescence angiography, and/or TCOM)
    • Wound exam and photographic documentation. Assess whether wound has decreased at least 50% over four weeks of adequate treatment.[7] 
    • This study design is important for us to understand. Sheehan, et. al. had only Wagner 1 and 2 patients enrolled. No DFU could have any evidence of infection or peripheral arterial disease. While the conclusion of the study is valid, it is only valid for patients who meet the above inclusion criteria. No DFU patients coming to the hyperbaric center fit this exclusion criteria. Therefore, the results of this paper cannot be used as a regulatory barrier to care. 
    • Imaging Studies: Plain Radiographs, MRI, or bone scan if the presence of osteomyelitis is suspected.
    • Laboratory Studies: 
      • Complete Blood Count (CBC)
      • HbA1c 
      • Estimated Average Glucose
      • Comprehensive Metabolic Profile (CMP)
      • Albumin
      • Prealbumin
      • Erythrocyte Sedimentation Rate (ESR)
      • C-Reactive Protein (CRP)

      • Perform normobaric TCOM in normobaric air and pressure. See topic "Transcutaneous Oximetry"
        • We admit that TCOM values have been a major factor used to decide whether or not a patient was a candidate for HBOT. This is not as crucial now that we have other modalities that can be used to assess the arterial flow of the lower extremities. In fact, advances in imaging and interventional techniques have been valuable in limb salvage. We will discuss some of the science and studies in the "Clinical Evidence" section below. 
        • Hypoxia (i.e. TCOM value <40 mm Hg) generally defines wounds appropriate for HBOT. Any patient who comes to the clinic with a Wagner 3 foot ulcer and a lower than expected TCOM value should be immediately placed in a limb salvage pathway. This is a critical step in avoiding major amputations of lower extremities.
        • TCOM values between 25-40 mmHg have been associated with poor healing of wound and amputation flaps in several retrospective reviews.  
        • Lack of hypoxia (i.e. TCOM >40-50 mm Hg) defines wounds that have high healing potential from an oxygen standpoint. HBOT is rarely needed for its ability to improve tissue oxygenation in these patients.
      • Assess TCOM in normobaric pressure and 100% oxygen: [8]
        • We make an assumption when using the "100% oxygen TCOM challenge." We assume that the oxygen delivery method for our facility actually delivers 100% oxygen during this challenge. Without placing the patient in an HBOT hood or a tight-fitting aviator mask, we cannot interpret this challenge correctly. A "green bag" oxygen mask, even with high flows can only deliver a FiO2 of 40% or so. 
        • In normal subjects breathing 100% oxygen at normobaric pressure, we expect to see TCOM values on the lower extremity increase to a value >100 mmHg.
        • If the DFU is hypoxic while breathing normobaric air, and TCOM values obtained while breathing 100% normobaric oxygen increase to above 35 mm Hg, with a significant rise > 50% above the normobaric air value, there is a likelihood of benefiting from HBOT.[8]
        • On the other hand, there is no absolute lowest value at which we can determine that wounds/DFU will not heal. Some patients with single-digit TCOM values have gone on to heal with aggressive wound care, limb salvage, and adjunctive HBOT. 
      • Nutritional assessment; dietary management; blood glucose control, and measurement of body mass index (BMI)
      • Baseline and as needed visual acuity assessment for evaluation of progressive myopia due to HBOT. 
      • Evaluation of tympanic membranes pre- and post-treatment as needed
      • Smoking/nicotine cessation
      Treatment
      • Hyperbaric oxygen therapy at 2.0 to 2.4 ATA for 90 minutes of oxygen breathing. (Table 1 or Table 3). Initiate "air breaks" if treating at pressures >2.0 ATA
      • HBOT sessions may be provided on a daily basis 5-7 times per week or twice daily in patients with serious infections requiring hospitalization for intravenous antibiotics, aggressive surgical intervention, and better diabetes control. 
      • 20-40 HBO sessions will be required to achieve sustained therapeutic benefit. 
      • Assess TCOM in chamber:
        • If the wound is hypoxic while breathing normobaric air, and a TCOM >200 mm Hg is achieved breathing hyperbaric oxygen, this suggests that the tissue may respond well to adjunctive HBO. This test has a 75% concordance with healing DFU. It also means that up to 25% of DFU do not go on to healing. [8] 
        • A minimum TCOM value of 200 mm Hg is necessary to confirm the adequate reversal of wound hypoxia during initial hyperbaric treatment. This suggests that increased tissue oxygen levels alone will not be adequate for healing. Hypoxic areas in/around the DFU should trigger a referral for vascular evaluation and intervention in order to restore good blood flow to the wounded angiosome.
        • In-chamber TCOM values <100 mm Hg are closely associated with failure of HBOT in DFU (The positive predictive value is 89%.). However, a trial of HBOT continues to be a reasonable approach.  A trial of 15-20 treatments is suggested. Document this decision as part of a complex medical decision making note. This not should be a separate document, rather than noting on a daily HBO treatment note. After the trial of HBOT, re-evaluate the DFU. If there is evidence of healing, then the recommendation is to continue HBOT. If there is no evidence of healing, we recommend stopping HBOT.  [8] 
        • There may be value in increasing the chamber pressure if TCOM values are low at 2.0 ATA. If possible, and air breaks can be provided, we recommend trying 2.4 ATA. There are times where the higher treatment pressure will increase periwound tissue oxygen. 
      • Reassessment after 14 sessions:
        • After 14 HBO sessions, re-evaluate tissue hypoxia with TCOM. At our institution, this would be a normobaric air reading, followed by an in-chamber reading. Evaluate the DFU for signs of healing and an oxygenated granulation bed. If no measurable signs of healing, then reassess for underlying pathology (i.e., infection, metabolic, nutritional, vascular, mechanical, etc.) We recommend following a clinical pathway or flowchart so that complicating factors to healing may be found and corrected in a stepwise manner. Flowcharts and checklists have been shown to be beneficial to patient care.  [9]
      • Reassess after 20 sessions:
        • If measurable signs of healing are present and periwound TCOM values reach 40 mm Hg, HBOT may be paused and the DFU followed clinically for continued healing. 
        •  If measurable signs of healing are present but periwound TCOM values have NOT reached 40 mm Hg, continue HBOT daily to 30 treatments and reassess until TCOM values reach 40 mm Hg.
        • You may use other methods of assessing for evidence of healing. Some units choose to use fluorescence angiography. This test provides valuable visual evidence of wound neovascularization and healing.
      Follow-Up
      • Continued wound evaluation and management 
      • Maintenance of advanced wound care in your wound clinic
      • Weekly visual acuity assessment to evaluate for progressive myopia. If the patient is driving, you should check the driver visual acuity statute for your state. If the patient's visual acuity falls below this level, we recommend a letter be given to the patient advising not to drive and a referral to an ophthalmologist, if needed. In most states, a 'best corrected vision' of 20/70 or worse requires an appointment with an eye care professional for further evaluation.
      Treatment Threshold
      14 – 40 treatments (Utilization review should be performed at least every 30 days during treatment and after 40 treatments.)
      Coding
      Refer to the ICD-10 Guideline for the appropriate ICD-10 code     
      Comments
      • Blood glucose should be checked within an hour prior to each treatment and immediately post-HBO by unit personnel. 
      • For HBOT to continue, the HBOT physician must evaluate clinical response every 30-day interval. There must be measurable signs of healing.
      Primary Sources: Whelan and Kindwall [10]Weaver [11][12]

      DOCUMENTATION

      The UHMS Guidelines Committee recommends patients with Wagner ≥3 diabetic foot ulcers that have not healed for 30 days be considered for adjunctive HBOT. There is sufficient evidence in the literature showing prevention of major lower extremity amputations and enhancement of the rate of DFU healing. Urgent HBOT should be added to the standard of care for patients with Wagner ≥3 diabetic foot ulcers who have had surgical debridement of an infected foot (e.g., partial toe or forefoot amputation, I&D of deep space abscess, necrotizing soft tissue infection) in order to reduce the risk of major amputation and incomplete healing. See also:

      History and Physical

      • An initial assessment including a history and physical that clearly supports the condition for which HBOT is recommended.
      • Prior medical, surgical and/or hyperbaric treatments.
      • Failure to respond to standard wound care occurs when there is no documentation of measurable signs of healing for at least 30 consecutive days. All components of standard wound care (determined by the payer in an NCD or LCD) shall be addressed in this documentation.

      Physical Exam

      • An initial assessment including a history and physical examination that clearly substantiates the condition for which HBO is recommended.
      • The DFU duration must be >30 days.
      • Documentation must demonstrate an ulcer with signs of infection, deep abscess, bone involvement (osteomyelitis), joint sepsis, localized gangrene, or gangrene of the forefoot. Wagner Grade 1 and 2 DFU are not candidates for adjunctive HBOT. (This can trigger a CMS Fraud and Abuse investigation.)
      • Documented evidence of lower extremity wound(s) healing failure despite at least 30 days of standard wound care.
        • Decrease in margin size or depth of the wound
        • Formation of healthy granulation tissue (NOT reactive mounds or polyps of granulation tissue)
        • Epithelial growth or advancing margins of epithelium
        • Documentation of vascular status, assessment, and intervention/correction of any vascular problems in the affected limb.
        • TCOM evidence demonstrating periwound hypoxia.
        • Include evidence of examination for foot pulses and record the ABI values.
      • Documentation of optimization of nutritional status
        • Albumin
        • Pre-Albumin
        • Use a validated tool such as a Nestle mini nutritional assessment (MNA) within the 12 month reporting period.  
      • Documentation of optimization of glucose control
        • HbA1c level. If the patient has had this performed within 30 days by the primary care office or diabetologist, it does not need to be repeated. We recommend getting a copy of recent laboratory studies for the wound/HBOT clinic.
      • Documentation that you have maintained a clean, moist bed of granulation tissue with appropriate dressings
        • Initial ulcer size - beginning of 30 days of standard wound care.
        • Current ulcer size - following 30 days of standard wound care
      • Document efforts to adequately offload the extremity. (In our opinion, this is the single most important intervention for DFU healing.)
        • The following modalities may be used: Total Contact Casting (TCC), CROW walker, crutches, a knee caddy, and/or wheelchair for mobility impaired patients.
      • Documentation of necessary treatment to resolve any infection present.

      Impression

      1. Diabetic Complications Code – (ICD-10 E series) 

      2. Wound diagnosis code – (ICD-10 L series)

      Plan

      A typical hyperbaric regimen for a patient with a Wagner III or worse diabetic foot ulcer consists of daily 2.0 atmospheres absolute hyperbaric oxygen treatments with 90 minutes of oxygen breathing time during a 120-minute treatment or 2.4 ATA with 90 minutes of oxygen breathing time. This continues until the tissue has stabilized and the patient demonstrates progress toward healing. Because patients with diabetic foot ulcers also have a high incidence of vascular inflow disease, these patients will be carefully monitored for improvement in tissue oxygenation by serial transcutaneous oximetry measurements.

      Risk and Benefit of Hyperbaric Oxygen Therapy 

      Indication for Hyperbaric Oxygen Therapy (HBOT)

      "Patients with diabetes are at high risk of developing foot ulcers due to neuropathy and peripheral arterial occlusive disease. The pathophysiology of diabetic foot ulcers includes progressive development of a sensory, motor, and autonomic neuropathy leading to loss of protective sensation, deformity causing increased plantar foot pressure, and alterations in autoregulation of dermal blood flow. Diabetes causes advanced peripheral vascular disease generally at the trifurcation level just below the knee. 
      Neuropathy, vascular disease, impaired white blood cell response to infection, and cellular dysfunction all contribute to the poor clinical outcomes of diabetic foot ulcers. Despite standard wound care, these foot ulcerations can progress and are associated with cellulitis, deep tissue necrosis, abscess formation, and the development of osteomyelitis. This type of ulcer is a Wagner grade III ulcer, an equivalent of the University of Texas IIB, IID, IIIB, or IIID ulcers. Progression to frank distal foot gangrene (Wagner grade IV) or gangrene involving the whole foot (Wagner grade V) can occur. 

      Hyperbaric oxygen therapy has been proven to be a beneficial adjunct to advanced wound care in diabetic foot ulcers meeting the following criteria: 1) the patient has type 1 or 2 diabetes and a lower extremity ulcer due to diabetes, 2) the ulcer is a Wagner grade III or higher, and 3) the patient has failed a 30-day standard wound therapy regimen that included assessment and attempts to correct vascular abnormalities, optimizing diabetes control, nutrition, debridement, moist wound dressing, off-loading, and treatment of underlying infection."

      Sample Order

      CLINICAL EVIDENCE AND RECOMMENDATIONS  

      Hyperbaric Oxygen Therapy for Diabetic Foot Ulcer

        Transcutaneous Oximetry (TCOM)

        • TCOM is a valuable tool to guide the management of hypoxia wounds or ulcers. It should never be used as a regulatory statute or requirement. 
        • While the Fife TCOM studies [15][16] have been used to predict DFU healing based on response to oxygen challenge, we submit that all of the results in these studies are retrospective in nature and cannot (with any degree of certainty) be used as predictors or diagnostic hurdles in order to decide whether or not to treat a patient with HBO therapy. There are nearly 20% of DFU in a study that are well below the predicted wound healing failure values that go on to heal. There are a significant number of DFU with TcPO2 values of less than 10mmHg who have little to no response to oxygen that go on to heal.  
        • In addition, the Fife studies  are not homogenous data pools. They consist of patients treated in monoplace and multiplace hyperbaric chambers. These patients were not divided by age, Wagner score, or any other criteria prior to data analysis. Some were treated at 2.0 ATA for 90 minutes of oxygen breathing. Some were treated at 2.0 ATA for 120 minutes. Some were treated at 2.4 ATA for 90 minutes and air breaks. Some were tobacco users and some not. This is a simple fact that is common with retrospective analysis of a large data pool. 

        Hemoglobin A1c

        • HbA1c is a test that give some idea of blood glucose control over the previous 3 to 4 weeks. [17]  While the HbA1c is an important parameter, this paper looked at 25 clinical studies of a variety of wounds or surgical incisions for wound healing implications. The authors looked at the HbA1c levels for wounds that healed and wounds that did not heal during the course of the study. They found no correlation between HbA1c levels and wound healing. There were patient outliers with HbA1c levels greater than 12.0% that went on to heal. Others with HbA1c levels less than 6.0% did not heal. HbA1c is a valuable resource and gives us opportunity to encourage patients to better manage blood glucose. However, HbA1c should never be used in a regulatory fashion. There is no scientific evidence to link HbA1c and wound healing. There are definite links to HbA1c control and microretinopathy (retinal bleeds) and microangiopathy with failure of the basement membrane leading to chronic kidney disease and dialysis.
        • In our opinion, any patient with a DFU needs to be evaluated with limb salvage in mind. We encourage wound care centers to become centers of limb salvage for patients with diabetes mellitus and end-stage organ changes due to diabetes. [9] This paper demonstrates prevention of major amputations of the lower extremity in patients with severe DFU. A multi-specialty staff is necessary in order to prevent amputations. In our institution, this staff consists of hyperbaric and wound care physicians, podiatrists, nurse practitioners, interventional radiologists, peripheral vascular cardiologists, and plastic/reconstructive surgeons. 

        CODING

        See specific ICD-10 coding for DFU in  "ICD-10 Coding "

        APPENDIX

        Summary of Evidence

        We reviewed the clinical guidelines, systematic reviews, meta-analyses and clinical trials summarized below. Applying the GRADE framework to the combined body of evidence, we found that:

        • Moderate certainty evidence supports the use of HBOT as adjunctive therapy to promote DFU healing and prevent amputation (evidence level B). The systematic reviews and meta-analyses [18][19] included the same RCTs. Both agreed that HBOT as adjunctive therapy significantly improved DFU healing, however they differed in regards to amputation prevention. The 2015 Cochrane meta-analysis [19] calculated the relative risk between intervention and control, and the 2016 SVS-commissioned meta-analysis [18]  calculated the Peto odds ratio, which was considered by authors of the 2016 meta-analysis as more precise. Clinical guidelines also relied on the same RCTs to grade evidence, however, their classification system differed. In analyzing the RCTs, most were small populations and were at high or moderate risk of bias, however, one larger RCT (94 participants) [20] was better designed and can be considered of moderate evidence level (evidence level B)

        - Systematic reviews and meta-analyses

        • A 2016 systematic review and meta-analysis [18] included 18 studies, of which 9 were RCTs, enrolling 1526 participants in total. Based on six RCTs, HBOT was associated with increased healing rate (OR, 14.25; 95% CI, 7.08-28.68, I2 = 0%) and reduced major amputation rate (OR, 0.30; 95% CI, 0.10-0.89, I2 = 59%) compared with conventional therapy. The quality of this evidence is considered low to moderate, potentially downgraded due to methodologic limitations of the included studies. In the experimental groups, HBOT was given in addition to conventional therapy (wound care and offloading). In most studies, HBO was given at 2.0 to 3.0 atmospheric pressure in daily 90-minute sessions in a monoplace or multilplace chamber. On average, patients received 30 sessions, although a few patients in one study received 60 sessions. [21] [22] Authors concluded that there is low- to moderate-quality evidence supporting the use of HBOT as adjunctive therapy to enhance DFU healing and potentially prevent amputation. 
        • A 2015 Cochrane systematic review and meta-analysis [19] pooled data of 5 RCTs [20] [22] [23] [24] , showed an increase in the rate of ulcer healing (RR: 2.35, 95% confidence interval (CI) 1.19 - 4.62; P = 0.01) with HBOT at six weeks but this benefit was not evident at longer-term follow-up at one year. There was no statistically significant difference in major amputation rate (pooled data of 5 RCTs with 312 participants, RR 0.36, 95% CI 0.11 - 1.18). Authors concluded that In people with foot ulcers due to diabetes, HBOT significantly improved the DFU healing rate in the short term but not the long term. The existing trials had various flaws in design and/or reporting that means we are not confident in the results. 

        - Clinical guidelines

        • The 2016 Society for Vascular Surgery in association with American Podiatric Medical Association (SVS) [25], the 2016 Wound Healing Society (WHS) [26], the 2012 Wound, Ostomy, and Continence Nurses Society (WOCN) (Wound, Ostomy, and Continence Nurses Society (WOCN) 2012) [27], the 2014 Undersea and Hyperbaric Medicine Society (UHMS)  [28] and the 2017 European Committee for Hyperbaric Medicine (ECHM)  [29] guidelines support the use of HBO as an adjunctive therapy to promote DFU healing and prevent amputation  Documentation: HBO Risks and Benefits [2] 
        • The Undersea and Hyperbaric Medical Society established a hyperbaric oxygen review committee, using GRADE methodology, to establish a clinical practice guideline for the use of HBOT and DFU. Through a rigorous review process, all of the randomized controlled trials (RCT), non-randomized clinical trials, observational studies, and retrospective review studies were identified. From the GRADE review, three recommendations emerged that were statistically significant: 1) There is no support for using HBOT in Wagner Grade 1 or 2 DFU, 2) There is moderate support for using HBOT in Wagner Grade 3 DFU that has failed to show significant improvement after 30 days of standard wound care. This is present in lower amputations rates and higher healing rates. 3) There is moderate support for adding emergent HBOT for patients with deep plantar abscesses, necrotizing infections, who require immediate surgical debridement and drainage. 
        Intervention  SVS WHS WOCN UHMS ECHM
        Hyperbaric oxygen therapy as adjunctive therapy to promote DFU healing and reduce amputation rates Grade 2B Level I Level B AHA Class I Grade 2B

        - Negative studies: 

        • A recent longitudinal observational cohort study by Margolis et al [30] on 6259 individuals with diabetes, adequate lower limb arterial perfusion, and foot ulcer found that the use of HBO neither improved the likelihood of healing nor prevented amputation in a cohort of patients defined by Centers for Medicare and Medicaid Services eligibility criteria. The authors concluded that the usefulness of HBOT in patients with DFUs needs to be re-evaluated. On the other hand, closer scrutiny of the Margolis database shows that there were nearly 4,000 people with Wagner Grade 3 DFU, of whom, 67.7% never had adjunctive HBOT. HBOT was provided to a significant number of Wagner Grade 2 patients. Of those who were treated, data was not presented to determine whether or not more than 20 treatments were administered. This is a database of USA patients. It appears that this wound care company did not follow a standardized pathway to treat DFU. This data and the results of this retrospective analysis are suspect. The best conclusion that comes from this paper is that we (as a wound care community) can do a much better job of clinical care for our patients.   
        • The Fedorko study is troubling [31]. While it presents a negative study in regard to the use of HBOT and prevention of major lower limb amputation, there were no actual amputations performed on any of the patients in the study. The actual treatment wound care, and HBOT course was well standardized between sites. However, Fedorko, took a paper out of context [32] and used it to adjudicate patients to an amputation based solely on the vascular surgeon looking at a digital picture of the DFU and extremity. The Wirthlin paper was clear that it was a pilot study, used to assist with wound care patients only, and in a telehealth situation for home health visits. The conclusion of the Wirthlin paper is that the physicians who only reviewed the photographs tended to over-diagnose and over-treat the wounds captured. Therefore, Fedorko took a study technique that had no validation, changed the scenario from wound care to amputation, and recorded amputations based solely on a photograph. The best conclusion is that Fedorko counted 'phantom' amputations. Fedorko and co-authors are either naive or fraudulent. We have rebuttals from other researchers associated with this clinical trial who have multiple patients that were relegated to amputation by Fedorko and are still walking on a healed lower extremity. 
        • Santema [33] and colleagues designed a nice study to compare HBOT to standard care in DFU patients. However, the study suffered from enrollment problems and the researchers chose to downsize the statistics and power analysis to fit the number of patients enrolled. This creates the potential for a statistical Type II error, one of discounting a therapy when it could well have been positive if enough patients were enrolled in the original study. There are other problems with the paper, including only 65% of patients receiving the 30 HBOT treatments specified by protocol. Finally, this study enrolled a significant number of Wagner Grade 2 DFU (45% of the group). Reviewers for this paper should not have allowed these design errors to be published. 
        Official reprint from WoundReference® woundreference.com ©2018 Wound Reference, Inc. All Rights Reserved
        Use of WoundReference is subject to the Subscription and License Agreement. ​
        NOTE: This is a controlled document. This document is not a substitute for proper training, experience, and exercising of professional judgment. While every effort has been made to ensure the accuracy of the contents, neither the authors nor the Wound Reference, Inc. give any guarantee as to the accuracy of the information contained in them nor accept any liability, with respect to loss, damage, injury or expense arising from any such errors or omissions in the contents of the work.

        REFERENCES

        1. Lindell Weaver Editor. Undersea and Hyperbaric Medical Society, Durham, North Carolina. Hyperbaric Oxygen Therapy: Indications, 13th Edition. Best Publishing. 2014;.
        2. Huang ET, Mansouri J, Murad MH, Joseph WS, Strauss MB, Tettelbach W, Worth ER, UHMS CPG Oversight Committee. et al. A clinical practice guideline for the use of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2015;volume 42(3):205-47.
        3. CMS. National Coverage Determination (NCD) for Hyperbaric Oxygen Therapy (20.29) . 2017;.
        4. Armstrong DG, Boulton AJM, Bus SA et al. Diabetic Foot Ulcers and Their Recurrence. The New England journal of medicine. 2017;volume 376(24):2367-2375.
        5. Eggert JV, Worth ER, Van Gils CC et al. Cost and mortality data of a regional limb salvage and hyperbaric medicine program for Wagner Grade 3 or 4 diabetic foot ulcers. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2016;volume 43(1):1-8.
        6. Armstrong, David G; Cohen, Kelman; Courric, Stephane; Bharara, Manish; Marston, William et al. Diabetic foot ulcers and vascular insufficiency: our population has changed, but our methods have not. Journal of diabetes science and technology. 2011;volume 5(6):1591-1595.
        7. Sheehan P, Jones P, Giurini JM, Caselli A, Veves A et al. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Plastic and reconstructive surgery. 2006;volume 117(7 Suppl):239S-244S.
        8. Fife CE, Smart DR, Sheffield PJ, Hopf HW, Hawkins G, Clarke D et al. Transcutaneous oximetry in clinical practice: consensus statements from an expert panel based on evidence. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2009;volume 36(1):43-53.
        9. Van Gils CC, Wheeler LA, Mellstrom M, Brinton EA, Mason S, Wheeler CG et al. Amputation prevention by vascular surgery and podiatry collaboration in high-risk diabetic and nondiabetic patients. The Operation Desert Foot experience. Diabetes care. 1999;volume 22(5):678-83.
        10. Harry T. Whelan, Eric Kindwall et al. Hyperbaric Medicine Practice 4th Edition Best Publishing Company. 2017;volume fourth():.
        11. Weaver L . "Hyperbaric Oxygen Therapy Indications” Best Publishing Company, North Palm Beach, FL . 2014;volume 469(13th Edition,):.
        12. Eugene R. Worth MD, MEd, William H Tettelbach, MD, FACP, Harriet W. Hopf MD et al. Undersea and Hyperbaric Medical Society, Hyperbaric Oxygen Indications, 13th edition: Arterial Insufficiencies: Enhancement of Healing in Selected Problem Wounds . 2014;.
        13. Guo S, Counte MA, Gillespie KN, Schmitz H et al. Cost-effectiveness of adjunctive hyperbaric oxygen in the treatment of diabetic ulcers. International journal of technology assessment in health care. 2003;volume 19(4):731-7.
        14. Alavi, Afsaneh; Sibbald, R Gary; Mayer, Dieter; Goodman, Laurie; Botros, Mariam; Armstrong, David G; Woo, Kevin; Boeni, Thomas; Ayello, Elizabeth A; Kirsner, Robert S et al. Diabetic foot ulcers: Part II. Management. Journal of the American Academy of Dermatolog.... 2014;volume 70(1):21.e1-24; quiz 45.
        15. Fife, Caroline E; Buyukcakir, Cem; Otto, Gordon H; Sheffield, Paul J; Warriner, Robert A; Love, Tommy L; Mader, Jon et al. The predictive value of transcutaneous oxygen tension measurement in diabetic lower extremity ulcers treated with hyperbaric oxygen therapy: a retrospective analysis of 1,144 patients. Wound Repair and Regeneration. 2002;volume 10(4):198-207.
        16. Fife CE, Buyukcakir C, Otto G, Sheffield P, Love T, Warriner R 3rd et al. Factors influencing the outcome of lower-extremity diabetic ulcers treated with hyperbaric oxygen therapy. Wound repair and regeneration : official publication of the Wound Healing Society [and] the Eur.... 2007;volume 15(3):322-31.
        17. Moffat AD, Worth ER, Weaver LK et al. Glycosylated hemoglobin and hyperbaric oxygen coverage denials. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... 2015;volume 42(3):197-204.
        18. Elraiyah T, Tsapas A, Prutsky G, Domecq JP, Hasan R, Firwana B, Nabhan M, Prokop L, Hingorani A, Claus PL, Steinkraus LW, Murad MH et al. A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers. Journal of vascular surgery. 2016;volume 63(2 Suppl):46S-58S.e1-2.
        19. Kranke, P; Mh, Bennett; M, Martyn-st James; Schnabel, A; Se, Debus; Weibel, S et al. Hyperbaric oxygen therapy for chronic wounds ( Review ) Cochrane Database of Systematic Reviews. 2017;.
        20. Löndahl M, Landin-Olsson M, Katzman P et al. Hyperbaric oxygen therapy improves health-related quality of life in patients with diabetes and chronic foot ulcer. Diabetic medicine : a journal of the British Diabetic Association. 2011;volume 28(2):186-90.
        21. Ma L, Li P, Shi Z, Hou T, Chen X, Du J et al. A prospective, randomized, controlled study of hyperbaric oxygen therapy: effects on healing and oxidative stress of ulcer tissue in patients with a diabetic foot ulcer. Ostomy/wound management. 2013;volume 59(3):18-24.
        22. Khandelwal S, Chaudhary P, Poddar DD, Saxena N, Singh RA, Biswal UC et al. Comparative Study of Different Treatment Options of Grade III and IV Diabetic Foot Ulcers to Reduce the Incidence of Amputations. Clinics and practice. 2013;volume 3(1):e9.
        23. Kessler L, Bilbault P, Ortéga F, Grasso C, Passemard R, Stephan D, Pinget M, Schneider F et al. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes care. 2003;volume 26(8):2378-82.
        24. Abidia A, Laden G, Kuhan G, Johnson BF, Wilkinson AR, Renwick PM, Masson EA, McCollum PT et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. European journal of vascular and endovascular surgery : the official journal of the European So.... 2003;volume 25(6):513-8.
        25. Hingorani, Anil; LaMuraglia, Glenn M; Henke, Peter; Meissner, Mark H; Loretz, Lorraine; Zinszer, Kathya M; Driver, Vickie R; Frykberg, Robert; Carman, Teresa L; Marston, William; Mills, Jose... et al. The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. Journal of Vascular Surgery. 2016;volume 63(2 Suppl):3S-21S.
        26. Lavery, Lawrence A; Davis, Kathryn E; Berriman, Sandra J; Braun, Liza; Nichols, Adam; Kim, Paul J; Margolis, David; Peters, Edgar J; Attinger, Chris et al. WHS guidelines update: Diabetic foot ulcer treatment guidelines. Wound Repair and Regeneration. 2016;volume 24(1):112-126.
        27. Crawford PE, Fields-Varnado M, WOCN Society. et al. Guideline for the management of wounds in patients with lower-extremity neuropathic disease: an executive summary. Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy an.... 2013;volume 40(1):34-45.
        28. Undersea and Hyperbaric Medical Society Hyperbaric Oxygen Committee,, et al. Hyperbaric Oxygen Therapy Indications . 2014;.
        29. Mathieu, Daniel; Marroni, Alessandro; Kot, Jacek et al. Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving and hyperbaric medicine. 2017;volume 47(1):24-32.
        30. Margolis, David J; Gupta, Jayanta; Hoffstad, Ole; Papdopoulos, Maryte; Glick, Henry A; Thom, Stephen R; Mitra, Nandita et al. Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: a cohort study. Diabetes Care. 2013;volume 36(7):1961-1966.
        31. Löndahl M, Fagher K, Katzman P et al. Comment on Fedorko et al. Hyperbaric Oxygen Therapy Does Not Reduce Indications for Amputation in Patients With Diabetes With Nonhealing Ulcers of the Lower Limb: A Prospective, Double-Blind, Randomized Controlled Clinical Trial. Diabetes Care 2016;39:392-399. Diabetes care. 2016;volume 39(8):e131-2.
        32. Wirthlin DJ, Buradagunta S, Edwards RA, Brewster DC, Cambria RP, Gertler JP, LaMuraglia GM, Jordan DE, Kvedar JC, Abbott WM et al. Telemedicine in vascular surgery: feasibility of digital imaging for remote management of wounds. Journal of vascular surgery. 1998;volume 27(6):1089-99; discussion 1099-100.
        33. Santema KTB, Stoekenbroek RM, Koelemay MJW, Reekers JA, van Dortmont LMC, Oomen A, Smeets L, Wever JJ, Legemate DA, Ubbink DT, DAMO2CLES Study Group. et al. Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower- Extremity Ulcers in Patients With Diabetes: Results of the DAMO<sub>2</sub>CLES Multicenter Randomized Clinical Trial. Diabetes care. 2018;volume 41(1):112-119.
        Topic 129 Version 1.0

        Subtopics