DOCUMENTATION

The UHMS Guidelines Committee recommends patients with Wagner ≥3 DFU 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 DFU healing. Urgent HBOT should be added to the standard wound care 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 topic "Standard of Care: Foundations for Wound Management" and checklist below: 

•   HBOT request requirements checklist  

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 are no measurable signs of healing for at least 30 consecutive days. All components of standard wound care (determined by the payer in the NCD) shall be addressed in this documentation.

Physical Exam

• An initial assessment including a history and physical examination that clearly substantiates the condition for which HBOT 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 (All callus must be removed.)
  • Documentation of vascular status, assessment, and intervention/correction of any vascular problems in the affected extremity.
  • TCOM evidence demonstrating periwound hypoxia.
  • Include evidence of examination for foot pulses and record the ABI values.
• Documentation of optimization of nutritional status
• • Use a validated screening tool such as a Nestle mini nutritional assessment (MNA) 
  • Of note, the nutritional status of patients referred for HBOT may be inadequate for healing wounds, despite the fact that patients are often overweight or obese based on body mass index. Daily attendance for HBOT provides a unique opportunity to monitor and correct these deficiencies. Routine screening for malnutrition and supplement deficiencies is recommended for patients referred for HBOT.[16]
  • For details, see topic "How to Screen, Assess and Manage Nutrition in Patients with Wounds".
  • Laboratory biomarkers 
  • Albumin
  • Pre-Albumin
  • Of note, albumin and pre-albumin are strongly influenced by inflammation and less so by protein energy stores.[17] As such, the current consensus is that these laboratory biomarkers may be used as a complement to a thorough history and physical examination, but should not be used as the main indicator of nutritional status.[17] 
• 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.
  • Consider serum insulin levels, if appropriate.
• 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 (Foot) – (ICD-10 L series)

Plan

A typical hyperbaric regimen for a patient with a Wagner 3 or worse diabetic foot ulcer consists of daily 2.0 atmospheres absolute hyperbaric oxygen treatments with at least 90 minutes of oxygen breathing time during an HBO treatment or 2.4 ATA with 90 minutes of oxygen breathing time and appropriate air break breathing. This continues until the tissue has stabilized and the patient demonstrates progress toward healing. We may use a normobaric air TCOM level >40mm Hg as a surrogate. 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 TCOM evaluations.

Risk and Benefit of Hyperbaric Oxygen Therapy 

• Please refer to the topic "Documentation HBO: Risks and Benefits"

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 3 ulcer, an equivalent of the University of Texas IIB, IID, IIIB, or IIID ulcers. Progression to frank distal foot gangrene (Wagner grade 4) or gangrene involving the whole foot (Wagner grade 5) 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 3 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

•  See Sample Physician Order

Documentation by Certified Hyperbaric Nurse and Certified Hyperbaric Technician

The certified hyperbaric technician (CHT) and certified hyperbaric nurse (CHRN) should maintain an accurate record of the care and related support services delivered during each patient’s course of hyperbaric oxygen therapy. The patient's chart is a legal document and as such, must reflect in meaningful terms the patient's condition, progress, and care rendered. The provider and nurse's notes must be concise, accurate, and support medical necessity for the treatment ordered. The notes must reflect responsibility for the care rendered. For details, see topic "Documentation: Hyperbaric Treatment Notes by the CHRN and CHT"

Daily treatment should include, but is not limited to the following: 

• Physician Order - confirm daily HBO treatment order.
• Patient Assessment (by the CHRN or CHT) 
• Pre-treatment Safety Check (by the CHRN or CHT)
• Documentation of the Treatment Log (by the CHRN or CHT)
• Physician Supervision (by the CHRN or CHT)
• Care Provided (by the CHRN or CHT)
• Plan of Care (by the CHRN or CHT, based on physician orders)

UTILIZATION REVIEW

Few patients will require more than 40 sessions, but conducting more than 40 sessions would still be within acceptable practice parameters provided there is objective utilization review. This section provides guidance on important elements of a utilization review for DFU patients undergoing HBOT.[18]

• Utilization review should be performed after the initial 30 days of treatment and at least that frequently thereafter. 
  
• The review should include periodic re-evaluation and documentation of the continued adherence to the fundamental tenets described in the section 'Hyperbaric Criteria' above, as well as documentation of signs of clinical progress.[18]
• Documentation of signs of clinical progress include documentation of wound dimensions and presence or absence of improvement in wound healing. If signs or improvement are absent, documentation should include:
• Confounding factors that may explain such absence of improvement (e.g., surgical debridement of wound causing DFU enlargement)
• Status of VOIDS efforts (e.g., 'V'ascular optimization, 'O'ffloading of the neuropathic ulcer, 'I'nfection control, 'D'iabetes control, and 'S'urgical debridement), and
• A rationale and plan for further HBOT if needed

For patients who have had tissue hypoxia documented by TCOM, one should begin to see the effects of neovascularization within two to three weeks. A lack of improvement in TCOM measurements should discourage further HBOT.[18]

CLINICAL EVIDENCE AND RECOMMENDATIONS  

Hyperbaric Oxygen Therapy for Diabetic Foot Ulcer

• 1B For patients with DFU classified as Wagner 3 or higher, which failed to respond to standard therapy administered for at least 30 days, we recommend HBOT as adjunctive therapy to promote DFU healing and decrease chances of amputation (Grade 1B).
• 2BFor other patients with DFUs that failed to respond to at least 30 days of standard therapy and have demonstrated good transcutaneous oxygen values response to 100% oxygen, clinicians might consider HBOT to promote DFU healing and decrease chances of amputation (Grade 2B).
• • Rationale: Several clinical guidelines, backed by moderate level evidence, supports the use of HBOT as adjunctive therapy to promote DFU healing and decrease amputation rates if the DFU fails to heal after 4-6 weeks of standard therapy. Standard wound care (at the least) includes assessment, correction of vascular abnormalities, optimization of nutritional status and glucose control, debridement, moist wound dressing, offloading, and treatment of infection. HBOT therapy in this context has been shown to be cost-effective particularly based on a long-term perspective.[8][19][20][21][22] 
  • Medicare covers HBOT as adjunctive therapy for patients with DFU classified as Wagner 3 or higher, which failed to respond to at least 30 days of standard wound care.[3] See topic "Standard of Care: Foundations for Wound Management".
  • Note: In the study published by Sheehan et. al., it is important for us to understand that the authors had only Wagner 1 and 2 patients enrolled.[23] In order to be in this study, the DFU could  not 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. DFU patients coming to your wound care/hyperbaric center will fit this exclusion criteria. (Remember that we can only use adjunctive HBOT for Wagner Grade 3 or 4 DFU.) Therefore, the results of the Sheehan paper should never be used as a regulatory barrier to care. You may need to carefully point this out to your fiscal intermediary in the appeal process.
    
  • Patients should be selected for this adjunctive therapy carefully because of the cost and burden of prolonged daily treatment. Transcutaneous oximetry is a tool that may help stratify patients who are most likely to benefit from HBOT. It should not be used as a tool to limit or regulate which patients may or may not benefit from HBOT.[24] 

• 2BFor patients with DFU classified as Wagner Grade 3 or higher, who have just undergone surgical debridement of an infected foot (e.g., partial toe or ray amputation; debridement of ulcer with underlying bursa, cicatrix or bone; foot amputation; incision or drainage (I&D) of deep space abscess; or necrotizing soft tissue infection), we suggest adding acute postoperative HBOT to standard wound care in order to reduce the risk of major amputation (Grade 2B)
• Rationale: Although not approved by many Medicare fiscal intermediaries, clinical practice and several articles have shown increased limb salvage and reduced infection when patients have HBOT daily or twice daily, in addition to standard hospital care.[2]  

Wagner Classification 

• In Wagner's original article, "The Dysvascular Foot: A System for Diagnosis and Treatment", the author mentions that "The chart of the natural history of foot breakdown depicts a return arrow to Grade zero from all of the grades except Grade Five. This indicates that any grade except "Five" may be converted back to a Grade Zero foot which has no open lesions. There may still be bony deformity or only a partial foot remaining."[7] Wagner's original intent seems to be to connect a particular Grade to a treatment algorithm.[25]
• While widely utilized to assess insurance coverage eligibility for HBOT, the Wagner classification system presents several limitations, as described in literature.[25][26] The Wagner classification system is based on the Meggit's classification system.[27] Both Meggitt's and Wagner's systems allow for bidirectional progression from Grade 0 to Grade 4 and regression from Grade 4 to Grade 0.[7][27] The property of bidirectionality is not generally accepted as a positive attribute to a classification system.[25] One reason is that many third-party reimbursement plans are tied to a particular wound description or class.[25] However, the original intent of Meggitt's and Wagner's was to allow for description of the dysvascular foot over a period of time pre- and post-surgery and for nonsurgical interventions.[25] In addition, the Wagner's classification system is a visual one, implemented without the aid of an objective precision device like a ruler, grid, or measuring tape. Subjective in nature, it may be considered a non-contact measurement system. Jeffcoate et al considers this subjectivity a major disadvantage of the system.[28] Furthermore, the the Wagner classification system does not account for severity of ischemia nor does it delineate gangrene due to infection versus ischemia.[26]
• As it relates to insurance coverage eligibility for HBOT and the use of the Wagner classification, Wagner describes Grade 3 ulcers as "Deeper tissues are involved and there is abscess, osteomyelitis, or tendonitis, usually with extension along the midfoot compartments of tendon sheaths".[7] Per the NCD for Hyperbaric Oxygen Therapy [3], in order for a DFU to qualify for HBO: 1. Standard Care as noted in the NCD must be performed; 2. The ulcer must be Wagner 3 or higher; 3. There must be no measurable signs of healing for 30 days. As a result, if a DFU is classified as Wagner 3 or higher but is healing, then HBOT is not indicated. Additionally, a strict reading of the NCD would preclude HBO beyond a total of 60 calendar days (two 30-calendar day periods).[3] Therefore, simply documenting a DFU as a 'healing Wagner Grade 3' DFU would not be sufficient to justify medical necessity for HBOT. 
•  For more information on Wagner and other DFU classifications see "Diabetic Foot Ulcers - Classification Systems". 
  

Transcutaneous Oximetry (TCOM)

• TCOM is a valuable tool to guide the management of hypoxia wounds or ulcers. It should never be used in a punitive form, such as a regulatory statute or requirement. 
  
• While the Fife TCOM studies [29][30] 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 of healing or failure. In addition, TCOM is a valuable tool and should not be a required diagnostic hurdle in order to decide if we should 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. In this Fife study set, there are a significant number of patients with DFU and critically low room air TCOM values of less than 10mmHg, and have little to no response to 1 ATA 100% 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 from multiple wound clinics. 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 were not. This is a simple fact that is common with retrospective analysis of a large data pool. Retrospective reviews may show us what has happened in a large population of patients, however the study cannot be used to predict effectiveness or failure of a treatment modality. This requires a randomized controlled trial with a structure that attempts to reduce/remove all bias from the study population.

In-Chamber TCOM

• Because TCOM at pressure (2.0-2.4) may be most predictive of response to HBOT, it is reasonable to make a TCOM measurement under hyperbaric conditions. In the case of critical limb ischemia and imminent lower extremity amputation, TCOM and hyperbaric oxygen may salvage the limb and prolong life. If the values obtained suggest a lack of efficacy, but no alternative to amputation exists, it is appropriate to treat a patient 10-15 times in order to determine whether they will respond. This is commonly called a "test of pressure." By two to three weeks into HBO treatment, we expect to see the effects of neovascularization. Lack of response corroborated with the TCOM findings should discourage further HBOT.[12] 
  

Hemoglobin A1c

• HbA1c is a test that give some idea of blood glucose control over the previous 3 to 4 months.[31]  While HbA1c is an important parameter, this paper looked at 25 clinical studies of a variety of wounds and types of surgical incisions for wound healing implications. The studies were specifically not DFU patients, and included surgical abdominal wounds, multiple tooth extractions, and other surgical sites.
• The authors looked at 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. [13] 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. 

OPERATIONAL CONSIDERATIONS

Providing HBOT in a safe manner is the primary objective with each and every treatment. The clinical team (physician, CHT, CHRN, etc) providing HBOT goes to great lengths to ensure patient safety with every treatment. A summary of operational considerations pertaining to adjunct HBOT for DFU is provided below:

Chamber Inspections

• Routine chamber inspections should be conducted to confirm chamber maintenance procedures and the safe operation of all equipment utilized during HBOT.
• To ensure the safety of the environment in the hyperbaric medicine facility, chamber inspections are to be performed routinely (i.e. daily, monthly, semi-annually, as needed). Processes and systems that meet standards set forth by "Deeming Authorities" i.e. The Joint Commission (TJC) and the Undersea and Hyperbaric Medical Society (UHMS) should be utilized, and elements that have been developed within the field (in some cases through “near misses”) may be incorporated. These processes and systems can be implemented through customized patient-centered checklists. Checklists have a wide range of applications, with the potential to improve patient education, pre-procedure planning, discharge instructions, care coordination, chronic care management, and plans for staying well. 
• For resources on chamber inspections, see topic "HBO Safety Inspections".
  

Ground testing

• NFPA 99 requires that all hyperbaric chambers be grounded and patients inside chambers filled with 100% oxygen be likewise grounded. Wrist continuity tests prior to each treatment and daily chamber checks including chamber stud to wall measurements and patient ground jack to chamber stud measurements ensure ongoing continuity.

Prohibited Item(s), Assessment and Authorization

• Wound dressings, devices, and other objects that go in the hyperbaric chamber with the patient may raise important safety concerns, including the production of heat, production of static electricity, production of flammable vapor, ignition temperature, and total fuel load. It is critical that clinicians understand which dressings, devices, and objects are prohibited, restricted or allowed inside a hyperbaric chamber during HBOT for DFU.
• Frequently, questions arise in regards to which items are prohibited, restricted or allowed inside a hyperbaric chamber during HBOT. The NFPA 99 2018 edition, chapter 14 "Hyperbaric Facilities", provides the process for effectively managing patient care product(s) during HBOT.  The NFPA 99 2018 edition - 14.3.1.6.4.4 states “Physician and Safety Director approval to use prohibited items shall be stated in writing for all prohibited materials employed”.[32]
• Each hyperbaric facility should maintain an internal list of items that are approved for use, should be used with caution and should not be used in the chamber. An authorization form is required for items that should be used with caution. To facilitate assessment, clinicians might opt to utilize the Go-No-Go Risk Assessment Tool. The tool is an interactive process that enables hyperbaric technicians, Safety and Medical Directors to document the product information necessary to complete the risk assessment process. Upon completion of the process, the user will have the ability to print or email the document. In addition, clinicians can review lists of items that are approved for use, should be used with caution and should not be used in the chamber. See " Go-No-Go Lists / Prohibited Items" and "Go-No-Go: Frequently Asked Questions". 

Ancillary Equipment

• All equipment utilized by the hyperbaric medicine facility is maintained through a program of regular preventative maintenance. The manufacturer maintains the hyperbaric chambers during the regularly scheduled service contract. Ancillary equipment (e.g. cardiac monitor leads, TCOM sensors) should be serviced by the Hospital's Biomedical Department and maintained in accordance with the recommendations of the manufacturer. See topics "Ear Exam - Barotrauma" and "Ancillary Equipment".

Air Breaks

• During HBOT for DFU, it is necessary to provide an alternative air breathing source. This may also be necessary to reduce the risk of central nervous system oxygen toxicity.  The air breathing system consists of an independent high-pressure air source, capable of providing flow that is sufficient to meet the patient's inspiratory demand. Air breathing systems may be provided by institutional gas outlet (wall outlet) or via portable "H" cylinders utilizing a diameter index safety system (DISS) regulator.  Delivery of the air break to the patient may be provided by disposable non-rebreather mask, demand valve and resuscitation mask or trach collar. For purposes of infection control, masks should be single patient use and cleaned or replaced (per patient) as needed. 
• While the use of air breaks to decrease the incidence of CNS oxygen toxicity has not been directly demonstrated, there is a large amount of published data on the cause of oxygen toxicity related directly to a combination of the level of FiO2, and time. As such, these air breaks limit the interval time exposure and are expected to decrease the risk of oxygen toxicity. [33]

Infection Control - Cleaning/ Disinfection of the Hyperbaric Chamber

• The cleaning and disinfection of acrylic monoplace chambers is done with caution because many commercial biohazard-cleaning agents contain alcohol. While alcohol is adequate to kill many pathogens, it is destructive to acrylic and can produce flammable fumes and vapors creating a fire hazard in the chamber and the immediate area. Therefore, only manufacturer-approved cleaning products are used for disinfection of the hyperbaric chamber and accompanying equipment. Particular cleaning and disinfecting tasks are divided among staff from environmental services, equipment or biomedical device services, respiratory services, nursing, and other departments of the health care team. 
• Adverse outcomes related the risk of infection stands at the forefront of concern for patients with DFU. Particular attention should be given to cleaning and disinfection of the hyperbaric chamber acrylic, stretcher and associated equipment, including observing the specific kill times of the solution used prior to the delivery HBOT. See topic: "Cleaning and Disinfection of Hyperbaric Oxygen Monoplace Chamber" 
  

Barotrauma

• Assessment of the patient and their past medical history is necessary to identify and minimize the risk of barotraumas. If the patient has history of sinus, tooth, and ear problems, compress slowly and observe patient for signs of pain. 
• Middle-ear barotrauma: The most common type of barotrauma experienced by patients receiving HBOT is middle-ear barotrauma (MEB). Normally, the middle ear is a closed, vascular lined space and therefore subject to pressure change. The normal means by which the middle ear remains at an equal pressure with the surrounding tissue is through the opening of the Eustachian tube. During descent, the increasing pressure of the surrounding water leads to “middle-ear squeeze.” If a patient is suffering from Eustachian tube dysfunction, he or she likely will be unable to equalize and will subsequently develop middle-ear barotrauma.[14]
• Pneumothorax: A complete and accurate pulmonary assessment is essential to avoid or prevent gas expansion problems. Assessing the patient with a significant pulmonary history is a key starting point. Identify any history of asthma, chronic obstructive pulmonary dysfunction (COPD), fibrosis, spontaneous pneumothorax, or chest trauma.
• The absolute contraindication for HBOT is the unvented pneumothorax.
• Signs and symptoms of pneumothorax include: Sudden shortness of breath, Sudden stabbing chest pain, Tracheal shift to affected side in cases of tension, Asymmetrical chest movement (lack or reduced chest excursion on affected side), Increase in respiratory distress with decompression, with relief on recompression. [14]

Blood Glucose Level and HBOT

• It is necessary to ensure that all patients who are currently being treated for irregular blood glucose levels do not experience a hypoglycemic event as a result of ongoing HBOT. Most studies suggest that blood glucose decreases in patients with diabetes who undergo HBOT. This decrease in blood glucose is estimated at 50 mg/dl. HBOT might not be as effective in patients with non-insulin dependent diabetes mellitus patients, compared to patients without diabetes.[14]
• For all patients with DFU, blood glucose should be checked within 1 hour prior to treatment and immediately post-HBOT. The goal is to ensure that all patients who are currently being treated do not experience a hypoglycemic event as a result of ongoing HBOT. Hypoglycemia in the hyperbaric environment may present similar symptoms as oxygen toxicity, including but not limited to sweating, pale skin, shakiness, anxiety, tingling or numbness of the tongue or cheek. See section 'Blood Glucose Level and HBOT' in topic "Patient Care".

Medications in the hyperbaric environment

• The hyperbaric environment creates numerous considerations for the use of drug therapies within it. Physiologic changes to the body due to HBOT may lead to pharmacokinetic changes in drug disposition. In addition, HBOT acts as a drug and can interact, enhance or lessen the physiologic effect of the drug. Most drugs will not interact unfavorably with oxygen. Unless specific contraindications or precautions have been addressed, it is generally safe to assume a medication can be used. [14] Pharmacodynamic interactions result in modification of the pharmacologic effect of the drug after administration. These interactions will increase or decrease the effects of oxygen or the drug. [14] 
• Patients receiving antibiotics with elastomeric infusion pumps (also known as "space balls") may continue to receive antibiotics in the chamber, however infusion amounts during changes of atmospheric pressure should still be monitored. If the pump is full of air, then it may not provide standardized infusion rate. A study shows that the antibiotic flow rate for ceftazidime 6g is not significantly affected by increases in ambient pressure across the pressure range of 101.3 kPa to 284 kPa. However, there was evidence that the specific antibiotic solution might affect flow rates and this requires further study. 
• For potential interactions of drugs administered to patients with DFU, see topic "Medications In The Hyperbaric Environment".

Oxygen Toxicity

• The hyperbaric staff should be skilled in reducing the potential for and management of oxygen toxicity for the patient receiving HBOT. 
• Central Nervous System (CNS) oxygen toxicity can occur in patients breathing oxygen at pressures of 2.0 ATA (atmosphere absolute) or greater. Convulsions may occur abruptly or may be preceded by other signs of central nervous system irritability.  [14] Early estimates of the seizure rate during therapeutic oxygen exposures at 2-3 ATA reported a convulsion incidence of about one per 10,000 therapies or 0.01%.[14]
• The hyperbaric physician will be notified immediately if a patient experiences signs or symptoms of oxygen toxicity during HBOT.

CNS toxicity

• Observe patient closely for premonitory signs and symptoms of CNS Oxygen Toxicity such as:
• V : Vision-visual changes, blurred vision, visual hallucinations
• E : Ears- Auditory hallucinations, ringing in the ears
• N : Nausea- May include emesis
• T : Twitching- Restlessness, numbness, focal twitching (note time, duration and site)
• I : Irritability- Change in personality
• D : Dizziness- Vertigo
• C : Convulsions- Seizure activity
• C : Change in mentation - Change in affect or of a non-descriptive complaint like, “I just don’t feel right”  [34]

Pulmonary Oxygen Toxicity

• Most current applications of HBOT do not cause pulmonary symptoms or clinically significant pulmonary functional deficits.[35] Prolonged exposure to oxygen pressures greater than 0.5 ATA is associated with the development of intratracheal and bronchial irritation.  Pulmonary oxygen toxicity is not expected from routine daily HBOT. The possibility of development does exist with prolonged exposure most typically related to long treatment tables such as US Navy Treatment Table 6 used for decompression illness, but even these cases would be mild and self-limiting. [36]
• Continued oxygen exposure may lead to impaired pulmonary function and eventually acute respiratory distress syndrome (ARDS). Symptoms include:
• Substernal burning
• Chest tightness
• Cough
• Dyspnea
• These changes are seen over the course of days to weeks at lower oxygen pressures and occur more rapidly as the oxygen pressure is increased.[14]

Ocular Oxygen Toxicity

• Vision changes as a side effect of HBOT have been observed in patients undergoing prolonged periods of daily HBOT.  The rate of these changes has been reported in the literature to be ∼0.25 diopter per week and progressive throughout the course of ongoing treatment. Myopia has been reported in 25–100% of patients undergoing HBOT after several weeks at pressures of 2.0 ATA and greater. [36] When providing HBO for the patient being treated for DFU it is important to discuss the risks, hazards and potential side effects with the patient and family.  Documentation of this discussion and patient/ family's understanding should be clearly stated in the patient record.  For further information See topic:"Hyperbaric Oxygen Therapy and Visual Acuity"

NURSING INTERVENTIONS

Nursing interventions that are relevant for adjunct HBOT of DFU are presented below. [37] For further information see topic "Nursing Interventions".

Knowledge deficit related to hyperbaric oxygen therapy and treatment procedures

• Assess and document the patient and/or family's understanding of purpose and goals of HBOT, procedures involved, and potential hazards of HBOT.
• Utilize the teach-back method to confirm patient understanding and identify and address barriers to learning. Involve an interpreter if indicated, apply age-specific teaching, consider cultural/religious factors, assess readiness to learn, and identify patient's expectations of treatment. 
• See section 'Knowledge deficit related to hyperbaric oxygen therapy and treatment procedures' in topic "Nursing Intervention"

Anxiety related to hyperbaric oxygen treatments or other medical problems 

• Assess the patient for a history of confinement anxiety and implement preventative measures as appropriate. It is important to reinforce to patient that someone will always be with them, and the staff are well trained for emergency procedures. Identify signs of symptoms of anxiety before and during HBOT such as:
• Patient states anxiety
• Tense-appearing facial/body posturing
• Complaint of nausea or diarrhea
• Feelings of being confined or smothered
• Defensive or argumentative attitude
• Hyperventilation
• Diaphoresis and hyperventilation
• Tachycardia
• Restlessness
• Sudden feeling of being hot
• See section 'Anxiety related to hyperbaric oxygen treatments or other medical problems' in topic "Nursing Intervention"

Potential for injury within the hyperbaric facility related to transferring the patient in and out of the chamber

• Fuel sources in an oxygen-enriched environment are an unavoidable circumstance of HBOT and include linens, equipment, dressings, and the patient.  The fire triangle consists of oxygen, fuel, and an ignition source (heat).  In HBOT an ignition source is needed to complete the fire triangle. This may occur due to a spark in the chamber. Follow facility fire prevention steps and NFPA chapter 14 probes for Class A and Class B hyperbaric chambers. HBOT teaching and consent should include the risks of fire in the chamber.  Provide the patient and family with written instructions regarding the risk of prohibited materials during HBOT.  Prior to each hyperbaric treatment, staff should perform and document the pre-treatment safety checklist. Ensure this has been performed and time-stamped prior to descent.  Patients receiving treatment for DFU may have surgical dressings that are ordered to remain intact.  A risk assessment per the Safety Director in collaboration with the Medical Director to determine if they may enter the chamber on a case by case basis. Safety measures should be initiated if the risk assessment allows for item to enter the chamber as well as completion of a prohibited item's authorization form signed by the Safety and Medical Directors.

Potential for injury related to changes in atmospheric pressure within the hyperbaric chamber

• Assess patient's and inside attendant's knowledge of ear clearing techniques and ability to equalize pressure. Collaborate with provider to assess tympanic membrane (TM) for suspected barotrauma prior to and after the first HBO treatment and per patient complaint. Collaborate with the provider to describe and document observations including color and visibility of TM, presence of wax, blood/fluid/air and any hearing deficits or changes. Methods to equalize pressure in the middle ear during HBO treatment include: yawning, swallowing, jaw thrust, head tilt, Valsalva, Toynbee, Roydhouse, Frenzel, etc. Reinforce the importance of notifying the chamber operator immediately when pressure or fullness is felt in the middle ear.

Potential for unstable blood glucose level related to hyperbaric oxygen therapy and disease pathology

• Literature notes HBOT carries its own mechanism for increased glucose usage through oxygen-mediated transport of glucose into muscle cells and may also increase insulin sensitivity.  Prevention of acute hypoglycemia in the hyperbaric chamber is vital for patient safety.  Follow facility policy and procedure guidelines for pre and post-treatment glucose control.  Prior to treatment assess the patient's knowledge level, recent hypoglycemic events, and patient-specific symptoms of hypoglycemia.  Proper glucose control < 200mg/dL is vital for wound healing.  Consider timing of short and long-acting glycemic control medications when scheduling HBO to avoid peak action time while at depth in the chamber.

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 [38][39] 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 [39] calculated the relative risk between intervention and control, and the 2016 SVS-commissioned meta-analysis [38] 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) [40] was better designed and can be considered of moderate evidence level (evidence level B)

- Systematic reviews and meta-analyses

• A 2022 systematic review and meta-analysis included 20 randomized clinical trials and 1263 trials.[22]  For each trial, the average difference, odds ratio and 95% confidence interval were calculated to evaluate the efficacy. Hyperbaric oxygen therapy increased the healing rate of diabetic foot ulcers (relative risk, 1.901; 95% CI = 1.484-2.435, p < 0.0001), shortened the healing time (MD = -19.360; 95% CI = -28.753~-9.966, p < 0.001), and reduced the incidence of major amputation (relative risk, 0.518, 95% CI = 0.323-0.830, P < 0.01). Authors concluded that the meta-analysis confirmed that hyperbaric oxygen therapy offers great benefits in the treatment of DFU and the reduction of amputation.
• A 2021 systematic review and meta-analysis included 14 studies (768 participants).[21] The results with pooled analysis have shown that HBOT was significantly effective in complete healing of diabetic foot ulcer (OR = 0.29; 95% CI 0.14–0.61; I2 = 62%) and reduction of major amputation (RR = 0.60; 95% CI 0.39–0.92; I2 = 24%). Although, it was not effective for minor amputations (RR = 0.82; 95% CI 0.34–1.97; I2 = 79%); however, less adverse events were reported in standard treatment group (RR = 1.68; 95% CI 1.07–2.65; I2 = 0%). Nevertheless, reduction in mean percentage of ulcer area and mortality rate did not differ in HBOT and control groups. Authors concluded that the review provides an evidence that hyperbaric oxygen therapy is effective as an adjunct treatment measure for the diabetes foot ulcers. 
• A 2020 systematic review and meta-analysis [41] included 11 studies (n=729 patients), of which 7 were RCTs. Authors concluded that adjuvant HBOT improves major amputation rate, but not wound healing, in patients with DFUs and peripheral artery disease (PAD). However, the review included patients with DFU Wagner grades 1 to 4, and not only DFUs with Wagner grade 3 or higher, as recommended by clinical guidelines.[2]  Authors acknowledge that given the wide range of patients included in the trials, better patient selection may help define which patients with DFUs and PAD benefit most from HBOT as standard adjunctive treatment.
• A 2016 systematic review and meta-analysis [38] 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 methodological 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 multiplace chamber. On average, patients received 30 sessions, although a few patients in one study received 60 sessions. [42] [43] 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 [39] pooled data of 5 RCTs [40][43][44][45][42], 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) [5], the 2016 Wound Healing Society (WHS) [46], the 2012 Wound, Ostomy, and Continence Nurses Society (WOCN) (Wound, Ostomy, and Continence Nurses Society (WOCN) 2012) [47], the 2014 Undersea and Hyperbaric Medicine Society (UHMS)  [48] and the 2017 European Committee for Hyperbaric Medicine (ECHM)  [49] guidelines support the use of HBO as 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 amputation 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.[2] 

- Negative studies: 

• A 2013 longitudinal observational cohort study by Margolis et al [50] 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. On the other hand, HBOT was provided to a significant number of Wagner Grade 2 patients in this cohort. 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 by a large wound healing company. 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.[51] 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 plan was well standardized between sites. However, Fedorko, took a paper out of context (Wirthlin) [52] and used it (never having scientifically validated use to this population of patients) 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 wound photographs captured. Therefore, Fedorko took a study technique that had no validation, changed the scenario from home health 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. Some were healed and walking with in weeks of being adjudicated to the amputation subgroup.
• Santema 2CLES Multicenter Randomized Clinical Trial. | 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. | 2018" target="_blank" style="background-color: rgb(255, 255, 255); color: rgb(35, 82, 124); outline: 0px;">[53] 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, that 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 a research protocol with these design errors to be published. 

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