Medical Policies - Therapy


Hyperbaric Oxygen (HBO2) Therapy

Number:THE801.003

Effective Date:10-01-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

ALERT: Health Care Services Corporation (HCSC) has created a form to facilitate review of requests for coverage of HBO2 therapy, located on the “Provider / Forms” page of each HCSC web site, i.e., BCBSIL.com, BCBSMT.com, BCBSNM.com, BCBSOK.com, or BCBSTX.com.

Therapy with TOPICAL hyperbaric oxygen (THBO2) pressurization for any indication or clinical condition is considered experimental, investigational and/or unproven.

NOTE 1: This medical policy does not address THBO2 therapy in the absence of pressurization (i.e., topical hyperbaric oxygen wound care).

Therapy with SYSTEMIC hyperbaric oxygen (HBO2) pressurization may be considered medically necessary for the medical conditions and circumstances listed below. ALL requests and claims must include documentation of medical necessity.

ALL the following documentation requirements for SYSTEMIC HBO2 pressurization therapy MUST accompany requests and claims for treatment:

When services are in excess of 1-month duration, AND/OR when services are in excess of the number of treatments listed in the grid below or listed as individual consideration; AND

Documentation must include AT LEAST TWO of the following:

1. Photo record(s), or

2. Consultation reports, or

3. Operative or treatment reports and/or other applicable hospital records (e.g., pathology report, history and physical), or

4. Office records; AND/OR

Documentation of wounds only, should include the following:

1. Primary diagnosis,

2. Secondary diagnosis,

3. Contributing factors to the primary diagnosis,

4. Co-morbid factors,

5. Prior therapy,

6. Wound description (cause, location, measurements [size, depth, undermining, granulation]),

7. Wagner classification system grade level (see NOTE 2 below in grid), AND

8. Whether this is initial treatment or extension of treatment.

ALERT: The prior approval process may be a useful method of establishing medical necessity.

The medical conditions and circumstances that may be considered medical necessary are listed in the grid below. This includes the number of treatments initially allowed for each approved condition. Approval of treatment or services beyond the number initially authorized requires review of pertinent medical record documentation. Additional information about these requirements is contained within the policy document.

IF THE MEDICALLY NECESSARY DIAGNOSIS IS:

THEN REVIEW (1) :

Diabetic wounds, which include foot wounds or marginally perfused wounds, are considered non-healing of the lower extremities in diabetic patients who meet ALL the following three criteria:

Patient has type 1 or type 2 diabetes and has a lower-extremity wound that is due to diabetes, AND

Patient has a wound classified as Wagner grade-3 or higher (see NOTE 2), AND

Patient has no measurable signs of healing after 30 days of an adequate course of standard wound therapy.

Acute postoperative foot surgical treatment for patients with Wagner grade-3 or higher diabetic foot ulcers.

NOTE 2: The Wagner classification system of wounds is defined as follows:

Grade-0 = no open lesion;

Grade-1 = superficial ulcer without penetration to deeper layers;

Grade-2 = ulcer penetrates to tendon, bone, or joint;

Grade-3 = lesion has penetrated deeper than grade-2 and there is abscess, osteomyelitis, pyarthrosis, plantar space abscess, or infection of the tendon and tendon sheaths;

Grade-4 = wet or dry gangrene in the toes or forefoot; and,

Grade-5 = gangrene involves the whole foot or such a percentage that no local procedures are possible and amputation (at least at the below the knee level) is indicated.

NOTE 3: Treatments are usually given daily for 90- to 120-minutes. The initial treatment depends on severity of disease. More serious diabetic wounds may require twice daily treatments; and once stabilized treatments may be done once daily.

After 30 treatments.

Chronic refractory osteomyelitis.

After 30 treatments.

Soft-tissue radiation necrosis (i.e., radiation enteritis, cystitis, proctitis) and osteoradionecrosis (ORN).

NOTE 4: For soft-tissue radiation necrosis, review is required after each 20 treatments. Treatments are usually given daily for 90 to 120 minutes. Beyond 60 treatments, individual consideration is applied.

NOTE 5: For ORN, the initial course of treatment for patients with Stage I osteoradionecrosis include HBO2 followed by débridement. Stage II, if the patients are not responding, more extensive débridement, followed by additional HBO2. For patients presenting at Stage III, HBO2 is started followed by mandibular segmental resection with additional HBO2 therapy. Beyond the initial therapy course, individual consideration is applied.

After 20 treatments.

Crush injury, reperfusion injury, compartment syndrome, and other acute traumatic ischemias.

NOTE 6: Three treatments per day for 48-hours followed by two treatments per day over the second 48-hours and one treatment per day over the third period of 48-hours. Beyond this time period, individual consideration is applied.

After 12 treatments.

Venous stasis ulcer, only if venous surgery, local wound care, leg elevation, counterpressure support, and skin grafting fails for patients who have a wound classified as Wagner grade-3 or higher (see NOTE 2).

NOTE 2: The Wagner classification system of wounds is defined as follows:

Grade-0 = no open lesion;

Grade-1 = superficial ulcer without penetration to deeper layers;

Grade-2 = ulcer penetrates to tendon, bone, or joint;

Grade-3 = lesion has penetrated deeper than grade-2 and there is abscess, osteomyelitis, pyarthrosis, plantar space abscess, or infection of the tendon and tendon sheaths;

Grade-4 = wet or dry gangrene in the toes or forefoot; and,

Grade-5 = gangrene involves the whole foot or such a percentage that no local procedures are possible and amputation (at least at the below the knee level) is indicated.

After 12 treatments.

Compromised skin graft or flap, or for enhancement of healing in a selected problem wound.

After 12 treatments.

Gas gangrene (i.e., clostridial myonecrosis) and includes Meleney's postoperative gangrene ulcer.

NOTE 7: Treatments may be as often as three during the first 24-hours for 90-minutes, then 2-sessions per day for the next 2- to 5-days, depending on the patient’s initial response.

After 10 treatments.

Soft tissue infections due to mixed aerobic and anaerobic organisms with tissue necrosis and refractory bacteroides infections.

After 10 treatments.

Decompression sickness.

NOTE 8: Treatment times vary; depending on length of time elapsed between symptoms and initiation of treatment and between residual symptoms after initial treatment. The majority of cases respond to a single treatment. Usual time between treatments ranges from 90-minutes to 14-hours. Repetitive treatments may be necessary, depending on the patient’s response.

After 10 treatments.

Acute air or gas embolism.

After 10 treatments.

Brown recluse spider bite.

After 5 treatments.

Acute carbon monoxide poisoning (intoxication) and smoke inhalation (not chronic) and may be complicated by cyanide poisoning.

NOTE 9: Treatments will vary based on persistent neurologic dysfunction after the initial treatment and may be as frequent as once or twice daily, until there is no additional improvement in cognitive function.

After 5 treatments.

Thermal burns, second or third degree burns involving 15% to 90% of total body surface and initiated within 24 hours of the burn injury.

After 5 treatments.

Idiopathic sudden sensorineural hearing loss (ISSNHL).

After 5 treatments.

Acute cyanide poisoning, and may be complicated by carbon monoxide poisoning.

NOTE 9: Treatments will vary based on persistent neurologic dysfunction after the initial treatment and may be as frequent as once or twice daily, until there is no additional improvement in cognitive function.

For individual consideration of number of treatments.

Exceptional blood loss anemia (profound/severe), as the result of class IV hemorrhage, HBO2 is indicated when the patient will not accept blood replacement for medical or religious reasons and the following symptoms are present:

  • Shock, systolic blood pressure below 90 mm Hg, or pressure maintained by vasopressors; and
  • Disorientation to coma; and
  • Ischemic changes of the myocardium as demonstrated on the electrocardiogram (EKG); and
  • Ischemic gut.

NOTE 10: HBO2 therapy is continued as needed and discontinued when the red blood cells have been replaced in numbers to alleviate the precipitating signs and symptoms.

For individual consideration of number of treatments.

Selected refractory mycoses (mucormycosis, actinomycosis, or canibolus coronato).

For individual consideration of number of treatments.

Intracranial abscess.

For individual consideration of number of treatments.

Acute cerebral edema.

For individual consideration of number of treatments.

Arterial insufficiency ulcer (not acute) which persists after reconstructive surgery has restored large vessel perfusion (includes peripheral vessels).

For individual consideration of number of treatments.

Decubitus ulcers.

For individual consideration of number of treatments.

Pre- and post-treatment for patients undergoing dental surgery (non-implant-related) of an irradiated jaw.

For individual consideration of number of treatments.

Special Comment: A course of treatment may range from less than 1 week to several months’ duration, depending on the severity of the patient's condition and response to therapy. The average length of treatment is 2 to 4 weeks.

SYSTEMIC HBO2 pressurization therapy is considered experimental, investigational and/or unproven, including but not limited to the following indications or clinical conditions and any diagnosis not previously listed as covered:

Actinic keratosis (AK) or actinic skin damage;

Amyotrophic lateral sclerosis;

Arterial peripheral insufficiency, acute;

Asthma;

Autistic spectrum disorders;

Avascular necrosis;

Bell’s palsy;

Bone grafts;

Carbon tetrachloride poisoning, acute;

Cardiogenic shock;

Cerebral palsy;

Cerebrovascular accident (CVA), acute thrombotic or embolic, or chronic;

Coronary syndromes, acute, and as an adjunct to coronary interventions, including but not limited to percutaneous coronary interventions (PCI) and cardiopulmonary bypass;

Depression;

Fibromyalgia;

Fracture healing;

Spinal cord injury, traumatic;

Hepatic necrosis;

Hepatitis;

Herpes zoster;

Human immunodeficiency virus infection or acquired immune deficiency syndrome (HIV/AIDS);

Hydrogen sulfide poisoning;

Idiopathic femoral neck necrosis;

Ileus, postoperative;

Inflammatory bowel disease, including Crohn’s disease (CD), severe or refractory or ulcerative colitis;

Intra-abdominal abscesses;

In-vitro fertilization;

Ischemic stroke, acute;

Lepromatous leprosy;

Lyme disease;

Lymphedema of arm, chronic, following radiotherapy for cancer;

Meningitis;

Mental illness, generalized anxiety disorder or depression;

Migraine or cluster headaches;

Motor dysfunction associated with stroke;

Multiple sclerosis;

Muscle soreness, delayed onset or sport’s injury;

Myocardial infarction (MI), acute;

Organ transplantation or storage;

Osteoarthritis;

Osteomyelitis, acute;

Osteonecrosis of the jaw, bisphosphonate-related;

Pancreatitis, acute;

Parkinson’s disease;

Post-traumatic stress disorder (PTSD), traumatic brain (head) injury (TBI) or other stress disorders;

Pseudomembranous colitis, antimicrobial agent-induced colitis;

Pulmonary emphysema;

Pyoderma gangrenosum;

Radiation-induced injury to head, neck, anus, or rectum (except proctitis);

Radiation necrosis of non-neurologic tissue;

Radiation-myelitis;

Radiation therapy, adverse effects, at any point of therapy, including early onset effects and delayed effects (i.e., extremity lymphedema associated with cancer radiation);

Retinal artery insufficiency, acute within the first 24 hours of diagnosis;

Retinopathy, as an adjunct to scleral buckling procedure in patients with sickle cell peripheral retinopathy and retinal detachment;

Rheumatoid arthritis;

Sickle cell crisis and/or hematuria;

Senility;

Septicemia, anaerobic (unrelated to clostridial), or systemic aerobic infection;

Surgical and traumatic wounds, acute;

Sudden deafness (unrelated to ISSNHL);

Tetanus;

Tumor sensitization for cancer treatments includes but not limited to, radiotherapy or chemotherapy; AND

Vascular dementia or chronic brain syndromes, neovascular causes (such as Pick’s disease, Alzheimer’s disease, and Korsakoff’s disease).

NOTE 11: Breathing 100% O2 at one atmosphere without the use of a pressurized chamber is not considered to be HBO2 pressurization.

Description:

Hyperbaric oxygen (HBO2) pressurization therapy is a technique of delivering higher pressures of oxygen (O2) to the tissues. Two methods of delivery are available, topical and systemic.

Background

Topical HBO2 (THBO2) Therapy

THBO2 therapy is a technique of delivering 100% O2 directly to an open, moist wound at a pressure slightly higher than atmospheric pressure. It is hypothesized that the high concentrations of O2 diffuse directly into the wound to increase the local cellular O2 tension, which in turn promotes wound healing. Devices consist of an appliance to enclose the wound area (frequently an extremity) and a source of O2; conventional O2 tanks may be used. The appliances may be disposable and may be used without supervision in the home by well-trained patients. THBO2 therapy has been investigated as a treatment of skin ulcerations resulting from diabetes, venous stasis, postsurgical infection, gangrenous lesion, decubitus ulcers, amputations, skin graft, burns, or frostbite. THBO2 may be performed in the provider office, clinic, or may be self-administered by the patient at home. Typically, the therapy is offered for 90 minutes per day for 4 consecutive days. After a 3-day break, the cycle is repeated. This regimen may last for 8- to 10-weeks.

Systemic HBO2 Therapy

In systemic or large HBO2 chambers, the patient is entirely enclosed in a pressure chamber and breathes 100% O2 at a pressure greater than 1 atmosphere (atm; the pressure of O2 at sea level). Thus, this technique relies on systemic circulation to deliver highly oxygenated blood to the target site, typically a wound. Systemic HBO2 therapy can be used to treat systemic illness, such as air or gas embolism, carbon monoxide poisoning, or clostridial gas gangrene, etc. Treatment may be carried out either in a monoplace chamber pressurized with pure O2 or in a larger, multiplace (multiple patient unit) chamber pressurized with compressed air, in which case the patient receives pure O2 by mask, head tent, or endotracheal tube. A cycle of pressurization, with or without air breaks, inside an HBO2 chamber may be called “a dive”, which may last for 90 minutes or more.

Systemic HBO2 is a generally accepted medical treatment. HBO2 services include both consultative and therapeutic services. The HBO2 physician, certified by the American College of Hyperbaric Medicine (ACHM) and American College of Preventive Medicine (ACPM), must be actively present during all treatments.

Adverse Events

HBO2 therapy is a generally safe therapy, with an estimated adverse side effect rate of 0.4%. (1) Adverse events may occur either from pressure effects or the O2. The pressure effect (barotrauma) may affect any closed air-filled cavity such as ears, sinus, teeth, and lungs. Pain and/or swelling may occur at these sites as pressure increases during the procedure, and decreases as the procedure is ending. O2 toxicity may affect the pulmonary, neurologic, or ophthalmologic systems. Pulmonary symptoms include a mild cough, substernal burning, and dyspnea. Neurologic effects include tunnel vision, tinnitus, nausea, and dizziness. Ophthalmologic effects include retinopathy in neonates, cataract formation, and transient myopic vision changes.

Regulatory Status

In February 1999, the Numobag™ Kit (Numotech Inc., Woodland Hills, CA) for application of topical hyperbaric therapy was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA determined that this device was substantially equivalent to existing devices. The most recent topical oxygen therapy delivery devices to be approved are the Natrox™ Topical Oxygen Delivery System (Inotec Amd Ltd.) and Epiflo® (Neogenix LLC). Both of these devices were approved in 2012. FDA Product Code: KPJ.

In May 2005, the ATA Monoplace Hyperbaric System (ATA Hyperbaric Chamber Manufacturing Inc.) was cleared for marketing by the FDA through the 510(k) process. The FDA determined that this device was substantially equivalent to existing hyperbaric devices. FDA Product Code: CBF.

In 2013, the FDA published a statement warning that non-FDA approved uses of HBO2 therapy may endanger the health of patients. (2) If patients mistakenly believe that HBO2 therapy devices have been proven safe for uses not cleared by the FDA, they may delay or forgo proven medical therapies.

Rationale:

The medical policy was created in May 1990 and was based on a search of the MedLine database and subsequently on the Undersea and Hyperbaric Medical Society (UHMS) Guidelines and the Centers for Medicare and Medicaid Services (CMS) National Coverage Determination policy. The most recent literature search of MedLine was performed through July 2018. The following is a summary of the key literature reviewed to date. Due to the different hyperbaric oxygenation or hyperbaric oxygen (HBO2) methods of delivery, topical HBO2 (THBO2) and systemic HBO2 are distinct technologies such that they must be examined separately.

This medical policy assesses the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function--including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Evidence for a majority of the indications consists of Cochrane systematic reviews, which focus on summarizing RCTs, and when possible, conducting pooled analyses of results, and from the current UHMS guidelines.

Topical Hyperbaric Oxygen (THBO2) Therapy

In 2017, de Smet et al. conducted a systematic review of various O2 therapies (O2 dressing therapy, THBO2, HBO2 therapy, inspired O2 therapy). (3) Three RCTs evaluating topical O2 therapy for chronic wound healing were identified (see Table 1). One RCT (n=100) administered treatment for 20 minutes 3 times per day for 12 days to the treatment group and standard care to the control group. The number of patients experiencing complete wound healing, defined as complete epithelialization of the wound without drainage, was 16 in the experimental group and 1 in the control group (p<0.001). Two of the RCTs, which had overlapping populations with refractory venous ulcers (n=83 in one and n=132 in the other) administered treatment for 180 minutes 2 times per day for 12 weeks to the treatment group and conventional compression dressing to the control group. In all trials, patients in the treatment group experienced significantly higher proportions of healed ulcers and significantly faster healing times.

A small RCT (1988) not included in the systematic review evaluated 28 patients with diabetic foot ulcers who were assigned to topical HBO2 therapy plus standard wound care or standard wound care alone. (4) Changes in ulcer size and depth did not differ between the 2 groups following 2 weeks of treatment.

Table 1. Systematic Reviews of Trials Assessing Topical Hyperbaric Oxygen for Wounds

Study (Year)

Literature Search

Studies

Participants

N (Range)

Design

Results

de Smet

et al. (2017) (3)

Feb 2016

3

Stage II-IV sacral or ischial pressure ulcers (1 RCT)

Refractory venous ulcers (2 RCTs)

315a (83-132)

RCT

Results not pooled

In all trials, patients in the treatment group experienced significantly higher wound healing rates

Table Key:

RCT: randomized controlled trial;

N/n: number;

a: Two of the trials had overlapping populations, so there were not 315 unique patients.

Section Summary: THBO2

A systematic review identified 3 RCTs on the use of topical HBO2 therapy for chronic wound healing. The results showed THBO2 therapy improved wound healing, but there was heterogeneity in the trial populations and treatment regimens. There is a small RCT on THBO2 therapy for diabetic foot ulcers; it showed no differences in outcomes between the treatment and control group. No controlled studies on THBO2 therapy for patients with burns or infections were identified. The data are insufficient to draw conclusions about the effect on the net health outcome.

Systemic Hyperbaric Oxygen (HBO2) Therapy

The original medical policy on systemic HBO2 therapy was based entirely on the 1996 guidelines published by the UHMS; it was subsequently revised in 1999 based on 3 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessments. (5-7) Those TEC Assessments had conclusions similar to the UHMS, except, in contrast to the Society guidelines, TEC stated that there was insufficient evidence to conclude that HBO2 therapy improved the net health outcome for compromised skin grafts, acute thermal burns, chronic refractory osteomyelitis, necrotizing soft tissue infections, and brown recluse spider bites. The TEC Assessments also stated that there was insufficient evidence to permit conclusions on the use of HBO2 therapy for treatment of brain injury, spinal cord injury, and Crohn’s disease, indications not addressed by the 1996 UHMS Guidelines. Literature updates have focused on identifying new RCTs and meta-analyses of RCTs, particularly on indications considered experimental, investigational and/or unproven.

Chronic Wounds, Including Diabetic Ulcers

A Cochrane review of RCTs on HBO2 therapy for chronic wounds was published by Kranke et al. in 2015 (see Table 2). (8) Reviewers identified 12 RCTs (total n=577 participants) comparing the effect of HBO2 therapy on chronic wound healing with an alternative treatment approach that did not use HBO2 therapy. Ten of the 12 trials evaluated HBO2 therapy in patients with diabetes (n=531). The trials were assessed as moderate quality using the GRADE system. HBO2 therapy regimens varied across studies, ranging from 3.0 atmospheres absolute (ATA) for 45 minutes to 2.2 ATA for 120 minutes. In a pooled analysis of 5 trials, a significantly higher proportion of ulcers had healed at the end of treatment (i.e., 6 weeks) in the group receiving HBO2 therapy than in the group not receiving HBO2 therapy, but there was no statistically significant difference in the risk of major amputations between groups.

A 2016 systematic review by Elraiyah et al. evaluated adjunctive therapies (HBO2 therapy, arterial pumps, and pharmacologic agents) used to treat diabetic foot ulcers (see Table 2). (9) RCTs and nonrandomized cohort studies were included. The RCTs were rated as low-to-moderate quality using the GRADE system. A pooled analysis of 6 RCTs found a significantly higher healing rate and a significantly lower major amputation rate (odds ratio, 0.30; 95% confidence interval, 0.10 to 0.89) with HBO2 therapy than with control.

Table 2. Systematic Reviews of Trials Assessing HBO2 Therapy for Chronic Diabetic Foot Ulcers

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Kranke et al. (2015) (8)

Feb 2015

12

Patients with chronic wounds associated with venous or arterial disease, diabetes, or external pressure

577

RCTs

10 of 12 trials focused on patients with diabetic foot ulcers (n=531)

Pooled analysis of 5 of 10 trials (n=205) reported higher heal rates with HBO2 therapy (RR=2.3; 95% CI, 1.2 to 4.6) and no difference in amputation risk (RR=0.4; 95% CI, 0.1 to 2.2)

Elraiyah et al. (2016) (9)

Oct 2011

18

Patients with diabetic foot ulcers

1526

RCTs Cohorts

16 of 18 trials included HBO2 therapy as a treatment option and 6 of those were RCTs

Pooled analysis of the 6 RCTs (n=340) reported higher heal rate with HBO2 therapy (OR=14.3; 95% CI, 7.1 to 28.7) and lower amputation risk (OR=0.3; 95% CI, 0.1 to 0.9)

Table Key:

CI: confidence interval;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

OR: odds ratio;

RCT: randomized controlled trial;

RR: relative risk.

Section Summary: Chronic Wounds, Including Diabetic Ulcers

Multiple RCTs and 2 systematic reviews have been published. Seven RCTs were common in the 2 systematic reviews. Pooled analyses of RCTs found significantly higher wound healing rates with HBO2 therapy than with control conditions. One of the 2 meta-analyses found that HBO2 therapy was associated with a significantly lower rate of major amputation.

Carbon Monoxide Poisoning

A 2011 Cochrane review by Buckley et al. included 6 RCTs evaluating HBO2 therapy for carbon monoxide poisoning (see Table 3). (10) Four of the 6 trials were assessed as having a high risk of bias due to non-blinding of treatment allocation. The trials had substantial methodologic and statistical heterogeneity. The outcome of interest was dichotomous, presence or absence of signs or symptoms indicative of neurologic injury at 4 to 6 weeks after study inclusion. Two of the 6 RCTs found that HBO2 therapy reduced the likelihood of neurologic sequelae at 1 month and 4 others did not find a significant effect. A pooled analysis of the 6 trials did not find a significant effect of HBO2 therapy on neurologic injury. Reviewers concluded that there was insufficient evidence to determine whether HBO2 therapy reduces the risk of adverse neurologic outcomes after carbon monoxide poisoning. Quality of the evidence was deemed very low, using the GRADE system.

Table 3. Systematic Reviews of Trials Assessing HBO2 Therapy for Carbon Monoxide Poisoning

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Buckley et al. (2011) (10)

Jun 2010

6

Non-pregnant adults with acute carbon monoxide poisoning

1361

RCTs

Studies extremely heterogeneous in: severity of CO poisoning, HBO2 therapy regimens, and comparators

Pooled analyses of 6 trials (n=1361) reported no statistical difference in neurologic deficits between treatment groups (OR=0.78; 95% CI, 0.54 to 1.12)

Table Key:

CI: confidence interval;

CO: carbon monoxide;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

OR: odds ratio;

RCT: randomized controlled trial.

Section Summary: Carbon Monoxide Poisoning

A Cochrane review identified 6 RCTs, the majority of which did not find a significant effect of HBO2 therapy on health outcomes. A pooled analysis of the RCT data did not find a significant effect of HBO2 therapy on neurologic injuries and the quality of the evidence was considered very low.

Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw

HBO2 has long been used to treat soft tissue and bone radiation necrosis and for pre- and post-treatment of dental surgery (non-implant-related) in an irradiated jaw.

In 2016, Bennett et al. published a Cochrane review on HBO2 therapy for late radiation tissue injury (see Table 4). (11) Reviewers identified 14 RCTs. There was a moderate level of evidence for 2 pooled analyses. In a pooled analysis of 3 studies, a significantly higher proportion of patients with osteoradionecrosis achieved complete mucosal cover after HBO2 therapy compared with control treatments, and in a pooled analysis of 2 trials, a significantly lower risk of wound dehiscence after surgery to repair mandibular osteoradionecrosis with HBO2 therapy than with control treatments was reported. A single trial found a significantly higher likelihood of successful healing with HBO2 therapy than with antibiotics for tooth extraction in irradiated jaws (absolute risk reduction, 25%; p=0.02). There were insufficient data to conduct meta-analyses on other outcomes.

In 2017, Borab et al. published a systematic review focusing on the use of HBO2 therapy to treat the subgroup of patients with late radiation tissue injury had skin necrosis (see Table 4). (12) Reviewers identified 8 studies, including a large observational cohort and several case series. No RCTs were identified. The risk of bias was high due to the design of the included studies. The studies reported improved healing, though, without a comparator, interpretation of the results is limited.

In 2017, Ravi et al. published a systematic review on the use of HBO2 therapy to treat patients who had received radiotherapy for head and neck cancer. (13) Ten prospective case series and comparative studies were identified. Qualitative summaries of outcomes were provided, but pooled analyses were not performed. Outcomes of interest included osteonecrosis and dental implant survival (see Table 4). Other outcomes of interest included salivary gland function and quality of life, which are discussed in the Radiotherapy Adverse Events section.

Table 4. Systematic Reviews of Studies Assessing HBO2 Therapy for Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Bennett et al. (2016) (11)

Dec 2015

14

Patients with late radiation tissue injury (including necrosis) and patients treated with large-dose radiotherapy likely to induce early necrosis

753

RCTs

Pooled analyses of 3 trials of patients with osteoradionecrosis (n=246) found a higher rate of complete mucosal cover after HBO2 therapy versus control (RR=1.3; 95% CI, 1.1 to 1.5)

Pooled analyses of 2 trials (n=264) found a lower risk of wound dehiscence following surgery to repair mandibular osteoradionecrosis in patients treated with HBO2 therapy versus control (RR=4.2; 95% CI, 1.1 to 16.8)

Borab et al. (2017) (12)

May 2016

8

Patients with radiation-induced skin necrosis

720

OBS cohort and case series

Adding across the studies, 80% reported complete healing and 86% reported symptom improvement

Studies had no comparators

Ravi et al. (2017) (13)

Dec 2016

10

Patients who received radiotherapy for head and neck cancer

375

PRO case series and PCS

Osteonecrosis prevention: 1 case series and 1 comparative study (n=77) reported low osteonecrosis rates with HBO2 therapy

Dental implant survival: 1 case series and 2 comparative studies (n=122) report mixed results, with 2 studies finding implant survival improved with HBO2 therapy and another finding no difference in survival

Table Key:

CI: confidence interval;

CO: carbon monoxide;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

OBS: observational;

PRO: prospective;

PCS: prospective comparative study(ies);

RCT: randomized controlled trial;

RR: relative risk.

Section Summary: Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw

A Cochrane review of RCTs found that HBO2 therapy improved some radionecrosis and osteoradionecrosis outcomes and resulted in better outcomes before tooth extraction in an irradiated jaw. Observational studies focused on skin necrosis and reported high rates of healing with HBO2 therapy, though with no comparators, interpretation of results is limited. Prospective observational studies using HBO2 therapy for treatment on patients with head and neck cancer receiving HBO2 therapy, have reported low osteonecrosis rates and inconsistent results for dental implant survival. The number of RCTs evaluating HBO2 therapy for these indications, especially in irradiated jaws, is limited.

Chronic Refractive Osteomyelitis

No prospective clinical trials on chronic or refractory osteomyelitis were identified in literature searches. The evidence for the use of HBO2 therapy in chronic osteomyelitis has been primarily based on case series.

Among the larger case series, Maynor et al. (1998) reviewed the records of all patients with chronic osteomyelitis of the tibia seen at a single institution. (14) Follow-up data were available on 34 patients who had received a mean of 35 adjunctive HBO2 therapy sessions (range, 6-99 sessions). Of the 26 patients with at least 24 months of follow-up after treatment, 81% (21/26) remained drainage-free. At 60 months of follow-up, 80% (12/15), and at 84 months, 63% (5/8) remained drainage-free.

A study by Davis et al. (1986) reviewed outcomes for 38 patients with chronic refractory osteomyelitis treated at another U.S. institution. (15) Patients received HBO2 therapy until the bone was fully recovered with healthy vascular tissue; this resulted in a mean of 48 daily treatments (range, 8-103 treatments). After a mean post-treatment follow-up of 34 months, 34 (89%) of 38 patients remained clinically free of infection (i.e., drainage-free and no tenderness, pain, or cellulitis). Success rates from several smaller case series (number range, 13-15 patients), all conducted in Taiwan (1998-2000), ranged from 79% to 92%. (16-18) A high percentage of refractory patients in these series had successful outcomes.

Section Summary: Chronic Refractory Osteomyelitis

Only case series data are available; no RCTs or comparative nonrandomized trials were identified. Case series tended to find high rates of successful outcomes in patients with chronic refractory osteomyelitis treated with HBO2 therapy. However, controlled studies are needed to determine conclusively that HBO2 therapy improves health outcomes in patients with chronic refractory osteomyelitis compared with other interventions.

Acute Thermal Burns

In 2004, a Cochrane review assessed HBO2 therapy for thermal burns (see Table 5). (19) Two RCTs were identified, published in 1974 and 1997. Sample sizes were 16 and 125. Both trials were judged by reviewers to have poor methodologic quality. Reviewers concluded that the evidence was insufficient to permit conclusions on whether HBO2 therapy improves health outcomes in patients with acute thermal burns. Note that no additional trials were identified when an updated literature search was conducted in 2009 (the 2004 publication date continues to be used).

Table 5. Systematic Reviews of Trials Assessing HBO2 Therapy for Acute Thermal Burns

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Villanueva et al. (2009) (19)

Jun 2009

5

Patients with thermal injuries to the epidermis, subcutaneous tissues, vessels, nerve, tendons, or bone

141

RCTs

1 trial (n=125) reported no difference in length of stay, mortality, or number of surgeries between HBO2 therapy and control groups

1 trial (n=16) reported shorter healing times (19.7 days versus 43.8 days; p<0.001) with HBO2 therapy versus control, and an RR for failed graft without HBO2 therapy of 2.0 (95% CI 0.5 to 8.0)

Table Key:

CI: confidence interval;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

RCT: randomized controlled trial;

RR: relative risk.

Section Summary: Acute Thermal Burns

A Cochrane review identified 2 RCTs on HBO2 therapy for thermal burns. Both were judged to have poor methodologic quality. There is insufficient evidence from well-conducted controlled studies to permit conclusions on the impact of HBO2 therapy on health outcomes in patients with acute thermal burns.

Acute Surgical and Traumatic Wounds

In 2013, a Cochrane review of RCTs on HBO2 therapy for acute surgical and traumatic wounds was published by Eskes et al. (see Table 6). (20) HBO2 therapy was administered at pressures above 1 atmosphere (atm). To be included, studies had to compare HBO2 therapy with a different intervention or compare 2 HBO2 therapy regimens; also, studies had to measure wound healing objectively. Four RCTs met reviewers’ inclusion criteria. Trials ranged in size from 10 to 135 participants. Due to differences among trials regarding patient population, comparison intervention, and outcome measurement, results could not be pooled. The primary outcome examined by Cochrane reviewers (wound healing) was not reported in either of the 2 trials comparing HBO2 therapy with usual care and was not reported in the trial comparing HBO2 therapy with dexamethasone or heparin. Complete wound healing was reported in the RCT comparing active HBO2 therapy with sham HBO2 therapy. In this study (n=36), there was a statistically higher rate of wound healing in the group, though the time point for outcome measurement in this trial was unclear. Also, there was no statistically significant difference between groups in the meantime to wound healing.

A 2014 systematic review of studies on HBO2 therapy for acute wounds, published by Dauwe et al., included RCTs and controlled nonrandomized studies (see Table 6). (21) Reviewers included 8 studies, with sample sizes ranging from 5 to 125 patients. Four studies were randomized, 3 were prospective observational studies, and one was a retrospective observational study. As in the Eskes systematic review, data were not pooled. Reviewers noted that 7 of the 8 studies reported statistically significant findings for their primary end points, but the end points differed among studies (e.g., graft survival, hospital length of stay, wound size). Moreover, the studies were heterogeneous regarding treatment regimens, patient indications (e.g., burns, facelifts), and study designs making it difficult to draw conclusions about the effect of HBO2 therapy on acute wound treatment.

Table 6. Systematic Reviews of Trials Assessing HBO2 Therapy for Acute Surgical and Traumatic Wounds

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Eskes et al. (2013) (20)

Aug 2013

4

Patients with acute wounds (skin injuries occurring due to surgery or trauma)

229

RCTs

3 of 4 trials did not include wound healing as an outcome measure

A small trial (n=36) reported patients receiving HBO2 therapy had significantly higher wound healing rate versus sham; however, no difference in time to healing

Dauwe et al. (2014) (21)

Oct 2012

8

Patients with acute wounds, grafts, and flaps

256

RCTs and non-RCTs studies

HBO2 therapy may augment healing of acute wounds

Not indicated for routine wound management

Table Key:

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

RCT: randomized controlled trial.

Section Summary: Acute Surgical and Traumatic Wounds

Two systematic reviews identified 4 RCTs; one of the reviews also included nonrandomized studies. Heterogeneity among studies (e.g., in patient population, treatment regimen, comparison group, outcomes) prevented pooling of study findings and limited the ability to draw conclusions about the impact of HBO2 therapy on health outcomes in patients with acute and traumatic wounds. Additional evidence from high-quality RCTs is needed.

Bisphosphonate-Related Osteonecrosis of the Jaw

An unblinded RCT by Freiberger et al. (2012) evaluated the use of HBO2 therapy as an adjunct therapy for patients with bisphosphonate-related osteonecrosis of the jaw (see Tables 7 and 8). (22) The investigators did a per-protocol analysis (actual treatment received) because of the relatively large amount of crossover. Participants were evaluated at 3, 6, 12, and 18 months. At 3 months, significantly more patients receiving HBO2 therapy as an adjunct to standard care experienced improvements in lesion size and number compared with patients receiving only standard care. When the change from baseline to 6, 12, or 18 months was examined, there were no statistically significant differences between groups in the proportion of patients with improvement or in the proportion of those who healed completely at any time point. This trial had a number of methodologic limitations (e.g., unblinded, crossover, per-protocol analysis rather than intention-to-treat). A disadvantage of the per-protocol analysis is that randomization is not preserved, and the 2 groups may differ on characteristics that affect outcomes.

Table 7. Characteristics of Trials Assessing HBO2 Therapy for Bisphosphonate-Related Osteonecrosis of the Jaw

Treatment

Study (Year)

Countries

Sites

Dates

Participants

Active (n=25)

Comparator (n=21)

Freiberger et al. (2012) (22)

United States

NRa

2006-2010

Patients with bisphosphonate-related osteonecrosis of the jaw

HBO2 plus standard oral care

100% O2 at 2 ATA

40 treatments

Standard oral care (antiseptic rinses, surgery, and antibiotics)

Table Key:

ATA: atmospheres absolute;

HBO2 Therapy: hyperbaric oxygen therapy;

NR: not reported;

O2: oxygen;

RCT: randomized controlled trial;

a: Number of sites not reported, though all oncologists, dentists, and oral-maxillofacial surgeons in the referral area of central North Carolina, southern Virginia, and northern South Carolina were eligible to participate.

Table 8. Results of Trials Assessing HBO2 Therapy for Bisphosphonate-Related Osteonecrosis of the Jaw

Improved, % (n)

Healed, % (n)

Study (Year)

3 mos

Between-Group p Value

18 mos

Between-Group p Value

3 mos

Between-Group p Value

18 mos

Between-Group p Value

Freiberger et al. (2012) (22)

46

46

46

46

HBO2 Therapy

68.0 (25)

0.03

58.3 (12)

0.31

36.0 (25)

0.04

33.3 (12)

1.0

Control

35.0 (20)

33.3 (6)

10.0 (20)

33.3 (6)

Table Key:

HBO2 Therapy: hyperbaric oxygen therapy;

mos: months;

N/n: number.

Section Summary: Bisphosphonate-Related Osteonecrosis of the Jaw

One RCT evaluated HBO2 therapy for patients with bisphosphonate-related osteonecrosis of the jaw. This unblinded study reported initial benefits at the 3-month follow-up; however, there were no significant benefits of HBO2 therapy for most health outcomes compared with standard care in the long-term (6 months to 2 years). Additional evidence from RCTs is needed to permit conclusions on the impact of HBO2 therapy on health outcomes in patients with bisphosphonate-related osteonecrosis of the jaw.

Necrotizing Soft Tissue Infections

A 2015 Cochrane review by Levett et al. evaluated the literature on HBO2 therapy as adjunctive therapy for necrotizing fasciitis. (23) No RCTs were identified. Previously, in 2005, a systematic review by Jallali et al. identified only a few retrospective studies with small sample sizes. (24) Findings from these studies were inconsistent. A 2009 retrospective cohort study compared outcomes in 48 patients at 1 center who received adjunctive HBO2 therapy for necrotizing soft tissue infections with those in 30 patients at a different center who did not receive HBO2 therapy. (25) There were no significant differences in the mortality rates between the HBO2 therapy group (8% [4/48]) and the non-HBO2 therapy group (13% [4/30]; p=0.48). The median number of days in the intensive care unit and the median number of days in the hospital also did not differ significantly between groups. There was a higher median number of débridement procedures per person in the HBO2 therapy group (3.0) than in the non-HBO2 therapy group (2.0; p=0.03). Despite the available evidence just cited, HBO2 therapy for necrotizing soft tissue infections remains a valid treatment as cited earlier from reviews by the Alberta Heritage Foundation for Medical Research’s (AHFMR) March 2003 Information Paper. (26)

Section Summary: Necrotizing Soft Tissue Infections

No RCTs have evaluated HBO2 therapy for necrotizing soft tissue infection. A retrospective cohort study did not find a difference in outcomes after HBO2 therapy or standard care. However, recognized opinions from technology assessments list HBO2 therapy as needed for the treatment for necrotizing soft tissue infections.

Acute Coronary Syndromes

A 2015 Cochrane review by Bennett et al. identified 6 trials (total n=665 patients) evaluating HBO2 therapy for acute coronary syndrome (see Table 9). (27) Included studies were published between 1973 and 2007. All studies included patients with acute myocardial infarction (MI); a study also included individuals with unstable angina. Additionally, all trials used HBO2 therapy, administered between 2 and 3 ATA, for 30 to 120 minute sessions, as an adjunct to standard care. Control interventions varied; only a trial described using a sham therapy to blind participants to treatment group allocation. In a pooled analysis of data from 5 trials, there was a significantly lower rate of death in patients who received HBO2 therapy compared with a control intervention. Due to the variability of outcome reporting across studies, few other pooled analyses could be conducted. Three trials reported outcomes related to left ventricular function. One did not find a statistically significant improvement in contraction with HBO2 therapy, while 2 trials showed left ventricular ejection fraction improved significantly with HBO2 therapy. Reviewers noted that, although some evidence from small trials correlated HBO2 therapy with a lower risk of death, larger trials with high-quality methods were needed to determine which patients, if any, could be expected to derive benefit from HBO2 therapy.

Table 9. Systematic Reviews of Trials Assessing HBO2 Therapy for Acute Coronary Syndrome

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Bennett et al. (2015) (27)

Jun 2010

6

Adults with acute coronary syndrome, with or without S-T segment elevation

665

RCTs

Pooled analyses of 5 trials (n=614) reported a lower mortality rate for patients in the HBO2 therapy group versus the control (RR=0.58; 95% CI, 0.36 to 0.92)

Left ventricular outcomes, 3 trials total: 1 trial reported no difference in contraction (RR=0.09; 95% CI, 0.01 to 1.4) and pooled analyses of 2 trials (n=190) found significant improvements in LVEF with HBO2 therapy (MD=5.5%; 95% CI, 2.2% to 8.8%)

Table Key:

CI: confidence interval;

HBO2 therapy: hyperbaric oxygenation therapy;

LVEF: left ventricular ejection fracture;

MD: mean difference;

N/n: number;

RCT: randomized controlled trial;

RR: relative risk.

Section Summary: Acute Coronary Syndrome

A Cochrane review of 6 RCTs found insufficient evidence that HBO2 therapy is safe and effective for acute coronary syndrome. One pooled analysis of data from 5 RCTs found a significantly lower rate of death with HBO2 therapy than with a comparison intervention; however, larger, higher quality trials are needed. Three trials measuring left ventricular function report inconsistent results.

Acute Ischemic Stroke

In a 2014 Cochrane systematic review of RCTs, Bennett et al. evaluated HBO2 therapy for acute ischemic stroke (see Table 10). (28) Reviewers identified 11 RCTs (total n=705 participants) that compared HBO2 therapy with sham HBO2 therapy or no treatment. Reviewers could pool study findings for only 1 outcome (mortality at 3-6 months), and no difference was detected between the treatment groups for that outcome. There was heterogeneity in the participants enrolled and in the clinical and functional outcomes measured across the studies.

Table 10. Systematic Reviews of Trials Assessing HBO2 Therapy for Acute Ischemic Stroke

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Bennett et al. (2014) (28)

Apr 2014

11

Patients with acute ischemic stroke, defined as sudden neurologic deficit of vascular origin for which hemorrhage was excluded by CT or MRI

705

RCTs

Pooled analyses of 4 trials (n=144) found no difference in mortality at 3 to 6 months (RR=0.97; 95% CI, 0.34 to 2.75)

Table Key:

CI: confidence interval;

CT: computed tomography;

HBO2 therapy: hyperbaric oxygenation therapy;

LVEF: left ventricular ejection fracture;

MRI: magnetic resonance imaging;

MD: mean difference;

N/n: number;

RCT: randomized controlled trial;

RR: relative risk.

Section Summary: Acute Ischemic Stroke

A Cochrane review of RCTs conducted a pooled analysis of 4 RCTs, and found no significant difference in mortality rates at 3 to 6 months when patients with acute ischemic stroke were treated with HBO2 therapy or a sham intervention. Additional RCT data are needed to permit conclusions on the impact of HBO2 therapy on the health outcome in patients with acute ischemic stroke.

Motor Dysfunction Associated with Stroke

In 2013, Efrati et al. published an RCT evaluating HBO2 therapy for treatment of neurologic deficiencies associated with a history of stroke (see Tables 11 and 12). (29) Patients in the treatment group were evaluated at baseline and 2 months. For patients in the delayed treatment control group, outcomes were evaluated at 4 months after crossing over and receiving HBO2 therapy. Outcome measures included the National Institutes of Health Stroke Scale (NIHSS), which was measured by physicians blinded to treatment group, and several patient-reported quality of life (QOL) and functional status measures. At the 2-month follow-up, there was a statistically significant improvement in function in the HBO2 therapy group compared with the control group, as measured by the National Institutes of Health Stroke Scale, QOL scales, and the ability to perform activities of daily living (ADLs). These differences in outcome measures were accompanied by improvements in single-photon emission computed tomography (SPECT) imaging in the regions affected by stroke. For the delayed treatment control group, there was a statistically significant improvement in function after HBO2 therapy compared with before HBO2 therapy. This RCT raises the possibility that HBO2 therapy may induce improvements in function and QOL for poststroke patients with motor deficits. However, the results are not definitive, as the RCT was small and enrolled a heterogeneous group of post-stroke patients. The trial was not double-blind and most outcome measures, except for NIHSS, were patient-reported and prone to the placebo effect. Also, there was a high total dropout rate (20%) at the 2-month follow-up. Larger, double-blind studies with longer follow-up are needed to corroborate these results.

Table 11. Characteristics of Trials Assessing HBO2 Therapy for Motor Dysfunction Associated With Stroke

Treatment

Study (Year)

Countries

Sites

Dates

Participants

Active (n=30)

Comparator (n=29)

Efrati et al. (2013) (29)

Israel

1

2008-2010

Patients ≥18 y with ischemic or hemorrhagic stroke 6 to 36 months prior to inclusion with ≥1 motor dysfunction

HBO2

100% O2 at 2 ATA

40 times over 2 months

Same as active, delayed after 2 months

Table Key:

ATA: atmospheres absolute;

HBO2 Therapy: hyperbaric oxygen therapy;

O2: oxygen;

RCT: randomized controlled trial;

Table 12. Results of Trials Assessing HBO2 Therapy for Motor Dysfunction Associated with Stroke

NIHSS

ADLsa

Study (Year)

Baseline

2 months

Between-Group p Value

Baseline

2 months

Between-Group p Value

Efrati et al. (2013) (29)

50

50

50

50

Mean HBO2 Therapy (SD)

8.5 (3.6)

5.5 (3.6)

0.004

16.1 (6.5)

12.8 (7.3)

0.02

Mean control (SD)

8.7 (4.1)

8.3 (4.3)

17.4 (9.5)

17.5 (9.5)

Table Key:

ADLs: activities of daily living;

HBO2 Therapy: hyperbaric oxygen therapy;

NIHSS: National Institutes of Health Stroke Scale;

N/n: number;

SD: standard deviation;

a: ADLs are 16 functions scored across a range whether patient was independent to did not perform at all. Range: 0 (best) to 51 (worst).

Section Summary: Motor Dysfunction Associated With Stroke

One crossover RCT evaluated HBO2 therapy in patients with a recent history of stroke. The RCT reported better outcomes at 2 months with HBO2 therapy than with delayed treatment. However, the trial had a number of methodologic limitations, making it difficult to draw conclusions about the efficacy of HBO2 therapy for this indication. Double-blind RCTs that address potential bias in subjective outcomes and studies with adequate follow-up are needed.

Bell’s Palsy

In 2012, Holland et al. published a Cochrane review evaluating HBO2 therapy in adults with moderate-to-severe Bell’s palsy. (30) The literature search, conducted through January 2012, identified 1 RCT with 79 participants, but this trial did not meet reviewers’ prespecified selection standards because the outcome assessor was not blinded to treatment allocation. The trial was therefore excluded with no further analysis.

Section Summary: Bell’s Palsy

There is a lack of evidence on use of HBO2 therapy for Bell’s palsy. A Cochrane review did not identify any eligible RCTs; the single RCT identified lacked blinded outcome assessment. Well-conducted RCTs are needed.

Traumatic Brain Injury

A 2016 meta-analysis by Wang et al. assessed HBO2 therapy for treatment of traumatic brain injury (traumatic brain injury [TBI] see Table 13). (31) Eight studies (total n=519 participants) met the eligibility criteria. HBO2 therapy protocols varied across studies in the levels of O2 and the length and frequency of treatments. The primary outcome was change in the Glasgow Coma Scale score. A pooled analysis of 2 studies found a significantly greater improvement in the mean Glasgow Coma Scale score in the HBO2 therapy group compared with control groups. Mortality (a secondary outcome) was reported in 3 of the 8 studies. Pooled analysis of these 3 studies found a significantly lower overall mortality rate in the HBO2 therapy group than in the control group.

Another 2016 systematic review, by Crawford et al., did not conduct pooled analyses (see Table 13). (32) Reviewers identified 12 RCTs evaluating HBO2 therapy for patients with TBI. Using SIGN (Scottish Intercollegiate Guidelines Network) 50 criteria, 8 trials were rated acceptable and 4 rated low. Four trials, all rated as having acceptable quality, addressed patients with mild TBI and compared HBO2 therapy with sham. None found statistically significant differences between groups on outcomes (i.e., postconcussive symptom severity, psychological outcomes). Seven trials evaluated HBO2 therapy for the acute treatment of patients with moderate-to-severe TBI. Four were rated as acceptable quality and three as low quality. Study protocols and outcomes varied and none used a sham control. Three acceptable quality studies with standard care controls reported the Glasgow Outcome Scale (GOS) score and mortality rate. In two of them, outcomes were better with HBO2 therapy than with standard care; in the third study, outcomes did not differ significantly.

In 2012, a Cochrane review by Bennett et al. evaluated HBO2 therapy as adjunctive therapy for acute TBI (see Table 13). (33) Reviewers identified 7 RCTs comparing a standard intensive treatment regimen with the same treatment regimen plus HBO2 therapy. Reviewers did not include studies with interventions in specialized acute care settings. The HBO2 therapy regimens varied among studies; e.g., the total number of individual sessions varied from 3 to 40. None of the trials used sham treatment or blinded staff treating patients, and only one had blinding of outcome assessment. Allocation concealment was inadequate in all studies. The primary outcomes of the review were mortality and functional outcomes. A pooled analysis of data from 4 trials showed that adding HBO2 therapy to standard care decreased mortality, but did not improve functional outcome at final follow-up. The unfavorable functional outcome was commonly defined as a GOS score of 1, 2, or 3, which are described as “dead,” “vegetative state,” or “severely disabled,” respectively. Studies were generally small and judged to have a substantial risk of bias.

Also, several trials on mild TBI in military populations have been published; they did not find significant benefits of HBO2 therapy compared with sham treatment. (34-37) In 2015, Miller et al. evaluated HBO2 therapy in 72 military service members with symptoms continuing at least 4 months after mild TBI. (37) Patients were randomized to 40 daily HBO2 therapy sessions at 1.5 atm, 40 sham sessions consisting of room air at 1.2 atm or standard care with no hyperbaric chamber sessions. The primary outcome was change in Rivermead Post-Concussion Symptoms Questionnaire (RPQ) score. A cutoff of 15% improvement was deemed clinically important, which translates to a change score of at least 2 points on the RPQ-3 subscale. The proportion of patients who met this prespecified change on the RPQ was 52% in the HBO2 therapy group, 33% in the sham group, and 25% in the standard care-only group. The difference between rates in the HBO2 therapy and sham groups was not statistically significant (p=0.24). None of the secondary outcomes significantly favored the HBO2 therapy group. A criticism of this trial, as well as the other military population studies, was that patient response in the sham group was not due to a placebo effect but to an intervention effect of slightly increased atmospheric pressure (1.2 atm). (38) Other researchers have noted that room air delivered at 1.2 atm would not be considered an acceptable therapeutic dose for any indication, and especially for a condition with persistent symptoms like post-concussive syndrome.

Table 13. Systematic Reviews of Trials Assessing HBO2 Therapy for Traumatic Brain Injury

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Wang et al. (2016) (31)

Dec 2014

8

Patients with mild or severe TBI

518

RCTs and 2-arm prospective studies

Pooled analyses of 2 trials (n=120) found significant improvements in GCS score change (3.1; 95% CI, 2.3 to 3.9) in HBO2 therapy versus control

Pooled analyses of 3 trials (n=263) found lower risk of mortality among patients treated with HBO2 therapy versus controls (OR=0.3; 95% CI, 0.2 to 0.6)

Crawford et al. (2016) (32)

Aug 2014

12

Military and civilian patients with TBI

NR

RCTs

Pooled analyses not performed

Among 3 trials with GCS outcomes, 2 reported improvements with HBO2 therapy and 1 found no difference

4 trials assessed as acceptable quality did not find significant differences in symptom severity or psychological outcomes

Bennett et al. (2012) (33)

Mar 2012

7

Patients with acute TBI following blunt trauma

571

RCTs

Pooled analyses of 4 trials (n=385) found that adding HBO2 therapy to standard care decreased mortality versus standard care alone (RR=0.7; 95% CI, 0.5 to 0.9)

Pooled analyses of 4 trials (n=380) reported no difference in functional status at final follow-up between groups (RR=1.9; 95% CI, 0.9 to 4.1

Table Key:

CI: confidence interval;

CT: computed tomography;

GCS: Glasgow Coma Scale;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

OR: odds ratio;

PTSD: post-traumatic stress disorder;

RCT: randomized controlled trial;

RR: relative risk;

TBI: traumatic brain injury.

Section Summary: Traumatic Brain Injury

A number of RCTs and systematic reviews have been published. RCTs were heterogeneous regarding intervention protocols, patient populations, and outcomes reported. Pooled analyses were only conducted on a minority of the published RCTs, and these analyses had inconsistent findings. Additionally, there was some overlap in RCTs included in the reviews. There is a lack of consistent evidence from well-conducted trials that HBO2 therapy improves the health outcome for patients with TBI.

Inflammatory Bowel Disease

A 2014 systematic review by Dulai et al. examined the evidence on HBO2 therapy for inflammatory bowel disease (IBD) (Crohn disease, ulcerative colitis; see Table 14). (38) The review was not limited by study design. One RCT identified was published in 2013; it was open-label and included 18 patients with ulcerative colitis. (39) Patients were randomized to standard medical therapy only (n=8) or medical therapy plus HBO2 therapy (n=10). The HBO2 intervention consisted of 90 minutes of treatment at 2.4 atm, 5 days a week for 6 weeks (total of 30 sessions). The primary outcome was the Mayo score, which has a potential range of 0 to 12, consisting of 4 components (bleeding, stool frequency, physician assessment, and endoscopic appearance) rated from 0 to 3, and added for a final score. (40) Patients with a score of 6 or more are considered to have moderate-to-severe active disease. At follow-up, there was no significant difference between groups in the Mayo score; the median score at 6 months was 0.5 in the HBO2 therapy group and 3 in the control group (p value not reported). Also, there were no significant differences in any secondary outcomes, including laboratory tests and fecal weight. This small trial might have been underpowered. Overall, reviewers found that the selected studies had a high risk of bias, due to attrition and reporting bias.

Table 14. Systematic Reviews of Studies Assessing HBO2 Therapy for Inflammatory Bowel Disease

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Dulai et al. (2014) (38)

Dec 2013

17

Patients with UC or CD

UC (n=327); CD (n=286)

11 case reports

3 case series

2 case-control

1 RCT

Overall HBO2 therapy response rate across studies: 86%

1 RCT (n=18) reported no difference in outcomes among patients with UC treated with HBO2 therapy versus HBO2 therapy plus medical therapy

Table Key:

CD: Crohn’s disease;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

RCT: randomized controlled trial;

UC: ulcerative colitis.

Section Summary: Inflammatory Bowel Disease

Only 1 small RCT has been published, and it did not find a significant improvement in health outcomes when HBO2 therapy was added to standard medical therapy. A systematic review of RCTs and observational studies found heterogeneity in HBO2 therapy protocols and high rates of bias in the literature (e.g., attrition, reporting bias).

Idiopathic Sudden Sensorineural Hearing Loss

A 2012 Cochrane review by Bennett et al. on HBO2 therapy for idiopathic sudden sensorineural hearing loss (ISSNHL) and/or tinnitus identified 7 RCTs (n=392; see Table 15). (41) Studies were small and generally of poor quality. Randomization procedures were only described in 1 study, and only 1 study stated they blinded participants to treatment group assignment using sham therapy. Six studies included time-based entry criteria for hearing loss and/or tinnitus (48 hours in 3 studies, 2 weeks in 2 studies, and 6 months in 1 study). The dose of O2 per treatment session and the treatment protocols varied across studies (e.g., the total number of treatment sessions ranged from 10-25).

All trials reported on the change in hearing following treatment, but specific outcomes varied. Two trials reported the proportion of participants with more than 50% and more than 25% return of hearing at the end of therapy. A pooled analysis of these studies did not find a statistically significant difference in outcomes between the HBO2 therapy and the control groups at the level of 50% or higher but did find a significantly higher rate of improvement at the level of 25% or higher (see Table 15). A pooled analysis of 4 trials found a significantly greater mean improvement in hearing over all frequencies with HBO2 therapy compared with control. Reviewers stated that, due to methodologic shortcomings of the trials and the modest number of patients, results of the meta-analysis should be interpreted cautiously; they did not recommend the use of HBO2 therapy for treating ISSNHL.

In a trial published after the review, Cvorovic et al. (2013) conducted an RCT that included 50 patients with ISSNHL who had failed primary therapy with intravenous steroids. (42) Patients were randomized to HBO2 therapy (20 sessions, 5 daily sessions per week) or intratympanic steroid injection (4 injections in 13 days). The HBO2 therapy sessions consisted of 10 minutes of compression on air, 60 minutes of 100% O2 at 2 atm, and 10 minutes of decompression on air. Outcomes were change in the mean hearing thresholds at each of 5 frequencies (0.25, 0.5, 1, 2, and 4 kHz [kilohertz]). After treatment, there were no statistically significant differences in mean hearing thresholds at 4 of the 5 frequencies. The exception was 2 kHz, and at that frequency, the improvement was significantly greater in the HBO2 therapy group.

Table 15. Systematic Reviews of Trials Assessing HBO2 Therapy for Idiopathic Sudden Sensorineural Hearing Loss

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Bennett et al. (2012) (41)

May 2012

7

Patients with ISSNHL and/or tinnitus

392

RCTs

Pooled analyses of 2 studies (n=114) showed HBO2 therapy did not result in >50% improvement in pure tone average threshold (RR=1.5; 95% CI, 0.9 to 2.8), but was able to achieve >25% improvement (RR=1.4; 95% CI, 1.1 to 1.8)

Pooled analyses of 4 trials (n=169) found a significantly greater mean improvement in hearing over all frequencies with HBO2 therapy versus control (mean difference, 15.6 dB; 95% CI, 1.5 to 29.8 dB)

Table Key:

CI: confidence interval;

dB: decibels;

HBO2 therapy: hyperbaric oxygenation therapy;

ISSNHL: idiopathic sudden sensorineural hearing loss;

N/n: number;

RCT: randomized controlled trial;

RR: relative risk.

Section Summary: Idiopathic Sudden Sensorineural Hearing Loss

A Cochrane review of RCTs had mixed findings. Some outcomes (i.e., improvement in hearing of all frequencies, >25% return of hearing) were better with HBO2 therapy than with a control intervention, but more than 50% return of hearing did not differ significantly between groups. The Cochrane reviewers noted methodologic limitations and variability across published studies. An RCT published after the review including patients with ISSNHL found no differences in HBO2 therapy treatment compared with steroid injections in mean hearing thresholds at 0.25, 0.5, 1, and 4 kHz; however, a significant difference was detected at the 2-kHz level.

Delayed-Onset Muscle Soreness

In a 2005 Cochrane review updated in 2010, Bennett et al. identified 9 small RCTs on HBO2 therapy for delayed-onset muscle soreness and closed soft tissue injury (see Table 16). (43) Included trials were published between 1996 and 2003. Methodologic quality was assessed as fair to high. Pooled analysis showed significantly higher pain in the group receiving HBO2 therapy compared with control. There were no between-group differences in long-term pain outcomes or other measures (e.g., swelling, muscle strength).

Table 16. Systematic Reviews of Trials Assessing HBO2 Therapy for Delayed-Onset Muscle Soreness

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Bennett et al. (2010) (43)

Feb 2010

9

Patients with acute closed soft tissue injuries or DOMS

219

RCTs

2 trials on closed soft tissue injuries: no significant difference in time to recovery, functional outcomes, or pain

7 DOMS trials, pooled: significantly higher pain at 48 and 72 hours in HBO2 therapy group, 0.9 (95% CI, 0.09 to 1.7); no differences in long-term pain, swelling, or muscle strength

Table Key:

CI: confidence interval;

DOMS: delayed-onset muscle soreness;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

RCT: randomized controlled trial.

Section Summary: Delayed-Onset Muscle Soreness

A Cochrane review of RCTs with fair to high methodologic quality found worse short-term pain outcomes with HBO2 therapy than with a control condition and no difference in longer term pain or other outcomes (e.g., swelling).

Autism Spectrum Disorders

A 2016 Cochrane review by Xiong et al. identified 1 RCT evaluating systemic HBO2 therapy for people with autism spectrum disorder that met eligibility criteria (see Table 17). (44) Criteria included a HBO2 intervention using 100% O2 at more than 1 atm. The trial, published by Sampanthaviat et al. (2012), was considered low-quality evidence as assessed by the GRADE approach. (45) The trial randomized children with autism to receive 20 1-hour sessions with HBO2 therapy or sham air (n=30 per group). The primary outcome measures were change in Autism Treatment Evaluation Checklist (ATEC) and Clinical Global Impression scores, evaluated separately by clinicians and parents. There were no statistically significant differences between groups for either primary outcome. Post-treatment clinician-assessed mean scores on Autism Treatment Evaluation Checklist were 52.4 in the HBO2 therapy group and 52.9 in the sham air group.

Table 17. Systematic Reviews of Trials Assessing HBO2 Therapy for Autism Spectrum Disorder

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Xiong et al. (2016) (44)

Dec 2015

1

Children aged 3-9 years with autism spectrum disorder

60

RCT

Parental assessed ATEC: 1.2 (95% CI, -2.2 to 4.6)

Clinician assessed ATEC: 1.5 (95% CI, -1.3 to 4.5)

Table Key:

ATEC: autism treatment evaluation checklist;

CI: confidence interval;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

RCT: randomized controlled trial.

Section Summary: Autism Spectrum Disorder

A Cochrane review identified a single small low-quality RCT on HBO2 therapy for autism spectrum disorder and that trial did not find significantly improved outcomes with HBO2 therapy versus sham.

Cerebral Palsy

Two published RCTs were identified on use of HBO2 therapy for cerebral palsy (see Tables 18 and 19). In 2012, Lacey et al. published a double-blind RCT that included 49 children ages 3 to 8 years with spastic cerebral palsy. (46) Participants were randomized to 40 treatments with HBO2 therapy or hyperbaric air to simulate 21% O2 at room air. The primary efficacy outcome was change in the Gross Motor Function Measure global score. The trial was stopped early due to futility when an interim analysis indicated that there was less than a 2% likelihood that a statistically significant difference between groups would be found.

Collet et al. (2001) randomized 111 children with cerebral palsy to 40 treatments over a 2-month period of HBO2 therapy or slightly pressurized room air. (47) Investigators found similar improvements in outcomes such as gross motor function and ADLs in both treatment groups.

In 2017, an observational study by Long et al. evaluated the effects of HBO2 therapy as a treatment for sleep disorders in children with cerebral palsy (n=71). (48) Children, aged 2 to 6 years, underwent 60-minute sessions of 100% O2, at 1.6 ATA, for 15 to 20 sessions total. Results showed improvements in average time to fall asleep, average hours of sleep duration, and an average number of night awakenings after 10 HBO2 therapy sessions compared with pretreatment.

Table 18. Characteristics of Trials Assessing HBO2 Therapy for Cerebral Palsy Treatment

Treatment

Study (Year)

Countries

Sites

Dates

Participants

Active

Comparator

Lacey et al. (2012) (46)

United States

2

2005- 2009

Children aged 3-8 years with spastic CP

n=25

HBO2

100% O2 at 1.5 ATA

40 times over 2 months

n=24

HBO2

14% O2 at 1.5 ATA

40 times over 2 months

Collet et al. (2001) (47)

Canada

17

NR

Children aged 3-2 years with CP

n=57

HBO2

100% O2 at 1.75 ATA

40 times over 2 months

n=54

Slightly pressurized air 100% O2 at 1.3 ATA

40 times over 2 months

Table Key:

ATA: atmospheres absolute;

CP: cerebral palsy;

HBO2 therapy: hyperbaric oxygenation therapy;

N/n: number;

NR: not reported;

O2: oxygen.

Table 19. Results of Trials Assessing HBO2 Therapy for Cerebral Palsy

Study

(Year)

Mean Change GMFMa

(95% CI)

Between-Group Difference

(95% CI)

Mean Change, Functional Skill

Between-Group Difference

(95% CI)

Lacey et al. (2012) (46)

46

46

HBO2 Therapy

1.5 (-0.3 to 3.3)

0.9 (-1.5 to 3.3)

4.4 (2.3 to 6.5)

1.1 (-1.5 to 3.7)

HBA Therapy

0.6 (-1.0 to 2.2)

3.3 (1.6 to 5.0)

Collet et al. (2001) (47)

Mean Change, PEDI Self Care

HBO2 Therapy

2.9 (1.9 to 3.9)

-0.4 (-1.7 to 0.9)

2.8 (1.6 to 4.0)

0.1 (-1.8 to 2.0)

Slight Pressure

3.0 (2.1 to 3.9)

2.7 (1.3 to 4.0)

Table Key:

CI: confidence interval;

GMFM: Gross Motor Function Measure;

HBA Therapy: hyperbaric air therapy;

HBO2 Therapy: hyperbaric oxygen therapy;

N/n: number;

PEDI: Pediatric Evaluation of Disability Inventory;

a: Positive score represents improvement in function from baseline.

Section Summary: Cerebral Palsy

Two RCTs and an observational study were identified. One RCT was stopped early due to futility and the other did not find significantly better outcomes with HBO2 therapy than with a sham intervention. The observational study, which focused on improving sleep in patients with cerebral palsy, reported improvements following HBO2 therapy.

Vascular Dementia

A 2012 Cochrane review identified a small RCT evaluating HBO2 therapy for vascular dementia (see Table 20). (49) This 2009 RCT, conducted in China, compared HBO2 therapy (30-day cycles of 1 hour/day for 24 days and 6 days of rest) plus donepezil to donepezil-only in 64 patients. The HBO2 therapy plus donepezil group had significantly improved cognitive function after 12 weeks of treatment, though the confidence intervals were wide due to the small sample size. Reviewers judged the trial to be of poor quality because it was not blinded and the methods of randomization and allocation concealment were not discussed.

Table 20. Systematic Reviews of Trials Assessing HBO2 Therapy for Vascular Dementia

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Xiao et al. (2012) (49)

Dec 2011

1

Patients with vascular dementia, according to DSM- IV criteria

64

RCT

WMD of MMSE score: 3.5 (95% CI, 0.9 to 6.1)

WMD of HDS score: 3.1 (95% CI, 1.2 to 5.0)

Table Key:

CI: confidence interval;

Diagnostic and Statistical Manual for Mental Disorders Fourth Edition;

HBO2 Therapy: hyperbaric oxygen therapy;

HDS: Hasegawa’s Dementia Rating Scale;

N/n: number;

MMSE: Mini-Mental State Examination;

WMD: weighted mean difference.

Section Summary: Vascular Dementia

A Cochrane review identified an RCT judged to be of poor quality. This trial provided insufficient evidence to permit conclusions on the impact of HBO2 therapy on health outcomes in patients with vascular dementia.

Radiotherapy Adverse Effects

This indication covers adverse events of radiotherapy other than osteoradionecrosis and treatment of irradiated jaw, which was covered in an earlier indication.

In 2010, Spiegelberg et al. conducted a systematic review of studies on HBO2 therapy to prevent or treat radiotherapy-induced head and neck injuries associated with the treatment of malignant tumors (see Table 21). (50) Reviewers identified 20 studies. Protocols and conclusions varied across the studies. Eight studies included control groups; their sample sizes ranged from 19 to 78 subjects. Four studies with a control group concluded that HBO2 therapy was effective; the other 4 did not. Reviewers noted a paucity of RCTs, though they did not state how many RCTs were included in the review, because studies were only identified only as prospective or retrospective.

In 2017, Ravi et al. conducted a systematic review assessing the effect of HBO2 therapy on patients with head and neck cancer who had received radiotherapy (see Table 21). (13) Pooled analyses were not performed; however, summary results were discussed for the following outcomes: salivary gland function, osteonecrosis prevention, dental implant survival, and QOL. Osteonecrosis prevention and dental implant survival outcomes were discussed in the earlier in the Rationale (see the Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw section).

Table 21. Systematic Reviews of Studies Assessing HBO2 Therapy for Radiotherapy Adverse Events

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Spiegelberg et al. (2010) (50)

Jun 2009

20

Patients who have received RT for malignant tumors in the head and neck

695

Prospective and retrospective studies

Due to the heterogeneity among studies, pooled analysis was not possible

8 studies had control groups and 4 concluded that HBO2 therapy was effective and 4 concluded that HBO2 therapy was not

Ravi et al. (2017) (13)

Dec 2016

10

Patients who have received RT for head and neck cancer

375

Prospective case series and prospective comparative studies

Salivary gland function: 2 case series (n=96) reported that patients receiving HBO2 therapy experienced improvements in salivary flow rates

QOL: 3 case series (n=106) administered various QOL instruments (e.g., SF-36, EORTC, HADS), reporting that many subsets of the questionnaires (e.g., swallowing, pain, salivary quantity) showed significant improvements with HBO2 therapy

Table Key:

EORTC: European Organization for Research and Treatment of Cancer;

HADS: Hospital Anxiety and Depression Scale;

HBO2 Therapy: hyperbaric oxygen therapy;

N/n: number;

QOL: quality of life;

RT: radiotherapy;

SF-36: 36-Item Short-Form Health Survey.

Several RCTs were identified in literature searches. A 2009 trial by Teguh et al., included in the reviews, evaluated 17 patients with oropharyngeal or nasopharyngeal cancer who were treated with radiotherapy; the trial was conducted in The Netherlands. (51) HBO2 therapy was used to prevent adverse events following radiotherapy. Eight patients were randomized to 30 sessions of HBO2 therapy, administered within 2 days of completing radiotherapy, and 9 patients to no additional treatment. QOL outcomes were assessed, and the primary outcome was xerostomia at 1 year. QOL measures did not differ significantly between groups in the acute phase (first 3 months). One month after treatment, the mean visual analog scale (VAS) score (0-to-10 scale) for xerostomia was 5 in the HBO2 therapy group and 6 in the control group. However, at 1 year, there was a statistically significant difference between groups in mean QOL score (0-to-100 scale) for swallowing, (7 in the HBO2 therapy group and 40 in the control group, [p<0.001]). The trial is limited by its small sample size and wide fluctuations over the follow-up in QOL ratings.

In a trial not included in the reviews, Gothard et al. (2010) in the U.K. published findings of an RCT using HBO2 therapy for arm lymphedema occurring after radiotherapy for cancer. (52) Fifty-eight patients with arm lymphedema (at least 15% increase in arm volume) following cancer treatment were randomized in a 2:1 ratio to HBO2 therapy (n=38) or usual care without HBO2 therapy (n=20). Fifty-three patients had baseline assessments, and 46 (79%) of 58 had 12-month assessments. At the 12-month follow-up, there was no statistically significant difference in the change from baseline in arm volume. Median change from baseline was -2.9% in the treatment group and -0.3% in the control group. The study protocol defined response as at least an 8% reduction in arm volume relative to the contralateral arm. By this definition, 9 (30%) of 30 of patients in the HBO2 therapy group were considered responders compared with 3 (19%) of 16 in the control group (p=NS). Other outcomes (e.g., QOL scores on the 36-Item Short-Form Health Survey [SF-36]) also did not differ significantly between groups.

Section Summary: Radiotherapy Adverse Events

Two systematic reviews have noted a lack of RCTs evaluating HBO2 therapy for radiotherapy adverse events. One review focused on salivary gland function, osteonecrosis prevention, dental implant survival, and QOL. The available RCTs had mixed findings. One found no short-term benefit and some benefits of HBO2 therapy 12 months after radiotherapy, while the other did not find a significant benefit of HBO2 therapy 12 months after radiotherapy. An RCT not included in the reviews focused on arm lymphedema; it found no significant differences between study groups.

Idiopathic Femoral Neck Necrosis

A double-blind RCT evaluating HBO2 therapy for treatment of femoral head necrosis was published in 2010 by Camporesi et al. (see Tables 22 and 23). (53) The trial included 20 adults with idiopathic unilateral femoral head necrosis. Patients received HBO2 therapy or a sham treatment of hyperbaric air. Mean severity of pain on a 0-to-10 scale was significantly lower in the HBO2 therapy group than in the control group after 30 sessions (p<0.001) but not after 10 or 20 sessions. The trial did not report exact pain scores. Several range-of-motion outcomes were reported. At the end of the initial treatment period, extension, abduction, and adduction, but not flexion, was significantly greater in the HBO2 therapy group than in the control group. Longer term comparative data were not available because the control group was offered HBO2 therapy after the initial 6-week treatment period.

Table 22. Characteristics of Trials Assessing HBO2 Therapy for Femoral Neck Necrosis

Treatment

Study (Year)

Countries

Sites

Dates

Participants

Active

(n=10)

Comparator

(n=10)

Camporesi et al. (2010) (53)

United States

1

NR

Patients with unilateral femoral neck necrosis

HBO2

100% O2 at 2.5 ATA

30 sessions over 6 weeks

Hyperbaric air

30 sessions over 6 weeks

Table Key:

ATA: atmospheres absolute;

HBO2 Therapy: hyperbaric oxygen therapy;

N/n: number;

NR: not reported;

O2: oxygen.

Table 23. Results of Trials Assessing HBO2 Therapy for Femoral Neck Necrosis

Study (Year)

Median (Range) Extension, After 10 Sessions

Between-Group Difference

p Value

Median (Range) Extension, After 30 Sessions

Between-Group Difference

p Value

Camporesi et al. (2010) (53)

HBO2 Therapy

7.5 (4.0-20.0)

NS

20.0 (15.0-20.0)

<0.001

HBA

Therapy

4.0 (3.0-6.0)

3.0 (0.0-5.0)

Table Key:

HBO2 Therapy: hyperbaric oxygen therapy;

HBA Therapy: hyperbaric air therapy;

NS: not significant.

Section Summary: Idiopathic Femoral Neck Necrosis

One small RCT (n=20) was identified. Six-week outcomes and results were mixed, with improvements reported in extension, abduction, and adduction, but not flexion. Significant improvements in pain were reported after 30 sessions, though no differences were detected after 10 or 20 sessions. This RCT does not provide insufficient data to permit conclusions about the efficacy of HBO2 therapy for femoral head necrosis.

Migraine

A 2015 Cochrane review by Bennett et al. identified 11 RCTs (total n=209 patients) comparing the effectiveness of systemic HBO2 therapy for preventing or treating migraine headache or cluster headaches with another treatment or a sham control (see Table 24). (54) A pooled analysis of 3 trials focusing on migraine headaches (n=58 patients) found a statistically significant increase in the proportion of patients with substantial relief of a migraine within 45 minutes of HBO2 therapy. No other pooled analyses were conducted due to variability in outcomes reported across trials. The meta-analysis did not report data on treatment effectiveness beyond the immediate post-treatment period, and the methodologic quality of selected trials was moderate to low (e.g., randomization was not well-described in any trial).

Table 24. Systematic Reviews of Trials Assessing HBO2 Therapy for Migraine or Cluster Headaches

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Bennett et al. (2015) (54)

Jun 2015

11

Patients with migraine or cluster headaches

209

RCT

For 3 trials focusing on migraine headaches (n=58) of low quality, HBO2 therapy was effective in relieving migraine (RR=6.21; 95% CI, 2.4 to 16.0)

No evidence that HBO2 therapy can prevent migraine, reduce nausea or vomiting, or reduce need for rescue medication

Table Key:

CI: confidence interval;

HBO2 Therapy: hyperbaric oxygen therapy;

N/n: number;

RR: relative risk.

Section Summary: Migraine

A Cochrane review identified 11 RCTs on HBO2 therapy for a migraine headache. However, only a single pooled analysis was conducted including 3 of the 11 trials. The pooled analysis found significantly greater relief of migraine symptoms with HBO2 therapy than with a comparator intervention within 45 minutes of treatment. Limitations included the availability of outcomes specific to the immediate post-treatment period, the variability of outcomes across trials, and generally low methodologic quality of trials.

Herpes Zoster

In 2012, Peng et al. in China published an RCT evaluating HBO2 therapy for herpes zoster (see Tables 25 and 26). (55) Sixty-eight patients with herpes zoster were randomized to HBO2 therapy with medication or medication treatment alone. The following outcomes were measured after 3 weeks of treatment: therapeutic efficacy, days to blister resolution, days to scar formation, and pain. Patient receiving HBO2 therapy experienced significantly improved outcomes compared with patients receiving medication alone. Limitations of the trial included a lack of blinding and long-term follow-up.

Table 25. Characteristics of Trials Assessing HBO2 Therapy for Herpes Zoster Treatment

Treatment

Study (Year)

Countries

Sites

Dates

Participants

Active

(n=36)

Comparator

(n=32)

Peng et al. (2012) (55)

China

NR

2008-2010

Patients diagnosed with herpes zoster within 2 weeks

HBO2

100% O2 at 2.2 ATA

2 sessions per day for 5 days

Thirty 120-min sessions; plus medications that control group received

Medication alone, including: antiviral, nerve nutritive, pain relief, and antidepressives

Table Key:

ATA: atmospheres absolute;

HBO2 Therapy: hyperbaric oxygen therapy;

NR: not reported;

O2: oxygen.

Table 26. Results of Trials Assessing HBO2 Therapy for Herpes Zoster

Study (Year)

Efficacya,b

Mean Days to Blister Resolutionb

Mean Days to Scar Formationb

NPRS Scoreb

Pretreatment

Post-treatment

Peng et al. (2012) (55)

68

68

68

68

68

Mean HBO2 Therapy and medication (SD)

97.2%

2.8 (1.5)

11.1 (4.0)

8.0 (1.8)

1.8 (2.7)

Mean medication alone (SD)

81.3%

3.3 (1.4)

13.9 (4.3)

8.1 (1.7)

3.5 (4.1)

Table Key:

HBO2 Therapy: hyperbaric oxygen therapy;

NPRS: Numeric Pain Rating Scale;

SD: standard deviation;

a: Calculation: (number cases with healing + number cases with improvement)/(total number cases × 100);

b: Between-group difference p<0.05.

Section Summary: Herpes Zoster

One RCT was identified. Only short-term outcomes were reported. Outcomes at the end of treatment were significantly better in the HBO2 therapy group than in the medication group. Trail limitations included lack of blinding and long-term outcomes.

Fibromyalgia

One delayed treatment RCT and a quasi-randomized trial on HBO2 therapy for fibromyalgia were identified.

In 2015, Efrati et al. published an RCT that included 60 symptomatic women who had fibromyalgia for at least 2 years (see Tables 27 and 28). (56) Patients were randomized to an immediate 2-month course of HBO2 therapy or delayed HBO2 therapy after 2 months. Forty-eight (80%) of 60 patients completed the trial. After the initial 2 months, outcomes including a number of tender points, pain threshold, and QOL (SF-36) were significantly improved in the immediate treatment group than in the delayed treatment group. After the delayed treatment group had undergone HBO2 therapy, outcomes were significantly improved compared with scores in the 2 months before HBO2 therapy treatment. These findings are not only consistent with a clinical benefit of HBO2 therapy, but also with a placebo effect. A sham control trial is needed to confirm the efficacy of HBO2 therapy in the treatment of fibromyalgia and other conditions where primary end points are pain and other subjective outcomes.

In 2004, Yildiz et al. assessed 50 patients with fibromyalgia (see Tables 27 and 28). (57) On an alternating basis, patients were assigned to HBO2 therapy or a control group. After HBO2 therapy treatment, the mean standard deviation, number of tender points, and mean VAS scale scores were improved in patients receiving HBO2 therapy compared with controls. It is unclear whether the control group received a sham intervention that would minimize any placebo effect (i.e., whether the control intervention was delivered in a hyperbaric chamber). The authors stated that the trial was double-blind, but did not provide details of patient blinding.

Table 27. Characteristics of Trials Assessing HBO2 Therapy for Fibromyalgia

Treatment

Study (Year)

Countries

Sites

Dates

Participants

Active

Comparator

Efrati et al. (2015) (56)

Israel

1

2010-2012

Patients with fibromyalgia based on: 1) widespread pain and 2) at least 11 of 18 tender points

n=24

HBO2

100% O2 at 2 ATA

1 session per day for 5 days

Forty 90-minute sessions

n=26

No treatment for 2 months, then same treatment as active group

Yildiz et al. (2004) (57)

Turkey

NR

NR

Patients meeting ACR criteria for fibromyalgia, with persistent symptoms despite medical therapy and PT

n=26

HBO2

100% O2 at 2.4 ATA

1 session per day for 5 days

Fifteen 90-min sessions

n=24

Air

1 ATA

1 session per day for 5 days

Fifteen 90-minute sessions

Table Key:

ACR: American College of Rheumatology;

ATA: atmospheres absolute;

HBO2 Therapy: hyperbaric oxygen therapy;

N/n: number;

NR: not reported;

O2: oxygen;

PT: physical therapy.

Table 28. Results of Trials Assessing HBO2 Therapy for Fibromyalgia

Study (Year)

Tender Points

Pain Threshold

Baseline

After HBO2 Therapy

Between-Group

p Value

Baseline

After HBO2 Therapy

Between-Group

p Value

Efrati et al. (2015) (56)

50

50

Mean HBO2 Therapy (SD)

17.3 (1.4)

8.9 (6.0)

<0.001

0.5 (1.2)

1.7 (0.8)

<0.001

Mean control (SD)

17.7 (0.7)

17.2 (1.1)

0.7 (0.5)

0.6 (0.5)

Yildiz et al. (2004) (57)

50

50

Mean HBO2 Therapy (SD)

15.0 (1.5)

6.0 (1.2)

<0.001

0.7 (0.1)

1.3 (0.1)

<0.001

Mean air (SD)

15.3 (1.2)

12.5 (1.1)

0.7 (0.1)

0.8 (0.1)

Table Key:

HBO2 Therapy: hyperbaric oxygen therapy;

SD: standard deviation.

Section Summary: Fibromyalgia

Two RCTs assessing HBO2 therapy for fibromyalgia were identified. Both had relatively small sample sizes and methodologic limitations (e.g., quasi-randomization, no or uncertain sham control for a condition with subjective outcomes susceptible to a placebo effect). Moreover, the HBO2 therapy protocols varied. Thus, the evidence is insufficient to permit conclusions on the impact of HBO2 therapy on health outcomes for patients with fibromyalgia.

Multiple Sclerosis

In 2010, Bennett, et al. published a systematic review on the use of HBO2 therapy for treatment of multiple sclerosis (see Table 29). (58) Nine RCTs (total n=504 participants) were identified that compared the effects of HBO2 therapy with placebo or no treatment. All trials used an initial course of 20 sessions over 4 weeks, although dosages among studies varied from 1.75 ATA for 90 minutes to 2.5 ATA for 90 minutes. The primary outcome of the review was Expanded Disability Status Scale score. A pooled analysis of data from 5 trials (n=271 patients) did not find a significant difference in mean Expanded Disability Status Scale (EDSS)score change after 20 HBO2 therapy treatments versus control or after 6 months of follow-up.

Table 29. Systematic Reviews of Trials Assessing HBO2 Therapy for Multiple Sclerosis

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Bennett et al. (2010) (58)

Jul 2009

9

Patients with multiple sclerosis, at any state or course of the condition

504

RCT

EDSS score difference between groups:

At 4-week follow-up: 0.07 (95% CI, -0.09 to 0.23)

At 6-month follow-up: 0.22 (95% CI, -0.09 to 0.54)

Table Key:

CI: confidence interval;

EDSS: Expanded Disability Status Scale;

HBO2 Therapy: hyperbaric oxygen therapy;

N/n: number;

RCT: randomized control trial.

Section Summary: Multiple Sclerosis

A Cochrane review of RCTs did not find a significant difference in outcomes when patients with multiple sclerosis were treated with HBO2 therapy versus a comparison intervention.

Tumor Sensitization During Cancer Treatment: Radiotherapy or Chemotherapy

In a 2005 Cochrane review, (59) which was updated in 2012, (60) Bennett et al. identified 19 randomized and quasi-randomized trials (total n=2286 patients) comparing outcomes following radiotherapy with and without HBO2 therapy in patients with solid tumors (see Table 30). The latest trial identified in the Cochrane search was published in 1999. Reviewers did not find any ongoing RCTs in this area. Results from the review reported that HBO2 therapy given with radiotherapy might be useful in tumor control in head and neck cancer. However, reviewers expressed caution because significant adverse events, such as severe radiation tissue injury (relative risk, 2.3; p<0.001) and seizures (relative risk, 6.8; p=0.03) occurred more frequently in patients treated with HBO2 therapy.

Table 30. Systematic Reviews of Trials Assessing HBO2 Therapy for Tumor Sensitization during Cancer Treatment with Radiotherapy

Study (Year)

Literature Search

Studies

Participants

N

Design

Results

Bennett et al. (2012) (60)

Sep 2008

19a

Head and neck:

10 trials

Uterine:

7 trials

Urinary bladder:

5 trials

Bronchus: 1 trial

Rectum:

1 trial

Brain:

1 trial

Esophagus: 1 trial

2286

RCT and quasi-RCT

Head and neck:

1-year mortality: RR=0.8 (p=0.03)

5-year mortality: RR=0.8 (p=0.03)

5-year recurrence: RR=0.8 (p=0.01

Uterine:

2-year recurrence: RR=0.6 (p=04)

Table Key:

HBO2 Therapy: hyperbaric oxygen therapy;

N/n: number;

RCT: randomized control trial;

RR: relative risk;

a: some including multiple cancer sites.

In an RCT of 32 patients, Heys et al. (2006) found no increase in 5-year survival for patients treated with HBO2 therapy to increase tumor vascularity before chemotherapy for locally advanced breast carcinoma. (61)

Section Summary: Tumor Sensitization During Cancer Treatment: Radiotherapy or Chemotherapy

A Cochrane review on the use of HBO2 therapy with radiotherapy and an RCT on the use of HBO2 therapy with chemotherapy were identified. While the Cochrane review found improvements in tumor control in patients with head and neck cancer, the adverse events accompanying HBO2 therapy treatment (e.g., radiation tissue injury, seizures) were significant. The RCT did not find a significant difference in survival in cancer patients who received HBO2 therapy before chemotherapy.

Fracture Healing

In 2012, Bennett et al. published a Cochrane review on HBO2 therapy to promote fracture healing and treat nonunion fractures. (62) The reviewers indicated since HBO2 therapy was being utilized for various conditions and had been described as a possible modality for fracture healing. The investigators did not identify any published RCTs on this topic that compared HBO2 therapy with no treatment, sham or another intervention and reported bony union as an outcome.

Section Summary: Fracture Healing

Due to the lack of RCTs, it is not possible to conclude whether the use HBO2 therapy to promote fracture healing improves outcomes. As of this update, 2 studies were listed in ClinicalTrials.gov, 1 suspended during recruitment and 1 having completed recruitment, but no further activity.

Additional Indications or Clinical Conditions

There is a lack of scientific evidence from which conclusions can be made concerning the safety and efficacy of utilizing HBO2 therapy for various other indications mentioned as clinical conditions and not a labeled indication by the FDA nor listed on the guidelines from the UHMS, or any other authoritative source, (63) such as:

Actinic skin damage;

Acute peripheral arterial insufficiency;

Amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s Disease;

Arthritic diseases;

Asthma;

Avascular necrosis;

Bone grafts;

Carbon tetrachloride poisoning;

Cardiogenic shock;

Compromised skin grafts and flaps;

Depression;

Spinal cord injury;

Hepatic necrosis;

Hepatitis;

Human immunodeficiency virus infection or acquired immune deficiency syndrome (HIV/AIDS);

Hydrogen sulfide poisoning;

Intra-abdominal abscesses;

In vitro fertilization (IVF);

Lepromatous leprosy;

Lyme disease;

Lymphedema of arm;

Meningitis;

Mental illness;

Motor dysfunction associated with stroke;

Multiple sclerosis;

Organ transplantation or storage;

Parkinson’s disease;

Postoperative ileus or acute pancreatitis;

Post-traumatic stress disorder (PTSD) or other stress disorders;

Pseudomembranous colitis, antimicrobial agent-induced colitis;

Pulmonary emphysema;

Pyoderma gangrenosum;

Radiation-induced injury to head, neck, anus, or rectum (except proctitis);

Radiation necrosis of non-neurologic tissue;

Radiation-myelitis;

Radiation tissue injury;

Refractory mycoses;

Retinal artery insufficiency;

Retinopathy, as an adjunct to scleral buckling procedure in patients with sickle cell peripheral retinopathy and retinal detachment;

Sickle cell crisis and/or hematuria;

Senility;

Septicemia, anaerobic (unrelated to clostridial), or systemic aerobic infection;

Sport’s injury;

Stroke and cerebrovascular disease;

Sudden deafness (unrelated to ISSNHL);

Tetanus; and/or

Vascular dementia or chronic brain syndromes, neovascular causes (such as Pick’s disease, Alzheimer’s disease, and Korsakoff’s disease).

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 31.

Table 31. Summary of Key Trials

NCT Number

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT01659723

Radiation Induced Cystitis Treated With Hyperbaric Oxygen - A Randomized Controlled Trial (RICH-ART)

80

Dec 2017

NCT03147352

Pro-Treat – Prognosis and Treatment of Necrotizing Soft Tissue Infections: a Prospective Cohort Study

310

Jan 2018

NCT02089594

Hyperbaric Oxygen Therapy Treatment of Chronic Mild Traumatic Brain Injury (mTBI)/Persistent Post-Concussion Syndrome (PCCS)

59

Mar 2019

NCT02714465

Treatment of Adverse Radiation Effects after Gamma Knife Radiosurgery (GKS) by Hyperbaric Oxygen Therapy (HBO)

65

May 2019

NCT03325959

Hyperbaric Oxygen versus Standard Pharmaceutical Therapies for Fibromyalgia Syndrome – Prospective, Randomized, Crossover Clinical Trial

70

Nov 2019

NCT00596180

Hyperbaric Oxygen Therapy and SPECT Brain Imaging in Carbon Monoxide Poisoning

40

Dec 2019

NCT01847755

Phase 1-2 Study of Hyperbaric Treatment of Traumatic Brain Injury

100

Dec 2020

Unpublished

NCT02085330

Hyperbaric Oxygen Therapy for Mild Cognitive Impairment

60

Feb 2017

(unknown)

NCT01002209

Postoperative Hyperbaric Oxygen Treatments to Reduce Complications in Diabetic Patients Undergoing Vascular Surgery (HODiVA)

112

Oct 2017

(unknown)

NCT01264146

Hyperbaric Oxygen Therapy in Calcaneal Intraarticular Fractures: Can it Decrease the Soft-tissue Complication Rate? (HOCIF)

20

Nov 2012

(unknown)

Table Key:

NCT: national clinical trial.

Practice Guidelines and Position Statements

Undersea and Hyperbaric Medical Society (UHMS)

In 2015, the UHMS published guidelines on the use of HBO2 therapy for treating diabetic foot ulcers. (63) This guideline is scheduled for a revision during 2018. Recommendations in the current version include:

Suggest against using HBO2 therapy in patients with “Wagner Grade 2 or lower diabetic foot ulcers….”

Suggest adding HBO2 therapy in patients with “Wagner Grade 3 or higher diabetic foot ulcers that have now shown significant improvement after 30 days of [standard of care] therapy….”

Suggest “adding acute postoperative hyperbaric oxygen therapy to the standard of care” in patients with “Wagner Grade 3 or higher diabetic foot ulcers” who have just had foot surgery related to their diabetic ulcers.

Additionally, the UHMS indications committee report included the following indications as recommended (63):

Air or gas embolism;

Carbon monoxide poisoning and carbon monoxide complicated by cyanide poisoning;

Clostridial myositis and myonecrosis (gas gangrene);

Crush injury, compartment syndrome, and other acute traumatic ischemias;

Decompression sickness;

Arterial insufficiencies:

o Central retinal artery occlusion,

o Enhancement of healing in selected problem wounds;

Severe anemia;

Intracranial abscess;

Necrotizing soft tissue infections;

Osteomyelitis (refractory);

Delayed radiation injury (soft tissue and bony necrosis);

Compromised skin grafts and flaps;

Acute thermal burn injury;

Idiopathic sudden sensorineural hearing loss (ISSNHL) (patients with moderate to profound

ISSNHL who present within 14 days of symptom onset).

UHMS has also published position statements that concluded there was insufficient evidence to recommend topical HBO2 therapy for chronic wounds (2005), (64) multiple sclerosis, (65) and autism spectrum disorder (2009). (66)

Infectious Disease Society of America

In 2012, the Infectious Disease Society of America published guidelines on the diagnosis and treatment of diabetic foot infections. (67) The guidelines stated that “for selected diabetic foot wounds that are slow to heal, clinicians might consider using hyperbaric oxygen therapy (strength of evidence: strong; quality of evidence: moderate).”

Society of Vascular Surgery (SVERSUS) et al.

In 2016, the SVERSUS in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine published guidelines on the management of the diabetic foot. (68) According to the guidelines, for diabetic foot ulcers that fail to demonstrate improvement (>50% wound area reduction) after a minimum of 4 weeks of standard wound therapy, adjunctive therapy such as HBO2 therapy is recommended (grade 1B). Also, for diabetic foot ulcers with adequate perfusion that fail to respond to 4 to 6 weeks of conservative management, HBO2 therapy is suggested (grade 2B).

American Academy of Otolaryngology-Head and Neck Surgery (AAOHNS)

In 2012, the AAOHNS published clinical guidelines on treatment of sudden hearing loss. (69) The guidelines included a statement that HBO2 therapy may be considered a treatment option for patients who present within 3 months of a diagnosis of ISSNHL: “Although HBO2 therapy is not widely available in the United States and is not recognized by many U.S. clinicians as an intervention for ISSNHL, the panel felt that the level of evidence for hearing improvement, albeit modest and imprecise, was sufficient to promote greater awareness of HBO2 therapy as an intervention for ISSNHL” (grade B recommendation, based on systematic review of RCTs with methodological limitations).

Tenth European Consensus Conference on Hyperbaric Medicine

The 10th European Consensus Conference on Hyperbaric Medicine (ECHM) convened in April 2016 to update HBO2 therapy indication recommendations. (70) Evidence was assessed using a modified GRADE system with the DELPHI system for consensus evaluation. Table 32 presents the updated recommendations:

Table 32. Recommendations on Hyperbaric Medicine (Adapted from Mathieu et al. [2017]. [71])

Condition

SOR

LOE

Carbon monoxide poisoning

Strong

Moderate

Open fractures with crush injury

Strong

Moderate

Prevention of osteoradionecrosis

Strong

Moderate

Osteoradionecrosis (mandible)

Strong

Moderate

Soft tissue radionecrosis (cystitis, proctitis)

Strong

Moderate

Decompression illness

Strong

Low

Gas embolism

Strong

Low

Anaerobic or mixed bacterial infection

Strong

Low

Sudden deafness

Strong

Moderate

Diabetic foot lesions

Weak

Moderate

Femoral head necrosis

Weak

Moderate

Compromised skin grafts and musculocutaneous flaps

Weak

Low

Central retinal artery occlusion

Weak

Low

Crush injury without fracture

Weak

Low

Osteoradionecrosis (other than mandible)

Weak

Low

Radio-induced lesions of soft tissues

Weak

Low

Radio-induced lesions of soft tissues (preventive)

Weak

Low

Ischemic ulcers

Weak

Low

Refractory chronic osteomyelitis

Weak

Low

Burns, second degree, >20% body surface area

Weak

Low

Pneumatosis cystoides intestinalis

Weak

Low

Neuroblastoma, stage IV

Weak

Low

Brain injury in highly selected patients

Neutral

Low

Radio-induced lesions of larynx

Neutral

Low

Radio-induced lesions of central nervous system

Neutral

Low

Post-vascular procedure reperfusion syndrome

Neutral

Low

Limb replantation

Neutral

Low

Selected non-healing wounds, secondary to systemic process

Neutral

Low

Sickle cell disease

Neutral

Low

Interstitial cystitis

Neutral

Low

Table Key:

LOE: level of evidence;

SOR: strength of recommendation.

Following the publication of the European Consensus Conference on Hyperbaric Medicine update, a letter to the editor requested details on the modified GRADE system and commented on the lack of a reference list in the update publication.

Dana Farber/Brigham and Women’s Cancer Center

In 2017, the Dana Farber/Brigham and Women’s Cancer Center conducted a systematic review of the evidence for HBO2 therapy for the prevention and management of osteoradionecrosis (ORN) of the jaw. (72) The literature search, conducted in January 2016, identified 3 studies on the prevention of ORN (1 RCT, 2 retrospective cohorts) and 4 studies on the management of ORN (1 RCT, 3 retrospective cohorts). Based on results from these studies, the Center “does not recommend the routine use of HBO for the prevention or management of ORN. Adjunctive HBO2 may be considered for use on a case-by-case basis in patients considered to be at exceptionally high risk who have failed conservative therapy and subsequent surgical resection.”

Medicare National Coverage

In 2003, the Centers for Medicare & Medicaid added Medicare coverage of HBO2 therapy for diabetic wounds of the lower extremities meeting certain criteria. As of the current coverage statement, Medicare coverage is provided for HBO2 therapy administered in a chamber for the following conditions (see Table 33) (73):

Table 33. CMS Medicare Coverage Approved Indications

No.

Indication

1.

Acute carbon monoxide intoxication.

2.

Decompression illness.

3.

Gas embolism.

4.

Gas gangrene.

5.

Acute traumatic peripheral ischemia. HBO2 therapy is a valuable adjunctive treatment to be used in combination with accepted standard therapeutic measures when loss of function, limb, or life is threatened.

6.

Crush injuries and suturing of severed limbs. As in the previous conditions, HBO2 therapy would be an adjunctive treatment when loss of function, limb, or life is threatened.

7.

Progressive necrotizing infections (necrotizing fasciitis).

8.

Acute peripheral arterial insufficiency.

9.

Preparation and preservation of compromised skin grafts (not for primary management of wounds).

10.

Chronic refractory osteomyelitis, unresponsive to conventional medical and surgical management.

11.

Osteoradionecrosis as an adjunct to conventional treatment.

12.

Soft tissue radionecrosis as an adjunct to conventional treatment.

13.

Cyanide poisoning.

14.

Actinomycosis, only as an adjunct to conventional therapy when the disease process is refractory to antibiotics and surgical treatment.

15.

Diabetic wounds of the lower extremities in patients who meet the following three criteria:

a. Patient has type I or type II diabetes and has a lower extremity wound that is due to diabetes;

b. Patient has a wound classified as Wagner grade III or higher; and

c. Patient has failed an adequate course of standard wound therapy.

Table Key:

No: number.

According to Medicare, “The use of HBO2 therapy is covered as adjunctive therapy only after there are no measurable signs of healing for at least 30-days of treatment with standard wound therapy and must be used in addition to standard wound care. 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. Failure to respond to standard wound care occurs when there are no measurable signs of healing for at least 30 consecutive days. Wounds must be evaluated at least every 30 days during administration of HBO2 therapy. Continued treatment with HBO2 therapy is not covered if measurable signs of healing have not been demonstrated within any 30-day period of treatment.”

Summary of Evidence

Topical Hyperbaric Oxygen (THBO2) Therapy

For individuals with wounds, burns or infections who receive THBO2 therapy, the evidence includes a systematic review, case series, and a randomized controlled trial (RCT). Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. The systematic review identified 3 RCTs including patients with sacral pressure ulcers, ischial pressure ulcers, and refractory venous ulcers. All trials reported that healing improved significantly after THBO2 therapy than after standard of care. Pooling of results was not possible due to heterogeneity in patient populations and treatment regimens. The single small RCT (n=28) was not included in the review and the uncontrolled studies do not provide sufficient data that THBO2 therapy is efficacious. The evidence is insufficient to determine the effects of the technology on health outcomes.

Systemic Hyperbaric Oxygen (HBO2) Therapy

Chronic Wounds

For individuals with chronic diabetic ulcers who receive systemic HBO2 therapy, the evidence includes RCTs and systematic reviews. Relevant outcomes are symptoms and change in disease status. Meta-analyses of RCTs found significantly higher diabetic ulcer healing rates with HBO2 therapy than with control conditions. One of the 2 meta-analyses found that HBO2 therapy was associated with a significantly lower rate of major amputation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Carbon Monoxide Poisoning

For individuals with carbon monoxide poisoning who receive systemic HBO2 therapy, the evidence includes RCTs and a systematic review. Relevant outcomes are overall survival and symptoms. A meta-analysis in a Cochrane review of low-quality RCT data did not find HBO2 therapy to be associated with a significantly lower risk of neurologic deficits after carbon monoxide poisoning. The evidence is insufficient to determine the effects of the technology on health outcomes.

Radionecrosis, Osteoradionecrosis, and Treatment of Irradiated Jaw

For individuals with radionecrosis, osteoradionecrosis, or treatment of irradiated jaw who receive systemic HBO2 therapy, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms and change in disease status. A meta-analysis in a Cochrane review of RCTs found evidence that HBO2 therapy improved radionecrosis and osteoradionecrosis outcomes and resulted in better outcomes before tooth extraction in an irradiated jaw. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Chronic Refractive Osteomyelitis

For individuals with chronic refractory osteomyelitis who receive systemic HBO2 therapy, the evidence includes case series. Relevant outcomes are symptoms and change in disease status. The case series reported high rates of successful outcomes (no drainage, pain, tenderness, or cellulitis) in patients with chronic refractory osteomyelitis treated with HBO2 therapy. However, controlled studies are needed to determine conclusively the impact of HBO2 therapy on health outcomes compared with other interventions. The evidence is insufficient to determine the effects of the technology on health outcomes.

Acute Thermal Burns

For individuals with acute thermal burns who receive systemic HBO2 therapy, the evidence includes a systematic review of 2 RCTs. Relevant outcomes are overall survival, symptoms, and change in disease status. Only 2 RCTs were identified, and both were judged to have poor methodologic quality. Evidence from well-conducted controlled trials is needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Acute Surgical and Traumatic Wounds

For individuals with acute surgical and traumatic wounds who receive systemic HBO2 therapy, the evidence includes RCTs, controlled nonrandomized studies, and systematic reviews. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. There was considerable heterogeneity across the 4 RCTs identified (e.g., patient population, comparison group, treatment regimen, outcomes). This heterogeneity prevented pooling of trial findings and limits the ability to conclude the impact of HBO2 therapy on health outcomes for patients with acute surgical and traumatic wounds. Additional evidence from high-quality RCTs is needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Bisphosphonate-Related Osteonecrosis of the Jaw

For individuals with bisphosphonate-related osteonecrosis of the jaw who receive systemic HBO2 therapy, the evidence includes an RCT. Relevant outcomes are symptoms and change in disease status. The RCT was unblinded and reported initial benefits at 3-month follow-up; however, there were no significant benefits of HBO2 therapy for most health outcomes compared with standard care in the long-term (6 months to 2 years). The evidence is insufficient to determine the effects of the technology on health outcomes.

Necrotizing Soft Tissue Infections

For individuals with necrotizing soft tissue infections who receive systemic HBO2 therapy, the evidence includes systematic reviews and a retrospective cohort study. Relevant outcomes are overall survival, symptoms, and change in disease status. A Cochrane review did not identify any RCTs. Another systematic review identified a retrospective cohort study, which did not find better outcomes after HBO2 therapy than after standard care without HBO2 therapy in patients with necrotizing soft tissue infections. The evidence is insufficient to determine the effects of the technology on health outcomes.

Acute Coronary Syndromes

For individuals with acute coronary syndrome who receive systemic HBO2 therapy, the evidence includes RCTs and a systematic review. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. A Cochrane review identified 6 RCTs. There were 2 pooled analyses, one found significantly lower rates of death with HBO2 therapy and the other reported inconsistent results in left ventricular function. Additional RCT data are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Acute Ischemic Stroke

For individuals with acute ischemic stroke who receive systemic HBO2 therapy, the evidence includes RCTs and a systematic review. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. Cochrane reviewers could only pool data for a single outcome (mortality at 3-6 months), and for that outcome, there was no significant difference between active and sham HBO2 therapy treatments. The evidence is insufficient to determine the effects of the technology on health outcomes.

Motor Dysfunction Associated with Stroke

For individuals with motor dysfunction associated with stroke who receive systemic HBO2 therapy, the evidence includes an RCT. Relevant outcomes are symptoms and functional outcomes. The RCT, which used a crossover design, found better outcomes with HBO2 therapy at 2 months than with delayed treatment. However, the trial had a number of methodologic limitations (e.g., lack of patient blinding, heterogeneous population, and high dropout rate) that make it difficult to evaluate the efficacy of HBO2 therapy. The evidence is insufficient to determine the effects of the technology on health outcomes.

Bell’s Palsy

For individuals with Bell’s palsy who receive systemic HBO2 therapy, the evidence includes a systematic review. Relevant outcomes are symptoms, change in disease status, and functional outcomes. A Cochrane review did not identify any RCTs meeting selection criteria; the single RCT found did not have a blinded outcome assessment. The evidence is insufficient to determine the effects of the technology on health outcomes.

Traumatic Brain Injury

For individuals with traumatic brain injury who receive systemic HBO2 therapy, the evidence includes RCTs and systematic reviews. Relevant outcomes are overall survival, symptoms, change in disease status, and functional outcomes. RCTs were heterogenous regarding intervention protocols, patient populations, and outcomes reported. Systematic reviews conducted pooled analyses only on a minority of the published RCTs, and these findings were inconsistent. The evidence is insufficient to determine the effects of the technology on health outcomes.

Inflammatory Bowel Disease

For individuals with inflammatory bowel disease who receive systemic HBO2 therapy, the evidence includes an RCT, observational studies, and a systematic review. Relevant outcomes are symptoms, change in disease status and functional outcomes. One small RCT has been published, and this trial did not find a significant improvement in health outcomes when HBO2 therapy was added to standard medical therapy. A systematic review including the RCT and observational studies found a high rate of bias in the literature due to attrition and reporting bias. The evidence is insufficient to determine the effects of the technology on health outcomes.

Idiopathic Sudden Sensorineural Hearing Loss

For individuals with idiopathic sudden sensorineural hearing loss who receive systemic HBO2 therapy, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms, change in disease status, and functional outcomes. A Cochrane review with pooled analysis of 2 RCTs did not find a statistically significant difference in outcomes between the HBO2 therapy and the control groups in hearing for all frequencies at a level greater than 50%, but did find a statistical difference at a level greater than 25%. An RCT published after the review reported no differences in hearing between groups at 4 different frequencies. The RCTs had methodologic limitations. The evidence is insufficient to determine the effects of the technology on health outcomes.

Delayed-Onset Muscle Soreness

For individuals with delayed-onset muscle soreness who receive systemic HBO2 therapy, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms and functional outcomes. A Cochrane review of RCTs found worse short-term pain outcomes with HBO2 therapy than with control and no difference in longer term pain or other outcomes (e.g., swelling). The evidence is insufficient to determine the effects of the technology on health outcomes.

Autism Spectrum Disorders

For individuals with autism spectrum disorder who receive systemic HBO2 therapy, the evidence includes an RCT and a systematic review. Relevant outcomes are symptoms and functional outcomes. A Cochrane review identified a single RCT on HBO2 therapy for autism spectrum disorder and this trial did not find significantly better parental-assessed or clinician-assessed outcomes with HBO2 therapy compared with sham. The evidence is insufficient to determine the effects of the technology on health outcomes.

Cerebral Palsy

For individuals with cerebral palsy who receive systemic HBO2 therapy, the evidence includes 2 RCTs and an observational study. Relevant outcomes are symptoms and functional outcomes. One RCT was stopped early due to futility, and the other did not find significantly better outcomes with HBO2 therapy than with a sham intervention. The observational study focused on sleep disorders in children with cerebral palsy and reported improvements with the HBO2 therapy treatment. The evidence is insufficient to determine the effects of the technology on health outcomes.

Vascular Dementia

For individuals with vascular dementia who receive systemic HBO2 therapy, the evidence includes an RCT and a systematic review. Relevant outcomes are symptoms and functional outcomes. The Cochrane review identified only a single RCT with methodologic limitations. Well-conducted controlled trials are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Radiotherapy Adverse Effects

For individuals with radiotherapy adverse events who receive systemic HBO2 therapy, the evidence includes RCTs, nonrandomized comparator trials, case series, and systematic reviews. Relevant outcomes are symptoms and functional outcomes. Two systematic reviews were identified, but pooled analyses were not possible due to heterogeneity in treatment regimens and outcomes measured. One systematic review concluded that more RCTs would be needed. The 2 RCTs identified had inconsistent findings. One reported no short-term benefit with HBO2 therapy, but some benefits 12 months after radiotherapy; the other did not find a significant benefit of HBO2 therapy at 12-month follow-up. The evidence is insufficient to determine the effects of the technology on health outcomes.

Idiopathic Femoral Neck Necrosis

For individuals with idiopathic femoral neck necrosis who receive systemic HBO2 therapy, the evidence includes an RCT. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The RCT, which had a small sample, only reported short-term (i.e., 6-week) outcomes. Larger well-conducted RCTs reporting longer term outcomes are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Migraine

For individuals with a migraine who receive systemic HBO2 therapy, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms, change in disease status, and functional outcomes. The Cochrane review conducted a pooled analysis including 3 of the 11 trials. Meta-analysis of these 3 RCTs found significantly greater relief of migraine symptoms with HBO2 therapy than with a comparator intervention within 45 minutes of treatment. Longer term data are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Herpes Zoster

For individuals with herpes zoster who receive systemic HBO2 therapy, the evidence includes an RCT. Relevant outcomes are symptoms and change in disease status. The RCT was unblinded and only reported short-term (i.e., 6-week) outcomes. Additional well-conducted RCTs with longer follow-up are needed. The evidence is insufficient to determine the effects of the technology on health outcomes.

Fibromyalgia

For individuals with fibromyalgia who receive systemic HBO2 therapy, the evidence includes RCTs. Relevant outcomes are symptoms, change in disease status, and functional outcomes. Only 2 RCTs were identified, and both reported positive effects of HBO2 therapy on tender points and pain. However, the trials had relatively small samples and methodologic limitations (e.g., quasi-randomization, no or uncertain sham control for a condition with subjective outcomes susceptible to a placebo effect). Moreover, the HBO2 therapy protocols varied. The evidence is insufficient to determine the effects of the technology on health outcomes.

Multiple Sclerosis

For individuals with multiple sclerosis who receive systemic HBO2 therapy, the evidence includes RCTs and a systematic review. Relevant outcomes are symptoms and functional outcomes. A Cochrane review of RCTs did not find a significant difference in Expanded Disability Status Scale scores when patients with multiple sclerosis were treated with HBO2 therapy versus a comparator intervention. The evidence is insufficient to determine the effects of the technology on health outcomes.

Tumor Sensitization during Cancer Treatment: Radiotherapy or Chemotherapy

For individuals with cancer and are undergoing chemotherapy who receive systemic HBO2 therapy, the evidence includes an RCT and a systematic review. Relevant outcomes are overall survival and change in disease status. While the systematic review reported improvements in tumor control in patients with head and neck cancer who received HBO2 therapy, the adverse events accompanying the treatment (e.g., radiation tissue injury, seizures) were significant. The single RCT did not find a significant difference in survival for cancer patients who received HBO2 therapy before chemotherapy compared with usual care. The evidence is insufficient to determine the effects of the technology on health outcomes.

Fracture Healing

For individuals with fractures that are not healing and nonunion fractures who receive systemic HBO2 therapy, the evidence is lacking as there are no RCTs or published literature found during a systematic review. Relevant outcomes are symptoms and functional outcomes. Since the Cochrane review did not find any RCTs when patients were treated for nonunion or failing to heal fractures with HBO2 therapy versus sham or another comparator intervention, assessment of relevant outcomes is difficult. The evidence is insufficient to determine the effects of the technology on health outcomes.

Other Conditions (Not Discussed Earlier)

The evidence for the use of systemic HBO2 therapy in individuals with other conditions (not discussed earlier), i.e., crush injury, reperfusion injury, compartment syndrome, and other acute traumatic ischemias; venous stasis ulcers; compromised skin graft or flap, or for enhancement of healing in a selected problem wound; gas gangrene; soft tissue infections due to mixed aerobic and anaerobic organisms with tissue necrosis and refractory bacteroides infections; decompression sickness; acute air or gas embolism; brown recluse spider bite; acute cyanide poisoning; profound anemia with exceptional blood loss when blood transfusion is impossible or must be delayed; selected refractory mycoses; intracranial abscess; acute cerebral edema; non-acute arterial insufficiency ulcer; decubitus ulcers; planned dental surgery (non-implant-related) of an irradiated jaw, and includes systematic reviews and/or recommendations from the UHMS’s guidelines. Relevant outcomes include overall survival, symptoms, change in disease status, and functional outcomes. For all of these indications, evidence and/or UHMS guidelines support use of systemic HBO2 therapy. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in health outcomes.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

HCPCS code A4575 is used to describe the disposable appliance that is positioned around the wound area for THBO2 therapy. Conventional O2 tanks, typically gas, are used to supply the O2.

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage versus. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

99183

HCPCS Codes

A4575, G0277

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. NCBI Bookshelf – Sadri RA, Cooper JS. Hyperbaric, complications (2017). National Center for Biotechnology Information, U.S. National Library of Medicine. Available at <https://www.ncbi.nlm.nih.gov> (accessed on July 31, 2018).

2. FDA – Hyperbaric Oxygen Therapy: Don't Be Misled (2013). U.S. Food and Drug Administration. Available at <http://www.fda.gov> (accessed on February 18, 2015).

3. de Smet GHJ, Kroese LF, Menon AG, et al. Oxygen therapies and their effects on wound healing. Wound Repair Regen. Aug 2017; 25(4):591-608. PMID 28783878

4. Leslie CA, Sapico FL, Ginunas VJ, et al. Randomized controlled trial of topical hyperbaric oxygen for treatment of diabetic foot ulcers. Diabetes Care. Feb 1988; 11(2):111-5. PMID 3289861

5. Hyperbaric Oxygen Therapy for Wound Healing – Part I. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (1999 August) 14(13):1-55.

6. Hyperbaric Oxygen Therapy for Wound Healing – Part II. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (1999 December) 14(15):1-55.

7. Hyperbaric Oxygen Therapy for Wound Healing – Part III. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (1999 December) 14(16):1-27.

8. Kranke P, Bennett MH, Martyn-St James M, et al. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. 2012; 4:CD004123. PMID 22513920

9. Elraiyah T, Tsapas A, Prutsky G, et al. A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers. J Vasc Surg. Feb 2016; 63(2 Suppl):46S-58S e41-42. PMID 26804368

10. Buckley NA, Juurlink DN, Isbister G, et al. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2011; (4):CD002041. PMID 21491385

11. Bennett MH, Feldmeier J, Hampson NB, et al. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. Apr 28 2016; 4:CD005005. PMID 27123955

12. Borab Z, Mirmanesh MD, Gantz M, et al. Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. J Plast Reconstr Aesthet Surg. Apr 2017; 70(4):529-38. PMID 28081957

13. Ravi P, Vaishnavi D, Gnanam A, et al. The role of hyperbaric oxygen therapy in the prevention and management of radiation-induced complications of the head and neck - a systematic review of literature. J Stomatol Oral Maxillofac Surg. Dec 2017; 118(6):359-62. PMID 28838774

14. Maynor ML, Moon RE, Camporesi EM, et al. Chronic osteomyelitis of the tibia: treatment with hyperbaric oxygen and autogenous microsurgical muscle transplantation. J South Orthop Assoc. Spring 1998; 7(1):43-57. PMID 9570731

15. Davis JC, Heckman JD, DeLee JC, et al. Chronic non-hematogenous osteomyelitis treated with adjuvant hyperbaric oxygen. J Bone Joint Surg Am. Oct 1986; 68(8):1210-7. PMID 3771602

16. Chen CE, Ko JY, Fu TH, et al. Results of chronic osteomyelitis of the femur treated with hyperbaric oxygen: a preliminary report. Chang Gung Med J. Feb 2004; 27(2):91-7. PMID 15095953

17. Chen CE, Shih ST, Fu TH, et al. Hyperbaric oxygen therapy in the treatment of chronic refractory osteomyelitis: a preliminary report. Chang Gung Med J. Feb 2003; 26(2):114-21. PMID 12718388

18. Chen CY, Lee SS, Chan YS, et al. Chronic refractory tibia osteomyelitis treated with adjuvant hyperbaric oxygen: a preliminary report. Changgeng Yi Xue Za Zhi. Jun 1998; 21(2):165-71. PMID 9729650

19. Villanueva E, Bennett MH, Wasiak J, et al. Hyperbaric oxygen therapy for thermal burns. Cochrane Database Syst Rev. Jul 2004(3):CD004727. PMID 15266540

20. Eskes A, Vermeulen H, Lucas C, et al. Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. Cochrane Database Syst Rev. 2013; 12:CD008059. PMID 24343585

21. Dauwe PB, Pulikkottil BJ, Lavery L, et al. Does hyperbaric oxygen therapy work in facilitating acute wound healing: a systematic review. Plast Reconstr Surg. Feb 2014; 133(2):208e-15e. PMID 24469192

22. Freiberger JJ, Padilla-Burgos R, McGraw T, et al. What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: a randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics. J Oral Maxillofac Surg. Jul 2012; 70(7):1573-83. PMID 22698292

23. Levett D, Bennett MH, Millar I. Adjunctive hyperbaric oxygen for necrotizing fasciitis. Cochrane Database Syst Rev. 2015; 1:CD007937. PMID 25879088

24. Jallali N, Withey S, Butler PE. Hyperbaric oxygen as adjuvant therapy in the management of necrotizing fasciitis. Am J Surg. Apr 2005; 189(4):462-6. PMID 15820462

25. Hyperbaric Oxygen Therapy – Recent Findings on Evidence for its Effectiveness. Calgary, Alberta, Canada: Alberta Heritage Foundation for Medical Research – Information Paper, Health Technology Assessment (2003 March) IP 13:1-25.

26. George ME, Rueth NM, Skarda DE, et al. Hyperbaric oxygen does not improve outcome in patients with necrotizing soft tissue infection. Surg Infect (Larchmt). Feb 2009; 10(1):21-8. PMID 18991520

27. Bennett MH, Lehm JP, Jepson N. Hyperbaric oxygen therapy for acute coronary syndrome. Cochrane Database Syst Rev. Jul 23 2015(7):CD004818. PMID 26202854

28. Bennett MH, Weibel S, Wasiak J, et al. Hyperbaric oxygen therapy for acute ischaemic stroke. Cochrane Database Syst Rev. Nov 12 2014;11(11):CD004954. PMID 25387992

29. Efrati S, Fishlev G, Bechor Y, et al. Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial PLoS One. 2013; 8(1):e53716. PMID 23335971

30. Holland NJ, Bernstein JM, Hamilton JW. Hyperbaric oxygen therapy for Bell's palsy. Cochrane Database Syst Rev. 2012; 2:CD007288. PMID 22336830

31. Wang F, Wang Y, Sun T, et al. Hyperbaric oxygen therapy for the treatment of traumatic brain injury: a meta-analysis. Neurol Sci. May 2016; 37(5):693-701. PMID 26746238

32. Crawford C, Teo L, Yang E, et al. Is hyperbaric oxygen therapy effective for traumatic brain injury? a rapid evidence assessment of the literature and recommendations for the field. J Head Trauma Rehabil. May/Jun 2017; 32(3):E27-E37. PMID 27603765

33. Bennett MH, Trytko B, Jonker B. Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury. Cochrane Database Syst Rev. 2012; 12:CD004609. PMID 23235612

34. Wolf G, Cifu D, Baugh L, et al. The effect of hyperbaric oxygen on symptoms after mild traumatic brain injury. J Neurotrauma. Nov 20 2012; 29(17):2606-12. PMID 23031217

35. Cifu DX, Walker WC, West SL, et al. Hyperbaric oxygen for blast-related postconcussion syndrome: three-month outcomes. Ann Neurol. Feb 2014; 75(2):277-86. PMID 24255008

36. Miller RS, Weaver LK, Bahraini N, et al. Effects of hyperbaric oxygen on symptoms and quality of life among service members with persistent postconcussion symptoms: a randomized clinical trial. JAMA Intern Med. Jan 2015; 175(1):43-52. PMID 25401463

37. Marois P, Mukherjee A, Ballaz L. Hyperbaric Oxygen Treatment for Persistent Postconcussion Symptoms-A Placebo Effect? JAMA Intern Med. Jul 1 2015; 175(7):1239-40. PMID 26146912

38. Dulai PS, Gleeson MW, Taylor D, et al. Systematic review: The safety and efficacy of hyperbaric oxygen therapy for inflammatory bowel disease. Aliment Pharmacol Ther. Jun 2014; 39(11):1266-75. PMID 24738651

39. Pagoldh M, Hultgren E, Arnell P, et al. Hyperbaric oxygen therapy does not improve the effects of standardized treatment in a severe attack of ulcerative colitis: a prospective randomized study. Scand J Gastroenterol. Sep 2013; 48(9):1033-40. PMID 23879825

40. Lewis JD, Chuai S, Nessel L, et al. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. Dec 2008; 14(12):1660-6. PMID 18623174

41. Bennett M, Kertesz T, Perleth M, et al. Hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss and tinnitus. Cochrane Database Syst Rev. 2005; (1):CD004739. PMID 23076907

42. Cvorovic L, Jovanovic MB, Milutinovic Z, et al. Randomized prospective trial of hyperbaric oxygen therapy and intratympanic steroid injection as salvage treatment of sudden sensorineural hearing loss. Otol Neurotol. Aug 2013; 34(6):1021-6. PMID 23820795

43. Bennett M, Best TM, Babul S, et al. Hyperbaric oxygenation therapy for delayed onset muscle soreness and closed soft tissue injury. Cochrane Database Syst Rev. 2005; (4):CD004713. PMID 16235376

44. Xiong T, Chen H, Luo R, et al. Hyperbaric oxygen therapy for people with autism spectrum disorder (ASD). Cochrane Database Syst Rev. Oct 13 2016; 10:CD010922. PMID 27737490

45. Sampanthavivat M, Singkhwa W, Chaiyakul T, et al. Hyperbaric oxygen in the treatment of childhood autism: a randomized controlled trial. Diving Hyperb Med. Sep 2012; 42(3):128-33. PMID 22987458

46. Lacey DJ, Stolfi A, Pilati LE. Effects of hyperbaric oxygen on motor function in children with cerebral palsy. Ann Neurol. Nov 2012; 72(5):695-703. PMID 23071074

47. Collet JP, Vanasse M, Marios P, et al. Hyperbaric oxygen for children with cerebral palsy: A randomized multicenter trial HBO-CP Research Group. Lancet. Feb 24 2001; 357(9256): 582-6. PMID 11558483

48. Long Y, Tan J, Nie Y, et al. Hyperbaric oxygen therapy is safe and effective for the treatment of sleep disorders in children with cerebral palsy. Neurol Res. Mar 2017; 39(3):239-47. PMID 28079475

49. Xiao Y, Wang J, Jiang S, et al. Hyperbaric oxygen therapy for vascular dementia. Cochrane Database Syst Rev. 2012; 7:CD009425. PMID 22786527

50. Spiegelberg L, Djasim UM, van Neck HW, et al. Hyperbaric oxygen therapy in the management of radiation-induced injury in the head and neck region: a review of the literature. J Oral Maxillofac Surg. Aug 2010; 68(8):1732-9. PMID 20493616

51. Teguh DN, Levendag PC, Noever I, et al. Early hyperbaric oxygen therapy for reducing radiotherapy side effects: early results of a randomized trial in oropharyngeal and nasopharyngeal cancer. Int J Radiat Oncol Biol Phys. Nov 1 2009; 75(3):711-6. PMID 19386439

52. Gothard L, Haviland J, Bryson P, et al. Randomized phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer. Radiother Oncol. Oct 2010; 97(1):101-7. PMID 20605648

53. Camporesi EM, Vezzani G, Bosco G, et al. Hyperbaric oxygen therapy in femoral head necrosis. J Arthroplasty. Sep 2010; 25(6 Suppl):118-23. PMID 20637561

54. Bennett MH, French C, Schnabel A, et al. Normobaric and hyperbaric oxygen therapy for migraine and cluster headache. Cochrane Database Syst Rev. 2008; (3):CD005219. PMID 18466121

55. Peng Z, Wang S, Huang X, et al. Effect of hyperbaric oxygen therapy on patients with herpes zoster. Undersea Hyperb Med. Nov-Dec 2012; 39(6):1083-7. PMID 23342765

56. Efrati S, Golan H, Bechor Y, et al. Hyperbaric oxygen therapy can diminish fibromyalgia syndrome - prospective clinical trial. PLoS One. 2015; 10(5):e0127012. PMID 26010952

57. Yildiz S, Kiralp MZ, Akin A, et al. A new treatment modality for fibromyalgia syndrome: hyperbaric oxygen therapy. J Int Med Res. May-Jun 2004; 32(3):263-7. PMID 15174219

58. Bennett M, Heard R. Hyperbaric oxygen therapy for multiple sclerosis. Cochrane Database Syst Rev. 2004(1):CD003057. PMID 14974004

59. Bennett MH, Feldmeier J, Hampson N, et al. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2012; 5:CD005005. PMID 22592699

60. Bennett M, Feldmeier J, Smee R, et al. Hyperbaric oxygenation for tumor sensitization to radiotherapy. Cochrane Database Syst Rev. (2005) (4):CD005007. PMID 16235387

61. Heys SD, Smith IC, Ross JA, et al. A pilot study with long term follow up of hyperbaric oxygen pretreatment in patients with locally advanced breast cancer undergoing neo-adjuvant chemotherapy. Undersea Hyperb Med. Jan-Feb 2006; 33(1):33-43. PMID 1660225

62. Bennett M, Stanford R, Turner R. Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union. Cochrane Database Syst Rev. 2012; (1):CD004712. PMID 23152225

63. UHMS.com – Weaver LK, editor. Hyperbaric Oxygen Therapy Indications, 13th Edition (2015). North Palm Beach, FL: Undersea and Hyperbaric Medical Society, HBO2 Therapy Committee. Available at <http://www.uhms.org> (accessed on July 31, 2018).

64. Feldmeier JJ, Hopf HW, Warriner RA, 3rd, et al. UHMS position statement: topical oxygen for chronic wounds. Undersea Hyperb Med. May-Jun 2005; 32(3):157-68. PMID 16119307

65. UHMS – Bennett M., Heard R. UHMS Position Paper: the treatment of multiple sclerosis with hyperbaric oxygen therapy (2009). Undersea & Hyperbaric Medical Society, HBO2 Therapy Committee. Available at <https://www.uhms.org> (accessed on July 31, 2017).

66. UHMS – Bennett M., B. H. UHMS Position Paper: the treatment of autism spectrum disorder with hyperbaric oxygen therapy (2009). Undersea & Hyperbaric Medical Society, HBO2 Therapy Committee. Available at <https://www.uhms.org> (accessed on July 31, 2017).

67. UHMS – Huang ET, et al. A Clinical Practice Guideline for the Use of Hyperbaric Oxygen Therapy in the Treatment of Diabetic Foot Ulcers (2015). Undersea & Hyperbaric Medical Society, HBO2 Therapy Committee. Available at <https://www.uhms.org> (accessed on July 1, 2015).

68. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 infectious diseases society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. J Am Podiatr Med Assoc. Jan-Feb 2013; 103(1):2-7. PMID 23328846

69. Hingorani A, LaMuraglia GM, Henke P, 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. J Vasc Surg. Feb 2016; 63(2 Suppl):3S-21S. PMID 26804367

70. AAOHNS – Clinical practice guideline: sudden hearing loss (2012). American Academy of Otolaryngology-Head and Neck Surgery. Available at <https://www.entnet.org> (accessed July 31, 2018).

71. Mathieu D, Marroni A, Kot J. Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving Hyperb Med. Mar 2017; 47(1):24-32. PMID 28357821

72. Sultan A, Hanna GJ, Margalit DN, et al. The use of hyperbaric oxygen for the prevention and management of osteoradionecrosis of the jaw: a Dana-Farber/Brigham and Women's Cancer Center Multidisciplinary Guideline. Oncologist. Mar 2017; 22(3):343-50. PMID 28209748

73. CMS – National Coverage Determination (NCD) for Hyperbaric Oxygen Therapy (20.29) (April 3, 2017). Centers for Medicare and Medicaid Services (CMS). Available at <https://www.cms.gov> (accessed July 31, 2018).

74. Hyperbaric Oxygen Therapy. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2018 January) Medicine 2.01.04.

Policy History:

Date Reason
10/1/2018 Document updated with literature review. Coverage unchanged. NOTEs renumbered, following addition of NOTE 1: “This medical policy does not address THBO 2 therapy in the absence of pressurization”. References 1, 3, 9, 11-13, 19, 27-28, 31-32, 40, 44, 48, 64-66, 68-73 added; numerous references removed.
7/15/2017 Reviewed. No changes.
10/1/2016 Document updated with literature review. The following indication was added as medically necessary: acute postoperative foot surgical treatment for patients with Wagner grade-3 or higher diabetic foot ulcers. The following indications were added as experimental, investigational and/or unproven: fibromyalgia and mental illness.
5/1/2015 Document updated with literature review. The following indications were added as experimental, investigational and/or unproven: Arthritic diseases, osteoarthritis or rheumatoid; Asthma; Cardiogenic shock; Depression; Inflammatory bowel disease; Hepatic necrosis; Hepatitis; Herpes zoster; Human immunodeficiency virus infection or acquired immune deficiency syndrome; Motor dysfunction associated with stroke; Organ transplantation or storage; Osteonecrosis of the jaw, bisphosphonate-related; Post-traumatic stress disorder or other stress disorders; Pulmonary emphysema; Senility; Sport’s injury; Septicemia, anaerobic (unrelated to clostridial), or systemic aerobic infection; Tetanus; Ulcerative Colitis; Vascular dementia or chronic brain syndromes, neovascular causes (such as Pick’s disease, Alzheimer’s disease, and Korsakoff’s disease). Title changed from Hyperbaric Oxygen (HBO 2 ) Pressurization.
12/1/2013 Document updated with literature review. The following was added: 1) New medically necessary indications for uses of HBO 2 therapy when criteria is met: Idiopathic sudden sensorineural hearing loss (ISSNHL); 2) New experimental, investigational and unproven indications for uses of HBO 2 therapy: Bell’s palsy; idiopathic femoral neck necrosis; lymphedema of the arm; acute osteomyelitis; radiation-induced injury to head, neck, anus, or rectum; radiation necrosis of non-neurologic tissue; reduction of adverse effects at any point of therapy, including early onset effects and delayed effects; and acute surgical and traumatic wounds. Otherwise, coverage for all other indications remains unchanged.
7/15/2011 Coverage revised only. The following changes were made: 1) Systemic HBO 2 may be considered medically necessary to treat soft-tissue radiation necrosis, including radiation enteritis, cystitis, or proctitis; 2) Review of diabetic wounds may occur after 30 systemic HBO 2 treatments.
3/1/2010 Revised/updated entire document, HBO 2 may be considered medically necessary when clinical criteria are met.
9/15/2008 Coverage revised, Rationale revised, References revised.
8/15/2007 Revised/updated entire document.
11/1/2000 Revised/updated entire document.
3/1/2000 Revised/updated entire document.
1/1/1996 Revised/updated entire document.
5/1/1996 Medical policy number changed.
5/1/1990 New medical document.

Archived Document(s):

Title:Effective Date:End Date:
Hyperbaric Oxygen (HBO2) Therapy07-15-201709-30-2018
Hyperbaric Oxygen (HBO2) Therapy10-01-201607-14-2017
Hyperbaric Oxygen (HBO2) Therapy05-01-201509-30-2016
Hyperbaric Oxygen (HBO2) Pressurization12-01-201304-30-2015
Hyperbaric Oxygen (HBO2) Pressurization07-15-201111-30-2013
Hyperbaric Oxygen (HBO2) Pressurization03-01-201007-14-2011
Hyperbaric Oxygen (HBO2) Pressurization09-15-200802-28-2010
Hyperbaric Oxygen (HBO2) Pressurization08-15-200709-14-2008
Hyperbaric Oxygen (HBO2) Pressurization11-01-200008-14-2007
Back to Top