| Coverage Policy Manual | |
| Policy #: | 1997088 |
| Category: | Medicine |
| Initiated: | April 1996 |
| Last Review: | January 2024 |
|
|
|
|||||||||||
| Hyperbaric Oxygen Pressurization (HBO) | |
|
|
|
| Description: |
Hyperbaric oxygen therapy (HBOT) involves breathing 100% oxygen at pressures between 1.5 and 3.0 atmospheres. It is generally applied systemically with the patient inside a hyperbaric chamber. HBOT can also be applied topically; that is, the body part to be treated is isolated (e.g., in an inflatable bag and exposed to pure oxygen). HBOT has been investigated for various conditions that have potential to respond to increased oxygen delivery to tissue.
Hyperbaric oxygen therapy (HBOT) is a technique for delivering higher pressures of oxygen to the tissues. Two methods of administration are available: topical and systemic.
Topical hyperbaric therapy is a technique of delivering 100% oxygen directly to an open, moist wound at a pressure slightly higher than atmospheric pressure. It is hypothesized that the high concentrations of oxygen diffuse directly into the wound to increase the local cellular oxygen tension, which in turn promotes wound healing. Topical hyperbaric oxygen devices consist of an appliance to enclose the wound area (frequently an extremity) and a source of oxygen; conventional oxygen tanks may be used. The appliances may be disposable and may be used without supervision in the home by well-trained patients. Topical hyperbaric oxygen 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.
In systemic or large hyperbaric oxygen chambers, the patient is entirely enclosed in a pressure chamber and breathes oxygen at a pressure greater than 1 atmosphere (the pressure of oxygen at sea level). Thus, this technique relies on systemic circulation to deliver highly oxygenated blood to the target site, typically a wound. Systemic HBOT can be used to treat systemic illness, such as air or gas embolism, carbon monoxide poisoning, or clostridial gas gangrene. Treatment may be carried out either in a monoplace chamber pressurized with pure oxygen or in a larger, multiplace chamber pressurized with compressed air, in which case the patient receives pure oxygen by mask, head tent, or endotracheal tube.
HBOT is a generally safe therapy, with an estimated adverse side effect rate of 0.4% (Sadri, 2017). Adverse events may occur either from pressure effects or the oxygen. 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. Oxygen 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
Since 1979, the U.S. Food and Drug Administration (FDA) has cleared multiple topical and systemic hyperbaric oxygen administration devices through the 510(k) pathway. In 2013, the FDA published a statement warning that non-FDA approved uses of HBOT may endanger the health of patients (FDA, 2013). If patients mistakenly believe that HBOT devices have been proven safe for uses not cleared by the FDA, they may delay or forgo proven medical therapies.
|
|
|
|
|
Policy/ Coverage: |
Effective January 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Systemic Hyperbaric Oxygen Pressurization (HBO) meets primary coverage criteria for effectiveness and is covered for the following indications. While the number of sessions to treat a condition may vary, Utilization Review is required for any service exceeding the number of sessions noted.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Hyperbaric Oxygen Pressurization (HBO) does not meet primary coverage criteria that there be scientific evidence of effectiveness in the treatment of any indication not described above as covered, including but not limited to the following listed indications. For contracts without primary coverage criteria, HBO is considered investigational in the treatment of any indication not described above as covered, including but not limited to the following listed indications. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body without use of a pressurized chamber (topical HBO) is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body (topical HBO) without use of a pressurized chamber are considered investigational. Investigational services are an exclusion in the member certificate of coverage.
Effective August 2011 through December 2022
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Systemic Hyperbaric Oxygen Pressurization (HBO) meets primary coverage criteria for effectiveness and is covered for the following indications. While the number of sessions to treat a condition may vary, Utilization Review is required for any service exceeding the number of sessions noted.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Hyperbaric Oxygen Pressurization (HBO) does not meet primary coverage criteria that there be scientific evidence of effectiveness in the treatment of the following indications. For contracts without primary coverage criteria, HBO is considered investigational in the following indications. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body without use of a pressurized chamber (topical HBO) is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body (topical HBO) without use of a pressurized chamber are considered investigational. Investigational services are an exclusion in the member certificate of coverage.
Effective March 2010 – July 2011
Hyperbaric Oxygen Pressurization (HBO) meets primary coverage criteria for effectiveness and is covered for the following indications. While the number of sessions to treat a condition may vary, Utilization Review is required for any service exceeding the number of sessions noted.
Hyperbaric Oxygen Pressurization (HBO) does not meet primary coverage criteria that there be scientific evidence of effectiveness in the treatment of the following indications. For contracts without primary coverage criteria, HBO is considered investigational in the following indications. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body without use of a pressurized chamber (topical HBO) is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body (topical HBO) without use of a pressurized chamber are considered investigational. Investigational services are an exclusion in the member certificate of coverage.
Effective August 2009
Hyperbaric Oxygen Pressurization (HBO) meets primary coverage criteria for effectiveness and is covered for the following indications. While the number of sessions to treat a condition may vary, Utilization Review is required for any service exceeding the number of sessions noted.
HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body without use of a pressurized chamber is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body without use of a pressurized chamber are considered investigational. Investigational services are an exclusion in the member certificate of coverage.
Effective October 2003
Hyperbaric Oxygen Pressurization (HBO) meets primary coverage criteria for effectiveness and is covered for the following indications. While the number of sessions to treat a condition may vary, Utilization Review is required for any service exceeding the number of sessions noted.
HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body without use of a pressurized chamber is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, HBO for preparation of a site for skin graft or flap and breathing 100% oxygen at one atmosphere pressure or the application of oxygen to parts of the body without use of a pressurized chamber are considered investigational. Investigational services are an exclusion in the member certificate of coverage.
|
|
|
|
| Rationale: |
“Due to the detail of the rationale, the complete document is not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com”
These coverage determinations were taken from the Undersea and Hyperbaric Medical Society Indications and were last accessed August 2009.
2010 Update
There have recently been several case studies, small uncontrolled trials and one RCT supporting the use of low pressure/low oxygenation concentration hyperbaric oxygen therapy in the treatment of autism. In addition, there was a RCT on the use of hyperbaric oxygen therapy for reducing side effects from radiation therapy and a new Cochrane meta-analysis on migraine and cluster headache.
Autism Spectrum Disorder
Rossignol and colleagues published results of their RCT of 62 children diagnosed with autism (Rossignol, 2209). The children were randomly assigned to receive 40 hourly treatments of either hyperbaric treatment at 1.3 atm and 24% oxygen (treatment group)or slightly pressurized room air at 1.03 atm and 21 % oxygen (control group). In this study, the children in the treatment group showed improvement compared to children in the control group in primary outcomes. The primary outcomes included subjective assessments using the Clinical Global Impression (CGI), a physician assessment ; the Autism Treatment Evaluation Checklist (ATEC), assessed by the parent or primary caregiver; and the Aberrant Behaviour Checklist (ABC),also assessed by a parent or primary caregiver. The authors report that further studies are needed to confirm these findings.
The Undersea & Hyperbaric Medical Society position paper on the treatment of autism spectrum disorder with hyperbaric oxygen therapy does not recommend the use of this therapy in the routine treatment of autism. The paper discusses the controversy surrounding the results of the RCT done by Rossignoli and colleagues, including the fact that both groups of children treated showed improvements in many of the outcomes which may suggest a placebo effect. In addition, according to the author of the position statement, the therapy used for the treatment group does not require a chamber to deliver the dose and some of the participating sites were above sea level “implying that the treatment effect may have been obtained with even lower absolute pressures than is being suggested” in the study. Additional concerns are included in the position paper. The author concludes, “there is very little evidence to support an effect of pressure alone, or that oxygen has differing effects whether given by increasing the ambient pressure or increasing the inspired fraction”. The UHMS does recommend that further trials need to be done in this area including trials that use more objective outcomes such as neuroimaging using PET or SPECT.
In summary, there is a lack of scientific evidence that the use of low pressure/low oxygenation concentration hyperbaric oxygen therapy improves health outcomes in the routine treatment of autism.
Radiotherapy Side Effects
Teguh and colleagues included 17 patients with oropharyngeal or nasopharyngeal cancer who were treated with radiation therapy; the study was conducted in the Netherlands (Teguh, 2009). Eight patients were randomized to receive 30 sessions of hyperbaric oxygen treatment, beginning within 2 days of completing radiation therapy, and 9 patients received no additional treatment. All patients were included in the analysis. Quality of life outcomes were assessed and the primary outcome was specified as xerostoma at one year. Quality of life measures did not differ significantly between groups in the acute phase (first 3 months). For example, one month after treatment, the mean visual analogue scale (VAS) score for xerostoma (0 to 10 scale) was 5 in the HBO group and 6 in the control group. However, at one year, there was a statistically significant difference between groups; the mean VAS score for xerostoma was 4 in the HBO group and 7 in the control group. Also at one year, the mean quality of life score for swallowing (0 to 100 scale) was 7 in the HBO group and 40 in the control group. The study is limited by the small sample size and the wide fluctuation over the follow-up period in quality of life ratings. There is insufficient evidence to assess the effectiveness of HBO to reduce side effects after radiation therapy.
Migraine
A Cochrane review by Bennett and colleagues identified randomized controlled trials that evaluated the effectiveness of systemic hyperbaric oxygen therapy for preventing or treating migraine headache compared to another treatment or a sham control (Bennett, 2008). In a search of the literature through May 2008, 5 trials with a total of 103 patients were identified that addressed treatment of acute migraine with HBO. A pooled analysis of three trials (total of 43 patients) found a statistically significant increase in the proportion of patients with substantial relief of migraine within 45 minutes of HBO treatment. No other pooled analyses were conducted due to variability in the outcomes reported in the trials. The meta-analysis does not report data on treatment effectiveness beyond the immediate post-treatment period and the methodological quality of trials was moderate to low e.g. randomization was not well-described in any trial.
2011 Update
A review of the available medical literature was conducted on the use of hyperbaric oxygen pressurization (HBO). A summary of the key studies and reviews are discussed below.
A 2011 double-blind RCT from Sweden evaluated HBO therapy in 75 diabetic patients with chronic wounds who had failed at least 2 months of treatment at a diabetic foot clinic (Londahi, 2011). After 12 months, the healing rate was 61% in the hyperbaric oxygen group and 27% in the sham hyperbaric group; this difference was statistically significant, p=0.009. This new study supports the findings of the 2004 Cochrane review, which has not been updated.
Acute surgical and traumatic wounds
In 2011, a Cochrane review of RCTs on HBO therapy for acute wounds (e.g., surgical wounds, lacerations, traumatic wounds, and animal bites) was published by Eskes and colleagues (Eskes, 2010). To be included, studies needed to compare HBO with a different intervention or compare 2 HBO regimens; in addition, studies needed to objectively measure wound healing. A total of 7 potentially relevant studies were identified; 3 of these met the review’s inclusion criteria. The 3 studies ranged in size from 36 to 135 participants. Due to differences among studies in terms of patient population, comparison intervention, outcome measurement, etc., study results could not be pooled. In addition, investigators identified biases in the studies such as insufficient reporting of randomization procedures and selective reporting of outcome data. Findings of individual studies were mixed. For example, one study found a significantly higher rate of complete wound healing with HBO compared to sham HBO treatment, and another study did not find a significant difference in complete healing rates between HBO therapy and dexamethosone or heparin treatment. The authors concluded that there is insufficient high-quality data on the effect of HBO therapy on treatment of acute wounds. The coverage statement was changed to indicate that acute surgical and traumatic wounds do not meet primary coverage criteria.
Radiotherapy Adverse Effects
In 2010, Spiegelberg and colleagues conducted a systematic review of studies on HBO therapy to prevent or treat radiotherapy-induced head and neck injuries associated with treatment of malignant tumors (Spiegelberg, 2010). The authors identified 20 studies. Eight of the studies included control groups, their sample sizes ranged from 19 to 78 individuals. Four (50%) of the studies with a control group concluded that HBO was effective, and the other 4 did not conclude that the HBO was effective. The authors noted a paucity of RCTs but did not state the number of RCTs that they identified in their review.
In 2010, Gothard and colleagues in the U.K. published findings of a RCT using HBO therapy to treat arm lymphedema occurring after radiotherapy for cancer (Gothard, 2010). Fifty-eight patients with arm lymphedema (at least 15% increase in arm volume) following cancer treatment were randomized in a 2:1 ratio to receive HBO (n=38) or usual care without HBO (n=20). Fifty-three patients had baseline assessments and 46/58 (79%) had 12-month assessments. At the 12-month follow-up, there was not a statistically significant difference in the change from baseline in arm volume. The 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. According to this definition, 9 of 30 (30%) of patients in the HBO group were considered responders compared with 3 of 16 (19%) in the control group; the difference between groups was not statistically significant. Other outcomes, e.g., quality-of-life scores on the Short-Form (SF)-36, were similar between groups.
Due to the limited data, the coverage statement was changed to indicate that the use of HBO to treat arm lymphedema or radiation-induced injury in the head and neck after radiotherapy, as well as early use of HBO after radiation therapy to reduce side effects does not meet primary coverage criteria.
Idiopathic femoral neck necrosis
A double-blind RCT that evaluated HBO therapy to treat femoral head necrosis was published in 2010 by Camporesi and colleagues (Camporesi, 2010). The study included 20 adult patients with idiopathic unilateral femoral head necrosis. Patients received 30 treatments over 6 weeks with either HBO at 2.5 ATA (n=10) or a sham treatment consisting of hyperbaric air (n=10). The mean severity of pain on a 0-to-10 scale was significantly lower in the HBO group than the control group after 30 sessions (p<0.001) but not after 10 or 20 sessions. (The article did not report exact pain scores). Several range-of-motion outcomes were also reported; degrees were the unit of measurement. At the end of the initial treatment period, extension, abduction and adduction, but not flexion, were significantly greater in the HBO group compared to the control group. Longer-term comparative data were not available because the control group was offered HBO at the end of the initial 6-week treatment period. This single, small short-term RCT represents insufficient data on which to draw conclusions about the efficacy of HBO for treating femoral head necrosis. Thus the coverage statement was change to indicate that the use of HBO for treating femoral head necrosis does not meet primary coverage criteria.
Ongoing clinical trials
Randomized controlled trials underway that are evaluating hyperbaric oxygen therapy for indications now considered investigational include the following:
Hyperbaric oxygen therapy in treating long-term gastrointestinal adverse effects caused by radiation therapy in patients with pelvic cancer (NCT01087268): This is a double-blind RCT that is comparing treatment with HBO (100% oxygen) and sham HBO (21% oxygen). The primary outcome is change in quality of life after treatment. The study is sponsored by the National Cancer Institute; the expected final data collection date is December 2011.
Hyperbaric oxygen therapy in distal radius fractures: Can it shorten recovery time and increase fracture healing? (NCT01365780): This non-blinded RCT is comparing HBO to usual care given to patients who undergo surgery for distal radius fractures. Outcomes include microcirculation and pain level. The study is sponsored by RWTH Aachen University in Germany. The expected date of final data collection is November 2012.
Two ongoing RCTs were identified that are studying HBO for treatment of postconcussive symptoms after mild traumatic brain injury in a military population (NCT01220713 and NCT01306968):
Both are comparing treatment with HBO to sham treatment, and evaluating change in symptoms. NCT01220713 is sponsored by the U.S. Naval Medical Center and Portsmouth Hunter McGuire Veteran Affairs Medical Center. It includes patients who experienced a blast event during deployment; the expected final data completion date is July 2011. NCT01306968 is sponsored by the U.S. Army Medical Research and Materiel Command and is including individuals who experienced a wider range of traumatic events during deployment. Its expected date of study completion is February 2012.
2012 Update
A literature search was conducted through July 2012. Literature was found on the use hyperbaric oxygen pressurization to treat stroke, Bell’s Palsy and idiopathic sudden sensorineural hearing loss (ISSNHL). The following is a summary of the relevant literature.
Stroke
In 2003, Rusyniak and colleagues reported on the results of a randomized, double-blind sham controlled study of 33 patients presenting with acute ischemic stroke who were randomly assigned to active or sham HBO (Rusyniak, 2003). No beneficial effect was reported for HBO therapy. In a 2005 systematic review, Carson and colleagues concluded that current available evidence does not demonstrate any benefit with the use of HBO therapy for the treatment of stroke (Carson, 2005). The authors noted it is undetermined whether there are any benefits with HBO therapy that would outweigh potential harms and further study is required. Based on the available evidence, acute ischemic stroke was added to the list of indications not meeting primary coverage criteria.
Bell’s Palsy
In 2012, Holland and colleagues published a Cochrane review evaluating HBO treatment in adults with Bell’s palsy (Holland, 2012). The authors identified one RCT with 79 participants, and this study did not meet the Cochrane review methodologic standards because the outcome assessor was not blinded to treatment allocation. Due to the publication of the Cochrane review and the finding of insufficient evidence, Bell’s palsy was added to the list of indications not meeting primary coverage criteria.
Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL)
In 2011, the Undersea and Hyperbaric Medical Society added idiopathic sudden sensorineural hearing loss (ISSNHL) within the past 14 days as an approved indication for HBO therapy (Murphy-Lavoie, 2012).
A Cochrane review on HBO for ISSNHL and tinnitus identified 7 trials with a total of 392 participants (Bennett, 2007). The literature search was last assessed as up-to-date in July 2009. All trials included patients with ISSNHL with and/or without tinnitus; 2 trials also included patients with tinnitus in the absence of ISSNHL. Randomization procedures were only described in one study, and only one study stated they blinded participants to treatment group assignment using sham therapy. Six of the studies included time-based entry criteria for hearing loss and/or tinnitus; this was 48 hours in 3 studies, 2 weeks in 2 studies (for acute presentation) and 6 months in 1 study. The dose of oxygen per treatment session and the treatment protocols varied among studies e.g., the total number of treatment sessions varied from 10 to 25. All trials reported on change in hearing following treatment; but specific outcomes varied. Two trials reported the proportion of participants with greater than 50% 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 HBO and control groups (RR: 1.53, 95% CI: 0.86 to 2.78). In contrast, a pooled analysis of 2 trials reporting the proportion of participants with greater than 25% return of hearing at the end of therapy found a significantly higher rate of improvement after HBO compared to a control intervention (RR: 1.39: 95% CI: 1.05 to 1.84). Moreover, a pooled analysis of 4 trials found a significantly greater mean improvement in hearing over all frequencies with HBO compared to control (mean difference: 15.6 decibels (dB); 95% CI: 1.5 to 29.8). The authors 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 use of HBO for treating ISSNHL.
Among the RCTs was a 2004 study by Topuz and colleagues in which 51 patients with ISSNHL were randomized to receive conventional therapy (i.e., steroids, plasma expanders) with or without HBO (Topuz, 2004). Patients were within the first 2 weeks of onset of sudden hearing loss. Audiologic assessment was performed immediately after treatment. Compared to the conventional therapy group, the HBO group reported statistically significant improvement in hearing at frequencies of 250, 500, 1,000, and 4,000 Hz, but not at 2,000 Hz.
In 2012, Suzuki and colleagues in Japan published findings of a non-randomized controlled trial in 276 consecutive patients with ISSNHL (Suzuki, 2012). All patients had been treated with intravenous hydrocortisone. In addition, 174 patients underwent HBO treatment and 102 patients received intratympanic dexamethasone injection. There was no significant difference in most outcomes e.g., cure rate, marked recovery rate and hearing gain (dB) between the groups of patients who received HBO treatment compared to dexamethasone injections. However, at the p<0.05 level, the recovery rate (complete, good, or fair recovery) was significantly higher in the dexamethasone injection group than the HBO group (79.4% vs. 68%, respectively p=0.048). Limitations of this study were that individuals were not randomized to treatment group, and the authors did not adjust the p value to account for multiple outcome variables.
Due to methodologic limitations and variability among published studies, the evidence is insufficient to draw conclusions about the effect of HBO on health outcomes in patients with ISSNHL.
2013 Update
This policy is updated with results of a literature search using the MEDLINE database through July 2013. The policy statement has been changed to address several new indications identified in the literature search, including bisphosphonate-related osteonecrosis of the jaw, motor dysfunction associated with stroke, herpes zoster and vascular dementia. The following is a summary of the identified literature for these indications and other previously addressed indications.
Bisphosphonate-related Osteonecrosis of the Jaw
An unblinded RCT was published by Freiberger and colleagues in 2012 on use of HBO as an adjunct therapy for patients with bisphosphonate-related osteonecrosis of the jaw (Freiberger, 2012). Forty-nine patients were randomly assigned to HBO in addition to standard care (n=22) or standard care alone (n=27). Five patients in the standard care group received HBO treatment and 1 patient assigned to the HBO group declined HBO. The investigators decided to do a per protocol analysis (actual treatment received) because of the relatively large degree of crossover. Participants were evaluated at 3, 6 12 and 18 months. Data were available on 46 patients, 25 received HBO in addition to standard care and 21 received standard care alone. The primary outcome measure was change in oral lesion size or number. When change from baseline to last available follow-up was examined, 17 of 25 (68%) of HBO-treated patients had improvement in oral lesion size or number compared to 8 of 21 (38%) in the standard care group, p=0.043. When change from baseline to 6, 12 or 18 months was examined, there was not a statistically significant difference between groups in the proportion of patients with improvement. In addition, the proportion of patients who healed completely did not differ significantly between groups at any time point. This single trial does not report consistent findings of benefit across outcome measures. It also has a number of methodologic limitations, e.g., unblinded, cross-over, and analysis performed on a per-protocol basis rather than intention to treat. A disadvantage of the per-protocol analysis is that randomization is not preserved, and the two groups may differ on characteristics that affect outcomes. As a result, this trial is insufficient to conclude that HBO improves health outcomes for patients with bisphosphonate-related osteonecrosis of the jaw.
Motor Dysfunction Associated with Stroke
In 2013, Efrati and colleagues published an RCT evaluating HBO therapy for treatment of neurologic deficiencies associated with a history of stroke (Efrati, 2013). The study included 74 patients with at least 1 motor dysfunction who had an ischemic or hemorrhagic stroke 6-36 months prior to study participation. Participants were randomly assigned to receive 2 months of HBO treatment (40 daily sessions, 5 days per week, n=30) or delayed treatment (n=32). Patients 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 HBO treatment. Twenty-nine of 32 patients (91%) in the delayed treatment group crossed over to the active intervention. 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 and functional status measures.
At 2 months’ follow-up, there was statistically significantly greater improvement in function in the HBO group compared to the control group as measured by the NIHSS, quality-of-life 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 HBO treatment compared to before treatment. This RCT raises the possibility that HBO may induce improvements in function and quality of life for post-stroke patients with motor deficits. However, the results are not definitive for a number of reasons. This RCT is small and enrolled a heterogeneous group of post-stroke patients. The study was not double-blind and the majority of outcome measures, except for the NIHSS, were patient reported and thus prone to the placebo effect. Also, there was a high total dropout rate of 20% at the 2-month follow-up point. Therefore, larger, double-blind studies with longer follow-up are needed to corroborate these results.
Vascular Dementia
A 2012 Cochrane review identified 1 RCT evaluating HBO for the treatment of vascular dementia (Xiao, 2012). The 2009 study, conducted in China compared HBO plus donepezil to donepezil-only in 64 patients. The HBO and donepezil group had significantly better cognitive function after 12 weeks of treatment, as assessed by the Mini-Mental State Examination. The Cochrane investigators judged the trial to be of poor methodologic quality because it was not blinded and the methods of randomization and allocation concealment were not discussed. This single trial with limitations provides insufficient evidence on the efficacy of HBO treatment on vascular dementia.
Herpes Zoster
In 2012, Peng and colleagues in China published an RCT evaluating HBO as a treatment of herpes zoster (Peng, 2012). Sixty-eight patients with herpes zoster diagnosed within the previous 2 weeks were randomized to 30 sessions of HBO therapy (n=36) or medication treatment (n=32). Pharmacotherapy included antiviral, pain, nerve nutritive and antidepressive medication. Therapeutic efficacy was calculated at the end of the 3-week treatment period and included the proportion of patients who were healed (i.e., complete subsidence of pain and rash) or improved (i.e., significant pain relief and rash subsistence). Rates of therapeutic efficacy were 97.2% in the HBO group and 81.3% in the medication group. The difference between groups was statistically significant, p<0.05. In the HBO group, 22 of 36 patients (61%) were considered to be healed and 13 (36%) were improved. In the medication group, 17 of 32 (53%) patients were healed and 9 (28%) were improved. Limitations of the study include a lack of blinding and lack of long-term follow-up. The evidence from this single RCT is insufficient to draw conclusions about the effect of HBO on health outcomes for patients with herpes zoster.
Fracture Healing
In 2012, Bennett and colleagues published a Cochrane review on HBO to promote fracture healing and treat non-union fractures (Bennett, 2012). The investigators did not identify any published RCTs on this topic that compared HBO to no treatment, sham or another intervention and reported bony union as an outcome. Due to the lack of RCTs, it is not possible to conclude whether the use HBO to promote fracture healing improves outcomes; therefore, the use of HBO for this indication is considered investigational.
Acute Ischemic Stroke
In a 2005 Cochrane systematic review, Bennett and colleagues evaluated HBO treatment for acute stroke; the content of this review was updated in 2009 (Bennett, 2005). The investigators identified 6 RCTs with a total of 283 participants that compared HBO to sham HBO or no treatment. The authors were only able to pool study findings for 1 outcome; the mortality rate at 3-6 months. A pooled analysis of date from 3 trials did not find a significant benefit of HBO compared to a control condition for this outcome (RR: 0.61, 95% CI: 0.17 to 2.20).
Traumatic Brain Injury
A 2012 Cochrane systematic review addressed HBO as adjunctive treatment for traumatic brain injury (Bennett, 2012). The investigators identified 7 RCTs with a total of 571 participants comparing a standard intensive treatment regimen to the same treatment regimen with the addition of HBO. The review did not include studies in which interventions occurred in a specialized acute care setting. The HBO regimens varied among studies; for example, the total number of individual sessions varied from 3 to 30-40. No trial used sham treatment or blinded the staff members who were treating the patients, and only 1 had blinding of outcome assessment. Allocation concealment was inadequate in all of the studies. The primary outcomes of the review were mortality and functional outcomes. A pooled analysis of data from 4 trials that reported this outcome found a statistically significantly greater reduction in mortality when HBO was added to a standard treatment regimen (RR: 0.69, 95% CI: 0.54 to 0.88). However, when data from the 4 trials were pooled, the difference in the proportion of patients with an unfavorable functional outcome at final follow-up did not quite reach statistical significance (RR: 0.71, 95% CI: 0.50 to 1.01). Unfavorable outcome was commonly define as a Glasgow Outcome Score (GOS) of 1, 2 or 3, which are described as ‘dead’, ‘vegetative state’ or ‘severely disabled’. Studies were generally small and were judged to have substantial risk of bias.
A sham-controlled double-blind trial evaluating HBO was published by Wolf and colleagues in 2012 (Wolf, 2012). The study included 50 military service members, 48 of whom were male, with combat-related mild traumatic brain injury. Participants were randomized to 30 sessions of HBO over 8 weeks (n=25) or a sham intervention (room air at 1.3 ATA) (n=25). The primary outcome measures were scores on the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT) and Post-Traumatic Disorder Check List- Military Version (PCL-M) instruments. Patients were evaluated after every 5 treatment sessions and at 6 weeks post-exposure. Forty-eight of 50 participants (96%) completed the study. There were no statistically significant differences on the ImPACT total mean score or the PCL-M composite score at any time point. For example, at the 6 week follow-up, mean composite PCL-M scores were 41.6 in the HBO group and 40.6 in the sham-control group, p=0.28. While the sample size was relatively small, the study was powered to detect clinically significant differences among groups on the cognitive tests.
In summary, systematic review of small trials with limitations found a mortality reduction with HBO but no significant improvement in patient function among survivors of traumatic brain injury. One additional trial, which was double-blind and sham-controlled, did not find a statistically significant benefit of HBO treatment in patients with mild traumatic brain injury. Thus, the evidence is insufficient that HBO treatment improves health outcomes in patients with traumatic brain injury, and this indication is considered investigational.
Cerebral Palsy
Two published RCTs were identified. In 2012, Lacey and colleagues published a double-blind RCT that included 49 children age 3-8 years with spastic cerebral palsy (Lacey, 2012). Participants were randomized to receive 40 treatments with either HBO (n=25) or hyperbaric air to simulate 21% oxygen at room air (n=24). The primary efficacy outcome was change in the Gross Motor Function Measure (GMFM-88) global score after the 8-week treatment period. The study 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. At the time of the interim analysis, the post-treatment GMFM-88 global score was a mean of 40.8 (standard deviation [SD]: 33.4) in the HBO group and 41.2 (SD: 29.6) in the hyperbaric air group. The between-group difference was 0.9 (95% CI: -1.5 to 3.3), p value=0.54.
2014 Update
A literature search conducted through September 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
In 2013, O’Reilly and colleagues published a systematic review of studies on HBO for treatment of diabetic ulcers (O’Reilly. 2013). The authors identified 6 RCTs and 6 non-randomized controlled studies that compared HBO to standard wound care or sham therapy in patients with diabetes who had non-healing lower limb ulcers. Pooled analyses of observational studies found statistically significant benefits of HBO on rates of major amputation, minor amputation and the proportion of wounds healed at the end of the study period.
However, in pooled analyses of RCT data, the stronger study design, there were not statistically significant differences between groups on key outcomes. This included the rate of major amputation (RR: 0.40, 95% CI: 0.07 to 2.23, p=0.29), minor amputation (RR: 0.79, 95% CI: 0.19 to 3.30, p=0.75) and the proportion of unhealed wounds at the end of the study period (RR: 0.54, 95% CI: 0.26 to 1.13, p=0.1).
Although at least some RCTs have found benefit, systematic reviews have had mixed findings regarding the impact of HBO on diabetic ulcers. A Cochrane review found short term, but not long-term benefit on wound healing, and a 2013 meta-analysis did not find significant benefits of HBO on outcomes in RCTs, but did find an effect in non-randomized controlled studies. There is insufficient evidence on HBO for treatment of chronic wounds in patients without diabetes.
Acute Surgical and Traumatic Wounds
In 2013, an updated Cochrane review of RCTs on HBO therapy for acute surgical and traumatic wounds as published by Eskes and colleagues (Eskes, 2013).HBO was defined as use of 100% oxygen at pressures above 1 ATM. To be included, studies needed to compare HBO with a different intervention or compare 2 HBO regimens; in addition, studies needed to objectively measure wound healing. A total of 4 met the review’s inclusion criteria. The studies ranged in size from 10 to 135 participants. Due to differences among studies in terms of patient population, comparison intervention, outcome measurement, etc., study results could not be pooled. The primary outcome examined by Cochrane reviewers, wound healing, was not reported in either of the 2 trials comparing HBO to usual care and was not reported in the 1 trial comparing HBO to dexamethasone or heparin. Complete wound healing was reported in the 1 RCT comparing active HBO to sham HBO. In this small study (n=36), there was a statistically higher rate of wound healing in the HBO group; the time point for outcome measurement in this study was unclear. In the sham-controlled study, there was not a statistically significant difference between groups in the mean time to wound healing.
Another 2014 systematic review of studies on HBO for acute wounds, published by Dauwe and colleagues, included randomized and non-randomized controlled studies (Dauwe, 2014). The review included 8 studies, with sample sizes ranging from 5 to 125 patients. Four studies were randomized, 3 were prospective non-randomized controlled studies and 1 was a retrospective non-randomized controlled study. As in the Eskes systematic review, data were not pooled. The authors noted that 7 of the 8 studies reported achieving statistical significance in their primary endpoints, but the endpoints differed among studies e.g. graft survival, length of hospital stay, wound size. Moreover, the studies were heterogeneous in terms of treatment regimens, patient indications (eg, burns, face lifts), and study designs, making it difficult to draw conclusions about the effect of HBO on acute wound treatment.
There is insufficient evidence supporting HBO for treatment of acute wounds; additional evidence from high-quality RCTs is needed
Traumatic Brain Injury
In 2014, Cifu and colleagues published findings of an RCT with 61 male Marines who had a history of mild traumatic brain injury and postconcussive syndrome (Cifu, 2014). The study was sham-controlled and doubleblinded. Patients were randomized to receive 1 of 3 treatments: 75% oxygen at 1.5 ATA (n=21); 100% oxygen at 2.0 ATA (n=19); and 3) sham treatment with normal air (n=21). Outcomes were assessed 3 months after the last exposure. The primary outcome was a clinically meaningful improvement, defined as a 10% difference between groups in the score on the Rivermead Post-Concussion Questionnaire (RPQ)-16 (scale ranges from 50–84, with higher values indicating more severe symptoms). At follow-up, there was not a statistically significant difference among groups on the RPQ-16 score (p=0.41). A variety of secondary outcomes were also assessed. None of these, including measures of attention, cognition and depression, differed significantly among groups at follow-up.
Inflammatory bowel disease
A 2014 systematic review by Dulai and colleagues examined the evidence on HBO for treatment of inflammatory bowel disease (Crohn’s disease and ulcerative colitis (Dulai. 2014). The review was not limited by study design. The authors included 17 studies: 1 RCT, 2 case-control studies, 3 case series and 11 case reports. The studies reported on a total of 613 patients, 286 with Crohn’s disease and 327 with ulcerative colitis. The only RCT identified was published in 2013; it was open-label and included 18 patients with ulcerative colitis (Pagoldh, 2013). Patients were randomized to treatment with standard medical therapy only (n=8) or medical therapy plus HBO (n=10). The HBO 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 (Mayo 2014). Patients with a score of 6 or more are considered to have moderate to severe active disease. At follow-up there was not a significant difference between groups in the Mayo score; the median score at 6 months was 0.5 in the HBO group and 3 in the control group (exact p value not reported). In addition, there were no significant differences in any of the secondary outcomes including laboratory tests and fecal weight. This is a small study that may have been underpowered.
Overall, the authors found that the studies had a high risk of bias, particularly in the areas of attrition and reporting bias.
In summary, there is insufficient evidence that HBO therapy is an effective for treating inflammatory bowel disease. Only 1 small RCT has been published and this study did not find a significant improvement in health outcomes with when HBO was added to standard medical therapy.
In 2013, Cvorovic and colleagues published an RCT that included 50 patients with ISSHL who had failed primary therapy with intravenous steroids (Cvorovic, 2013). Patients were randomized to receive HBO (20 treatments, 5 daily treatments per week) or intratympanic steroid injection (4 injections in 13 days). The HBO treatments consisted of 10 minutes of compression on air, 60 minutes of 100% oxygen at 2 ATA and 1 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). 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 this frequency, the improvement was significantly greater in the HBO group.
2016 Update
A literature search conducted through January 2016 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Assessment of efficacy for therapeutic interventions involves a determination of whether the intervention improves health outcomes. The optimal study design for a therapeutic intervention is a randomized controlled trial (RCT) that includes clinically relevant measures of health outcomes. Intermediate outcome measures, also known as surrogate outcome measures, may also be adequate if there is an established link between the intermediate outcome and true health outcomes. When the primary outcomes are subjective (eg, pain, depression), sham-controlled RCTs are needed to assess the effect of the intervention beyond that of a placebo effect.
Necrotizing Soft Tissue Infections
A 2015 Cochrane review by Levett and colleagues evaluated the literature on HBOT as adjunctive therapy for necrotizing fasciitis (Levett, 2015). No RCTs were identified.
Acute Ischemic Stroke
In a 2014 update of a Cochrane systematic review, Bennett and colleagues evaluated HBOT for acute ischemic stroke (Bennett, 2014). The investigators identified 11 RCTs with a total of 705 participants that compared HBOT with sham HBOT or no treatment. The authors were only able to pool study findings for 1 outcome; mortality at 3 to 6 months. A pooled analysis of data from 4 trials with a total of 106 participants did not find a significant benefit of HBOT compared with a control condition for this outcome (RR=0.97; 95% CI, 0.34 to 2.75).
Traumatic Brain Injury
Also in 2014, Miller and colleagues evaluated HBOT in 72 military service members with continuing symptoms at least 4 months after mild traumatic brain injury (Miller, 2014). Patients were randomized to receive 40 daily HBO sessions at 1.5 ata, 40 sham sessions consisting of room air at 1.2 ata or standard care with no hyperbaric chamber sessions. The primary outcome was change in the RPQ. 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 the prespecified change of at least 2 points on the RPQ-3 was 52% in the HBOT group, 33% in the sham group and 25% in the standard care-only group. The difference between rates in the HBOT and sham groups was not statistically significant (p=0.24). None of the secondary outcomes significantly favored the HBOT group. A criticism of this study, as well as the other military population studies, was that the response in the sham group was not due to a placebo effect but to an intervention effect of slightly increased atmospheric pressure (1.2 ata) (Marois, 2015). Other researchers have noted that room air delivered at 1.2 ata would not be considered an acceptable therapeutic dose for any indication, and especially for a condition with persistent symptoms like postconcussive syndrome.
Fibromyalgia
One quasi-randomized trial and 1 delayed-treatment RCT on HBOT for fibromyalgia were identified. In 2004, a study by Yildiz and colleagues included 50 patients with fibromyalgia who had ongoing symptoms despite medical and physical therapy (Yildiz, 2004). On an alternating basis, patients were assigned to HBOT or a control group. The HBOT consisted of fifteen 90-minute sessions at 2.4 ata (1 session per day, 5 d/wk). The control group breathed room air at 1 ata on the same schedule. Baseline values on the 3 outcomes were similar in the 2 groups. After the course of HBOT treatment, the mean (SD) number of tender points were 6.04 (1.18) in the HBO group and 12.54 (1.10) in the control group. The mean (SD) pain threshold was 1.33 kg (0.12) and 0.84 kg (0.12), respectively, and the mean VAS was 31.54 (8.34) and 55.42 (6.58), respectively. In the study abstract, the authors stated that there were statistically significant differences between the HBO and control groups after 15 therapy sessions, but the table presenting outcomes lacked the notation used to indicate between-group statistical significance. It is not clear whether the control group actually received a sham intervention that would minimize any placebo effect ie whether or not the control intervention was delivered in a hyperbaric chamber. The authors stated that the study was double-blind but did not specify any details of patient blinding.
In 2015, Efrati and colleagues published an RCT that included 60 female patients who had fibromyalgia for at least 2 years and were symptomatic (Efrati, 2015). Patients were randomized to an immediate 2 month course of HBOT or delayed HBOT after 2 months. The HBOT protocol was forty 90-minute sessions of 100% oxygen at 2 ata (1 session per day, 5 d/wk). Forty-eight of 60 patients (80%) completed the study and were included in the analysis. After the initial 2 months, outcomes including number of tender points, pain threshold, and quality of life (SF-36) were significantly better in the immediate treatment group compared with the delayed treatment group (which received no specific intervention during this time). After the delayed treatment group had undergone HBOT, outcomes were significantly improved compared with scores prior to HBOT treatment. These findings are consistent with a clinical benefit of HBOT, but also with a placebo effect. A sham-control is needed to confirm the efficacy of HBOT in the treatment of fibromyalgia and other conditions where primary end points are pain and other subjective outcomes.
The above studies were few in number with relatively small sample sizes and had methodological limitations, eg, quasi-randomization and no or uncertain sham control for a condition with subjective outcomes susceptible to a placebo effect. Moreover, the HBO protocol varied (eg, 15 HBOT sessions vs 40 HBOT sessions). Thus, the evidence is insufficient to draw conclusions about the impact of HBOT on health outcomes for patients with fibromyalgia.
Mental Illness
A Rapid Response Report from the Canadian Agency for Drugs and Technologies in Health (CADTH) searched the literature through July 2014 on the clinical effectiveness of hyperbaric oxygen therapy for treatment of adults with posttraumatic stress disorder, generalized anxiety disorder, and/or depression (Ottawa ON: 2014). The review’s inclusion criteria were health technology assessments, systematic reviews, meta-analyses, RCTs or nonrandomized studies comparing HBOT to any active treatment and reporting clinical outcomes. No eligible studies were identified.
Multiple Sclerosis
A Cochrane review of RCTs on HBOT for multiple sclerosis was published by Bennett and colleagues in 2004 (Bennett, 2014). The authors identified 9 RCTs, with a total of 504 participants that compared the effects of HBOT with placebo or no treatment. The primary outcome of the review was score on the Expanded Disability Status Scale (EDSS). A pooled analysis of data from 5 trials (N=271) did not find a significant difference in change in the mean EDSS after 20 HBOT treatments versus control (mean difference [MD], -0.07; 95% CI, -0.23 to 0.09). Moreover, a pooled analysis of data from 3 trials (n=163) comparing HBOT and placebo did not find a significant difference in mean EDSS after 6 months of follow-up (MD = -0.22; 95% CI, -0.54 to 0.09).
Other indications
For the indications listed below, insufficient evidence to support the use of HBOT was identified. Since
2000, there have been no published controlled trials or large case series (ie, ≥25 patients):
Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in January 2016 did not identify any ongoing or unpublished trials that would likely influence this policy.
2017 Update
A literature search conducted through January 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Chronic Diabetic Ulcers
Several systematic reviews of RCTs have been published. A Cochrane review of RCTs on HBOT for chronic wounds was published by Kranke and colleagues (Kranke, 2015). Reviewers identified 12 RCTs (total N=577 participants) that compared the effect of HBOT on chronic wound healing with an alternative treatment approach that did not use HBOT. Ten of the 12 trials included in the review evaluated HBOT in patients with diabetes. In a pooled analysis of data from 5 trials, a significantly higher proportion of ulcers had healed at the end of treatment (i.e., 6 weeks) in the group receiving HBOT than the group not receiving HBOT (relative risk [RR], 2.35; 95% confidence interval [CI], 1.19 to 4.62). However, in a pooled analysis of 5 trials, there was not a statistically significant difference in the risk of major amputations in patients assigned to HBOT compared to a control condition (RR: 0.36, 95% CI: 0.11 to 2.23). There were insufficient data to conduct pooled analyses of studies evaluating HBOT for treating patients with chronic wounds who did not have diabetes.
A 2016 systematic review by Elraiyah and colleagues evaluated adjunctive therapies used to treat diabetic foot ulcers (Elraiyah, 216). A pooled analysis of 6 RCTs found a significantly higher healing rate with HBOT than control conditions (odds ratio [OR]: 0.30, 95% CI 7.08 to 28.68). Another pooled analysis of the 6 trials found that HBOT was associated with a significantly lower major amputation rate (OR: 0.30, 95% CI: 0.10 to 0.89). The studies were rated as low to moderate quality.
Radionecrosis, Osteoradionecrosis and Treatment of Irradiated Jaw
In 2016, Bennett and colleagues published a Cochrane review on HBOT for late radiation tissue injury (Bennett, 2016). Reviewers identified a total of 14 RCTs. In a pooled analysis of 3 studies, a significantly higher proportion of patients with osteoradionecrosis achieved complete mucosal cover after HBOT compared with controls (RR=1.30; 95% CI, 1.09 to 1.55). In addition, a pooled analysis of 2 trials found a significantly lower risk of wound dehiscence after surgery to repair mandibular osteoradionecrosis with HBOT versus control (RR: 4.23, 95% CI: 1.06 to 16.83). A single trial found a significantly higher likelihood of successful healing with HBOT versus antibiotics for tooth extraction in irradiated jaws (absolute risk reduction [ARR]: 25%, p=0.02). There were insufficient data to conduct meta-analyses on other outcomes.
Acute Thermal Burns
In 2004, a Cochrane review was published on HBOT for thermal burns (Villanueva, 2004). Two RCTs were identified. Sample sizes were 16 and 125. Both of these were judged by reviewers to have poor methodologic quality. They concluded that the evidence was insufficient to draw conclusions about the effect of HBOT on health outcomes in patients with acute thermal burns. No additional trials were identified when the Cochrane reviewers conducted an updated literature search in 2009 (the 2004 publication date continues to be used).
Traumatic Brain Injury
A 2016 systematic review by Wang and colleagues addressed HBOT for treatment of traumatic brain injury (TBI) (Wang, 2016). The review included RCTs or non-randomized 2 arm trials comparing hyperbaric oxygen therapy and normobaric oxygen therapy in patients with mild or severe TBI. Eight studies with a total of 519 participants met the eligibility criteria. HBOT protocols varied among studies in the levels of oxygen and the length and frequency of treatments. The primary outcome was change in the Glasgow Coma Scale (GCS). Only 2 of the 8 included trials had data on GCS scores suitable for pooling. A pooled analysis of 2 studies found a significantly greater improvement in the mean GCS score in the HBOT versus control groups (mean difference: 3.13, 95% CI: 2.34 to 3.92, p<0.001). Mortality was a secondary outcome and 3 of the 8 studies were included in a meta-analysis. The pooled analysis of 3 studies, there was a significantly lower overall mortality rate in the HBOT group than the control group, OR: 0.32, 95% CI: 0.18 to 0.57, p<0.001). Most of the trials included in the systematic review were not included in the pooled analyses.
Another 2016 systematic review, by Crawford and colleagues, did not conduct pooled analyses (Crawford, 216). The authors identified 12 RCTs evaluating HBOT for patients with TBI. Four trials, all rated as having acceptable quality, addressed patients with mild TBI and compared HBOT with sham. None of these studies found statistically significant differences between groups on outcomes (ie, postconcussive symptom severity and psychological outcomes). Seven trials evaluated HBOT for acute treatment of patients with moderate to severe TBI. Four studies were rated as acceptable quality and 3 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) and mortality. In 2 of these, outcomes were better in the HBOT than standard care groups, and in the third study, outcomes did not differ significantly.
Autism Spectrum Disorder
A 2016 Cochrane review by Xiong and colleagues identified 1 RCT evaluating systemic hyperbaric oxygen therapy for people with autism spectrum disorder (ASD) that met the review’s eligibility criteria (Xiong, 2016). Eligibility included a hyperbaric oxygen intervention using 100% oxygen at more than 1 ATA. The trial, published by Sampanthaviat in 2012, randomly assigned 60 children with autism to receive 20 one-hour sessions with HBOT or sham air (n=30 per group).54 The primary outcome measures were change in ATEC and CGI scores, evaluated separately by clinicians and parents. There were no statistically significant differences between groups for any primary outcomes. For example, posttreatment clinician-assessed mean scores on ATEC were 52.4 in the HBOT group and 52.9 in the sham air group.
Migraine
A 2015 Cochrane review by Bennett and colleagues identified RCTs that evaluated the effectiveness of systemic HBOT for preventing or treating migraine headache compared with another treatment or a sham control (Bennett, 2015). Eleven trials (total N=209 patients) were identified that addressed treatment of acute migraine with HBOT. A pooled analysis of 3 trials (n=58 patients) found a statistically significant increase in the proportion of patients with substantial relief of migraine within 45 minutes of HBOT (RR=6.21; 95% CI, 2.41 to 16.00; p=0.001). No other pooled analyses were conducted due to variability in the outcomes reported in the trials. The meta-analysis does not report data on treatment effectiveness beyond the immediate post treatment period, and the quality of trials’ methodology was moderate to low (eg, randomization was not well-described in any trial).
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2018 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Radionecrosis, Osteoradionecrosis and Treatment of Irradiated Jaw
In 2017, Borab et al published a systematic review focusing on the use of HBOT to treat the subgroup of patients with late radiation tissue injury had skin necrosis (Borab,2017). 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 HBOT to treat patients who had received radiotherapy for head and neck cancer (Ravi 2017). 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. Other outcomes of interest included salivary gland function and quality of life.
Infectious Disease Society of America
In 2012, the Infectious Disease Society of America published guidelines on the diagnosis and treatment of diabetic foot infections (Lipsky, 2013). 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 et al
In 2016, the Society of Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine published guidelines on the management of the diabetic foot (Hingorani, 2016). 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 HBOT is recommended (grade 1B). Also, for diabetic foot ulcers with adequate perfusion that fail to respond to 4 to 6 weeks of conservative management, HBOT is suggested (grade 2B).
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 HBOT for the prevention and management of osteoradionecrosis (ORN) of the jaw (Sultan, 2017). 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 HBO 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.”
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2019. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Rhee et al performed a systematic review and meta-analysis through February 2018 for patients comparing HBOT plus medical therapy (MT) with medical therapy alone for SSNHL treatment (Rhee, 2018). Randomized clinical trials and nonrandomized studies were included. The main outcomes considered were complete hearing recovery, any hearing recovery, and absolute hearing gain. Nineteen studies (3 randomized and 16 nonrandomized) with a total of 2401 patients (mean age, 45.4 years; 55.3% female) were included. In the HBOT+MT group, rates of complete hearing recovery and any hearing recovery were 264/897 (29.4%) and 621/919 (67.6%), respectively, and in the MT alone group were 241/1167 (20.7%) and 585/1194 (49.0%), respectively. Pooled HBOT+MT also showed favorable pooled results from random-effects models for both complete hearing recovery (OR, 1.61; 95% CI, 1.05-2.44) and any hearing recovery (OR, 1.43; 95% CI, 1.20-1.67). The study was limited by the following: (1) differences in clinical and methodological characteristics of selected studies, (2) considerable heterogeneity, (3) the possibility of measure or unmeasured confounder effects, and (4) difficulty in evaluating the benefit of treatment due to a substantial proportion of patients experiencing spontaneous recovery.
Sun et al compared the efficacy of intratympanic dexamethasone therapy and hyperbaric oxygen therapy for salvage treatment of 104 patients with refractory high-frequency SSNHL (Sun, 2018). Patient charts were retrospectively allocated into three groups: ITD alone group (n=31), HBO alone group (n=32), and a control group in which patients received no salvage therapy (n=41). No significant difference was found between the groups for total effective rate of hearing recovery (p=0.213); also, no significant differences were found between ITD and HBO (p=0.368) or between ITD and the control group (p=0.197). At 2 and 4 KHz, no significant differences were found between any groups; however, at 8 KHz, there was a significant difference for ITD vs HBO (p=0.049) and for ITD vs control (p=0.025), but not for HBO vs control (p=0.873).
Almosnino et al conducted a matched control retrospective case series evaluating hyperbaric oxygen (HBO2) as salvage therapy for sudden sensorineural hearing loss (SSNHL) (Almosnino, 2018). In total, 36 (18 received IT steroids and HBO2 and 18 received IT steroids alone) SSNHL patients >18 years were included in the study. The post-treatment pure tone average (PTA) did not vary significantly between the HBO2 (60.3 dB) and non-HBO2 (53.2 dB) groups; the mean post-treatment word recognition scores (WRSs) also did not differ significantly (HBO2 42%, WRS 51%). In the HBO2 group, 33% of patients improved from non-serviceable hearing (WRS of <50%) to serviceable hearing (WRS of ≥50%) after treatment, while 42% of non-HBO2 patients went from non-serviceable hearing to serviceable hearing (p>0.05). The study was limited by its retrospective nature, small sample size, lack of randomization, and differences in dosing and duration of treatment between patients.
In a retrospective chart review of 178 idiopathic SSNHL patients, Xie et al evaluated potential prognostic factors of idiopathic SSNHL treated with HBOT (Xie, 2018). Overall recovery rate was 37.1%; complete recovery was 19.7% and partial recovery was 17.4%. Higher initial hearing threshold and later onset of HBOT were associated with a poor prognosis in idiopathic SSNHL patients treated with HBOT. The study was limited by its retrospective chart review design.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2020. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Nakajima et al conducted a retrospective cohort study comparing the effect of HBOT versus control (no HBOT) on mortality and morbidity in patients with carbon monoxide poisoning (Nakajima, 2020). The median number of HBOT sessions was 3 (range 2 to 5). After propensity score matching of study participants (N=4,068) the study found no significant difference between groups in-hospital mortality (mean rate difference -0.4%, 95% confidence interval -1.0 to 0.2%). Results were consistent across subgroups according to severity of carbon monoxide poisoning, age and number of HBOT sessions. However, the study found HBOT associated with lower rates of depressed mental status (mean difference -3.2%, 95% confidence interval -4.9% to -1.5%) and reduced activities of daily living (mean difference -5.3%, 95% confidence interval -7.8% to -2.7%) relative to no HBOT.
The systematic review and pooled analysis by Hart et al evaluated HBOT for mild traumatic brain injury (mTBI)–associated post-concussive symptoms (PCS) and posttraumatic stress disorder (PTSD) (Hart, 2019). Data were aggregated from 4 Department of Defense (DoD) studies that included participant-level data on 254 patients assigned to either HBOT or sham intervention. An additional 3 studies with summary-level participant data were summarized (n=135). The authors assessed changes from baseline to post-intervention on PCS, PTSD, and neuropsychological measures. The DoD data analyses indicated improvements with HBOT for PCS, measured by the Rivermead Total Score. Statistically significant improvements were seen for PTSD based on the PTSD Checklist Total Score, as well as for verbal memory based on CVLT-II Trial 1-5 Free Recall.
Hart et al describe BIMA, which assessed HBOT for U.S. service members with mTBI (Hart, 2019). BIMA initially planned for 12-month follow-up but was amended to include PCS and PTSD, quality of life, pain, depression, anxiety, and alcohol use assessments at 24 and 36 months. Investigators saw no significant differences at 24 or 36 months between the HBOT and sham groups, and group mean scores had returned to near pre-intervention values.
Weaver et al evaluated BIMA and a second RCT of U.S. service members for the efficacy of HBOT in treating persistent PCS after mTBI (Weaver, 2019). The second study, titled “A Pilot Phase II Study of Hyperbaric Oxygen for Persistent Post-concussive Symptoms After Mild Traumatic Brain Injury (HOPPS),” was completed in 2012 (NCT01306968). The 3 outcomes assessed in the pooled analyses of the 2 studies were symptoms, cognitive impairment, and functional impairment; they were weighted and grouped into different domains to calculate the composite outcome score. A total of 143 service members were randomized to receive either HBOT (1.5 ATA, > 99% oxygen) or sham therapy (1.2 ATA, room air). In HOPPS, composite total scores improved from baseline for HBOT (mean = -2.9 ± 9.0) and sham treatment (-2.9 ± 6.6), but the groups did not differ significantly from each other (p=.33). The BIMA trials results showed a greater improvement from baseline in the HBOT group (-3.6 ± 6.4) versus sham (-0.3 ± 5.2; p=.02). The authors concluded that composite total scores in HOPPS and BIMA were consistent with primary study results.
Churchill et al reported on the chamber- and protocol-related AEs in the HOPPS and BIMA trials (Churchill, 2019). In addition to AEs, they assessed the success of maintaining the blind with a low-pressure sham control group. Of the total 4,245 total chamber sessions, AEs were rare, at 1.1% in the HOPPS study and 2.2% in BIMA. Most AEs were minor, non-limiting barotrauma, and a few were headaches. Results of a questionnaire that followed the intervention showed that the sham group blind was adequately maintained in both trials.
Villeirs et al conducted a systematic review on the effect of HBOT on cystitis following pelvic radiotherapy (Villeirs, 2020). The review included 20 studies, only one of which was an RCT; the remaining studies were cohort studies. The number of HBOT sessions ranged widely from 1 to 179 (mean or median number of sessions was not reported). The review broadly assessed cystitis response across studies, generally based on absence of hematuria. Complete response was achieved in a weighted mean of 63.6% of patients receiving HBOT (range 20% to 100%) while 35.2% of patients showed no response. In 11 studies reporting follow-up greater than 1 year, recurrence ranged from 0% to 40.7%. Other pooled outcomes were not reported.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Sharma et al conducted a systematic review and meta-analysis of 14 studies (N=768) comparing the effect of HBOT with standard care on diabetic foot ulcers (Sharma, 2021). Study authors noted that various modalities can be considered standard care including, but not limited to, debridement, antibiotics, and blood sugar control. However, the specific standard care modality in each included study was not reported. HBOT duration ranged from 45 to 120 minutes (median 90 minutes). All included studies had methodological limitations, including selection, performance, detection, attrition and reporting bias. The review found those treated with standard care were less likely to have complete ulcer healing versus HBOT, based on pooled analysis of 11 studies (OR 0.29,
|
|
|
|
| CPT/HCPCS: | |
|
|
|
| References: |
. Borab Z, Mirmanesh MD, Gantz M, et al.(2017) Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. J Plast Reconstr Aesthet Surg. Apr 2017;70(4):529-538. PMID 28081957 Almosnino G, Holm JR, Schwartz SR, et al.(2018) The Role of Hyperbaric Oxygen as Salvage Therapy for Sudden Sensorineural Hearing Loss. Ann Otol Rhinol Laryngol. Oct 2018;127(10):672-676. PMID 30009614 Am College Hyperbaric Med Accepted indications. http//hyperbaricMed.org/indications.htm. Accessed May 24 1999. Am College Hyperbaric Med Chicago Report: status of hyperbarics before the AMA. http//hyperbaricMed.org/news.htm.htm. Accessed April 18 1998. Amar AP, Levy ML.(1999) Surgical controversies in the management of spinal cord injury. J Am Col Surg 1999; 188 :550-566. APC Update. Undersea Hyperbaric Medical Society (UHMS). http://www.uhms.org/q&a.htm. April 14, 1998. Asci R, Sarikaya S, Buyukalpelli R, et al.(1998) Fournier’s gangrene: risk assessment and enzymatic debridement with lyophilized collagenase application. Eur Urol 1998; 34:411-418. Baker AJ.(1999) Management of the severely head injured patients. Can J Anesthesiol 1999; 46:R35-R40. Bangasser R.(1999) Treatment of the brown recluse spider (Loxosceles reclusa) bite with hyperbaric oxygen. Hyperbaric Med Practice 1999; edited by EP Kindwall and HT Whelan; Best Publishing Co; pp 869-877. Bennett M, Feldmeier J, Smee R, et al.(2005) Hyperbaric oxygenation for tumour sensitisation to radiotherapy. Cochrane Database Syst Rev. Oct 19 2005(4):CD005007. PMID 16235387 Bennett M, Heard R.(2004) Hyperbaric oxygen therapy for multiple sclerosis. Cochrane Database Syst Rev. 2004(1):CD003057. PMID 14974004 Bennett M., B. H.(2009) UHMS Position Paper: the treatment of autism spectrum disorder with hyperbaric oxygen therapy. North Palm Beach, FL: Undersea & Hyperbaric Medical Society (UHMS); Bennett M., Heard R.(2018) UHMS Position Paper: the treatment of multiple sclerosis with hyperbaric oxygen therapy. North Palm Beach, FL: Undersea & Hyperbaric Medical Society (UHMS); n.d. Bennett MH, Feldmeier J, Hampson NB, et al.(2016) Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. Apr 28 2016;4:CD005005. PMID 27123955 Bennett MH, Feldmeier J, Smee R, et al.(2012) Hyperbaric oxygenation for tumour sensitisation to radiotherapy. Cochrane Database Syst Rev. Apr 18 2012(4):CD005007. PMID 22513926 Bennett MH, French C, Schnabel A et al.(2008) Normobaric and hyperbaric oxygen therapy for migraine and cluster headache. Cochrane Database Syst Rev 2008, (3):CD005219. Bennett MH, French C, Schnabel A, et al.(2015) Normobaric and hyperbaric oxygen therapy for the treatment and prevention of migraine and cluster headache Cochrane Database Syst Rev. Dec 28 2015(12):CD005219. PMID 26709672 Bennett MH, Lehm JP, Jepson N.(2015) Hyperbaric oxygen therapy for acute coronary syndrome. Cochrane Database Syst Rev. Jul 23 2015(7):CD004818. PMID 26202854 Bennett MH, Stanford RE, Turner R.(2012) Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union. Cochrane Database Syst Rev 2012; 11:CD004712. Bennett MH, Trytko B, Jonker B.(2012) Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury. Cochrane Database Syst Rev 2012; 12:CD004609. Bennett MH, Wasiak J, Schnabel A.(2005) Hyperbaric oxygen therapy for acute ischaemic stroke. Cochrane Database Syst Rev 2005; (3):CD004954. Bennett MH, Weibel S, Wasiak J, et al.(2014) Hyperbaric oxygen therapy for acute ischaemic stroke. Cochrane Database Syst Rev. 2014;11:CD004954. PMID 25387992 Bilton BD, Zibari GB, McMillan RW, et al.(1998) Aggressive surgical management of necrotizing fasciitis serves to decrease mortality: a retrospective study. Am Surg 1998; 64:397-400. Bouachour MD, Cronier P, Gouello JP, et al.(1996) Hyperbaric oxygen therapy in the management of crush injuries: a randomized double-blind placebo-controlled clinical trial. J Trauma Injury Infec Crit Care 1996; 41 :333-339. Boykin JV.(1996) Hyperbaric oxygen therapy: a physiological approach to selected problem wound healing. Wounds 1996; 8 :183-198. Brady CE.(1993) Hyperbaric oxygen and perineal Crohn’s disease: a follow-up. Gastro 1993; 105:1264. Brannen AL, Still J, Haynes M, et al.(1997) A randomized prospective trial of hyperbaric oxygen in a referral burn center population. Am Surg 1997; 63:205-208. Brown DR, Davis NL, Lepawsky M, et al.(1994) A multicenter review of the treatment of major truncal necrotizing infections with and without hyperbaric oxygen therapy. Am J Surg 1994; 167:485-489. Bullock R, Chesnut RM, Clifton G, et al.(1995) Head injury guidelines. Brain Trauma Foundation; The AmAssociation Neurological Surgeons; The Joint Section on Neurotrauma and Critical Care 1995. Camporesi EM, Vezzani G, Bosco G et al.(2010) Hyperbaric oxygen therapy in femoral head necrosis. J Arthroplasty 2010; 25(6 suppl):118-23. Camporesi EM.(1996) Hyperbaric oxygen therapy: a committee report. Undersea and Hyperbaric Med Society. Kensington; MD 1996. Camporesi EM.(1999) Hyperbaric oxygen therapy: applications in the trauma patient. Anes Clin N Am 1999; 17 :311-323. Cavaliere M, De Luca P, Scarpa A, et al.(2022) Combination of Hyperbaric Oxygen Therapy and Oral Steroids for the Treatment of Sudden Sensorineural Hearing Loss: Early or Late?. Medicina (Kaunas). Oct 10 2022; 58(10). PMID 36295581 Chapnick EK, Abter EI.(1996) Necrotizing soft-tissue infections. Infec Dis Clin N Am 1996; 10 :835-855. Chesnut RM.(1997) The management of severe traumatic brain injury. Emer Med Clin N Am 1997; 15 :581-604. Churchill S, Deru K, Weaver LK, et al.(2019) Adverse events and blinding in two randomized trials of hyperbaric oxygen for persistent post-concussive symptoms. Undersea Hyperb Med. BIMA 2019; 46(3): 331-340. PMID 31394602 Cianci P.(1994) Adjunctive hyperbaric oxygen therapy in the treatment of the diabetic foot. J Am Pod Med Assoc 1994; 84 :448-455. Cifu DX, Walker WC, West SL, et al.(2014) Hyperbaric oxygen for blast-related postconcussion syndrome: three-month outcomes. Ann Neurol. Feb 2014;75(2):277-286. PMID 24255008 Clark LA, Moon RE.(1999) Hyperbaric oxygen in the treatment of life-threatening soft-tissue infections. Respir Care Clin N Am 1999; 5 :203-219. Colombel JF, Mathieu D, Bouault JM, et al.(1995) Hyperbaric oxygenation in severe perineal Crohn’s disease. Dis Colon Rectum 1995; 38:609-614. Crawford C, Teo L, Yang E, et al(2016) 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. Sep 06 2016. PMID 27603765 Cvorovic L, Jovanovic MB, Milutinovic Z, et al.(2013) 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):1021-1026. PMID 23820795 Dauwe PB, Pulikkottil BJ, Lavery L, et al.(2014) Does hyperbaric oxygen therapy work in facilitating acute wound healing: a systematic review. Plast Reconstr Surg. Feb 2014;133(2):208e-215e. PMID 24469192 de Smet GHJ, Kroese LF, Menon AG, et al.(2017) Oxygen therapies and their effects on wound healing. Wound Repair Regen. Aug 2017;25(4):591-608. PMID 28783878 Doctor N, Pandya S, Supe A.(1992) Hyperbaric oxygen therapy in diabetic foot. J Postgrad Med 1992; 38 :112-114. Dulai PS, Buckey JC, Raffals LE, et al.(2018) Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis patients hospitalized for moderate-severe flares: a phase 2A pilot multi-center, randomized, double-blind, sham-controlled trial. Am J Gastroenterol. Oct 2018; 113(10): 1516-1523. PMID 29453383 Dulai PS, Gleeson MW, Taylor D, et al(2014) Systematic review: The safety and efficacy of hyperbaric oxygen therapy for inflammatory bowel disease. Aliment Pharmacol Ther. Jun 2014;39(11):1266- 1275. PMID 24738651 Dulai PS, Raffals LE, Hudesman D, et al.(2020) A phase 2B randomised trial of hyperbaric oxygen therapy for ulcerative colitis patients hospitalised for moderate to severe flares. Aliment Pharmacol Ther. Sep 2020; 52(6): 955-963. PMID 32745306 Efrati S, Fishlev G, Bechor Y et al.(2013) Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial. PLoS One 2013; 8(1):e53716. Efrati S, Golan H, Bechor Y, et al.(2015) Hyperbaric oxygen therapy can diminish fibromyalgia syndrome - prospective clinical trial. PLoS One. 2015;10(5):e0127012. PMID 26010952 Elraiyah T, Tsapas A, Prutsky G, et al.(2016) 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 Eskes A, Ubbink DT, Lubbers M et al.(2010) Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. Cochrane Database Syst Rev 2010; (10):CD008059. Eskes A, Vermeulen H, Lucas C, et al.(2013) Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. Cochrane Database Syst Rev. 2013;12:CD008059. PMID 24343585 Faglia E, Favale F, Aldeghi A, et al.(1996) Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. Diabetes Care 1996; 19:1338-1343. Feldmeier JJ, Hopf HW, Warriner RA, 3rd, et al.(2005) UHMS position statement: topical oxygen for chronic wounds. Undersea Hyperb Med. May-Jun 2005;32(3):157-168. PMID 16119307 Fitzpatrick DT, Murphy PT.(1998) Adjunctive treatment of compartment syndrome with hyperbaric oxygen. Military Med 1998; 163:577-579. Freiberger JJ, Padilla-Burgos R, McGraw T et al.(2012) 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 2012; 70(7):1573-83. Gonzalez MH.(1998) Necrotizing fasciitis and gangrene of the upper extremity. Hand Clin 1998; 14 :635-645. Gothard L, Haviland J, Bryson P et al.(2010) Randomized phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer. Radiother Oncol 2010; 97(1): 101-7. Hammarlund C, Sundberg T.(1994) Hyperbaric oxygen reduced size of chronic leg ulcers: a randomized double blind study. Plast Reconstr Surg 1994; 93 :829-833. Hampson NB.(1999) Hyperbaric oxygen therapy: 1999 committee report. Undersea and Hyperbaric Medical Society, 1999, Kensington, MD. Hanauer SB.(1999) Medical therapy for Crohn’s disease. Curr Opin Gastro 1999; 15:308-314. Hart BB, Weaver LK, Gupta A, et al.(2019) Hyperbaric oxygen for mTBI-associated PCS and PTSD: Pooled analysis of results from Department of Defense and other published studies. Undersea Hyperb Med. BIMA 2019; 46(3): 353-383. PMID 31394604 Hart BB, Wilson SH, Churchill S, et al.(2019) Extended follow-up in a randomized trial of hyperbaric oxygen for persistent post-concussive symptoms. Undersea Hyperb Med. BIMA 2019; 46(3): 313-327. PMID 31394601 Hayes, Inc; October 2003. Hedetoft M, Bennett MH, Hyldegaard O.(2021) Adjunctive hyperbaric oxygen treatment for necrotising soft-tissue infections: A systematic review and meta-analysis. Diving Hyperb Med. Mar 31 2021; 51(1): 34-43. PMID 33761539 Heng MCY.(1993) Topical hyperbaric therapy for problem skin wounds. J Derm Surg Oncol 1993; 19:784-93. Hingorani A, LaMuraglia GM, Henke P, et al.(2016) 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 Hirn M.(1993) Hyperbaric oxygen in the treatment of gas gangrene and perineal necrotizing fasciitis. Eur J Surg 1993; (sup 570):7-36. Hobbs GD, Anderson AR, Greene TJ, Yealy DM.(1996) Comparison of hyperbaric oxygen and dapsone therapy for loxosceles envenomation. Acad Emerg Med 1996; 3:758-761. Hollabaugh RS, Dmochowski RR, Hickerson WL, et al.(1998) Fournier’s gangrene: therapeutic impact of hyperbaric oxygen. Plast Reconstr Surg 1998; 101:94-100. Huang ET, Mansouri J, Murad MH, et al.(2015) A Clinical Practive Guideline for the Use of Hyperbaric Oxygen Therapy in the Treatment of Diabetic Foot Ulcers. 2015 https://www.uhms.org/images/CPG/UHM_42-3_CPG_for_DFU.pdf. Accessed July 1, 2015. Hyperbaric oxygen therapy (HBO2) for persistent post-concussive symptoms after mild traumatic brain injury (mTBI) (HOPPS).(2014) U.S. National Library of Medicine. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01306968. Updated September 5, 2014. Accessed November 14, 2020. Hyperbaric oxygen therapy for burns, infections and wounds. Hayes Assessment June 2002. Hyperbaric oxygen therapy for carbon monoxide poisoning. Hayes, Inc. May 2002. Hyperbaric oxygen therapy for persistent post-concussive symptoms after mild traumatic brain injury (NCT01306968). Sponsored by the U.S. Army Medical Research and Materiel Command. Last updated June 30, 2011. Available online at: www.clinicaltrials.gov. Last accessed July 2011. Hyperbaric oxygen therapy for post-concussive symptoms after mild traumatic brain injury (NCT01220713). Sponsored by the U.S. Naval Medical Center and Portsmouth Hunter Mcguire Veteran Affairs Medical Center. Last updated October 12, 2010. Available online at: www.clinicaltrials.gov. Last accessed July 2011. Hyperbaric oxygen therapy for wound healing, part I, II, III. 1999 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; Tabs 14, 15. Hyperbaric oxygen therapy in distal radius fractures: Can it shorten recovery time and increase fracture healing? (NCT01365780) Sponsored by RWTH Aachen University. Last updated July 6, 2011. Available online at: www.clinicaltrials.gov. Last accessed July 2011. Hyperbaric oxygen therapy in treating long-term gastrointestinal adverse effects caused by radiation therapy in patients with pelvic cancer (NCT01087268). Sponsored by the National Cancer Institute. Last updated July 14, 2011. Available online at: www.clinicaltrials.gov. Last accessed July 2011. Iorianni P, Oliver GC.(1992) Synergistic soft tissue infections of the perineum. Dis Colon Rectum 1992; 35:640-644. Jarvis RM, Neufeld MV, Westfall CT.(2000) Brown recluse spider bite to the eyelid. Ophthalmology 2000; 107:1492-1496. Joshua TG, Ayub A, Wijesinghe P, et al.(2021) Hyperbaric Oxygen Therapy for Patients With Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. Oct 28 2021. PMID 34709348 Kawakami K.(1994) Hyperbaric oxygen therapy on cervical cord injury following emergency surgery. Spine Spinal Cord 1994; 7:399-403. Kindwall EP.(1992) Uses of hyperbaric oxygen therapy in the 1990’s. Clev Clin J Med 1992; 59 :517-528. Kindwall EP.(1993) Hyperbaric oxygen: more indications than many doctors realize. BMJ 1993; 307:515-516. Korhonen K, Hirn M, Niinikoski J.(1998) Hyperbaric oxygen in the treatment of Fournier’s gangrene. Eur J Surg 1998; 164:251-255. Korhonen K, Klossner J, Hirn M, et al.(1999) Management of clostridial gas gangrene and the role of hyperbaric oxygen. Ann Chir Gynaecol 1999; 88:139-142. Kranke P, Bennett MH, Martyn-St James M, et al.(2015) Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. Jun 24 2015(6):CD004123. PMID 26106870 Lacey DJ, Stolfi A, Pilati LE.(2012) Effects of hyperbaric oxygen on motor function in children with cerebral palsy. Ann Neurol 2012; 72(5):695-703. Landau Z.(1998) Topical hyperbaric oxygen and low energy laser for the treatment of diabetic foot ulcers. Arch Orthop Trauma Surg 1998; 117:156-8. Langford FP, Moon RE, Stolp BW, et al.(1995) Treatment of cervical necrotizing fasciitis with hyperbaric oxygen therapy. Otolaryngol Head Neck Surg 1995; 112:274-278. Lavy A, Weisz G, Adir Y, et al.(1994) Hyperbaric oxygen for perianal Crohn’s disease. J Clin Gastro 1994; 19 :202-205. Leach RM, Rees PJ, Wilmshurst P.(1998) ABC of oxygen. Hyperbaric oxygen therapy. BMJ 1998; 317:1140-1143. Levett D, Bennett MH, Millar I.(2015) Adjunctive hyperbaric oxygen for necrotizing fasciitis. Cochrane Database Syst Rev. 2015;1:CD007937. PMID 25879088 Lipsky BA, Berendt AR, Cornia PB, et al.(2013) 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 Litovitz TL, Klein-Schwartz W, Dyer KS, et al.(1998) 1997 annual report of the American Association of Poison Control Centers toxic exposure surveillance system. Am J Emerg Med 1998; 16:443-447. Long Y, Tan J, Nie Y, et al.(2017) Hyperbaric oxygen therapy is safe and effective for the treatment of sleep disorders in children with cerebral palsy. Neurol Res. Mar 2017;39(3):239-247. PMID 28079475 Mader JT, Shirtliff ME, Bergquist SC, et al.(1999) Antimicrobial treatment of chronic osteomyelitis. Clin Orthop Rel Res 1999; 360:47-65. Magnant CM, Milzman DP, Dhindsa H.(1992) Hyperbaric medicine for outpatient wound care. Emer Med Clin N Am 1992; 10 :847-860. Marion DW.(1998) Head and spinal cord injury. Neuro Clin N Am 1998; 16 :485-502. Marois P, Mukherjee A, Ballaz L.(2015) Hyperbaric Oxygen Treatment for Persistent Postconcussion Symptoms-A Placebo Effect? JAMA Intern Med. Jul 1 2015;175(7):1239-1240. PMID 26146912 Mathieu D, Marroni A, Kot J.(2017) 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 Maynor ML, Abt JL, Osborne PD.(1992) Brown recluse spider bites: beneficial effects of hyperbaric oxygen. J Hyperbaric Med 1992; 7:89-102. Maynor ML, Moon RE, Klitzman B, et al.(1997) Brown recluse spider envenomation: a prospective trial of hyperbaric oxygen therapy. Acad Emerg Med 1997; 4:184-192. Mayo Endoscopic Scoring of Ulcerative Colitis http://www.sages.co.za/images/MAYO%203.pdf. Accessed June, 2014. McCurdy J, Siw KCK, Kandel R, et al.(2022) The Effectiveness and Safety of Hyperbaric Oxygen Therapy in Various Phenotypes of Inflammatory Bowel Disease: Systematic Review With Meta-analysis. Inflamm Bowel Dis. Mar 30 2022; 28(4): 611-621.PMID 34003289 McHenry CR, Piotrowski JJ, Petrinic D, et al.(1995) Determinants of mortality for necrotizing soft tissue infections. Ann Surg 1995; 221:558-565. Medical devices advisory committee. FDA 1998. Miller RS, Weaver LK, Bahraini N, et al.(2015) 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 Mink RB, Dutka AJ.(1995) Hyperbaric oxygen after global cerebral ischemia in rabbits reduces brain vascular permeability and blood flow. Stroke 1995; 26:2307-2312. Mitton C, Hailey D.(1998) Hyperbaric oxygen treatment in Alberta: health technology assessment report. CCOHTA 1998. Monestersky JH, Myers RA.(1995) Hyperbaric oxygen treatment of necrotizing fasciitis. Am J Surg 1995; 169:187. Nakajima M, Aso S, Matsui H, et al.(2020) Hyperbaric oxygen therapy and mortality from carbon monoxide poisoning: A nationwide observational study. Am J Emerg Med. Feb 2020; 38(2): 225-230. PMID 30797609 Niezgoda JA, Cianci P, Folden BW, et al.(1997) The effect of hyperbaric oxygen therapy on a burn wound model in human volunteers. Plast Reconstr Surg 1997; 99:1620-1625. Noyer CM, Brandt LJ.(1999) Hyperbaric oxygen therapy for perineal Crohn’s disease. Am J Gastro 1999; 94 :318-321. Nwomeh BC, Yager DR, Cohen IK.(1998) Physiology of the chronic wound. Clin Plast Surg 1998; 25 :341-356. O'Reilly D, Pasricha A, Campbell K, et al(2013) Hyperbaric oxygen therapy for diabetic ulcers: systematic review and meta-analysis. Int J Technol Assess Health Care. Jul 2013;29(3):269-281. PMID 23863187 Ottawa ON:(2014) Hyperbaric Oxygen Therapy for Adults with Mental Illness: A Review of the Clinical Effectiveness. 2014 Canadian Agency for Drugs and Technologies in Health.; 2014. Pagoldh M, Hultgren E, Arnell P, et al.(2013) 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 Pagoldh M, Hultgren E, Arnell P, et al.(2013) 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):1033-1040. PMID 23879825 Pellitteri PK, Kennedy TL, Youn BA.(1992) The influence of intensive hyperbaric oxygen therapy on skin flap survival in a swine model. Arch Otolaryngol Head Neck Surg 1992; 118:1050-1054. Peng Z, Wang S, Huang X et al.(2012) Effect of hyperbaric oxygen therapy on patients with herpes zoster. Undersea Hyperb Med 2012; 39(6):1083-7. Phillips S, Kohn M, Baker D, et al.(1995) Therapy of brown spider envenomation: a controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine. Ann Emerg Med 1995; 25:363-368. Pizzorno R, Bonini F, Donelli A, et al.(1997) Hyperbaric oxygen therapy in the treatment of Fournier’s disease in 11 male patients. J Urol 1997; 158:837-840. Quirinia A, Viidki A.(1995) The effect of hyperbaric oxygen on different phases of healing ischemic flap wounds and incisional wounds in skin. Brit J Plast Surg 1995; 48:583-589. Radonic V, Baric D, Giunio L, et al.(1997) War injuries of the femoral artery and vein: a report on 67 cases. CV Surg 1997; 5 :641-647. Ravi P, Vaishnavi D, Gnanam A, et al.(2017) 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):359-362. PMID 28838774 Reher P.(1999) Treatment of mandibular osteoradionecrosis by cancellous bone grafting. J Oral Maxillofac Surg 1999; 57:936-942. Rhee TM, Hwang D, Lee JS, et al.(2018) Addition of Hyperbaric Oxygen Therapy vs Medical Therapy Alone for Idiopathic Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. Sep 27 2018. PMID 30267033 Roberts I, Schierhout G, Alderson P.(1998) Absence of evidence for the effectiveness of five interventions routinely used in the intensive care management of severe head injury: a systematic review. J Neurol Neurosurg Psych 1998; 65:729-733. Rockswold GL, Ford SE, Anderson DC, et al.(1992) Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen. J Neurosurg 1992; 76:929-934. Rossignol DA, Rossignol LW, Smith S, et al.(2009) Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial. BMC Pediatr. 2009; 9:21. Roth RN, Weiss LD.(1994) Hyperbaric oxygen and wound healing. Clin Derm 1994; 12:141-156. Rudge FW.(1993) The role of hyperbaric oxygenation in the treatment of clostridial myonecrosis. Military Med 1993; 158:80-83. Sadri RA, Cooper JS.(2017) Hyperbaric, complications. NCBI Bookshelf 2017; https://www.ncbi.nlm.nih.gov/books/NBK459191/. Accessed November 21, 2017. Savvidou OD, Kaspiris A, Bolia IK, et al.(2018) Effectiveness of Hyperbaric Oxygen Therapy for the Management of Chronic Osteomyelitis: A Systematic Review of the Literature. Orthopedics. Jul 01 2018; 41(4): 193-199. PMID 30035798 Schaefer SE.(1992) Fundamentals of hyperbaric oxygen therapy. Orthop Nurs 1992; 11:9-15. Sharma R, Sharma SK, Mudgal SK, et al.(2021) Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials. Sci Rep. Jan 26 2021; 11(1): 2189. PMID 33500533 Sheffield PJ.(1998) Measuring tissue oxygen tension: a review. Undersea Hyperbaric Med 1998; 25 :179-188. Sheridan RL, Shank ES.(1999) Hyperbaric oxygen treatment: a brief overview of a controversial topic. J Trauma 1999; 47 :426-435. Shupak A, Shoshani O, Goldenberg I, et al.(1995) Necrotizing fasciitis: an indication for hyperbaric oxygen. Surg 1995; 118:873-878. Skinner WM, Butler CS.(1995) Necrotizing arachnidism treated with hyperbaric oxygen. Med J Aust 1995; 162:372-373. Smith GL, Bunker CB, Dinneen MD.(1998) Fournier’s gangrene. Br J Urol 1998; 81:347-355. Sonis ST, DeVita VT, Hellman S, Rosenberg SA,.(1993) Oral complications of cancer therapy. Cancer Principles and Practice Oncology; Volume 2; 4th edition. Philadelphia; PA:JB Lippincott Co; 2385-2394; 1993. Spiegelberg L, Djasim UM, van Neck H et al.(2010) 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 2010; 68(8):1732-9. Stewart RJ, Moore T, Bennett B, et al.(1994) Effect of free-radical scavengers and hyperbaric oxygen on random pattern skin flaps. Arch Surg 1994; 129:982-987. Sultan A, Hanna GJ, Margalit DN, et al.(2017) he 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):343-350. PMID 28209748 Sun H, Qiu X, Hu J, et al.(2018) Comparison of intratympanic dexamethasone therapy and hyperbaric oxygen therapy for the salvage treatment of refractory high-frequency sudden sensorineural hearing loss. Am J Otolaryngol. Sep - Oct 2018;39(5):531-535. PMID 29891394 Teguh DN, Levendag PC, Noever I et al.(2009) Early hyperbaric oxygen therapy for reducing radiotherapy side effects: Early results of a randomized trial in oropharyngeal and nasopharyngeal cancer. Int J Radiation Oncol Biol Phys 2009; 75(3): 711-6. Tibbles PM, Edelsberg JS.(1996) Hyperbaric oxygen therapy. NEJM 1996; 334 :1642-1648. Toljanic JA, Ali M, Haraf DJ, et al.(1998) Osteoradionecrosis of the jaws as a risk factor in radiotherapy: a report of an eight-year retrospective review. Oncol Rep 1998; 5:345-349. Tomaszewski CA, Thom SR.(1994) Concepts and Controversies in toxicology, Use of hyperbaric oxygen in toxicology. Emer Med Clin N Am 1994; 12:437-459. U.S. Food and Drug Administration (FDA).(2013) Hyperbaric Oxygen Therapy: Don't Be Misled. 2013; https://www.talkingaboutthescience.com/studies/FDA2013.pdf. Accessed November 16, 2022. Ueda H, Shien CW, Miyazawa T, et al.(1998) Otological complications of hyperbaric oxygen therapy. Adv Otorhinolaryngol 1998; 54:119-126. UHMS indications. Indications for treatment. Undersea Hyperbaric Medical Society (UHMS). http://www.uhms.org/indications.htm. Accessed January 22 1999. Undersea & Hyperbaric Medical Society.(2009) Indications for Hyperbaric Oxygen Therapy http://www.uhms.org/Default.aspx?tabid=270. Last accessed Aug. 2008. Undersea and Hyperbaric Medical Society. Position Paper. The treatment of autism spectrum disorder with hyperbaric oxygen therapy. 12/5/09. http://www.uhms.org/portals/0/pdf/Autism_POSITION_PAPER.pdf Villanueva E, Bennett MH, Wasiak J, et al.(2004) Hyperbaric oxygen therapy for thermal burns. Cochrane Database Syst Rev. 2004(3):CD004727. PMID 15266540 Villeirs L, Tailly T, Ost P, et al.(2020) Hyperbaric oxygen therapy for radiation cystitis after pelvic radiotherapy: Systematic review of the recent literature. Int J Urol. Feb 2020; 27(2): 98-107. PMID 31617263 Walter FG, Bilden EF, Gibly RL.(1999) Envenomations. Crit Care Clin 1999; 15 :353-386. Wang C, Lau J.(2001) Hyperbaric oxygen therapy in treatment of hypoxic wounds. Agency for Healthcare Research and Quality; November 2001. Wang F, Wang Y, Sun T, et al.(2016) Hyperbaric oxygen therapy for the treatment of traumatic brain injury: a meta-analysis. Neurol Sci. May 2016;37(5):693-701. PMID 26746238 Weaver LK, Churchill S, Wilson SH, et al.(2019) A composite outcome for mild traumatic brain injury in trials of hyperbaric oxygen. Undersea Hyperb Med. BIMA 2019; 46(3): 341-352. PMID 31394603 Weiss LD, Van Meter KW.(1992) The applications of hyperbaric oxygen therapy in emergency medicine. Am J Emerg Med 1992; 10 :558-568. Weisz G, Lavy A, Adir Y, et al.(1997) Modification of in vivo and in vitro TNF-a, IL-1, and IL-6 secretion by circulating monocytes during hyperbaric oxygen treatment in patients with perianal Crohn’s disease. J Clin Immunol 1997; 17 :154-159. Whelan HT, Kindwall EP.(1998) Hyperbaric oxygen: some unanswered questions despite clinical usefulness. Adv Exp Med Biol 1998; 454:441-445. White RJ, Likavec MJ.(1992) The diagnosis and initial management of head injury. NEJM 1992; 327 :1507-1511. Williams RL.(1997) Hyperbaric oxygen therapy and the diabetic foot. J Am Pod Med Assoc 1997; 87 :279-292. Wolf G, Cifu D, Baugh L et al.(2012) The effect of hyperbaric oxygen on symptoms after mild traumatic brain injury. J Neurotrauma 2012; 29(17):2606-12. Xiao Y, Wang J, Jiang S et al.(2012) Hyperbaric oxygen therapy for vascular dementia. Cochrane Database Syst Rev 2012; 7:CD009425. Xie S, Qiang Q, Mei L, et al.(2018) Multivariate analysis of prognostic factors for idiopathic sudden sensorineural hearing loss treated with adjuvant hyperbaric oxygen therapy. Eur Arch Otorhinolaryngol. Jan 2018;275(1):47-51. PMID 29071444 Xiong T, Chen H, Luo R, et al.(2016) Hyperbaric oxygen therapy for people with autism spectrum disorder (ASD). Cochrane Database Syst Rev. Oct 13 2016;10:CD010922. PMID 27737490 Yildiz S, Kiralp MZ, Akin A, et al.(2004) A new treatment modality for fibromyalgia syndrome: hyperbaric oxygen therapy. J Int Med Res. May-Jun 2004;32(3):263-267. PMID 15174219 Zamboni WA, Wong HP, Stephenson LL, et al.(1997) Evaluation of hyperbaric oxygen for diabetic wounds: a prospective study. Undersea Hyperbaric Med 1997; 24 :175-179. Zhou YY, Liu W, Yang YJ, et al.(2014) Use of hyperbaric oxygen on flaps and grafts in China: analysis of studies in the past 20 years. Undersea Hyperb Med. 2014; 41(3): 209-16. PMID 24984315 |
|
|
|
|
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association. |
|