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Aetna Aetna
Clinical Policy Bulletin:
Hyperbaric Oxygen Therapy (HBOT)
Number: 0172


Policy

  1. Aetna considers systemic hyperbaric oxygen therapy (HBOT) medically necessary for any of the following conditions:

    1. Acute air or gas embolism
    2. Acute carbon monoxide poisoning
    3. Acute cerebral edema
    4. Acute peripheral arterial insufficiency (i.e., compartment syndrome)
    5. Acute traumatic peripheral ischemia (including crush injuries and suturing of severed limbs) when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy
    6. Chronic refractory osteomyelitis, unresponsive to conventional medical and surgical management
    7. Compromised skin grafts and flaps
    8. Cyanide poisoning (with co-existing carbon monoxide poisoning)
    9. Decompression illness (“the bends”)
    10. Exceptional blood loss anemia only when there is overwhelming blood loss and transfusion is impossible because there is no suitable blood available, or religion does not permit transfusions
    11. Gas gangrene (Clostridial myositis and myonecrosis)
    12. Idiopathic sudden deafness, acoustic trauma or noise-induced hearing loss, when HBOT is initiated within 3 months after onset
    13. Non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity in diabetic adults unresponsive to at least 1 month of meticulous wound care.  Standard wound care in persons with diabetic wound includes (i) assessment of vascular status and correction of any vascular problems in the affected limb if possible, (ii) optimization of nutritional status, (iii) optimization of glucose control, (iv) debridement by any means to remove devitalized tissue, (v) maintenance of clean, moist bed of granulation tissue with appropriated moist dressings, (vi) appropriate off-loading, and (vii) necessary treatment to resolve any infection that might be present.  Failure to respond to standard wound care occurs when there are no measurable signs of healing for at least 30 consecutive days.  Wounds must be evaluated at least every 30 days during the administration of HBOT.  Continued treatment with HBOT is not considered medically necessary if measurable signs of healing have not been demonstrated within any 30-day period of treatment.  Note: HBOT is not considered medically necessary for superficial lesions.
    14. Pneumatosis cystoides intestinalis
    15. Progressive necrotizing soft tissue infections, including mixed aerobic and anaerobic infections (Meleney's ulcer, necrotizing fasciitis)
    16. Prophylactic pre- and post-treatment for members undergoing dental surgery of a radiated jaw
    17. Radiation-induced hemorrhagic cystitis
    18. Radiation necrosis (brain radionecrosis, myoradionecrosis, osteoradionecrosis, and other soft tissue radiation necrosis)
    19. Radiation proctitis
       
  2. Aetna considers the use of systemic HBOT experimental and investigational for the following conditions (not an all inclusive list) because there is insufficient evidence in the medical literature establishing that systemic HBOT is more effective than conventional therapies:

    1. Actinic skin damage
    2. Actinomycosis and other mycoses
    3. Acute coronary syndrome
    4. Acute or chronic cerebrovascular insufficiency/accident (including thrombotic or embolic stroke)
    5. Acute renal arterial insufficiency
    6. Acute thermal and chemical pulmonary damage, i.e., smoke inhalation (e.g., carbon tetrachloride, hydrogen sulfide) with pulmonary insufficiency
    7. Aerobic septicemia and systemic aerobic infection
    8. Anaerobic septicemia and infection other than clostridial
    9. Anoxic brain injury
    10. Arthritic diseases
    11. Arthritis
    12. Aseptic necrosis of the femoral head and neck
    13. Autism
    14. Bell's palsy
    15. Bone grafts or fracture healing (e.g., nonunion fractures)
    16. Calciphylaxis (calcific uremic arteriolopathy)
    17. Cancer
    18. Cardiogenic shock
    19. Cerebral palsy
    20. Chronic peripheral vascular insufficiency
    21. Closed head and/or spinal cord injury
    22. Cognitive impairment (e.g., senility, senile dementia)
    23. Crohn's disease
    24. Cystic acne
    25. Diabetic foot ulcers that are not infected
    26. Diabetic superficial wounds
    27. Facial neuritis
    28. Frostbite
    29. Hepatic artery thrombosis
    30. Hepatic necrosis
    31. HIV infection
    32. Infective polyneuritis
    33. Interstitial cystitis
    34. Intra-abdominal abscess, pseudomembranous colitis (antibiotic-induced colitis)
    35. Intracranial abscesses
    36. Ischemia due to lupus vasculitis
    37. Legg-Calve Perthes disease
    38. Lepromatous leprosy
    39. Lyme disease
    40. Lymphedema
    41. Melasma
    42. Meningitis
    43. Migraine or cluster headaches
    44. Multiple sclerosis
    45. Myocardial infarction
    46. Myofascial pain syndrome
    47. Necrotizing arachnidism
    48. Non-compromised skin grafts and flaps
    49. Non-diabetic cutaneous, decubitus, pressure and venous stasis ulcers
    50. Non-vascular causes of chronic brain syndrome (e.g., Alzheimer's disease, Korsakoff's disease, Pick's disease)
    51. Ophthalmologic diseases (including central retinal artery occlusion, central retinal vein occlusion, diabetic retinopathy, glaucoma, keratoendotheliosis, radiation injury to the optic nerve, retinal detachment)
    52. Organ transplantation and storage
    53. Osteonecrosis of the jaw
    54. Osteoporosis
    55. Otitis externa
    56. Parkinson's disease
    57. Post-organ transplantation re-vascularization
    58. Pulmonary emphysema
    59. Pyoderma gangrenosum
    60. Radiation-induced cholangitis, myelitis, enteritis, sarcoma
    61. Recto-vaginal fistula
    62. Reflex sympathetic dystrophy (complex regional pain syndrome)
    63. Seizure disorders
    64. Sickle cell crisis or hematuria
    65. Skin burns (thermal)
    66. Superficial and/or non-infected diabetic ulcers
    67. Surgical wound dehiscence
    68. Tetanus
    69. Tinnitus
    70. Traumatic brain injury 
    71. Xerostomia/salivary gland dysfunction
       
  3. Aetna considers systemic HBOT experimental and investigational for members with any of the following contraindications to systemic HBOT, as the safety of systemic HBOT for persons with these contraindications to HBOT has not been established:

    1. Concurrent administration of doxorubicin, cisplatin, or disulfiram
    2. Premature infants (birth prior to 37 weeks gestation)
    3. Untreated pneumothorax
       
  4. Aetna considers topical HBOT directly administered to the open wound, and limb-specific hyperbaric oxygen pressurization in small limb-encasing devices experimental and investigational because its efficacy has not been established through well-controlled clinical trials.



Background

Hyperbaric oxygen therapy (HBOT) is defined as systemic treatment in which the entire patient is placed inside a pressurized chamber and breathes 100 % oxygen under a pressure greater than 1 atmosphere (atm).  It is used to treat certain diseases and conditions that may improve when an increased partial pressure of oxygen is present in perfused tissues.

The literature states that HBOT should not be a replacement for other standard successful therapeutic measures.  Depending on the response of the individual patient and the severity of the original problem, treatment may range from less than 1 week to several months' duration, the average being 2 to 4 weeks.  Hyperbaric oxygen therapy for more than 2 months is usually not necessary.

Hyperbaric oxygen therapy has been shown to be an effective method for treating diabetic foot wounds in carefully selected cases of lower extremity lesions.  Although the results of multiple retrospective studies involving a significant number of patients have consistently indicated a high success rate in patients who had been refractory to other modes of therapy, several recent prospective, randomized studies have only supported the adjunctive role of systemic hyperbaric oxygen therapy in the treatment of non-healing infected deep lower extremity wounds in patients with diabetes.  Such evidence is lacking, however, for superficial diabetic wounds and non-diabetic cutaneous, decubitus, and venous stasis ulcers.

A number of technology assessment organizations, including the Cochrane Collaboration, the Wessex Institute, the Alberta Heritage Foundation for Medical Research, and the Agency for Healthcare Research and Quality (AHRQ), have systematically reviewed the evidence supporting the use of hyperbaric oxygen for each of the indications for which it has been used.

An evidence review conducted by the Alberta Heritage Foundation for Medical Research (Hailey, 2003) concluded that use of HBOT is not supported for a number of conditions, including non-diabetic wounds, multiple sclerosis, cerebral palsy, decubitus ulcers, necrotizing arachnidism, actinomycosis, cardiovascular conditions, Bell's palsy, cluster and migraine headaches, Legg-Calve Perthes disease, Crohn's disease, osteoporosis, cancer, head trauma, cognitive impairment, senile dementia, glaucoma, keratoendotheliosis, HIV infection, facial neuritis, and nonunion of fractures. 

A systematic evidence review conducted for the Agency for Healthcare Research and Quality (AHRQ) (McDonagh et al, 2003) found insufficient evidence to support the use of HBOT in brain injury.  The assessment concluded that "The balance of benefits and harms of HBOT for brain injury, cerebral palsy, or stroke has not been adequately studied."

Denton et al (2004) systematically reviewed the evidence regarding HBOT for radiation cystitis.  Of the 19 studies that met inclusion criteria, all the reports were case series and only 1 was a prospective series.  The authors stated that "[t]he level of evidence that these data represent is essentially IIIC (weak evidence), apart from one prospective case series of forty patients."  The latter study (Bevers et al, 1995) was graded IIC (prospective study without calculation of sample size and without accurate and standard definition of outcome variables).

In a Cochrane review, Bennett et al (2005) concluded that for people with acute coronary syndrome, individual small trials suggest the addition of HBOT reduced the risk of major adverse cardiac events, some dysrrhythmias, and reduced the time to relief from ischemic pain, but did not reduce mortality.  They noted that in view of the modest number of patients, methodological shortcomings and poor reporting, this result should be interpreted cautiously, and an appropriately powered trial of high methodological rigor is justified to define those patients (if any) who can be expected to derive most benefit from HBOT.  The routine application of HBOT to these patients can not be justified from this review.

A Cochrane review (Bennett et al, 2005) assessed the evidence of effectiveness of HBOT for long-term radiation injury to the anus and rectum.  The investigators found HBOT significantly improved chance of healing for radiation proctitis (relative risk 2.7, 95 % confidence interval [CI]: 1.2 to 6.0).  The investigators concluded that small trials suggest that HBOT is useful for treatment of long-term radiation injury to the anus and rectum.

Absolute contraindications to HBOT include: untreated pneumothorax, concurrent administration of disulfuram (Antabuse); concurrent administration of the antineoplastic agents doxorubicin and cisplatinum; and administration to premature infants (due to risk of retrolental fibroplasia).  Relative contraindications to the use of HBOT include prior chest surgery, lung disease, viral infections, recent middle ear surgery, optic neuritis, seizure disorders, high fever, congenital spherocytosis, and claustrophobia.

Topical HBOT administered to the open wound in small limb-encasing devices is not systemic HBOT and its efficacy has not been established due to the lack of controlled clinical trials.  In addition, in vitro evidence suggests that topical HBOT does not increase tissue oxygen tension beyond the superficial dermis.  Examples of topical HBOT devices are TOPOX portable hyperbaric oxygen extremity and sacral chambers (Jersey City, NJ), Oxyboot and Oxyhealer from GWR Medical, L.L.P. (Chadds Ford, PA).

The Undersea and Hyperbaric Medical Society issued the following policy statement on topical oxygen, often referred to as “topical hyperbaric oxygen therapy” (Feldmeier et al, 2005): “1. Topical oxygen should not be termed hyperbaric oxygen since doing so either intentionally or unintentionally suggests that topical oxygen treatment is equivalent or even identical to hyperbaric oxygen.  Published documents reporting experience with topical oxygen should clearly state that topical oxygen not hyperbaric oxygen is being employed.  2. Mechanisms of action or clinical study results for hyperbaric oxygen can not and should not be co-opted to support topical oxygen since hyperbaric oxygen therapy and topical oxygen have different routes and probably efficiencies of entry into the wound and their physiology and biochemistry are necessarily different.  3. The application of topical oxygen cannot be recommended outside of a clinical trial at this time based on the volume and quality of scientific supporting evidence available, nor does the Society recommend third party payor reimbursement.  4. Before topical oxygen can be recommended as therapy for non-healing wounds, its application should be subjected to the same intense scientific scrutiny to which systemic hyperbaric oxygen has been held”.

There is insufficient evidence of the effectiveness of hyperbaric oxygen as a treatment for autism.  Rossignol (2007) stated that autism is a neurodevelopmental disorder currently affecting as many as 1 out of 166 children in the United States.  Numerous studies of autistic individuals have revealed evidence of cerebral hypoperfusion, neuro-inflammation and gastrointestinal inflammation, immune dysregulation, oxidative stress, relative mitochondrial dysfunction, neurotransmitter abnormalities, impaired detoxification of toxins, dysbiosis, and impaired production of porphyrins.  Many of these findings have been correlated with core autistic symptoms.  For example, cerebral hypoperfusion in autistic children has been correlated with repetitive, self-stimulatory and stereotypical behaviors, and impairments in communication, sensory perception, and social interaction.  Hyperbaric oxygen therapy might be able to improve each of these problems in autistic persons.  Specifically HBOT has been used with clinical success in several cerebral hypoperfusion conditions and can compensate for decreased blood flow by increasing the oxygen content of plasma and body tissues.  Hyperbaric oxygen therapy has been reported to possess strong anti-inflammatory properties and has been shown to improve immune function.  There is evidence that oxidative stress can be reduced with HBOT through the upregulation of antioxidant enzymes.  Hyperbaric oxygen therapy can also increase the function and production of mitochondria and improve neurotransmitter abnormalities.  In addition, HBOT up-regulates enzymes that can help with detoxification problems specifically found in autistic children.  Dysbiosis is common in autistic children and HBOT can improve this.  Impaired production of porphyrins in autistic children might affect the production of heme, and HBOT might help overcome the effects of this problem.  Finally, HBOT has been shown to mobilize stem cells from the bone marrow to the systemic circulation.  Recent studies in humans have shown that stem cells can enter the brain and form new neurons, astrocytes, and microglia.  It is expected that amelioration of these underlying pathophysiological problems through the use of HBOT will lead to improvements in autistic symptoms.  Several studies on the use of HBOT in autistic children are currently underway and early results are promising.

An systematic evidence review of hyperbaric oxygen therapy for autism (Moqadem and Pineau, 2007) prepared for AETMIS, a Canadian technology assessment agency, concluded: "In light of its assessment, AETMIS concludes that there is insuffi cient evidence to build a strong case for the efficacy of hyperbaric oxygen therapy in the management of autistic disorders.  In these circumstances, a literature watch should be conducted to evaluate the results of the current and future studies.  In short, for the management of autism, hyperbaric oxygen therapy should, for now, be considered an experimental treatment modality.  Consequently, this treatment should be limited to formal research projects."

Rossignol et al (2009) carried out a multi-center, randomized, double-blind, controlled study to evaluate the effectiveness of HBOT in children with autism.  A total of 62 children with autism recruited from 6 centers, aged 2 to 7 years (mean of 4.92 +/- 1.21) were randomly assigned to 40 hourly treatments of either HBOT at 1.3 atm and 24 % oxygen ("treatment group", n = 33) or slightly pressurized room air at 1.03 atm and 21 % oxygen ("control group", n = 29).  Outcome measures included Clinical Global Impression (CGI) scale, Aberrant Behavior Checklist (ABC), and Autism Treatment Evaluation Checklist (ATEC).  After 40 sessions, mean physician CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0008), receptive language (p < 0.0001), social interaction (p = 0.0473), and eye contact (p = 0.0102); 9/30 children (30 %) in the treatment group were rated as "very much improved" or "much improved" compared to 2/26 (8 %) of controls (p = 0.0471); 24/30 (80 %) in the treatment group improved compared to 10/26 (38 %) of controls (p = 0.0024).  Mean parental CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0336), receptive language (p = 0.0168), and eye contact (p = 0.0322).  On the ABC, significant improvements were observed in the treatment group in total score, irritability, stereotypy, hyperactivity, and speech (p < 0.03 for each), but not in the control group. In the treatment group compared to the control group, mean changes on the ABC total score and subscales were similar except a greater number of children improved in irritability (p = 0.0311).  On the ATEC, sensory/cognitive awareness significantly improved (p = 0.0367) in the treatment group compared to the control group.  Post-hoc analysis indicated that children over age 5 and children with lower initial autism severity had the most robust improvements.  Hyperbaric treatment was safe and well-tolerated.  The authors reported that children with autism who received HBOT at 1.3 atm and 24 % oxygen for 40 hourly sessions had significant improvements in overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness compared to children who received slightly pressurized room air.

Rossignol et al (2009) concluded that "[g]iven the positive findings of this study, and the shortage of proven treatments for individuals with autism, parents who pursue hyperbaric treatment for their child with autism can be assured that it is a safe treatment modality at the pressure used in this study (1.3 atm), and that it may improve certain autistic behaviors.  Further studies are needed by other investigators to confirm these findings; we are aware of several other planned or ongoing studies of hyperbaric treatment in children with autism.  However, in light of the positive results of this study and those of several previous studies, the use of hyperbaric treatment appears to be a promising treatment for children with autism".

The study by Rossignol et al (2009) had several major limitations.  First, there were no significant differences between the treatment and control groups for most of the primary outcomes.  In the treatment group compared to the control group, mean changes on the ABC total score and subscales were similar except a greater number of children improved in irritability (p = 0.0311).  There were no significant differences between treatment and control groups in total ABC score, and in the subscales for social withdrawal, stereotypy, hyperactivity, and speech.  Furthermore, analysis of changes in ATEC total score and subscale scores between the treatment and control groups showed a significant differences between treatment and controls only in the sensory/cognitive awareness subscale.  There were no significant differences between treatment and control groups in total score, and in the subscales for speech, sociability, and health.  In addition, while mean physician CGI scores significantly improved in the treatment group compared to controls in overall functioning, receptive language, social interaction, and eye contact; there were no significant differences between treatment and control groups in the other subscales: expressive language, sleep pattern, attention span, activity level, bowel movement pattern, self-stimulatory behavior, social awareness/alertness, play skills, self-injurious behavior, mood, anxiety level, aggression, general health, gross motor skills, and fine motor skills.  Also, while mean parental CGI scores significantly improved in the treatment group compared to controls in overall functioning, receptive language, and eye contact; there were no significant differences in the treatment group compared to controls in expressive language, sleep pattern, attention span, activity level, bowel movement pattern, self-stimulatory behavior, social awareness/alertness, social interaction, play skills, self-injurious behavior, mood, anxiety level, aggression, general health, gross motor skills, and fine motor skills.  Moreover, while post-hoc analysis was able to identify subgroups of subjects who demonstrated additional statistically significant differences, these findings would need to be confirmed by a prospective study of these subgroups.

Another important issue that was not fully addressed was the adequacy of blinding.  The study states that 6 adults were not able to reliably distinguish between the treatment and control situation.  But the usual method of testing the adequacy of blinding is to query study subjects (children and parents) and investigators themselves to ascertain if they are able to distinguish between treatment and control better than would be expected by chance, which was not done in this study.  The important issue is whether or not the persons who actually participated in the study were able to distinguish between treatment and control better than would be expected by chance, and formal tests of statistical significance are employed in this analysis.

The most critical issue that was not addressed in this study was the durability of results.  These investigators measured outcomes at study initiation and immediately upon completion of 40 HBOT sessions.  However, the treatment and control groups were not followed for any substantial period of time after the study was completed to determine whether significant differences between treatment and control groups persisted.  In other words, does HBOT result in durable benefits, or do any improvements dissipate after completion of treatment?

It should also be noted that autism is not approved as an indication for HBOT neither by the Undersea and Hyperbaric Medical Society nor the European Committee for Hyperbaric Medicine (Yildiz et al, 2008).  Furthermore, in a review on autism, Levy and colleagues (2009) stated that popular biologically based treatments include anti-infectives, chelation medications, gastrointestinal medications, HBOT, and immunoglobulins.  Non-biologically based treatments include auditory integration therapy, chiropractic therapy, cranio-sacral manipulation, interactive metronome, and transcranial stimulation.  However, few studies have addressed the safety and effectiveness of most of these treatments.

Ghanizadeh (2012) stated that there is a controversy regarding the effectiveness of HBOT for the treatment of autism.  This investigator systematically reviewed the current evidences for treating of autism with HBOT.  According to PRISMA guidelines for a systematic review, the databases of MEDLINE/PubMed, Google Scholar, and Randomized Controlled Trials in Hyperbaric Medicine were electronically searched.  In addition, medical subject heading terms and text words for hyperbaric oxygen therapy and autism were used.  The main inclusion criteria were published studies that reported the original data from the trials conducted on the patients with autism and assessed outcomes with a valid and reliable instrument.  A quality assessment was also conducted.  The electronically search resulted in 18 publications.  Two studies were randomized, double-blind, controlled-clinical trials.  While some uncontrolled and controlled studies suggested that HBOT is effective for the treatment of autism, these promising effects are not replicated.  The authors concluded that sham-controlled studies with rigorous methodology are needed to provide scientific evidence-based HBOT for autism treatment.

Although a recent article (Butler et al, 2008) included ischemic central retinal vein and artery occlusions among indications for HBOT, there is no reliable evidence that supports the effectiveness of this treatment for these indications.

Folio et al (2007) described a case of frostbite to all fingers of a mountain climber, treated with HBOT.  All fingers eventually healed to full function, with only some cosmetic deformity to the tip of the most severely affected finger.  Because few cases of frostbite treated with HBOT have been reported, these researchers hoped that such case reports will stimulate future research in this area.  It is hoped that multiple anecdotal cases may help guide future research in this area.  Sequential digital photographs were taken at various stages of healing during HBOT.  They raised the possibility of photographic techniques and standards that may facilitate planning of therapy for frostbite with improved treatment comparisons, resulting in more consistency in the future.  For example, a graphical software application was described that allows morphing of sequential images to demonstrate healing progress in a concise movie format.  The morphing allows concise demonstration of healing to the referring provider and patient and helps in teaching and research on frostbite treatment outcomes.

Kiralp et al (2009) evaluated the effects of HBOT on myofascial pain syndrome (MPS).  A total of 30 patients with the diagnosis of MPS were divided into HBOT (n = 20) and control groups (n = 10).  Patients in the HBOT group received a total of 10 HBOT sessions in 2 weeks.  Patients in the control group received placebo treatment in a hyperbaric chamber.  Pain threshold and visual analog scale (VAS) measurements were performed immediately before and after HBOT and 3 months thereafter.  Additionally, Pain Disability Index (PDI) and Short Form 12 Health Survey (SF-12) evaluations were done before HBOT and after 3 months.  Hyperbaric oxygen therapy was well-tolerated with no complications.  In the HBOT group, pain threshold significantly increased and VAS scores significantly decreased immediately after and 3 months after HBOT.  Furthermore, PDI, Mental and Physical Health SF-12 scores improved significantly with HBOT after 3 months compared with pre-treatment values.  In the control group, pain thresholds, VAS score, and Mental Health SF-12 scores did not change with placebo treatment; however, significant improvement was observed in the Physical Health SF-12 test.  The authors concluded that  HBOT may be a valuable alternative to other methods in the management of MPS.  They stated that these findings warrant further randomized, double-blinded and placebo-controlled studies to evaluate the possible role of HBOT in the management of MPS.

Urade (2009) stated that bisphosphonates (BPs) are effective in the treatment of hypercalcemia of malignancy, multiple myeloma, skeletal events associated with metastatic breast cancer and prostate cancer, and osteoporosis.  Despite these benefits, however, the emergence of BP-related osteonecrosis of the jaws (BRONJ) becomes a growing and significant problem in a subset of patients receiving these drugs, especially intravenous preparations.  Bisphosphonate-related osteonecrosis of the jaws has also been reported in the patients receiving oral BPs, although the incidence is extremely low.  Most of BRONJ cases occur after dental treatments such as tooth extraction, periodontal surgery, and dental implants, and are refractory to conventional treatment modalities such as debridement, antibiotics and HBOT.  As compared to EU and USA, the number of BRONJ case is still small in Japan, but it is exactly increasing year by year.  The ratio of the number of BRONJ in patients receiving oral BPs to that in patients receiving intravenous BPs is higher in Japan than in EU and USA, speculating due to the difference of time of approval.  In this communication, the practical guidelines for prevention, diagnosis and treatment of BRONJ recently released from USA and Canada were introduced.  Although no effective therapy for BRONJ has been established yet, the importance of oral hygiene, patient education and treatments suitable for clinical stage was emphasized.

Freiberger (2009) stated that BPs suppress bone turnover by disrupting osteoclast signal transduction, maturation, and longevity.  In some patients, it has been hypothesized that suppressed turnover can impair oral wound healing, leading to BRONJ.  Hyperbaric oxygen therapy, as an adjunct to surgery and antibiotics, might have utility in the treatment of BRONJ because it produces reactive oxygen and nitrogen species that positively modulate the redox-sensitive intracellular signaling molecules involved in bone turnover.  The effectiveness of HBOT in the treatment of BRONJ is currently under investigation in randomized controlled trials (RCTs) at Duke University and the University of Minnesota, and the early results have been encouraging.  This report discussed osteoclast biology, how HBOT has the potential to augment bone turnover by way of the signaling effects on osteoclasts, the available clinical data on HBOT in the treatment of BRONJ, the ongoing RCTs of HBOT, and the study-associated efforts to find biomarkers to characterize an individual's risk of developing this disease.

Vescovi and Nammour (2010) stated that BRONJ is an area of uncovered bone in the maxillo-facial region that did not heal within 8 weeks after identification by health care provider, in a patient who was receiving or had been exposed to BP therapy (BPT) without previous radiation therapy to the craniofacial region.  Low-grade risk of ONJ is connected with oral BPT used in the treatment of osteopenia, osteoporosis and Paget's disease (from 0.01 % to 0.04 %) while higher-grade risk is associated with intravenous (IV) administration in the treatment of multiple myeloma and bone metastases (from 0.8 % to 12 %).  The management of BRONJ currently is a dilemma.  No effective treatment has yet been developed and interrupting BPT does not seem to be beneficial.  Temporary suspension of BPs offers no short-term benefit, while long-term discontinuation (if systemic conditions permit it) may be beneficial in stabilizing sites of ONJ and reducing clinical symptoms.  The use of oral anti-microbial rinses in combination with oral systemic antibiotic therapy -- penicillin, metronidazole, quinolones, clindamycin, doxycycline, erythromycin -- is indicated for stages I and II of Ruggiero's staging.  The role of HBOT is still unclear but some benefits of this treatment have recently been described in association with discontinuation of BPT and conventional therapy (medical or/and surgical).

In a Cochrane review, Eskes and colleagues (2010) examined the effects of HBOT as a treatment for acute wounds (e.g., those arising from surgery and trauma).  Randomized controlled trials comparing HBOT with other interventions or comparisons between alternative HBOT regimens were selected.  Two review authors conducted selection of trials, risk of bias assessment, data extraction and data synthesis independently.  Any disagreements were referred to a third review author.  A total fo 3 trials involving 219 subjects were included.  The studies were clinically heterogeneous, therefore a meta-analysis was inappropriate.  One trial (48 participants with burn wounds undergoing split skin grafts) compared HBOT with usual care and reported a significantly higher complete graft survival associated with HBOT (95 % healthy graft area risk ratio [RR] 3.50; 95 % CI: 1.35 to 9.11).  A second trial (36 participants with crush injuries) reported significantly more wounds healed with HBOT than with sham HBOT (RR 1.70; 95 % CI: 1.11 to 2.61) and fewer additional surgical procedures required with HBOT: RR 0.25; 95 % CI: 0.06 to 1.02 and significantly less tissue necrosis: RR 0.13; 95 % CI: 0.02 to 0.90).  A third trial (135 subjects undergoing flap grafting) reported no significant differences in complete graft survival with HBOT compared with dexamethasone (RR 1.14; 95 % CI: 0.95 to 1.38) or heparin (RR 1.21; 95 % CI: 0.99 to 1.49).  Many of the pre-defined secondary outcomes of the review, including mortality, pain scores, quality of life, patient satisfaction, activities daily living, increase in transcutaneous oxygen pressure (TcpO(2)), amputation, length of hospital stay and costs, were not reported.  All 3 trials were at unclear or high risk of bias.  The authors concluded that there is a lack of high quality, valid research evidence regarding the effects of HBOT on wound healing.  While 2 small trials suggested that HBOT may improve the outcomes of skin grafting and trauma, these trials were at risk of bias.  They stated that further evaluation by means of high quality RCTs is needed.

The Canadian Agency for Drugs and Technologies in Health's review on the use of HBOT for difficult wound (Boudreau et al, 2010) identified 7 health technology assessments, 5 systematic reviews, and 1 RCT.  Overall, the authors of the identified studies found that HBOT was clinically effective as well as cost-effective when it was used to treat patients with diabetes who have lower extremity chronic ulcers.  There was some positive evidence to suggest that HBOT was clinically effective when it was used to treat radiation proctitis.  The evidence base was considered insufficient to promote the routine use of HBOT for non-diabetic pressure ulcers, delayed radiation-induced injury, thermal burns, as well as skin grafts and flaps.  No evidence was identified on the use of HBOT in post-organ transplantation re-vascularization.  The authors concludd that overall, the best evidence on the use of adjunctive HBOT was associated with the treatment of chronic diabetic wounds.  The evidence that supported its use, however, was not reliable.  Although there were many recommendations on the use of HBOTas adjunctive treatment for specific indications, there is little evidence on its clinical and economic benefits.

Gallego et al (2011) evaluated the effectiveness of HBOT as a potential treatment for patients with hemorrhagic radio-induced cystitis (RADC).  This prospective study included 38 patients, 21 men and 17 women, mean age of 66.5 years (46 to 75), who had been subjected to pelvic radiotherapy, with the diagnosis of RADC with or without radio-induced proctitis (RADP), gross hematuria and lower urinary tract symptoms.  Hyperbaric oxygen therapy was applied in a multi-place chamber; patients breathed pure oxygen (100 %) at 2 to 2.5 atmospheres of pressure (ATAs).  Patients received an average of 31.2 sessions (10 to 48 sessions) and the median follow-up period was 56 months (4 to 72 months).  Hematuria was completely resolved in 34 of the 38 patients.  After HBOT, 6 patients required re-admission, 5 for anemic hematuria and 1 for acute obstructive pyelonephritis.  In general, patients tolerated treatment well; however, 1 patient experienced barotrauma requiring myringotomy.  The authors concluded that HBOT can be used to satisfactorily treat RADC, leading to clinical improvements that begin during the initial sessions in the majority of cases, and with a more than acceptable level of patient tolerance.

Shao and colleagues (2012) compared the efficacy of intravesical hyaluronic acid (HA) instillation and HBOT in the treatment of radiation-induced hemorrhagic cystitis (HC).  In total 36 patients who underwent radiotherapy for their pelvic malignancies and subsequently suffered from HC were randomly divided into an HA group and an HBOT group.  Symptoms of hematuria, frequency of voiding and the visual analog scale of pelvic pain (range of  0 to 10) were evaluated before and after the treatment with follow-up of 18 months.  All patients completed this study and no obvious side effects of intravesical HA were recorded.  The improvement rate showed no statistical difference between the two groups at 6, 12 and 18 months after treatment.  Decrease of frequency was significant in both groups 6 months after treatment, but was only significant in the HA group 12 months after therapy.  The improvement in the visual analog scale remained significant in both groups for 18 months.  The authors concluded that intravesical instillation of HA was as effective in treating radiation-induced HC as HBOT.  It is well-tolerated and resulted in a sustained decrease of bladder bleeding, pelvic pain and frequency of voiding for at least 12 months.

Parra et al (2011) assessed the efficacy of HBOT in HC cases.  A retrospective analysis of patients with HC after pelvic radiotherapy receiving HBOT at the authors' center between January 2002 and January 2010 was performed.  Their protocol included 40 sessions of HBOT in a multi-place hyperbaric chamber with 90 mins of 100 % oxygen breathing at 2.2 ATAs.  Success was evaluated in terms of total or partial stop of bladder bleeding.  Telephone follow-up was updated at the time of submission in all cases.  A total of 25 patients were treated (21 males, 4 females); the mean age was 66.7 years.  Twenty men were irradiated for prostate cancer and 1 for bladder cancer; 3 women had cervix cancer and 1 endometrial cancer.  In all cases previous conservative treatment had failed and HBOT was considered only after other measures failed.  All the patients responded to HBOT and none recurred after end of treatment at a mean follow-up of 21.2 months.  There were no serious complications.  The authors concluded that HBOT is a highly effective and safe, non-invasive therapy for HC secondary to pelvic radiation; it should be considered as first line alternative in these difficult cases.

Savva-Bordalo et al (2012) stated that late-onset HC after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV).  Anti-viral drugs are of limited efficacy and the optimal treatment for HC has not yet been established.  Hyperbaric oxygen therapy may benefit these patients.  These researchers retrospectively evaluated the effectiveness of HBOT in 16 patients with HC after allogeneic HSCT.  All 16 patients had macroscopic hematuria and BKV infection.  Patients received 100 % oxygen in a hyperbaric chamber at 2.1 ATAs for 90 mins, 5 days per week, with a median 13 treatments (range of 4 to 84).  Fifteen patients (94 %) showed complete resolution of hematuria.  Median urinary DNA BKV titers declined after HBOT (p < 0.05).  Patients started on HBOT earlier after diagnosis of HC responded sooner (p < 0.05).  The authors concluded that HBOT was generally well-tolerated and proved to be a reliable option for this difficult to manage condition.

Craighead et al (2011) reviewed the evidence regarding HBOT for late radiation tissue injury in gynecologic malignancies.  The Ovid Medline, Embase, Cochrane Library, National Guidelines Clearinghouse, and Canadian Medical Association Infobase databases were searched to June 2009 for clinical practice guidelines, systematic reviews, randomized controlled trials, or other relevant evidence.  Studies that did not evaluate soft tissue necrosis, cystitis, proctitis, bone necrosis, and other complications were excluded.  Two randomized trials, 11 non-randomized studies, and 5 supporting documents comprise the evidence base.  In addition, information on the harms and safety of treatment with HBOT were reported in 3 additional sources.  There is modest direct evidence and emerging indirect evidence that the use of HBOT is broadly effective for late radiation tissue injury of the pelvis in women treated for gynecologic malignancies.  The authors concluded that based on the evidence and expert consensus opinion, HBOT is likely effective for late radiation tissue injury of the pelvis, with demonstrated efficacy specifically for radiation damage to the anus and rectum; the main indication for HBOT therapy in gynecologic oncology is in the management of otherwise refractory chronic radiation injury; HBOT may provide symptomatic benefit in certain clinical settings (e.g., cystitis, soft-tissue necrosis, and osteonecrosis); and HBOT may reduce the complications of gynecologic surgery in patients undergoing surgical removal of necrosis.

Also, an UpToDate review on "Cystitis in patients with cancer" (Moy, 2011) states that "[h]yperbaric oxygen therapy appears to be effective but is limited to stable patients and those with access to a hyperbaric chamber".

Matchett et al (2009) stated that numerous studies have demonstrated a protective effect of HBOT in experimental ischemic brain injury, and many physiological and molecular mechanisms of HBOT-related neuro-protection have been identified.  These researchers reviewed articles pertaining to HBOT and cerebral ischemia in the National Library of Medicine and National Institutes of Health database, emphasizing mechanisms of HBOT-related neuro-protection.  Hyperbaric oxygen therapy has been shown to ameliorate brain injury in a variety of animal models including focal cerebral ischemia, global cerebral ischemia, neonatal hypoxia-ischemia and subarachnoid hemorrhage.  Small human trials of HBOT in focal ischemia have not shown benefit, although 1 trial of HBOT before cardiopulmonary bypass demonstrated improved neuropsychological and inflammatory outcomes with hyperbaric oxygen therapy.  Hyperbaric oxygen therapy is associated with improved cerebral oxygenation, reduced blood-brain barrier breakdown, decreased inflammation, reduced cerebral edema, decreased intracranial pressure, reduced oxidative burden, reduced metabolic derangement, decreased apoptotic cell death and increased neural regeneration.  The authors concluded that on a molecular level, HBOT leads to activation of ion channels, inhibition of hypoxia inducible factor-1alpha, up-regulation of Bcl-2, inhibition of MMP-9, decreased cyclooxygenase-2 activity, decreased myeloperoxidase activity, up-regulation of superoxide dismutase and inhibition of Nogo-A (an endogenous growth-inhibitory factor).  Ongoing research will continue to describe the mechanisms of HBOT-related neuro-protection, and possibly expand HBOT use clinically.

Michalski et al (2011) stated that high socioeconomic burden is attributed to acute ischemic stroke, but treatment strategies are still limited.  Normobaric oxygen therapy (NBOT) and HBOT were frequently investigated in pre-clinical studies following acute focal cerebral ischemia with predominantly beneficial effects in different outcome measurements.  Best results were achieved in transient cerebral ischemia, starting HBOT early after artery occlusion, and by using relatively high pressures.  On molecular level, oxygen application leads to blood-brain barrier stabilization, reduction of excito-toxic metabolites, and inhibition of inflammatory processes.  Therefore, NBOT and HBOT appear excessively hopeful in salvaging impaired brain cells during ischemic stroke.  However, harmful effects have been noted contributing to damaging properties, e.g., vasoconstriction and free oxygen radicals.  In the clinical setting, NBOT provided positive results in a single clinical trial, but HBOT failed to show efficacy in 3 randomized trials.  To date, the translation of numerous evidentiary experimental results into clinical implementation remains open.  Recently, oxygen became interesting as an additional therapy to neuro-protective or re-canalization drugs to combine positive effects.  The authors concluded that further preclinical research is needed exploring interactions between NBOT, HBOT, and key factors with multi-phasic roles in acute damaging and delayed inflammatory processes after cerebral ischemia, e.g., matrix-metallo-proteinase's and hypoxia-inducible factor-1α.

Calciphylaxis, also referred to as calcific uremic arteriolopathy (CUA), is a syndrome associated with end-stage renal disease, and causes necrotic skin ulcers, often leading to a fatal outcome.  Hyperbaric oxygen has been used to enhance wound healing, but its role in the treatment of calciphylaxis is unclear.  Rogers and Coates (2008) stated that CUA is a rare but important cause of morbidity and mortality in patients with chronic kidney disease.  The prevalence of CUA is increasing in patients with renal failure, and the condition is also being recognized in non-uremic patients.  There has been increasing understanding of the molecular basis of vascular calcification, in particular on the important role of the uremic microenvironment in the factors implicated in the differentiation of vascular smooth muscle cells into osteoblasts.  New options for treatment of hyperphosphatemia and secondary hyperparathyroidism in patients with chronic kidney disease have become available in the last few years and these have begun to be used in patients with CUA.  These include bisphosphonates, newer non-calcium/non-aluminum-containing phosphate binders and case reports of use of cinacalcet.  Other treatments for CUA that are not targeted directly at calcium/phosphate homeostasis include HBOT and the antioxidant cation chelator sodium thiosulphate.  The authors concluded that clinicians managing patients with CUA should consider a combination approach of treating deranged calcium/phosphate with newer therapeutic agents and promoting wound healing with other older modalities such as HBOT and sodium thiosulphate infusions.  They stated that randomized controlled trials for treatments in CUA are still lacking.

In a randomized study, Gothard et al (2010) examined effect of HBOT on arm lymphedema following adjuvant radiotherapy for early breast cancer.  A total of 58 patients with greater than or equal to 15 % increase in arm volume after supraclavicular +/- axillary radiotherapy (axillary surgery in 52/58 patients) were randomized in a 2:1 ratio to HBOT (n = 38) or to best standard care (n = 20).  The HBOT group breathed 100 % oxygen at 2.4 ATAs for 100 mins on 30 occasions over 6 weeks.  Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume.  Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire.  Of 53/58 (91.4 %) patients with baseline assessments, 46 had 12-month assessments (86.8 %).  Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5 % (IQR 126.0 to 152.3 %) in the control group, and 135.5 % (IQR 126.5 to 146.0 %) in the treatment group.  Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2 % (IQR 122.7 to 151.5 %) in the control group and 133.5 % (IQR 122.3 to 144.9 %) in the treatment group.  Results for the secondary endpoints were similar between randomized groups.  The authors concluded that no evidence has been found of a beneficial effect of HBOT in the treatment of arm lymphedema following primary surgery and adjuvant radiotherapy for early breast cancer.

Radiotherapy is generally used in the treatment of malignant tumors in the head and neck region.  It causes a hypoxic, hypocellular, and hypovascular environment that leads to injury to surrounding normal tissue, both acute and chronic, ranging from xerostomia to osteoradionecrosis.  These side effects are debilitating and greatly influence quality of life in these patients.  Hyperbaric oxygen therapy is clinically used to prevent or treat these side effects by enhancing oxygen pressure and thereby regeneration.  Although this therapy is widely applied, its mechanism of action is still poorly understood, and controversy exists in the literature about its clinical use.  Spiegelberg et al (2010) conducted a review on HBOT in the management of radiation-induced injury in the head and neck.  A systematic search was performed in PubMed for experimental and clinical studies conducted regarding the use of HBOT in previously irradiated tissue, in the period from January 1990 to June 2009.  Experimental research is scarce, and clinical studies are especially lacking in terms of RCTs.  Although discussions on the subject are ongoing, most studies suggest a beneficial role for HBOT in previously irradiated tissue.  The authors concluded that further research, both experimental and clinical, is needed to unravel the working mechanism of HBOT and validate its clinical use.

Furthermore, in a  systematic review of salivary gland hypo-function and xerostomia induced by cancer therapies, Jensen et al (2010), on behalf of the Salivary Gland Hypo-function/Xerostomia Section; Oral Care Study Group; Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology), assessed the literature for management strategies and economic impact of salivary gland hypo-function and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations.  The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive.  For each article, 2 independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions.  A total of 72 interventional studies met the inclusion criteria.  In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage.  Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer.  The authors concluded that there is evidence that salivary gland hypo-function and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment.  Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer.  Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, HBOT, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypo-function and xerostomia.

Also, UpToDate reviews on "Treatment of Sjögren's syndrome" (Fox and Creamer, 2012) and "Hyperbaric oxygen therapy" (MeChem and Manaker, 2012) do not mention the use of HBOT for the tretment of xerostomia. 

An UpToDate review on "Hyperbaric oxygen therapy" (MeChem and Manaker, 2012) does not mention the use of HBOT for radiation-induced cholangitis.

The Cancer Care Ontario’s clinical practice guideline on “The management of head and neck cancer in Ontario” (Gilbert et al, 2009) did not mention the use of HBOT for radiation-induced sarcoma of the scalp.  UpToDate reviews on “Treatment protocols for soft tissue and bone sarcoma” (Brenner et al, 2012) and “Local treatment for primary soft tissue sarcoma of the extremities and chest wall” (Delaney et al, 2012) do not mention the use of HBOT.  Furthermore, the National Comprehensive Cancer Network’s clinical practice guideline on “Soft tissue sarcoma” (Version 3.2012) does not mention “hyperbaric oxygen therapy”.

In a Cochrane review, Bennett et al (2012a) evaluated the effects of adjunctive HBOT for traumatic brain injury (TBI).  These investigators searched CENTRAL, MEDLINE, EMBASE, CINAHL and DORCTHIM electronic databases.  They also searched the reference lists of eligible articles, hand-searched relevant journals and contacted researchers.  All searches were updated to March 2012.  Randomized studies comparing the effect of therapeutic regimens that included HBOT with those that did not, for people with TBI were selected for analysis.  Three authors independently evaluated trial quality and extracted data.  A total of 7 studies are included in this review, involving 571 people (285 receiving HBOT and 286 in the control group).  The results of 2 studies indicated the use of HBOT resulted in a statistically significant decrease in the proportion of people with an unfavorable outcome 1 month after treatment using the Glasgow Outcome Scale (GOS) (relative risk (RR) for unfavorable outcome with HBOT 0.74, 95 % CI: 0.61 to 0.88, p = 0.001).  This 5-point scale rates the outcome from 1 (dead) to 5 (good recovery); an 'unfavorable' outcome was considered as a score of 1, 2, or 3.  Pooled data from final follow-up showed a significant reduction in the risk of dying when HBOT was used (RR 0.69, 95 % CI: 0.54 to 0.88, p = 0.003) and suggested that one would have to treat 7 patients to avoid 1 extra death (number needed to treat (NNT) 7, 95 % CI: 4 to 22).  Two trials suggested favorably lower intra-cranial pressure in people receiving HBOT and in whom myringotomies had been performed.  The results from 1 study suggested a mean difference (MD) with myringotomy of -8.2 mmHg (95 % CI: -14.7 to -1.7 mmHg, p = 0.01).  The Glasgow Coma Scale (GCS) has a total of 15 points, and 2 small trials reported a significant improvement in GCS for patients treated with HBOT (MD 2.68 points, 95 % CI: 1.84 to 3.52, p < 0.0001), although these 2 trials showed considerable heterogeneity (I(2) = 83 %).  Two studies reported an incidence of 13 % for significant pulmonary impairment in the HBOT group versus 0 % in the non-HBOT group (p = 0.007).  In general, the studies were small and carried a significant risk of bias.  None described adequate randomization procedures or allocation concealment, and none of the patients or treating staff was blinded to treatment.  The authors concluded that in people with TBI, while the addition of HBOT may reduce the risk of death and improve the final GCS, there is little evidence that the survivors have a good outcome.  The improvement of 2.68 points in GCS is difficult to interpret.  This scale runs from 3 (deeply comatose and unresponsive) to 15 (fully conscious), and the clinical importance of an improvement of approximately 3 points will vary dramatically with the starting value (e.g., an improvement from 12 to 15 would represent an important clinical benefit, but an improvement from 3 to 6 would leave the patient with severe and highly dependent impairment).  The authors stated that the routine application of HBOT to these patients cannot be justified from this review.  Given the modest number of patients, methodological shortcomings of included trials and poor reporting, the results should be interpreted cautiously.  An appropriately powered trial of high methodological rigor is required to define which patients, if any, can be expected to benefit most from HBOT.

In a Cochrane review, Phillips and Jones (2013) evaluated the effectiveness of adjunctive HBOT for malignant otitis externa.  These investigators searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; ICTRP and additional sources for published and unpublished trials.  The date of the most recent search was April 4, 2013.  Randomized controlled trials, involving adults, undergoing hyperbaric oxygen therapy in malignant otitis externa were selected for analysis.  No identified articles described RCTs of HBOT in the treatment of malignant otitis externa.  The authors concluded that no clear evidence exists to demonstrate the effectiveness of HBOT when compared to treatment with antibiotics and/or surgery.  They found no data to compare rates of complication between the different treatment modalities; further research is required.

Margolis et al (2013) compared the effectiveness of HBOT with other conventional therapies administered in a wound care network for the treatment of a diabetic foot ulcer and prevention of lower-extremity amputation.  This was a longitudinal observational cohort study.  To address treatment selection bias, these investigators used propensity scores to determine the "propensity" that an individual was selected to receive HBOT.  They studied 6,259 individuals with diabetes, adequate lower limb arterial perfusion, and foot ulcer extending through the dermis, representing 767,060 person-days of wound care.  In the propensity score-adjusted models, individuals receiving HBOT were less likely to have healing of their foot ulcer (hazard ratio 0.68 [95 % CI: 0.63 to 0.73]) and more likely to have an amputation (2.37 [1.84 to 3.04]).  Additional analyses, including the use of an instrumental variable, were conducted to assess the robustness of these results to unmeasured confounding.  Hyperbaric oxygen therapy was not found to improve the likelihood that a wound might heal or to decrease the likelihood of amputation in any of these analyses.  The authors concluded that the use of HBOT neither improved the likelihood that a wound would heal nor prevented amputation in a cohort of patients defined by Centers for Medicare and Medicaid Services eligibility criteria.  They noted that the usefulness of HBOT in the treatment of diabetic foot ulcers needs to be re-evaluated.

Limb-specific HBOT entails sealing an individual's arm or leg into an air-tight plastic container that is sealed with pliable gaskets, and exposing the limb to pure oxygen greater than 1 atm of pressure.  Much of the research on this form of therapy has centered on chronic wounds arising in individuals with diabetic foot ulcers.  However, there is currently insufficient evidence from RCTs to determine the effectiveness of limb-specific HBOT.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
CPT codes covered if selection criteria are met:
99183
HCPCS codes covered if selection criteria are met:
C1300 Hyperbaric oxygen under pressure, full body chamber, per 30 minute interval
HCPCS codes not covered for indications listed in the CPB:
A4575 Topical hyperbaric oxygen chamber, disposable
E0446 Topical oxygen delivery system, not otherwise specified, includes all supplies and accessories
Other HCPCS codes related to the CPB:
J9000 Injection, doxorubicin HCl, 10 mg
J9060 Injection, cisplatin, powder or solution, 10 mg
Q2050 Injection, doxorubicin hydrochloride, liposomal, not otherwise specified, 10 mg
ICD-9 codes covered if selection criteria are met:
038.3 Septicemia due to anaerobes [progressive necrotizing soft tissue anaerobic infections]
040.0 Gas gangrene [Clostridial myositis and myonecrosis]
250.70 - 250.71 Diabetes with peripheral circulatory disorders [non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity unresponsive to at least 1 month of meticulous wound care, including aggressive debridement, maximal antibiotic therapy, tight glycemic control, and appropriate treatment of arterial insufficiency, including revascularization if necessary]
250.80 - 250.81 Diabetes with other specified manifestations [non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity unresponsive to at least 1 month of meticulous wound care, including aggressive debridement, maximal antibiotic therapy, tight glycemic control, and appropriate treatment of arterial insufficiency, including revascularization if necessary] [not covered for diabetic superficial wounds]
280.0 Iron deficiency anemia secondary to blood loss (chronic) [overwhelming and transfusion is impossible because there is no suitable blood available or religion does not permit]
285.1 Acute posthemorrhagic anemia [overwhelming and transfusion is impossible because there is no suitable blood available or religion does not permit]
348.5 Cerebral edema [acute]
388.10 - 388.12 Noise effects on inner ear [noise-induced hearing loss when HBOT is initiated within 3 months after onset]
388.2 Sudden hearing loss, unspecified [idiopathic when HBOT is initiated within 3 months after onset]
440.20 - 440.9 Atherosclerosis of native arteries and bypass graft of extremities [non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity unresponsive to at least 1 month of meticulous wound care, including aggressive debridement, maximal antibiotic therapy, tight glycemic control, and appropriate treatment of arterial insufficiency, including revascularization if necessary]
442.0 - 442.3 Other aneurysm of extremities
443.0 - 443.1 Other peripheral vascular disease [acute peripheral arterial insufficiency]
443.81 - 443.9 Other specified peripheral vascular diseases [acute peripheral arterial insufficiency]
444.21 - 444.22 Arterial embolism of the extremities [acute peripheral arterial insufficiency]
444.81 Arterial embolism and thrombosis of the iliac artery [acute peripheral arterial insufficiency]
454.0 Varicose veins of lower extremities with ulcer [non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity unresponsive to at least 1 month of meticulous wound care, including aggressive debridement, maximal antibiotic therapy, tight glycemic control, and appropriate treatment of arterial insufficiency, including revascularization if necessary]
454.2 Varicose veins of lower extremities with ulcer and inflammation [non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity unresponsive to at least 1 month of meticulous wound care, including aggressive debridement, maximal antibiotic therapy, tight glycemic control, and appropriate treatment of arterial insufficiency, including revascularization if necessary]
459.81 Venous (peripheral) insufficiency, unspecified [venous stasis ulcer - non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity unresponsive to at least 1 month of meticulous wound care, including aggressive debridement, maximal antibiotic therapy, tight glycemic control, and appropriate treatment of arterial insufficiency, including revascularization if necessary]
526.4 Inflammatory conditions of the jaws [radiation necrosis of jaw]
526.89 Other specified diseases of jaw [prophylactic pre- and post-treatment for members undergoing dental surgery of a radiated jaw]
595.82 Irradiation cystitis
673.00 - 673.04 Obstetrical air embolism
728.86 Necrotizing fasciitis
730.10 - 730.19 Chronic osteomyelitis [unresponsive to conventional medical and surgical management]
733.45 Aseptic necrosis of bone, jaw
733.49 Other aseptic necrosis of bone [osteoradionecrosis]
885.0 - 887.7 Traumatic amputation thumb, finger(s), arm and hand [when loss of function or life is threatened and HBOT is used in combination with standard therapy]
895.0 - 897.7 Traumatic amputation toe(s), foot, leg(s) [when loss of function or life is threatened and HBOT is used in combination with standard therapy]
902.53 Injury to the iliac artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
903.00 - 903.01 Injury to axillary blood vessels [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
903.4 Injury to palmar artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
903.8 Injury to other specified blood vessels of upper extremity [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
904.0 Injury to common femoral artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
904.1 Injury to superficial femoral artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
904.41 Injury to popliteal artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
904.51 Injury to anterior tibial artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
904.53 Injury to posterior tibial artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
904.7 Injury to other specified blood vessels of lower extremity [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
925.1 - 929.9 Crush injuries [when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]
951.5 Injury to acoustic nerve [acoustic trauma when HBOT is initiated within 3 months after onset]
958.0 Air embolism [acute]
958.90 - 959.99 Compartment syndrome
986 Toxic effect of carbon monoxide [acute]
987.7 Toxic effect of hydrocyanic acid gas [with co-existing carbon monoxide poisoning]
989.0 Toxic effect of hydrocyanic acid and cyanides [with co-existing carbon monoxide poisoning]
990 Effects of radiation, unspecified [radiation necrosis (osteoradionecrosis, myoradionecrosis, brain radionecrosis, and other soft tissue radiation necrosis) or proctitis] [not covered for radiation induced cholangitis, myelitis, enteritis, or optic nerve injury] [not covered for radiation-induced sarcoma]
993.3 Caisson disease [decompression illness]
996.52 Mechanical complications due to graft of other tissue, not elsewhere classified [compromised skin grafts and flaps]
996.55 Mechanical complications due to artificial skin graft and decellularized allodermis [compromised skin grafts and flaps]
996.69 Infection and inflammatory reaction due to other internal prosthetic device, implant, and graft [compromised skin grafts and flaps]
996.79 Other complications due to other internal prosthetic device, implant, and graft [compromised skin grafts and flaps]
998.59 Other postoperative infection [non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity unresponsive to at least 1 month of meticulous wound care, including aggressive debridement, maximal antibiotic therapy, tight glycemic control, and appropriate treatment of arterial insufficiency, including revascularization if necessary]
998.83 Non-healing surgical wound [non-healing infected deep ulcerations (reaching tendons or bone) of the lower extremity unresponsive to at least 1 month of meticulous wound care, including aggressive debridement, maximal antibiotic therapy, tight glycemic control, and appropriate treatment of arterial insufficiency, including revascularization if necessary]
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
003.21 Salmonella meningitis
008.45 Clostridium difficile [intra-abdominal abscess, pseudomembranous colitis (antibiotic-induced colitis)]
013.0 Tuberculous meningitis
030.0 Lepromatous (type L) [leprosy]
036.0 Meningococcal meningitis
037 Tetanus
038.0 - 038.2, 038.4 - 038.9 Septicemia [except anaerobic infection]
039.0 - 039.9 Actinomycotic infections
042 Human immunodeficiency virus [HIV] disease
088.81 Lyme disease
090.42 Congenital syphilitic meningitis
091.81 Acute syphilitic meningitis (secondary)
094.2 Syphilitic meningitis
098.82 Gonococcal meningitis
100.81 Leptospiral meningitis (aseptic)
110.0 - 118 Mycoses
140.0 - 208.92 Malignant neoplasm [cancer]
230.0 - 234.9 Carcinoma in situ [cancer]
275.49 Other disorders of calcium metabolism [calciphylaxis (calcific uremi arteriolopathy)]
282.62 Hb-SS disease with mention of crisis [sickle cell crisis]
290.0 - 290.9 Dementias [cognitive impairment]
294.8 Other persistent mental disorders due to conditions classified elsewhere [dementia NOS] [cognitive impairment]
299.00 - 299.01 Autistic disorder
310.1 Personality change due to conditions classified elsewhere [cognitive impairment]
310.8 Other specified nonpsychotic mental disorders following organic brain damage [cognitive impairment]
320.0 - 322.9 Meningitis- bacterial, due to other organisms, and of unspecified cause
324.0 Intracranial abscess
331.0 - 331.9 Other cerebral degenerations [cognitive impairment]
332.0 Paralysis agitans
332.1 Secondary Parkinsonism (parkinsonism due to drugs)
337.20 - 337.29 Reflex sympathetic dystrophy [complex regional pain syndrome]
339.00 - 339.02 Cluster headaches
340 Multiple sclerosis
341.20 - 341.9 Acute (transverse) myelitis [radiation induced]
343.0 - 343.9 Infantile cerebral palsy
345.00 - 345.91 Epilepsy and recurrent seizures
346.00 - 346.93 Migraine
348.1 Anoxic brain damage
351.0 Bell's palsy
351.8 Other facial nerve disorders [facial neuritis]
357.0 Acute infective polyneuritis
360.00 - 379.99 Disorders of the eye and adnexa [ophthalmologic diseases]
380.10 Infective otitis externa, unspecified
388.30 - 388.32 Tinnitus
410.00 - 412 Myocardial infarction
433.00 - 434.91 Occlusion and stenosis of precerebral and cerebral arteries [acute or chronic cerebrovascular insufficiency/accident including thrombotic or embolic stroke]
435.0 - 435.9 Transient cerebral ischemia [acute or chronic cerebrovascular insufficiency]
436 Acute, but ill-defined, cerebrovascular disease [acute or chronic cerebrovascular insufficiency/accident including thrombotic or embolic stroke]
437.0 - 437.9 Other and ill-defined, cerebrovascular disease [acute or chronic cerebrovascular insufficiency/accident including thrombotic or embolic stroke]
438.0 Late effects of cerebrovascular disease, cognitive deficits
444.89 Arterial embolism and thrombosis of other specified artery [hepatic]
447.6 Arteritis, unspecified [Lupus vasculitis]
457.0 - 457.1 Lymphedema
491.20 - 491.22 Obstructive chronic bronchitis [bronchitis with emphysema]
492.0 - 492.8 Emphysema
506.0 - 506.9 Respiratory conditions due to chemical fumes and vapors [Acute thermal and chemical pulmonary damage, i.e., smoke inhalation (e.g., carbon tetrachloride, hydrogen sulfide) with pulmonary insufficiency]
508.0 - 508.9 Respiratory conditions due to other and unspecified external agents [Acute thermal and chemical pulmonary damage, i.e., smoke inhalation (e.g., carbon tetrachloride, hydrogen sulfide) with pulmonary insufficiency]
527.7 - 527.9 Xerostomia and salivary gland dysfunction
555.0 - 555.9 Crohn's disease
558.1 Gastroenteritis and colitis due to radiation
567.22 Peritoneal abscess [intra-abdominal]
570 Acute and subacute necrosis of liver [hepatic]
576.1 Cholangitis [radioation-induced hemorrhagic]
595.1 Chronic interstitial cystitis
595.82 Irradiation cystitis
599.70 - 599.72 Hematuria
619.1 Digestive-genital tract fistula, female [rectovaginal fistula]
674.10 - 674.14 Disruption of cesarean wound
686.0 - 686.9 Other local infections of skin and subcutaneous tissues [except Meleney's ulcer] [infection other than clostridial]
692.70 - 692.79 Contact dermatitis and other eczema due to solar radiation [actinic skin damage]
706.1 Other acne [cystic]
709.09 Other disorders of skin and subcutaneous tissues [melasma]
710.0 Systemic lupus erythematosus [ischemia due to lupus vasculitis]
711.00 - 716.99 Arthropathies
729.1 Myalgia and myositis, unspecified [myofascial pain syndrome]
732.1 Juvenile osteochondrosis of head of femur [Legg-Calve-Perthes disease]
733.00 - 733.09 Osteoporosis
733.10 - 733.19 Pathologic fracture [fracture healing]
733.42 Aseptic necrosis of head and neck of femur
733.45 Aseptic necrosis of bone, jaw
733.81 - 733.82 Malunion and nonunion of fracture
743.20 - 743.22 Buphthalmos [ophthalmologic diseases]
757.0 Hereditary edema of legs
770.2 Interstitial emphysema and related conditions
780.31 - 780.39 Convulsions
780.97 Altered mental status [cognitive impairment]
781.8 Neurologic neglect syndrome [cognitive impairment]
785.51 Cardiogenic shock
797 Senility without mention of psychosis [cognitive impairment]
800.00 - 829.1 Fractures [fracture healing (e.g., nonunion fractures)]
850.0 - 854.19 Intracranial injury, excluding those with skull fracture [cognitive impairment] [not covered for traumatic brain injury]
907.0 Late effect of intracranial injury without mention of skull fracture [cognitive impairment]
941.00 - 946.5 Burns of face, head, neck, trunk, upper limb, wrist and hand, lower limb, and multiple specified sites [skin, thermal]
950.0 - 950.9 Injury to optic nerve and pathways [ophthalmologic diseases (including diabetic retinopathy, retinal detachment, central retinal artery occlusion, radiation injury to the optic nerve, glaucoma, keratoendotheliosis)]
952.00 - 952.9 Spinal cord injury without evidence of spinal bone injury
959.01 Head injury, unspecified [cognitive impairment] [closed head injury]
987.0 - 987.6 Toxic effects of other gases, fumes, or vapors [other than carbon monoxide] [Acute thermal and chemical pulmonary damage, i.e., smoke inhalation (e.g., carbon tetrachloride, hydrogen sulfide) with pulmonary insufficiency]
989.5 Toxic effect of venom [necrotizing arachnidism ]
991.0 - 991.3 Frostbite [face, hand, foot, and other and unspecified sites]
996.40 - 996.49 Mechanical complication of internal orthopedic device, implant, and graft [bone grafts]
996.67 Infection and inflammatory reaction due to other internal orthopedic device, implant or graft [bone grafts]
998.30 - 998.33 Disruption of wound [dehiscence of operation wound]
V42.0 - V43.89 Organ or tissue replacement by transplant or other means [organ transplant or storage]
V49.83 Awaiting organ transplant status [organ transplant or storage]
V54.10 - V54.29 Aftercare for healing fracture [fracture healing (e.g., nonunion fractures)]
V58.44 Aftercare following organ transplant [post organ transplant revascularization]
Other ICD-9 codes related to the CPB:
569.89 Other specified disorders of intestine [pneumatosis cystoides intestinalis]
707.00 - 707.9 Chronic ulcer of skin [see criteria for coverage in diabetic adults only]
E863.4 Accidental poisoning by other and unspecified insecticides [cyanide]
E863.8 Accidental poisoning by fumigants [cyanide]
E868.0 - E868.9 Accidental poisoning by other utility gas and other carbon monoxide
ICD-9 codes contraindicated for this CPB:
045.00 - 079.99 Viral infections and diseases
282.0 Hereditary spherocytosis [congenital]
460 - 519.9 Disease of the respiratory system [lung disease including 512.0 - 512.8 untreated pneumothorax]
765.00 - 765.28 Disorders relating to short gestation and low birthweight [premature infants (birth prior to 37 weeks)]
780.60 Fever [high]


The above policy is based on the following references:
  1. U.S. Department of Health and Human Services, Health Care Financing Administration (HCFA). Hyperbaric Oxygen Therapy. Coverage Issues Manual §35-10. Baltimore, MD: HCFA; August 11, 1997.
  2. Leach RM, Rees PJ, Wilmshurst P. Hyperbaric oxygen therapy. Br Med J. 1998;317:1140-1143.
  3. Agency for Health Care Policy and Research (AHCPR). Treatment of pressure ulcers. Clinical Guideline Number 15. AHCPR Publication No. 95-0652. Bethesda, MD: AHCPR; December 1994.
  4. The Undersea and Hyperbaric Medical Society (UHMS), Hyperbaric Oxygen Therapy Committee. Guidelines: Indications for Hyperbaric Oxygen. Kensington, MD: UHMS; 2000. Available at: http://www.uhms.org/Indications/indications.htm. Accessed January 22, 2001.
  5. Tibbles PM, Edelsberg JS. Hyperbaric oxygen therapy. N Engl J Med. 1996;334(25):1642-1648.
  6. Zamboni WA, Wong HP, Stephenson T, et al. Evaluation of hyperbaric oxygen for diabetic wounds: A prospective study. Undersea Hyperbar Med. 1997;24(3):175-179.
  7. Faglia E, Favales F, Aldeghi A, et al. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer: A randomized study. Diabetes Care.1996;19(12):1338-1343.
  8. Paw HG, Reed PN. Pneumatosis cystoides intestinalis confined to the small intestine treated with hyperbaric oxygen. Undersea Hyperb Med. 1996;23(2):115-117.
  9. Lukich VL, Poliakova LV, Sotnikova TI, et al. Hyperbaric oxygenation in the comprehensive therapy of patients with rheumatoid arthritis (clinico-immunologic study). Fiziol Zh. 1991;37(5):55-60.
  10. Davis TR, Griffiths ID, Stevens J. Hyperbaric oxygen treatment for rheumatoid arthritis; failure to show worthwhile benefit. Br J Rheumatol. 1988;27(1):72.
  11. Saikovskii RS, Alekberova ZS, Dmitriev AA, et al. Place of hemocarboperfusion and hyperbaric oxygenation in the treatment of patients with rheumatoid arthritis with systemic symptoms. Ter Arkh. 1986;58(7):105-109.
  12. Shank ES, Muth CM. Decompression illness, iatrogenic gas embolism, and carbon monoxide poisoning: The role of hyperbaric oxygen therapy. Int Anesthesiol Clin. 2000;38(1):111-138.
  13. Caplan ES. Hyperbaric oxygen. Pediatr Infect Dis J. 2000;19(2):151-152.
  14. Mitton C, Hailey D. Health technology assessment and policy decisions on hyperbaric oxygen treatment. Int J Technol Assess Health Care. 1999;15(4):661-670.
  15. Sheridan RL, Shank ES. Hyperbaric oxygen treatment: A brief overview of a controversial topic. J Trauma. 1999;47(2):426-435.
  16. Stone JA, Cianci P. The adjunctive role of hyperbaric oxygen therapy in the treatment of lower extremity wounds in patients with diabetes. Diabetes Spectrum. 1997;10(2):118-123.
  17. Mathews R, Rajan N, Josefson L, et al. Hyperbaric oxygen therapy for radiation induced hemorrhagic cystitis. J Urol. 1999;161(2):435-437.
  18. Weiss JP, Neville EC. Hyperbaric oxygen: Primary treatment of radiation-induced hemorrhagic cystitis. J Urol. 1989;142(1):43-45.
  19. Del Pizzo JJ, Chew BH, Jacobs SC, et al. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen: Long-term followup. J Urol. 1998;160(3 Pt 1):731-733.
  20. Bevers RF, Bakker DJ, Kurth KH. Hyperbaric oxygen treatment for haemorrhagic radiation cystitis. Lancet. 1995;346(8978):803-805.
  21. Weiss JP, Boland FP, Mori H, et al. Treatment of radiation-induced cystitis with hyperbaric oxygen. J Urol. 1985;134(2):352-354.
  22. Rijkmans BG, Bakker DJ, Dabhoiwala NF, et al. Successful treatment of radiation cystitis with hyperbaric oxygen. Eur Urol. 1989;16(5):354-356.
  23. Norkool DM, Hampson NB, Gibbons RP, et al. Hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis. J Urol. 1993;150(2 Pt 1):332-334.
  24. Weiss JP, Mattei DM, Neville EC, et al. Primary treatment of radiation-induced hemorrhagic cystitis with hyperbaric oxygen: 10-year experience. J Urol. 1994;151(6):1514-1517.
  25. U.S. Department of Health and Human Services (DHHS), Public Health Service. Hyperbaric oxygen therapy for treatment of soft tissue radionecrosis and osteoradionecrosis. Health Technology Assessment Reports. DHHS Publication No. (PHS) 84.3371. Washington, DC: DHHS; 1982.
  26. Saunders P. Hyperbaric oxygen therapy in the management of carbon monoxide poisoning, osteoradionecrosis, burns, skin grafts and crush injury. DPHE Report No. 23. West Midlands Development and Evaluation Service Report. Birmingham, UK: West Midlands Health Technology Assessment Collaboration, University of Birmingham (Collaborative effort with Wessex Institute) (WMHTAC); April 2000.
  27. Saunders PJ. Hyperbaric oxygen therapy in the management of carbon monoxide poisoning, osteoradionecrosis, burns, skin grafts, and crush injury. Int J Technol Assess Health Care. 2003;19(3):521-525.
  28. Guo S, Counte MA, Romeis JC. Hyperbaric oxygen technology: An overview of its applications, efficacy, and cost-effectiveness. Int J Technol Assess Health Care. 2003;19(2):339-346.
  29. Mitton C, Hailey D. Hyperbaric oxygen treatment in Alberta. HTA 8. Edmonton, AB: Alberta Heritage Foundation for Medical Research; 1998:39.
  30. Medicare Services Advisory Committee (MSAC). Hyperbaric oxygen therapy. Assessment Report. MSAC applications 1018 - 1020. Canberra, ACT: MSAC; 2000.
  31. Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS). Hyperbaric oxygen therapy in Quebec. AETMIS 2000-3 RE. Montreal, QC: AETMIS; 2000.
  32. Wang C, Lau J. Hyperbaric oxygen therapy in treatment of hypoxic wounds. Technology Assessment. Prepared by the New England Medical Center Evidence-Based Practice Center for the Agency for Healthcare Research and Quality (AHRQ) under Contract No. 270-97-0019. Rockville, MD: AHRQ; November 2, 2001.
  33. Wang C, Schwaitzberg S, Berliner E, et al. Hyperbaric oxygen for treating wounds: A systematic review of the literature. Arch Surg. 2003;138(3):272-280.
  34. Lamm K, Lamm H, Arnold W. Effect of hyperbaric oxygen therapy in comparison to conventional or placebo therapy or no treatment in idiopathic sudden hearing loss, acoustic trauma, noise-induced hearing loss and tinnitus. A literature survey. Adv Otorhinolaryngol. 1998;54:86-99.
  35. Ennis RD. Hyperbaric oxygen for the treatment of radiation cystitis and proctitis. Curr Urol Rep. 2002;3(3):229-231.
  36. Denton AS, Andreyev HJ, Forbes A, Maher EJ. Systematic review for non-surgical interventions for the management of late radiation proctitis. Br J Cancer. 2002;87(2):134-143.
  37. Wang J, Li F, Calhoun JH, Mader JT. The role and effectiveness of adjunctive hyperbaric oxygen therapy in the management of musculoskeletal disorders. J Postgrad Med. 2002;48(3):226-231.
  38. Edsberg LE, Brogan MS, Jaynes CD, Fries K. Topical hyperbaric oxygen and electrical stimulation: Exploring potential synergy. Ostomy Wound Manage. 2002;48(11):42-50.
  39. Gordillo GM, Sen CK. Revisiting the essential role of oxygen in wound healing. Am J Surg. 2003;186(3):259-263.
  40. Alternative Therapy Evaluation Committee for the Insurance Corporation of British Columbia. A review of the scientific evidence on the treatment of traumatic brain injuries and strokes with hyperbaric oxygen. Brain Inj. 2003;17(3):225-236.
  41. Hailey D. Hyperbaric oxygen therapy - recent findings on evidence for its effectiveness. Information Paper. IP 13. Edmonton, AB: Alberta Heritage Foundation for Medical Research (AHFMR); March 2003. Available at: http://www.ahfmr.ab.ca/publications.html. Accessed February 9, 2004.
  42. Denton AS, Clarke NW, Maher EJ. Non-surgical interventions for late radiation cystitis in patients who have received radical radiotherapy to the pelvis. Cochrane Database Syst Rev. 2002;(3):CD001773. 
  43. Denton A, Forbes A, Andreyev J, Maher EJ. Non surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis. Cochrane Database Syst Rev. 2002;(1):CD003455.
  44. Denton AS, Maher EJ. Interventions for the physical aspects of sexual dysfunction in women following pelvic radiotherapy. Cochrane Database Syst Rev. 2003;(1):CD003750. 
  45. McDonagh M, Carson S, Ash J. Hyperbaric oxygen therapy for brain injury, cerebral palsy, and stroke. Evidence Report/Technology Assessment No. 85. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); 2003.
  46. McDonagh M, Helfand M, Carson S, Russman BS. Hyperbaric oxygen therapy for traumatic brain injury: A systematic review of the evidence. Arch Phys Med Rehabil. 2004;85(7):1198-1204.
  47. Bennett M, Heard R. Hyperbaric oxygen therapy for multiple sclerosis. Cochrane Database Syst Rev. 2004(1):CD003057.
  48. Juurlink DN, Buckley NA, Stanbrook MB, et al. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2005;(1):CD002041.
  49. Hunt D. Diabetes: Foot ulcers and amputations (updated). In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; November 2007.
  50. Savage J, Cook S, Waddell A. Tinnitus. In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; December 2006.
  51. Esposito M, Grusovin MG, Patel S, et al. Interventions for replacing missing teeth: Hyperbaric oxygen therapy for irradiated patients who require dental implants. Cochrane Database Syst Rev. 2008;(1):CD003603. 
  52. Coulthard P, Esposito M, Worthington HV, Jokstad A. Therapeutic use of hyperbaric oxygen for irradiated dental implant patients: A systematic review. J Dent Educ. 2003;67(1):64-68.
  53. Greaves I, Porter K, Smith JE, et al. Consensus statement on the early management of crush injury and prevention of crush syndrome. J R Army Med Corps. 2003;149(4):255-259.
  54. Rosenbaum P. Controversial treatment of spasticity: Exploring alternative therapies for motor function in children with cerebral palsy. J Child Neurol. 2003;18 Suppl 1:S89-S94.
  55. Patterson J. Hyperbaric oxygen therapy for central osteoradionecrosis. STEER: Succint and Timely Evaluated Evidence Reviews. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2002;2(16).
  56. Patterson J. Hyperbaric oxygen therapy for central retinal artery occlusion. STEER: Succint and Timely Evaluated Evidence Reviews. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2002;2(13).
  57. Dent THS. Hyperbaric oxygen therapy for carbon monoxide poisoning. STEER: Succint and Timely Evaluated Evidence Reviews. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2002;2(13).
  58. Ball CM. Hyperbaric oxygen therapy for multiple sclerosis. STEER: Succint and Timely Evaluated Evidence Reviews. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2002;2(6).
  59. Bisset F. Hyperbaric oxygen therapy in people with necrotising fasciitis or Fournier's gangrene. STEER: Succint and Timely Evaluated Evidence Reviews. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2002;2(14).
  60. Kranke P, Bennett M, Roeckl-Wiedmann I, Debus S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. 2004;(1):CD004123.
  61. Villanueva E, Bennett MH, Wasiak J, Lehm JP. Hyperbaric oxygen therapy for thermal burns. Cochrane Database Syst Rev. 2004;(2):CD004727.
  62. Ubbink DT, Westerbos SJ, Evans D, Land L. Topical negative pressure for treating chronic wounds. Cochrane Database Syst Rev. 2008;(3):CD001898.
  63. Lawson R. Hyperbaric oxygen for osteomyelitis. STEER: Succint and Timely Evaluated Evidence Reviews. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2003;3(18).
  64. van Ophoven A, Rossbach G, Oberpenning F, Hertle L. Hyperbaric oxygen for the treatment of interstitial cystitis: Long-term results of a prospective pilot study. Eur Urol. 2004;46(1):108-113.
  65. Bennett MH, Kertesz T, Yeung P. Hyperbaric oxygen for idiopathic sudden sensorineural hearing loss and tinnitus. Cochrane Database Syst Rev. 2007;(1): CD004739.
  66. Phillips JS, Jones SEM. Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa. Cochrane Database Syst Rev. 2005;(2): CD004617.
  67. Bennett M, Jepson N, Lehm P. Hyperbaric oxygen therapy for acute coronary syndrome. Cochrane Database Syst Rev. 2005;(2):CD004818.
  68. Bennett MH, Wasiak J, Schnabel A, et al. Hyperbaric oxygen therapy for acute ischaemic stroke. Cochrane Database Syst Rev. 2005;(3): CD004954.
  69. Bennett M, Best TM, Babul S, Taunton J. Hyperbaric oxygen therapy for delayed onset muscle soreness and closed soft tissue injury. Cochrane Database Syst Rev. 2005;(4): CD004713.
  70. Bennett MH, Feldmeier J, Hampson N, et al. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2005;(3):CD005005.
  71. Bennett MH, Stanford R, Turner R. Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union. Cochrane Database Syst Rev. 2005;(1):CD004712.
  72. Bennett MH, Trytko B, Jonker B. Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury. Cochrane Database Syst Rev. 2004;(4):CD004609.
  73. Bennett M, Feldmeier J, Smee R, Milross C. Hyperbaric oxygenation for tumour sensitisation to radiotherapy. Cochrane Database Syst Rev. 2005;(4):CD005007.pub2.
  74. Lueck C, McIlwaine G. Interventions for idiopathic intracranial hypertension. Cochrane Database Syst Rev. 2005;(3):CD003434.
  75. Smolin C, Olson K. Carbon monoxide poisoning (acute). In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; March 2007.
  76. Bennett MH, Feldmeier J, Hampson N, et al. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2005;(3):CD005005.
  77. Schwarz S, Leweling H, Meinck HM. Alternative and complementary therapies in multiple sclerosis. Fortschr Neurol Psychiatr. 2005;73(8):451-462.
  78. Taylor RS, Simpson IN. Review of treatment options for Lyme borreliosis. J Chemother. 2005;17 Suppl 2:3-16.
  79. Carson S, McDonagh M, Russman B, Helfand M. Hyperbaric oxygen therapy for stroke: A systematic review of the evidence. Clin Rehabil. 2005;19(8):819-833.
  80. Feldmeier JJ, Hopf HW, Warriner RA 3rd, UHMS position statement: Topical oxygen for chronic wounds. Undersea Hyperb Med. 2005;32(3):157-168.
  81. Liptak GS. Complementary and alternative therapies for cerebral palsy. Ment Retard Dev Disabil Res Rev. 2005;11(2):156-163.
  82. Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat (MAS). Hyperbaric oxygen therapy for non-healing ulcers in diabetes mellitus. Health Technology Literature Review. Toronto, ON: MAS; 2005.
  83. Pichon Riviere A, Augustovski F, Alcaraz A, et al. Hyperbaric oxygen therapy: Diagnostic usefulness and indications [summary]. Report ITB No. 94. Buenos Aires, Argentina: Institute for Clinical Effectiveness and Health Policy (IECS); 2006.
  84. NHS Quality Improvement Scotland (NHS QIS). Evidence note 15: Hyperbaric Oxygen Therapy (HBOT) for the prevention and treatment of osteoradionecrosis following radiotherapy of head and neck cancer. Glasgow, Scotland: NHS QIS; 2006.
  85. Hailey D, Jacobs P, Perry DC, et al. Overview of adjunctive hyperbaric oxygen therapy for diabetic foot ulcer. Technology Overview No. 25. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health (CADTH); 2007.
  86. Hailey D, Jacobs P, Perry DC, et al. Adjunctive hyperbaric oxygen therapy for diabetic foot ulcer: An economic analysis. Technology Report No. 75. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health (CADTH); 2007.
  87. Raman G, Kupelnick B, Chew P, Lau J. A horizon scan: Uses of hyperbaric oxygen therapy. Technology Assessment Report. Prepared by the Tufts-New England Medical Center Evidence Based Practice Center for the Agency for Healthcare Research and Quality (AHRQ). Rockville, MD: AHRQ; October 5, 2006. Available at: http://www.cms.hhs.gov/determinationprocess/downloads/id42TA.pdf. Accessed February 13, 2007.
  88. McGuire W. Perinatal asphyxia. In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; March 2007.
  89. Helms AK, Whelan HT, Torbey MT. Hyperbaric oxygen therapy of cerebral ischemia. Cerebrovasc Dis. 2005;20(6):417-426.
  90. Wahl MJ. Osteoradionecrosis prevention myths. Int J Radiat Oncol Biol Phys. 2006;64(3):661-669.
  91. Rossignol DA, Rossignol LW. Hyperbaric oxygen therapy may improve symptoms in autistic children. Med Hypotheses. 2006;67(2):216-228.
  92. Rossignol DA. Hyperbaric oxygen therapy might improve certain pathophysiological findings in autism. Med Hypotheses. 2007;68(6):1208-1227.
  93. McDonagh MS, Morgan D, Carson S, Russman BS. Systematic review of hyperbaric oxygen therapy for cerebral palsy: The state of the evidence. Dev Med Child Neurol. 2007;49(12):942-947.
  94. Matharu M, Silver N. Cluster headache. In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; September 2006.
  95. Moqadem K, Pineau G. The role of hyperbaric oxygen therapy in the management of autism [summary]. Montreal, QC: Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS); 2007.
  96. Pineau G, Moqadem K, Obadia A, Perron S. Place of hyperbaric oxygen therapy in the management of cerebral palsy [summary]. AETMIS 07-01. Montreal, QC: Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS); 2007.  
  97. Bennett MH, Kertesz T, Yeung P. Hyperbaric oxygen for idiopathic sudden sensorineural hearing loss and tinnitus. Cochrane Database Syst Rev. 2007;(1):CD004739.
  98. Bennett MH, Lehm JP, Mitchell SJ, Wasiak J. Recompression and adjunctive therapy for decompression illness. Cochrane Database Syst Rev. 2007;(2):CD005277.
  99. Rouleau G, Moqadem K, Pineau G. Indications for hyperbaric oxygen therapy: Update [summary]. ETMIS 2008. Montreal, QC: Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS); October 2008;4(5).
  100. Bennett MH, French C, Schnabel A, et al. Normobaric and hyperbaric oxygen therapy for migraine and cluster headache. Cochrane Database Syst Rev. 2008;(3):CD005219.
  101. Butler FK Jr, Hagan C, Murphy-Lavoie H. Hyperbaric oxygen therapy and the eye. Undersea Hyperb Med. 2008;35(5):333-387.
  102. Ritchie K, Baxter S, Craig J, et al. The clinical and cost-effectiveness of hyperbaric oxygen therapy. HTA Programme: Systemic Review 2. Glasgow, Scotland: NHS Quality Improvement Scotland (NHS QIS); July 2008.
  103. Folio LR, Arkin K, Butler WP. Frostbite in a mountain climber treated with hyperbaric oxygen: Case report. Mil Med. 2007;172(5):560-563.
  104. Yildiz S, Aktas S, Uzun G. Hyperbaric oxygen therapy in autism: Is there evidence? Undersea Hyperb Med. 2008;35(6):453-455.
  105. Rossignol DA, Rossignol LW, Smith S, et al. Hyperbaric treatment for children with autism: A multicenter, randomized, double-blind, controlled trial. BMC Pediatr. 2009;9:21.
  106. Levy SE, Mandell DS, Schultz RT. Autism. Lancet. 2009;374(9701):1627-1638.
  107. Kiralp MZ, Uzun G, Dinçer O, et al. A novel treatment modality for myofascial pain syndrome: Hyperbaric oxygen therapy. J Natl Med Assoc. 2009;101(1):77-80.
  108. Urade M. New development in bisphosphonate treatment. Bisphosphonate therapy and osteonecrosis of the jaws. Clin Calcium. 2009;19(1):100-108.
  109. Freiberger JJ. Utility of hyperbaric oxygen in treatment of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2009;67(5 Suppl):96-106.
  110. Vescovi P, Nammour S. Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) therapy. A critical review. Minerva Stomatol. 2010;59(4):181-203, 204-213.
  111. Mohamad Al-Ali B, Trummer H, Shamloul R, et al. Is treatment of hemorrhagic radiation cystitis with hyperbaric oxygen effective? Urol Int. 2010;84(4):467-470.
  112. Eskes A, Ubbink DT, Lubbers M, et al. Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. Cochrane Database Syst Rev. 2010;(10):CD008059.
  113. Boudreau R, Moulton K, McGill S. Hyperbaric oxygen therapy for difficult wound healing: Systematic review of clinical effectiveness and cost-effectiveness. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2010. available at: http://64.26.163.205/media/pdf/M0016_HBOT_L3_e.pdf. Accessed February 7, 2011.
  114. Rogers NM, Coates PT. Calcific uraemic arteriolopathy: An update. Curr Opin Nephrol Hypertens. 2008;17(6):629-634.
  115. Matchett GA, Martin RD, Zhang JH. Hyperbaric oxygen therapy and cerebral ischemia: Neuroprotective mechanisms. Neurol Res. 2009;31(2):114-121.
  116. Gothard L, Haviland J, Bryson P, et al. Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer. Radiother Oncol. 2010;97(1):101-107.
  117. Spiegelberg L, Djasim UM, van Neck HW, et al. Hyperbaric oxygen therapy in the management of radiation-induced injury in the head and neck region: A review of the literature. J Oral Maxillofac Surg. 2010;68(8):1732-1739.
  118. Jensen SB, Pedersen AM, Vissink A, et al; Salivary Gland Hypofunction/Xerostomia Section; Oral Care Study Group; Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO). A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: Management strategies and economic impact. Support Care Cancer. 2010;18(8):1061-1079.
  119. Michalski D, Härtig W, Schneider D, Hobohm C. Use of normobaric and hyperbaric oxygen in acute focal cerebral ischemia -- a preclinical and clinical review. Acta Neurol Scand. 2011;123(2):85-97.
  120. Gallego Vilar D, García Fadrique G, Povo Martín IJ, et al. Hyperbaric oxygen therapy for the management of hemorrhagic radio-induced cystitis. Arch Esp Urol. 2011;64(9):869-874.
  121. Parra C, Gómez R, Marchetti P, et al. Management of hemorrhagic radiation cystitis with hyperbaric oxygen therapy. Actas Urol Esp. 2011;35(3):175-179.
  122. Craighead P, Shea-Budgell MA, Nation J, et al. Hyperbaric oxygen therapy for late radiation tissue injury in gynecologic malignancies. Curr Oncol. 2011;18(5):220-227.
  123. Moy B. Cystitis in patients with cancer. Last reviewed September 2011. UpTodate, Inc. Waltham, MA.
  124. Bennett MH, Lehm JP, Jepson N. Hyperbaric oxygen therapy for acute coronary syndrome. Cochrane Database Syst Rev. 2011;(8):CD004818.
  125. Fox R, Creamer P. Treatment of Sjögren's syndrome. Last reviewed January 2012. UpToDate Inc. Waltham, MA.
  126. Mechem CC, Manaker S. Hyperbaric oxygen therapy. Last reviewed January 2012. UpToDate Inc. Waltham, MA.
  127. Shao Y, Lu GL, Shen ZJ. Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis. BJU Int. 2012;109(5):691-694.
  128. Savva-Bordalo J, Pinho Vaz C, Sousa M, et al. Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation. Bone Marrow Transplant. 2012;47(8):1095-1098.
  129. Gilbert R, Devries-Aboud M, Winquist E, et al, Head and Neck Disease Site Group. The management of head and neck cancer in Ontario: Organizational and clinical practice guideline recommendations. Toronto (ON): Cancer Care Ontario (CCO); December 15, 2009. Available at: http://www.guideline.gov/content.aspx?id=24046&search=hyperbaric+oxygen+AND+radiation+induced+sarcoma. Accessed January 29, 2013.
  130. Brenner T, duggal S, Natale J, Wirth SM. Treatment protocols for soft tissue and bone sarcoma. Last reviewed December 2012. UpToDate Inc., Waltham, MA.
  131. Delaney TF, Harmon DC, Gebhardt MC. Local treatment for primary soft tissue sarcoma of the extremities and chest wall. Last reviewed December 2012. UpToDate Inc., Waltham, MA.
  132. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Soft tissue sarcoma. Version 3.2012. NCCN: Fort Washington, PA.
  133. Stachler RJ, Chandrasekhar SS, Archer SM, et al; American Academy of Otolaryngology-Head and Neck Surgery. Clinical practice guideline: Sudden hearing loss. Otolaryngol Head Neck Surg 2012;146(3 Suppl):S1-S35. Available at: http://www.guideline.gov/content.aspx?id=36054&search=hyperbaric+oxygen+therapy+. Accessed January 29, 2013.
  134. Holland S, Silberstein SD, Freitag F, et al. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012a;78(17):1346-1353. Available at: http://www.guideline.gov/content.aspx?id=36897&search=hyperbaric+oxygen+therapy+. Accessed January 29, 2013.
  135. Holland NJ, Bernstein JM, Hamilton JW. Hyperbaric oxygen therapy for Bell's palsy. Cochrane Database Syst Rev. 2012b;2:CD007288.
  136. Ghanizadeh A. Hyperbaric oxygen therapy for treatment of children with autism: A systematic review of randomized trials. Med Gas Res. 2012;2:13.
  137. Xiao Y, Wang J, Jiang S, Luo H. Hyperbaric oxygen therapy for vascular dementia. Cochrane Database Syst Rev. 2012;7:CD009425.
  138. Bennett MH, Trytko B, Jonker B. Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury. Cochrane Database Syst Rev. 2012a;12:CD004609.
  139. Bennett MH, Stanford RE, Turner R. Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union. Cochrane Database Syst Rev. 2012b;11:CD004712.
  140. Bennett MH, Kertesz T, Perleth M, et al. Hyperbaric oxygen for idiopathic sudden sensorineural hearing loss and tinnitus. Cochrane Database Syst Rev. 2012c;10:CD004739.
  141. Phillips JS, Jones SE. Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa. Cochrane Database Syst Rev. 2013;5:CD004617.
  142. Margolis DJ, Gupta J, Hoffstad O, et al. Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: A cohort study. Diabetes Care. 2013;36(7):1961-1966.


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