Aetna considers systemic hyperbaric oxygen therapy (HBOT) medically necessary for any of the following conditions:
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:
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:
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.
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.
The Washington State Health Care Authority’s Technology Assessment on “Hyperbaric Oxygen Therapy (HBOT) for Tissue Damage, Including Wound Care and Treatment of Central Nervous System (CNS) Conditions” (2013) stated that “The available data from 13 studies provides insufficient evidence to determine the optimal treatment frequency duration or dose for HBOT. No studies reported on the optimal duration of treatment sessions; there were mixed results from subgroup analysis involving 8 studies looking at frequency; and significant heterogeneity means that we have low confidence in the available results from 5 studies that looked at dose” However, it noted that “No difference between a longer treatment course (greater than 30 sessions) and a shorter course (less than 30 sessions) among patients with diabetic foot ulcers or sensorineural hearing loss; conflicting results for patients with multiple sclerosis.
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 absolute(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.
In a prospective and controlled study, Lisagors et al (2008) evaluated the feasibility of HBOT as an efficient and safe adjunct to the standardized treatment protocol and its possible immunomodulatory impact of 44 patients with diagnosed acute pancreatitis (AP). The course of the disease was accompanied by systemic inflammatory response syndrome in all the patients on admission. The impact of AP and HBOT on homeostasis, the number of performed operations, mortality rates, the levels of 2 cytokines, intra-abdominal pressure, and side effects caused by HBOT were evaluated. A treatment group consisted of 22 patients receiving HBOT for 3 days (twice-daily) using a mono-place chamber under pressures of 1.7 to 1.9 ATA. Patients (n = 22) in the control group were managed in accordance with the standardized treatment protocol. The authors found more stable homeostasis, decreased mortality rate, and the number of operations in the HBOT group. This type of additional therapy, possibly contributed to the decrease of intra-abdominal pressure within the first 6 days after admission. The authors concluded that these findings suggested HBOT can affect an inflammatory response, by decreasing the levels pro-inflammatory cytokines and increasing those of anti-inflammatory ones.
An UpToDate review on “Hyperbaric oxygen therapy” (Mechem and Manaker, 2014) states that “A number of potential HBO uses remain poorly validated and require more rigorous evaluation. Future indications for HBO may be derived from its apparent modulation of ischemia-reperfusion injury and inflammation. Preliminary animal and human studies evaluating uses in syndromes as disparate as myocardial infarction, the systemic inflammatory response syndrome, traumatic brain or spinal cord injury, sickle cell crisis, fibromyalgia, and acute stroke have been conducted, with variable results. Further investigation will need to be conducted before HBO can be endorsed for these potential indications”.
In a phase II clinical trial, Ogawa al (2012) analyzed the long-term results of radiotherapy given immediately after HBOT with multi-agent chemotherapy in adults with high-grade gliomas. Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBOT, with the time interval from completion of decompression to start of irradiation being less than 15 minutes. Chemotherapy consisting of procarbazine, nimustine, and vincristine and was administered during and after radiotherapy. A total of 57 patients (39 patients with glioblastoma and 18 patients with Grade 3 gliomas) were enrolled from 2000 to 2006, and the median follow-up of 12 surviving patients was 62.0 months (range of 43.2 to 119.1 months). All 57 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBOT with 1 course of concurrent chemotherapy. The median overall survival times in all 57 patients, 39 patients with glioblastoma and 18 patients with Grade 3 gliomas, were 20.2 months, 17.2 months, and 113.4 months, respectively. On multi-variate analysis, histologic grade alone was a significant prognostic factor for overall survival (p < 0.001). During treatments, no patients had neutropenic fever or intracranial hemorrhage, and no serious non-hematologic or late toxicities were seen in any of the 57 patients. The authors concluded that radiotherapy delivered immediately after HBOT with multi-agent chemotherapy was safe, with virtually no late toxicities, and seemed to be effective in patients with high-grade gliomas. Moreover, they stated that this treatment strategy seemed promising and merited further investigation.
Furthermore, the National Comprehensive Cancer Network’s clinical practice guideline on “Central nervous system cancers” (Version 1.2014) does not mention the use of HBOT as a therapeutic option.
Dulai et al (2014) stated that although there is experience using HBOT in Crohn's disease and ulcerative colitis, the safety and overall effectiveness of HBOT in inflammatory bowel disease (IBD) is unknown. These researchers quantified the safety and effectiveness of HBOT for Crohn's disease (CD) and ulcerative colitis (UC). The rate of adverse events with HBOT for IBD was compared to the expected rate of adverse events with HBOT. MEDLINE, EMBASE, Cochrane Collaboration and Web of Knowledge were systematically searched using the PRISMA standards for systematic reviews. A total of 17 studies involving 613 patients (286 CD, 327 UC) were included. The overall response rate was 86 % (85 % CD, 88 % UC). The overall response rate for perineal CD was 88 % (18/40 complete healing, 17/40 partial healing). Of the 40 UC patients with endoscopic follow-up reported, the overall response rate to HBOT was 100 %. During the 8,924 treatments, there were a total of 9 adverse events, 6 of which were serious. The rate of adverse events with HBOT in IBD is lower than that seen when utilizing HBOT for other indications (p < 0.01). The risk of bias across studies was high. The authors concluded that HBOT is a relatively safe and potentially effective treatment option for IBD patients. Moreover, they stated that to understand the true benefit of HBOT in IBD, well-controlled, blinded, randomized trials are needed for both CD and UC.
The Infectious Diseases Society of America’s clinical practice guideline on “The diagnosis and treatment of diabetic foot infections” (Lipsky et al, 2012) stated that “For specifically treating DFO [diabetic foot osteomyelitis], the developers do not currently support using adjunctive treatments such as hyperbaric oxygen therapy …. Consider providing empiric therapy directed against methicillin-resistant Staphylococcus aureus (MRSA) in a patient with a prior history of MRSA infection; when the local prevalence of MRSA colonization or infection is high; or if the infection is clinically severe”.
Also, an UpToDate review on “Treatment of invasive methicillin-resistant Staphylococcus aureus infections in adults” (Lowy, 2014) does not mention the use of HBOT as a therapeutic option.
The European Society of Clinical Microbiology and Infectious Diseases Fungal Infection Study Group and the European Confederation of Medical Mycology’s joint clinical guidelines on “The diagnosis and management of mucormycosis” (Cornely et al, 2014) stated that “Hyperbaric oxygen is supported with marginal strength only”. Furthermore, an UpToDate review on “Hyperbaric oxygen therapy” (Mechem and Manaker, 2014) states that “HBO has been advocated for use in other severe invasive infections such as cutaneous soft-tissue and rhinocerebral mucormycosis (or zygomycosis) and actinomycotic brain abscesses, although data in support of these indications are less robust”.
An UpToDate review on “Treatment of the Raynaud phenomenon resistant to initial therapy” (Wigley, 2014) does not mention the use of HBOT as a therapeutic option.
A clinical cases summary by the University of Michigan Medical School on “Vesicocutaneous fistula” (2000) did not mention use of HBOT. Furthermore, an UpToDate review on “Hyperbaric oxygen therapy” (Mechem and Manaker, 2014) does not list fistula as an indication.
Anti-phospholipid antibody syndrome:
Lazurova and colleagues (2007) reported an episode of gastroenteritis triggered severe necrosis of all extremities in a previously asymptomatic male. Hepatic and renal involvement were also manifest, while the hematological picture was one of thrombotic microangiopathic hemolytic anemia. Anti-phospholipid antibodies were negative. He responded well to a combination of plasma exchange, anti-coagulation (heparin), parenteral steroids, and antibiotics, as well as vasodilators (prostacycline) and HBOT, but died because of a cerebral hemorrhage. The differential diagnosis included thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, or sero-negative catastrophic anti-phospholipid (Asherson's) syndrome. The dangers of administering such a combination of therapies with anti-coagulation, as well as vasodilatation (prostacycline) and HBOT, were highlighted by the case report.
Furthermore, an UpToDate review on “Treatment of the antiphospholipid syndrome” (Schur and Kaplan, 2015) does not mention HBOT as a therapeutic option.
Oines et al (2014) identified pharmaceuticals for the prophylaxis of anastomotic leakage (AL). These investigators systematically reviewed studies on anastomosis repair after colorectal surgery. They searched PubMed and EMBASE for articles published between January 1975 and December 2012 and included studies in English with the primary purpose of promoting healing of anastomoses made in the colon or rectum under uncomplicated conditions. These researchers excluded studies on adverse events from interventions, nutritional interventions or in-situ physical supporting biomaterials. The primary outcome was biomechanical strength or AL. The authors performed meta-analyses on therapeutic agents investigated by 3 or more independent research groups using the same outcome. The DerSimonian-Laird method for random effects was applied with p < 0.05. Of the 56 different therapeutic agents assessed, 7 met the inclusion criteria for the meta-analysis. The prostacyclin analog iloprost increased the weighted mean of the early bursting pressure of colonic anastomoses in male rats by 60 mmHg (95 % CI: 30 to 89) versus the controls, and the immunosuppressant tacrolimus increased this value by 29 mmHg (95 % CI: 4 to 53) versus the controls. Erythropoietin showed an enhancement of bursting pressure by 45 mmHg (95 % CI: 14 to 76). The anabolic compound growth hormone augmented the anastomotic strength by 21 mmHg (95 % CI: 7 to 35), possibly via the up-regulation of insulin-like growth factor-1, as this growth factor increased the bursting pressure by 61 mmHg (95 % CI: 43 to 79) via increased collagen deposition. Hyperbaric oxygen therapy increased the bursting pressure by 24 mmHg (95 % CI: 13 to 34). Broad-spectrum matrix metalloproteinase inhibitors increased the bursting pressure by 48 mmHg (95 % CI: 31 to 66) on post-operative days 3 to 4. In the only human study, the AL incidence was not significantly reduced in the 103 colorectal patients treated with aprotinin (11.7 %) compared with the 113 placebo-treated patients (9.7 %). The authors concluded that this systematic review identified only 1 randomized clinical trial and 7 therapeutic agents from pre-clinical models that could be explored further for the prophylaxis of AL after colorectal surgery. Moreover , they noted that although the results from animal studies on oxygen therapy were inconsistent, HBO significantly increased BPR by 24 mmHg (95 % CI: 13 to 34, p < 0.0001) in the meta-analysis. However, the sole human study on oxygen therapy that the authors retrieved was recently retracted by the journal that published it.
Lui et al (2009) stated that large refractory vasculitic ulcers are not commonly seen in systemic lupus erythematosus (SLE) patients. These investigators reported a case of refractory vasculitic ulcers responding to rituximab. This treatment was initiated after treatment with high-dose steroids and other immunosuppressants were ineffective/associated with significant side-effects. Following treatment with rituximab, there was sustained clinical improvement and subsequent reduction of prednisolone dose. Rituximab was well-tolerated. Concomitant methotrexate therapy and HBOT may have aided the recovery of the patient's vasculitic ulcers. The authors concluded that this case and anecdotal reports have illustrated the safety and effectiveness of rituximab in the treatment of refractory SLE-related vasculitic ulcers. They stated that further studies are needed to determine the long-term efficacy and side-effects. This was a single-case study; and its findings were confounded by the combinational use of rituximab, methotrexate and HBOT.
Olivieri et al (2010) noted that skin ulcers are a dangerous and uncommon complication of vasculitis. These researchers described the case of a teenager suffering from SLE with digital ulcer resistant to conventional therapy, treated successfully with HBOT. The application of hyperbaric oxygen, which was used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. The authors concluded that further studies are needed to evaluate its role as primary therapy for this group of patients.
Furthermore, an UpToDate review on “Overview of the management of vasculitis in adults” (Merkel, 2015) does not mention HBOT as a therapeutic option.
Osteonecrosis of the jaw:
Chiu and colleagues (2010) offered recommendations of risk factors, prevention, and treatment of oral bisphosphonate and steroid-related osteonecrosis of the jaw (BSRONJ) in Taiwan. A total of 12 patients were clinicopathologically proved to have bisphosphonate-related osteonecrosis of the jaw (BRONJ). All of the patients were taking oral bisphosphonates and were concurrently administered long-term steroids. Of the 12 patients, 3 patients were assigned to the 1st stage of BRONJ; 5 patients were assigned to the 2nd stage, and 4 patients were assigned to the 3rd stage. The patients' symptoms, localization of necrosis, presence of a fistula, and association with possible triggering factors for onset of the lesion were recorded. The radiologic investigations revealed osteolytic areas and scintigraphy demonstrated increased bone metabolism. Microbiologic analysis showed pathogenic actinomycosis organisms in a majority of patients (91.6 %). Antibiotic therapy, minor debridement surgery, and combined hyperbaric oxygen therapy (HBOT) were useful in obtaining short-term symptomatic relief. The authors concluded that co-morbidities of steroid use along with bisphosphonates may cause osteonecrosis of the jaw to occur sooner, be more severe, and respond more slowly to a drug discontinuation. The clinical disease of BSRONJ is more severe and more unpredictable to treat than BRONJ. From the data gained from other published studies of BRONJ and the authors’ clinical experience with the series of cases of BSRONJ, they offered recommendations of risk factors, prevention, and treatment of BSRONJ in southern Taiwan. This was a small study (n = 12) and its findings were confounded by the combinational use of antibiotics, debridement surgery, and HBOT. Moreover, the authors stated that long-term follow-up studies are needed to better understand treatment outcomes.
Freiberger et al (2012) examined the use of HBOT as an adjunct to surgery and antibiotics in the treatment of BRONJ and evaluated its effects on gingival healing, pain, and quality of life. The investigators implemented a randomized controlled trial and enrolled a sample composed of patients with ONJ, where the predictor variable was HBOT administered at 2 ATM twice-daily for 40 treatments as an adjunct to conventional therapy of surgery and antibiotics versus conventional therapy alone. Over the next 24 months, oral lesion size and number, pain, and quality of life were assessed. A total of 46patients (mean age of 66 years; 57 % women) contributed data to the trial. There were no statistically significant differences in the distribution of variables used to assess randomization success between the HBOT and standard treatment groups. Seventeen of 25 HBOT-treated patients (68 %) improved versus 8 of 21 controls (38.1 %; p = 0.043, χ(2) test). Mean time to improvement was 39.7 weeks (95 % confidence interval [CI]: 22.4 to 57.0 weeks) for HBOT-treated patients versus 67.9 weeks (95 CI: 48.4 to 87.5 weeks) for controls (p = 0.03, log-rank test). However, complete gingival healing occurred in only 14 of 25 HBOT-treated patients (52 %) versus 7 of 21 controls (33.3 %; p = 0.203, χ(2) test), and time to healing was 59 weeks (95 % CI: 42.8 % to 75.8 %) for HBOT-treated patients versus 70 weeks (95 CI: 52.2 % to 88.36 %) for controls (p = 0.32, log-rank test). Pain decreased faster for HBOT-treated subjects (p < 0.01, linear regression). Quality-of-life scores for physical health (p = 0.002) and perceived health (p = 0.043) decreased at 6 months for control group but for not the HBOT group. The authors concluded that ONJ is multi-factorial and no single treatment modality is likely to reverse it; however, it is treatable and even advanced presentations can improve with intensive multi-modal therapy. Clinically, HBOT appears to be a useful adjunct to ONJ treatment, particularly for more severe cases, although this study was under-powered to fully support this claim.
Spanou et al (2015) stated that osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate use in patients with osteoporosis, Paget's disease, hypercalcemia of malignancy, metastatic bone disease and multiple myeloma, although recently this complication has also been reported in patients under non-bisphosphonate medication, such as denosumab and bevacizumab. The occurrence of ONJ is higher in oncology patients treated with high-dose iv bisphosphonates than in osteoporosis patients treated with oral bisphosphonates. Although multiple hypotheses have been proposed, the exact pathogenic mechanism of ONJ still remains unclear. Since treatment protocols based on randomized controlled trials (RCTs) do not exist, these researchers critically reviewed the existing data concerning the management of bisphosphonate-related osteonecrosis of the jaw, including the most recent data for the use of teriparatide and hyperbaric oxygen.
On behalf of the International Task Force on Osteonecrosis of the Jaw, Khan et al (2015) provided a systematic review of the literature from January 2003 to April 2014 pertaining to the incidence, pathophysiology, diagnosis, and treatment of ONJ, and offered recommendations for its management based on multi-disciplinary international consensus. ONJ is associated with oncology-dose parenteral anti-resorptive therapy of bisphosphonates (BP) and denosumab (Dmab). The incidence of ONJ is greatest in the oncology patient population (1 % to 15 %), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of ONJ is estimated at 0.001 % to 0.01 %, marginally higher than the incidence in the general population (less than 0.001 %). New insights into the pathophysiology of ONJ include anti-resorptive effects of BPs and Dmab, effects of BPs on gamma delta T-cells and on monocyte and macrophage function, as well as the role of local bacterial infection, inflammation, and necrosis. Advances in imaging include the use of cone beam computerized tomography assessing cortical and cancellous architecture with lower radiation exposure, magnetic resonance imaging, bone scanning, and positron emission tomography, although plain films often suffice. Other risk factors for ONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures, as well as other drugs, including antiangiogenic agents. Prevention strategies for ONJ include elimination or stabilization of oral disease prior to initiation of anti-resorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of ONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding anti-resorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of ONJ is based on the stage of the disease, size of the lesions, and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Localized surgical debridement is indicated in advanced non-responsive disease and has been successful. Early data have suggested enhanced osseous wound healing with teriparatide in those without contraindications for its use. Experimental therapy includes bone marrow stem cell intralesional transplantation, low-level laser therapy, local platelet-derived growth factor application, hyperbaric oxygen, and tissue grafting.
Harch et al (2012) provided a preliminary report on the safety and effectiveness of 1.5 ATA HBOT in military subjects with chronic blast-induced mild-to-moderate TBI/post-concussive syndrome (PCS) and post-traumatic stress disorder (PTSD). A total of 16 military subjects received 40 1.5 ATA/60 min HBOT sessions in 30 days. Symptoms, physical and neurological exams, SPECT brain imaging, and neuropsychological and psychological testing were completed before and within 1 week after treatment. Subjects experienced reversible middle ear barotrauma (n = 5), transient deterioration in symptoms (n = 4), and reversible bronchospasm (n = 1); 1 subject withdrew. Post-treatment testing demonstrated significant improvement in: symptoms, neurological exam, full-scale IQ (+14.8 points; p < 0.001), WMS IV Delayed Memory (p = 0.026), WMS-IV Working Memory (p = 0.003), Stroop Test (p < 0.001), TOVA Impulsivity (p = 0.041), TOVA Variability (p = 0.045), Grooved Pegboard (p = 0.028), PCS symptoms (Rivermead PCSQ: p = 0.0002), PTSD symptoms (PCL-M: p < 0.001), depression (PHQ-9: p < 0.001), anxiety (GAD-7: p = 0.007), quality of life (MPQoL: p = 0.003), and self-report of percent of normal (p < 0.001), SPECT coefficient of variation in all white matter and some gray matter ROIs after the first HBOT, and in 50 % of white matter ROIs after 40 HBOT sessions, and SPECT statistical parametric mapping analysis (diffuse improvements in regional cerebral blood flow after 1 and 40 HBOT sessions). The authors concluded that 40 1.5 ATA HBOT sessions in 1 month was safe in a military cohort with chronic blast-induced PCS and PTSD. Significant improvements occurred in symptoms, abnormal physical exam findings, cognitive testing, and quality-of-life measurements, with concomitant significant improvements in SPECT. This was a small (n = 15) phase I study. The authors noted that more objective psychometric testing and SPECT imaging were not performed to confirm the durability of the HBOT treatment effect …. These data are preliminary and need confirmation with larger numbers of subjects or with a stronger design such as a randomized or Bayesian study.
Boussi-Gross et al (2013) noted that TBI is the leading cause of death and disability in the US. Approximately 70 to 90 % of the TBI cases are classified as mild, and up to 25 % of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of HBOT in improving brain function and quality of life in mild TBI (mTBI) patients suffering chronic neurocognitive impairments. The trial population included 56 mTBI patients 1 to 5 years after injury with prolonged PCS. The HBOT effect was evaluated by means of prospective, randomized, cross-over controlled trial: the patients were randomly assigned to treated or cross-over groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the cross-over group were evaluated 3 times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100 % oxygen at 1.5 ATA. "Mindstreams" was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements. The authors concluded that HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage. The authors stated that these results call for better understanding of how to set the optimal HBOT protocol for the specific patients and how to determine which patients benefit the most from this treatment. The findings reported here bear the promises that HBOT can be effective in treating other brain impairments, like easing PTSD symptoms or repairing radiation damage. This was a small study; its findings need to be validated by well-designed studies.
Efrati and Ben-Jacob (2014) stated that TBI and stroke are the major causes of brain damage and chronic neurological impairments. There is no agreed-upon effective metabolic intervention for TBI and stroke patients with chronic neurological dysfunction. Clinical studies published this year presented convincing evidence that HBOT might be the coveted neuro-therapeutic method for brain repair. These researchers discussed the multi-faceted role of HBOT in neuro-therapeutics, in light of recent persuasive evidence for HBOT efficacy in brain repair and the new understanding of brain energy management and response to damage. They discussed optimal timing of treatment, dosage, suitable candidates and promising future directions. The authors stated that there is an urgent need for additional, larger-scale, multi-center clinical studies to further confirm the findings and determine the most effective and personalized treatment protocols. To guarantee effective and well-designed clinical studies, wide-scale biomedical research is required. Such research will also provide validation of the clinical findings, crucial aid in interpretation of the results and important clues to additional applications of HBOT.
Kraitsy et al (2014) stated that cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive HBOT improves outcomes in TBI patients. However, there are no experimental studies investigating the mechanism of repetitive long-term HBOT treatment-associated protective effects. These investigators analyzed the effect of long-term repetitive HBOT treatment on brain trauma-associated cerebral modulations using the lateral fluid percussion model for rats. Trauma-associated neurological impairment regressed significantly in the group of HBO-treated animals within 3 weeks post-trauma. Evaluation of somatosensory-evoked potentials indicated a possible re-myelination of neurons in the injured hemisphere following HBOT. This presumption was confirmed by a pronounced increase in myelin basic protein isoforms, PLP expression as well as an increase in myelin following 3 weeks of repetitive HBO treatment. The authors concluded that these findings indicated that protective long-term HBOT effects following brain injury is mediated by a pronounced re-myelination in the ipsilateral injured cortex as substantiated by the associated recovery of sensorimotor function. Moreover, these researchers stated that their results indicated that HBO treatment might augment neuronal and neurophysiological function in damaged cerebral tissue due to re-myelination events. Their results also indicated that these regenerative processes are based on the repetitive long-term HBO treatment of the injured animals. However, a direct extrapolation of these promising observations to trauma patients or patients suffering from demyelination diseases should be regarded with caution. In order to translate these experimental observations into clinical settings it is a pre-requisite to understand the particular cerebral conditions that allow for the HBO-mediated induction of regenerative processes. In this standardized setting the first HBO treatment was administered immediately following trauma during the acute phase of the cerebral response. The perceptibility of the cerebral environment to HBO treatment during later stages of injury induced inflammatory responses or during chronic cerebral inflammation has yet to be shown.
In a single-center, double-blind, randomized, sham-controlled, prospective trial, Cifu et al (2014) examined the effects of HBOT on persistent post-concussion symptoms in 60 military service members with at least 1 combat-related mild TBI. Over a 10-week period, subjects received a series of 40, once-daily, hyperbaric chamber compressions at 2.0 ATA. During each session, subjects breathed 1 of 3 pre-assigned oxygen fractions (10.5 %, 75 %, or 100 %) for 60 minutes, resulting in an oxygen exposure equivalent to breathing surface air, 100 % oxygen at 1.5 ATA, or 100 % oxygen at 2.0 ATA, respectively. Individual, subscale and total item responses on the Rivermead Postconcussion Symptom Questionnaire and individual and total Posttraumatic Disorder Checklist-Military Version were measured just prior to intervention and immediately post-intervention. Between-group testing of pre- and post-intervention means revealed no significant differences on individual or total scores on the Posttraumatic Disorder Checklist-Military Version or Rivermead Postconcussion Symptom Questionnaire, demonstrating a successful randomization and no significant main effect for HBOT at 1.5 or 2.0 ATA equivalent compared with the sham compression. Within-group testing of pre- and post-intervention means revealed significant differences on several individual items for each group and difference in the Posttraumatic Disorder Checklist-Military Version total score for the 2.0 ATA HBOT group. The primary analyses of between group differences found no evidence of effectiveness for HBOT. The scattered within group differences were threatened by type 2 errors and could be explained by non-specific effects. The authors concluded that this study demonstrated that HBOT at either 1.5 or 2.0 ATA equivalent had no effect on post-concussion symptoms after mild TBI when compared with sham compression.
In a randomized, multi-center, double-blind, sham-controlled clinical trial, Miller et al (2015) compared the safety of and estimated the effectiveness for symptomatic outcomes from standard PCS care alone, care supplemented with HBO, or a sham procedure. A total of 72 military service members with ongoing symptoms at least 4 months after mild TBI enrolled at military hospitals in Colorado, North Carolina, California, and Georgia between April 26, 2011, and August 24, 2012 were included in this study. Assessments occurred before randomization, at the mid-point, and within 1 month after completing the interventions. Routine PCS care was provided in specialized clinics. In addition, participants were randomized 1:1:1 to 40 HBO sessions administered at 1.5 (ATA, 40 sham sessions consisting of room air at 1.2 ATA, or no supplemental chamber procedures. The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) served as the primary outcome measure. A change score of at least 2 points on the RPQ-3 subscale (range of 0 to 12) was defined as clinically significant. Change scores from baseline were calculated for the RPQ-3 and for the total RPQ. Secondary measures included additional patient-reported outcomes and automated neuropsychometric testing. On average, participants had sustained 3 lifetime mild TBIs; the most recent occurred 23 months before enrollment. No differences were observed between groups for improvement of at least 2 points on the RPQ-3 subscale (25 % in the no intervention group, 52 % in the HBO group, and 33 % in the sham group; p = 0.24). Compared with the no intervention group (mean change score, 0.5; 95 % CI: -4.8 to 5.8; p = 0.91), both groups undergoing supplemental chamber procedures showed improvement in symptoms on the RPQ (mean change score, 5.4; 95 % CI: -0.5 to 11.3; p = 0.008 in the HBO group and 7.0; 95 % CI: 1.0 to 12.9; p = 0.02 in the sham group). No difference between the HBO group and the sham group was observed (p = 0.70). Chamber sessions were well-tolerated. The authors concluded that among service members with persistent PCS, HBO showed no benefits over sham compressions. Both intervention groups demonstrated improved outcomes compared with PCS care alone. They stated that this finding suggested that the observed improvements were not oxygen-mediated but may reflect non-specific improvements related to placebo effects.
Documentation Requirements: Wounds must be evaluated, with photographic documentation with ruler, after every 15 treatments and/or at least every 30 days during 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.
Table: Wagner Grading System
Grade 0: Intact skin
Grade 1: Superficial diabetic ulcer
Grade 2: Ulcer extensionInvolves ligament, tendon, joint capsule or fascia; no abscess or osteomyelitis
Grade 3: Deep ulcer with abscess, infectious tendonitis, or osteomyelitis
Grade 4: Gangrene to portion of forefoot
Grade 5: Extensive gangrene of foot
Source: Wagner, 1987.
Requirements for documentation of Grade 3 Wagner lesion: For documentation of presence of abscess, medical record should note the presence of some fluid release during the course of a surgical debridement or incision. For documentation of osteomyelitis, X-rays or culture are required. For infectious tendonitis, clinical observation (rubor, calor, discharge) with photographic documentation or culture is required.
|CPT Codes / HCPCS Codes / ICD-10 Codes|
|Information in the [brackets] below has been added for clarification purposes.  Codes requiring a 7th character are represented by "+":|
|CPT codes covered if selection criteria are met:|
|99183||Physician attendance and supervision of hyperbaric oxygen therapy, per session|
|HCPCS codes covered if selection criteria are met:|
|G0277||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-10 codes covered if selection criteria are met:|
|A41.4||Septicemia due to anaerobes [progressive necrotizing soft tissue anaerobic infections]|
|A48.0||Gas gangrene [Clostridial myositis and myonecrosis]|
|D50.0||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]|
|D62||Acute posthemorrhagic anemia [overwhelming and transfusion is impossible because there is no suitable blood available or religion does not permit]|
|E10.51 - E10.59
E11.51 - E11.59
|Diabetes mellitus with circulatory complications [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]|
|E10.618 - E10.638
E10.649 - E10.69
E11.618 - E11.638
E11.649 - E11.69
|Diabetes mellitus with other specified complications [non-healing infected deep ulcerations (reaching tendons or bone) Wagner grade 3 of the lower extremity]|
|G93.6||Cerebral edema [acute]|
|H83.3x1 - H83.3x9||Noise effects on inner ear [noise-induced hearing loss when HBOT is initiated within 3 months after onset]|
|H91.20 - H91.23||Sudden idiopathic hearing loss [idiopathic when HBOT is initiated within 3 months after onset]|
|I70.201 - I70.92||Atherosclerosis of native arteries and bypass graft(s) of the 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]|
|I72.1 - I72.4||Other aneurysm of extremities|
|I73.00 - I73.1||Other peripheral vascular disease [acute peripheral arterial insufficiency]|
|I73.81 - I73.9
|Other specified peripheral vascular diseases [acute peripheral arterial insufficiency]|
|I74.2 - I74.3||Arterial embolism of the extremities [acute peripheral arterial insufficiency]|
|I74.5||Arterial embolism and thrombosis of the iliac artery [acute peripheral arterial insufficiency]|
|I83.001 - I83.029||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]|
|I83.201 - I83.229||Varicose veins of lower extremities with both 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]|
|I87.2||Venous insufficiency (chronic) (peripheral) [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]|
|L97.101 - L97.929||Non-pressure chronic ulcer of lower limb [diabetic ulcers] [non-healing infected deep ulcerations (reaching tendons or bone) Wagner grade 3 of the lower extremity]|
|M27.2||Inflammatory conditions of the jaws [radiation necrosis of jaw]|
|M27.8||Other specified diseases of jaw [prophylactic pre- and post-treatment for members undergoing dental surgery of a radiated jaw]|
|M86.60 - M86.69
M86.8x0 - M86.8x9
|Chronic osteomyelitis [unresponsive to conventional medical and surgical management]|
|M87.08||Idiopathic aseptic necrosis of bone, other site [jaw]|
|N30.41||Irradiation cystitis with hematuria|
|O88.011 - O88.019||Obstetric air embolism in pregnancy|
|S04.60x+ - S04.62x+||Injury to acoustic nerve [acoustic trauma when HBOT is initiated within 3 months after onset]|
|S07.0xx+ - S07.9xx+
S17.0xx+ - S17.9xx+
S38.001+ - S38.1xx+
S47.1xx+ - S47.9xx+
S57.00x+ - S57.82x+
S67.00x+ - S67.92x+
S77.00x+ - S77.22x+
S87.00x+ - S87.82x+
S97.00x+ - S97.82x+
|Crushing injuries [when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]|
|S35.511+ - S35.513+||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]|
|S45.001+ - S45.099+||Injury to axillary artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]|
|S48.011+ - S48.929+
S58.011+ - S58.929+
S68.011+ - S68.729+
|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]|
|S45.301+ - S45.399+
S45.801+ - S45.899+
S55.201+ - S55.299+
S55.801+ - S55.899+
S65.801+ - S65.899+
|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]|
|S65.201+ - S65.299+
S65.301+ - S65.399+
|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]|
|S75.001+ - S75.099+||Injury of femoral artery [acute peripheral ischemia when loss of function, limb, or life is threatened and HBOT is used in combination with standard therapy]|
|S75.801+ - S75.899+
S85.801+ - S85.899+
S95.801+ - S95.899+
|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]|
|S78.011+ - S78.929+
S88.011+ - S88.929+
S98.011+ - S98.929+
|Traumatic amputation toe(s), foot, leg(s) [when loss of function or life is threatened and HBOT is used in combination with standard therapy]|
|S85.001+ - S85.099+||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]|
|S85.131+ - S85.159+||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]|
|S85.161+ - S85.189+||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]|
|T57.3x1+ - T57.3x4+||Toxic effect of hydrogen cyanide [with co-existing carbon monoxide poisoning]|
|T58.01x+ - T58.94x+||Toxic effect of carbon monoxide [acute]|
|T65.0x1+ - T65.0x4+||Toxic effect of cyanides [with co-existing carbon monoxide poisoning]|
|T66.xxx+||Radiation sickness, 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]|
|T70.3xx+||Caisson disease [decompression illness]|
|T79.0xx+||Air embolism (traumatic) [acute]|
|T79.a0x+ - T79.a9x+||Traumatic compartment syndrome|
|T81.4xx+||Infection following a procedure (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]|
|T81.89x+||Other complications of procedures, not elsewhere classified (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]|
|T85.693+||Other mechanical complication of artificial skin graft and decellularized allodermis [compromised skin grafts and flaps]|
|T85.79x+||Infection and inflammatory reaction due to other internal prosthetic devices, implants and grafts [compromised skin grafts and flaps]|
|T85.810+ -T85.898+||Other specified complications of internal prosthetic devices, implants and grafts, not elsewhere classified [compromised skin grafts and flaps]|
|T86.820 - T86.829||Complications of skin graft (allograft) (autograft) [compromised skin grafts and flaps]|
|ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):|
|A04.7||Enterocolitis due to Clostridium difficile [intra-abdominal abscess, pseudomembranous colitis (antibiotic-induced colitis)]|
|A27.81||Aseptic meningitis in leptospirosis|
|A40.0 - A41.3
A41.50 - A41.9
|Sepsis [except sepsis due to anaerobes]|
|A42.0 - A42.2
A42.81 - A42.9
A43.0 - A43.9
B47.0 - B47.9
|A49.02||Methicillin resistant Staphylococcus aureus infection, unspecified site|
|A50.41||Late congenital syphilitic meningitis|
|A51.41||Secondary syphilitic meningitis|
|A52.13||Late syphilitic meningitis|
|A69.20 - A69.9||Lyme disease|
|B15.0 - B19.9||Viral hepatitis|
|B20||Human immunodeficiency virus [HIV] disease|
|B35.0 - B47.0
B48.0 - B49
|C00.0 - C43.9
C44.0 - C75.9
C76.0 - C86.6
C88.4 - C94.32
C94.80 - C96.4
C96.6 - C96.9
|Malignant neoplasm [cancer]|
|C71.0 - C71.9||Malignant neoplasm of brain [glioblastoma]|
|D00.00 - D09.9||In situ neoplasms [cancer]|
|D57.00 - D57.819||Hb-SS disease with crisis [sickle cell crisis]|
|D68.62||Lupus anticoagulant syndrome|
|E11.311 - E11.39||Type 2 diabetes mellitus with ophthalmic complications|
|E83.2||Disorders of zinc metabolism|
|E83.59||Other disorders of calcium metabolism [calciphylaxis (calcific uremic arteriolopathy)]|
|F01.50 - F01.51
F03.90 - F03.91
|Dementias [cognitive impairment]|
|F06.8||Other persistent mental disorders due to conditions classified elsewhere [dementia NOS] [cognitive impairment]|
|F07.0||Personality change due to known physiological condition [cognitive impairment]|
|F07.89||Other personality and behavioral disorders due to known physiological condition [cognitive impairment]|
|F32.0 - F33.9||Depression|
|F80.0 - F89||Pervasive and specific developmental disorders|
|G00.0 - G03.1
G03.8 - G03.9
|Meningitis- bacterial, due to other organisms, and of unspecified cause|
|G06.0||Intracranial abscess and granuloma|
|G21.11 - G21.19||Other drug-induced secondary parkinsonism|
|G30.0 - G31.2
G31.83 - G31.9
G91.0 - G91.2
|Alzheimer's disease and other degenerative diseases of nervous system [cognitive impairment]|
|G37.1 - G37.3
G37.8 - G37.9
|Acute transverse myelitis in demyelinating diseases of central nervous system [radiation induced]|
|G40.001 - G40.919||Epilepsy and recurrent seizures|
|G43.001 - G43.919||Migraine|
|G44.001 - G44.029||Cluster headaches|
|G45.0 - G45.1
G45.8 - G45.9
|Transient cerebral ischemic attacks and related syndromes [acute or chronic cerebrovascular insufficiency]|
|G45.4||Other specified cerebrovascular diseases [acute or chronic cerebrovascular insufficiency/accident including thrombotic or embolic stroke]|
|G51.8||Other disorders of facial nerve [facial neuritis]|
|G80.0 - G80.9||Cerebral palsy|
|G90.50 - G90.59||Complex regional pain syndrome I (CRPSI)|
|G93.1||Anoxic brain damage, not elsewhere classified|
|H00.011 - H57.9||Diseases of the eye and adnexa|
|H60.00 - H60.93||Otitis externa|
|H93.11 - H93.19||Tinnitus|
I21.01 - I22.9
I24.0 - I24.9
|Ischemic heart diseases|
|I26.01 - I52||Heart disease|
|I63.00 - I66.9||Cerebral infarction and occlusion and thrombosis of precerebral and cerebral arteries, not resulting in cerebral infarction [acute or chronic cerebrovascular insufficiency/accident including thrombotic or embolic stroke]|
|I67.1 - I67.2
I67.4 - I67.9
|Other cerebrovascular diseases [acute or chronic cerebrovascular insufficiency/accident including thrombotic or embolic stroke]|
|I69.910 - I69.919||Cognitive deficits following unspecified cerebrovascular disease|
|I73.00 - I73.01||Raynaud's syndrome|
|I74.8||Arterial embolism and thrombosis of other arteries [hepatic]|
|I77.6||Arteritis, unspecified [Lupus vasculitis]|
|J43.0 - J43.9||Emphysema|
|J44.0 - J44.9||Other chronic obstructive pulmonary disease [bronchitis with emphysema]|
|J45.20 - J45.998||Asthma|
|J68.0 - J68.9||Respiratory conditions due to inhalation of chemicals, gases, fumes and vapors [Acute thermal and chemical pulmonary damage, i.e., smoke inhalation (e.g., carbon tetrachloride, hydrogen sulfide) with pulmonary insufficiency]|
|J70.0 - J70.9||Respiratory conditions due to other external agents [Acute thermal and chemical pulmonary damage, i.e., smoke inhalation (e.g., carbon tetrachloride, hydrogen sulfide) with pulmonary insufficiency]|
|K11.7 - K11.9||Disturbances and diseases of salivary glands|
|K50.00 - K50.919||Crohn's disease [regional enteritis]|
|K51.00 - K51.919||Ulcerative colitis|
|K52.0||Gastroenteritis and colitis due to radiation|
|K63.89||Other specified diseases of intestine [intestinal anastomosis]|
|K65.1||Peritoneal abscess [intra-abdominal]|
|K72.00 - K72.01
|Acute and subacute hepatic failure|
|K73.0 - K73.9||Chronic hepatitis, NEC|
|K83.0||Cholangitis [radiation-induced hemorrhagic]|
|L08.0, L08.81 - L08.9
|Other local infections and disorders of the skin and subcutaneous tissue [except Meleney's ulcer] [infection other than clostridial]|
|L55.0 - L55.9
L56.0 - L56.9
L57.0 - L57.1
L57.5 - L57.9
|Contact dermatitis and other eczema due to solar radiation [actinic skin damage]|
|L70.0||Acne vulgaris [cystic]|
|M00.00 - M12.19
M12.50 - M19.93
|M32.0 - M32.9||Systemic lupus erythematosus (SLE) [ischemia due to lupus vasculitis]|
|M48.50x+ - M48.58x+
M80.00x+ - M80.88x+
M84.40x+ - M84.48x+
|Pathologic fracture [fracture healing]|
|M79.1||Myalgia [myofascial pain syndrome]|
|M81.0 - M81.8||Osteoporosis without current pathological fracture|
|M87.059||Idiopathic aseptic necrosis of unspecified femur [head and neck]|
|M87.08||Idiopathic aseptic necrosis of bone, other site [jaw]|
|M91.10 - M91.12||Juvenile osteochondrosis of head of femur [Legg-Calve-Perthes]|
|N30.10 - N30.11||Interstitial cystitis (chronic)|
|N30.40||Irradiation cystitis without hematuria|
|N32.2||Vesical fistula, not elsewhere classified|
|N64.4||Mastodynia [post-radiation therapy]|
|N82.4||Other female intestinal-genital tract fistulae [rectovaginal fistula]|
|O90.0||Disruption of cesarean delivery wound|
|P25.0 - P25.8||Interstitial emphysema and related conditions originating in the perinatal period|
|Q82.0||Hereditary lymphedema [legs]|
|R31.0 - R31.9||Hematuria|
|R41.4||Neurologic neglect syndrome [cognitive impairment]|
|R41.81||Age-related cognitive decline|
|R41.82||Altered mental status [cognitive impairment]|
|R56.00 - R56.9||Convulsions, not elsewhere classifiedConvulsions|
|R65.10 - R65.11||Systemic inflammatory response syndrome (SIRS) of non-infectious origin|
|S04.011+ - S04.049+||Injury of optic nerve and pathways [ophthalmologic diseases (including diabetic retinopathy, retinal detachment, central retinal artery occlusion, radiation injury to the optic nerve, glaucoma, keratoendotheliosis)]|
|S06.0x0+ - S06.9x9+||Intracranial injury [cognitive impairment] [not covered for traumatic brain injury]|
|S09.8xx+ - S09.90x+||Specified and unspecified head injury [cognitive impairment] [closed head injury]|
|S14.101+ - S14.139+
S14.151+ - S14.159+
S24.101+ - S24.139+
S24.151+ - S24.159+
S34.101+ - S34.139+
|Other and unspecified injury of cervical, thoracic, lumbar and sacral spinal cord|
|T20.00x+ - T25.799+
T30.0 - T30.4
|Burns and corrosions of head, face, neck, trunk, upper limb, wrist and hand, lower limb, and multiple and unspecified body regions [skin, thermal]|
|T33.011+ - T34.99x+||Frostbite [face, hand, foot, and other and unspecified sites]|
|T53.0x1+ - T53.0x4+
T53.5x1+ - T53.5x4+
T59.0x1+ - T59.1x4+
T59.3x1+ - T59.6x4
|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]|
|T63.001+ - T63.94x+||Toxic effect of contact with venomous animals and plants [necrotizing arachnidism ]|
|T81.30x+ - T81.33x+||Disruption of wound [dehiscence of operation wound]|
|T84.010+ - T84.498+||Mechanical complication of internal orthopedic devices, implants and grafts [bone grafts]|
|T84.60x+ - T84.7xx+||Infection and inflammatory reaction due to internal fixation devices and other internal orthopedic prosthetic devices, implants and grafts [bone grafts]|
|Z48.21 - Z48.298||Encounter for aftercare following organ transplant [post organ transplant revascularization]|
|Z76.82||Awaiting organ transplant status [organ transplant or storage]|
|Z94.0 - Z94.9
Z95.2 - Z95.4
Z95.811 - Z95.812
Z95.820 - Z95.828
Z96.0 - Z96.1
Z96.3, Z96.5 - Z97.16
|Transplanted organ and tissue status, and presence of cardiac and vascular implants and grafts and other functional implants and other devices [organ transplant or storage]|
|Numerous options||Aftercare for healing fracture [Codes not listed due to expanded specificity]|
|Numerous options||Fractures, including malunion and nonunion [Codes not listed due to expanded specificity]|
|Numerous options||Intracranial injury, sequela [Codes not listed due to expanded specificity]|
|ICD-10 codes contraindicated for this CPB:|
|A28.1, A60.00 - A99
B00.0 - B19.9
B25.0 - B34.9
B97.0 - B97.89
|Viral infections and diseases|
J00 - J99
|Diseases of the respiratory system [lung disease including J93.0 - J93.9 untreated pneumothorax]|
|D58.0||Hereditary spherocytosis [congenital]|
|P07.00 - P07.32||Disorders of newborn related to short gestation and low birth weight, not elsewhere classified [premature infants (birth prior to 37 weeks)]|