Hyperbaric oxygen therapy


C Crawford Mechem, MD, FACEP
Scott Manaker, MD, PhD
 

INTRODUCTION — Hyperbaric oxygen (HBO) serves as primary or adjunctive therapy for a diverse range of medical conditions. In the United States, over 500 hyperbaric facilities offer either single occupant ("monoplace") or multiple occupant ("multiplace") chambers. Information regarding the location of hyperbaric facilities can be accessed through the Undersea and Hyperbaric Medical Society website (www.uhms.org) or via the Divers Alert Network Emergency Hotline (US phone numbers: 919-684-8111 or 919-684-4326; website: www.diversalertnetwork.org).

The mechanisms of action, administration, risks, and outcomes of HBO therapy for its currently accepted indications will be reviewed here.

MECHANISMS OF ACTION — Most of the benefits of HBO are explained by the simple physical relationships determining gas concentration, volume, and pressure. HBO is most commonly used under conditions of tissue hypoxia or to treat decompression sickness or gas embolism, in which gas bubbles obstruct blood flow.

Increased oxygen delivery — Henry's Law states that the amount of an ideal gas dissolved in solution is directly proportional to its partial pressure. Thus, the dissolved plasma oxygen concentration of 0.3 mL/dL at sea level (1.0 atm) increases to 1.5 mL/dL upon administration of 100 percent oxygen, while hyperbaric oxygen delivered at 3.0 atm yields a dissolved oxygen content of 6 mL/dL. The latter figure is sufficient to meet resting tissue oxygen extraction requirements irrespective of the adequacy of the hemoglobin-bound oxygen pool. The ability of HBO to augment oxygen content and independently meet resting tissue oxygen requirements has led to its use in conditions of compromised oxygen delivery, such as profound anemia, carbon monoxide (CO) poisoning, and both acute and chronic ischemia

Reduction of gas bubble size — The use of hyperbaric oxygen therapy for decompression illness is based upon Boyle's Law, since the volume of nitrogen bubbles is inversely related to the pressure exerted upon it. At 3.0 atm, bubble volume decreases by approximately two-thirds. Further bubble dissolution is accomplished by the replacement of inert nitrogen within the bubbles with oxygen, which is then rapidly metabolized by tissues .

Improved wound healing — In vitro, HBO modulates local and systemic effects found in both acute and chronic injury, ischemia, and inflammation. Local hyperoxia induces vasoconstriction and reduces vasogenic edema following acute trauma. HBO ameliorates ischemia-reperfusion-induced leukocyte influx. By altering conditions of local hypoxia, HBO facilitates fibroblast proliferation, angiogenesis, and wound healing. HBO augments neutrophil bactericidal activity, limits clostridial exotoxin and spore production, kills anaerobes such as Clostridium perfringens, and inhibits the growth of several other bacterial pathogens.

TECHNIQUE — Multiplace chambers allow closer monitoring of critically ill patients, while single occupancy chambers are most appropriate for the treatment of chronic medical conditions in stable patients. Chamber pressure is usually maintained between 2.5 and 3.0 atm, with treatment lasting 45 to 300 minutes depending upon the indication. Acute therapy may require only one or two treatments, while chronic medical conditions may warrant up to 30 or more sessions. Typically, hyperbaric therapy is administered with pressurized oxygen or air. Pressures exceeding 2.8 to 3.0 atm, particularly over prolonged exposure hyperbaric periods, dramatically increase the risk of both neurologic and pulmonary oxygen toxicity. Helium/oxygen (heliox) or nitrogen/oxygen (nitrox) mixtures are indicated only in certain instances of decompression illness

The only absolute contraindication to HBO therapy is untreated pneumothorax. Relative contraindications include obstructive lung disease, upper respiratory or sinus infections, recent ear surgery or injury, fever, and claustrophobia. Pregnancy was once believed to represent a contraindication to HBO, but now is considered an impetus to pursue HBO therapy among patients with CO intoxication. Patients with a history of a seizure disorder, pneumothorax, or chest surgery are at highest risk for complications related to barotrauma or central nervous system oxygen toxicity.

COMPLICATIONS — Hyperbaric therapy is generally safe and well tolerated. Most side effects are mild and reversible, although severe consequences can occur in rare cases.

  bullet Reversible myopia due to direct oxygen toxicity to the lens is the most common side effect of HBO and occurs in up to 20 percent of patients; weeks to months may be required for complete recovery.

  bullet Symptomatic otic barotrauma occurs in up to 3 to 20 percent of patients. Middle ear effusions (which may be hemorrhagic) and tympanic membrane rupture occur infrequently. Middle ear symptoms preclude repeat therapy in less than 1 percent of patients; they may be alleviated by the placement of tympanostomy tubes.

  bullet Pulmonary barotrauma is unusual, provided any pneumothoraces have been identified and decompressed before initiating HBO.

  bullet Pulmonary oxygen toxicity, manifested by chest tightness, cough, and a reversible decline of pulmonary function, occurs most commonly in patients receiving multiple treatments or previously exposed to high oxygen levels
  bullet Seizures due to central nervous system oxygen toxicity are a rare but dramatic consequence of HBO treatment; estimates of incidence range from 1 in 11,000 to 2.4 per 100,000 treatments. The risk is increased by HBO exposure greater than 90 to 120 minutes and by pressures greater than 2.8 to 3.0 atm. Patients receiving glucocorticoids, insulin, thyroid replacement, and sympathomimetic medications may be at higher risk of central nervous system oxygen toxicity. HBO has been associated with hypoglycemia in some patients with diabetes, and hypoglycemia should therefore be considered in the differential diagnosis of HBO-associated seizures Seizures due to oxygen toxicity do not typically result in permanent structural brain damage

Seizures should be managed acutely by reducing the inspired oxygen concentration to that of air (FIO2 = 0.21), administering anticonvulsant therapy, and, if necessary, terminating hyperbaric treatment. Oxygen toxicity may be prevented by alternating between short (5 minute) intervals of air and longer intervals (30 minutes) of 100 percent oxygen, to limit oxygen free radical formation. Patients in monoplace chambers should have therapy terminated, as airway management and monitoring are compromised. The need for further treatment with lower FIO2 should be addressed.

  bullet Decompression sickness may occur in patients breathing compressed air that contains nitrogen. The likelihood of decompression sickness is reduced by administration of 100 percent oxygen toward the end of the treatment period and by adherence to standard US Navy guidelines governing gradual decompression. Decompression sickness does not occur in patients breathing 100 percent oxygen.

CLINICAL USE — Hyperbaric oxygen (HBO) serves as primary or adjunctive therapy for a diverse range of medical conditions

Radiation injury — Previously irradiated tissue is characterized by fibro-atrophic changes, with decreased vascularity, impaired cellular proliferation, and local hypoxia that can persist long after radiation therapy. Subsequent injury (eg, dental extraction) or surgical manipulation may lead to soft tissue radionecrosis and osteoradionecrosis, manifested by edema, ulceration, poor wound healing, and infection. The value of HBO has been studied in patients with laryngeal, oropharyngeal, and other head and neck cancers who develop osteoradionecrosis following radiation therapy. In theory, HBO has the potential to improve this condition because of its impact on collagen synthesis and vascular density.

Unfortunately, the available data are conflicting, and the benefit of HBO to prevent or treat established osteoradionecrosis of the jaw in irradiated patients with head and neck cancer is uncertain.

Several studies suggest that HBO may reduce soft tissue radionecrosis and improve reconstructive outcome in patients who have received chest, pelvic, perineal, or extremity irradiation. Furthermore, a Cochrane Collaboration review suggested that HBO may be of benefit for patients with late radiation tissue injury to the head, neck, anus, and rectum, and to promote healing of irradiated sockets after dental extraction. There was no benefit for neural tissue; however, randomized trials have not been conducted, and questions persist regarding the ultimate benefit of this approach.

Protocols for prevention and treatment of osteoradionecrosis and soft tissue radionecrosis generally have included 20 to 30 preoperative HBO sessions at 2.4 atm delivered over 90 minutes, followed by 10 postoperative treatments

Future directions — 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.

RECOMMENDATIONS — Based upon clinical experience and the data detailed above, we recommend HBO in the following circumstances:

  bullet Severe decompression sickness or arterial gas embolism.

  bullet Carbon monoxide poisoning associated with a history of loss of consciousness, altered mental status, an abnormal neurologic exam, cardiac dysfunction, or in pregnant women with a COHb >20 percent or evidence of fetal distress.

  bullet HBO may be useful in the care of patients with cyanide poisoning, severe anemia, actinomycotic brain abscesses, acute crush injuries, prior radiation therapy, aggressive soft tissue infections, nonhealing ulcers, or compromised skin grafts and flaps. Further research is required in these situations in order to confirm the benefits of HBO and justify its significant costs and potential risks.
 

Hyperbaric oxygen therapy for late radiation tissue injury.
Bennett M; Feldmeier J; Hampson N; Smee R; Milross C. Cochrane Database Syst Rev 2005;(3):CD005005.

BACKGROUND: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of patients having radiotherapy with be long-term survivors. Some will experience LRTI developing months or years later. HBOT has been suggested for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery. OBJECTIVES: To assess the benefits and harms of HBOT for treating or preventing LRTI. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2004, MEDLINE, EMBASE, CINAHL and DORCTHIM (hyperbaric RCT register) in September 2004. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook Clarke 2003) and extracted the data from the included trials. MAIN RESULTS: Six trials contributed to this review (447 participants). For pooled analyses, investigation of heterogeneity suggested important variability between trials. From single studies there was a significantly improved chance of healing following HBOT for radiation proctitis (relative risk (RR) 2.7), and following both surgical flaps (RR 8.7) and hemimandibulectomy (RR 1.4). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse effects.

AUTHORS' CONCLUSIONS: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of osteoradionecrosis following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected patients and tissues may be justified. Further research is required to establish the optimum patient selection and timing of any therapy. An economic evaluation should be also be undertaken. There is no useful information from this review regarding the efficacy or effectiveness of HBOT for other tissues.
 

Hyperbaric oxygen as an adjunctive treatment for delayed radiation injury of the chest wall: a retrospective review of twenty-three cases.
Feldmeier JJ; Heimbach RD; Davolt DA; Court WS; Stegmann BJ; Sheffield PJ. Undersea Hyperb Med 1995 Dec;22(4):383-93.

Since 1979, 23 cases of radiation-induced chest wall necrosis have been treated in the Hyperbaric Medicine Departments of Southwest Texas Methodist Hospital and the Nix Hospital, San Antonio, Texas. Eight cases involved soft tissue only. Six of eight (75%) patients with soft tissue involvement healed without requiring surgical debridement, although four patients (50%) did have flaps or grafts. Fifteen patients had bony and soft tissue necrosis. Eight of these patients (53%) resolved with adjunctive hyperbaric oxygen (HBO), but all required aggressive surgical debridement including skeletal resection. Four (27%) had reconstructive flaps as well. Six patients (40%) with bony necrosis who had either no or incomplete debridement failed to heal. Three patients (13%)(two soft tissue and one bony) were found to have residual tumor during HBO and were discontinued from treatment. HBO is an effective adjunctive therapy for soft tissue chest-wall, radiation-induced necrosis, but must be coupled with appropriate debridement to include surgical removal of all necrotic bone to ensure a successful outcome of bony plus soft tissue necrosis.

 

Hyperbaric oxygen an adjunctive treatment for delayed radiation injuries of the abdomen and pelvis.
Feldmeier JJ; Heimbach RD; Davolt DA; Court WS; Stegmann BJ; Sheffield PJ. Undersea Hyperb Med 1996 Dec;23(4):205-13.

Radiation therapy is often utilized as adjunctive or primary treatment for malignancies of the abdomen and pelvis. Radiation complications are infrequent, but can be life threatening or significantly diminish the quality of life. Radiation necrosis is an approved indication for hyperbaric oxygen (HBO2). Previous publications have reported results in treating delayed radiation injuries involving many sites. This paper reports the experience of a single physician group in treating delayed injuries of the abdomen and/or pelvis. Forty-four such patients have been treated since 1979. Of the 41 patients available for follow up, 26 have healed; 6 failed to heal; and 9 patients had an inadequate course of therapy (fewer than 20 treatments). Especially encouraging was the resolution of fistulae in six of eight patients with only three requiring surgery for closure. Overall, the success rate in patients receiving at least 20 HBO2 treatments was 81%. Hyperbaric oxygen is a useful adjunct in treatment of delayed radiation injuries of the pelvis and abdomen.

 

Hyperbaric oxygen in the treatment of delayed radiation injuries of the extremities.
Feldmeier JJ; Heimbach RD; Davolt DA; McDonough MJ; Stegmann BJ; Sheffield PJ. Undersea Hyperb Med 2000 Spring;27(1):15-9.

Hyperbaric oxygen (HBO2) is used as an adjunct in the treatment of radiation injury at many sites, including the mandible, larynx, chest wall, bladder, and rectum. In these disorders, HBO2 is effective in stimulating neovascularization and reducing fibrosis. No previous publications report the application of HBO2 to radiation injuries of the extremities. From 1979 until 1997, 17 patients were treated at the Southwest Texas Methodist and Nix Hospitals for nonhealing necrotic wounds of the extremities within previously irradiated fields. All but one wound involved a lower extremity. Most of the patients had been irradiated for soft tissue sarcomas or skin cancers. The rest were irradiated for a variety of malignancies. HBO2 was delivered in a multiplace chamber at 2.4 atm abs daily for 90 min of 100% oxygen at pressure. This report is a retrospective, uncontrolled review of these patients. Eleven patients (65%) healed completely whereas five (29%) failed to heal and one (6%) was lost to follow-up. Three (60%) of those who failed were found to have local or distant recurrence of their tumor early in their course of hyperbaric treatment and were discontinued from therapy at that time. When last seen in the clinic, the wound of the patient who was lost to follow-up was improved but not completely healed. Four of those who failed (including the two with local tumor recurrence) required amputation. If we exclude those with active cancer and the patient lost to follow-up, the success rate was 11 of 13 or 85%. HBO2 was applied successfully with complete wound healing and the avoidance of amputation in a majority of these patients. The consequences of failure in patients suffering from radiation necrosis of the extremities (some complicated by the presence of tumor) are significant, with 80% of the five failures requiring amputation. In radiation injuries of the extremities as in delayed radiation injury at other sites, HBO2 is a useful adjunct and should be part of the overall management.

Hyperbaric oxygen therapy for late sequelae in women receiving radiation after breast-conserving surgery.

Carl UM; Feldmeier JJ; Schmitt G; Hartmann KA. Int J Radiat Oncol Biol Phys 2001 Mar 15;49(4):1029-31.

PURPOSE: Persisting symptomatology after breast-conserving surgery and radiation is frequently reported. In most cases, symptoms in the breast resolve without further treatment. In some instances, however, pain, erythema, and edema can persist for years and can impact the patient's quality of life. Hyperbaric oxygen therapy was shown to be effective as treatment for late radiation sequelae. The objective of this study was to assess the efficacy of hyperbaric oxygen therapy in symptomatic patients after breast cancer treatment. PATIENTS AND METHODS: Forty-four patients with persisting symptomatology after breast-conservation therapy were prospectively observed. Thirty-two women received hyperbaric oxygen therapy in a multiplace chamber for a median of 25 sessions (range, 7-60). One hundred percent oxygen was delivered at 240 kPa for 90-min sessions, 5 times per week. Twelve control patients received no further treatment. Changes throughout the irradiated breast tissue were scored prior to and after hyperbaric oxygen therapy using modified LENT-SOMA criteria. RESULTS: Hyperbaric oxygen therapy patients showed a significant reduction of pain, edema, and erythema scores as compared to untreated controls (p < 0.001). Fibrosis and telangiectasia, however, were not significantly affected by hyperbaric oxygen therapy. Seven of 32 women were free of symptoms after hyperbaric oxygen therapy, whereas all 12 patients in the control group had persisting complaints. CONCLUSIONS: Hyperbaric oxygen therapy should be considered as a treatment option for patients with persisting symptomatology following breast-conserving therapy

The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects.
Bui QC; Lieber M; Withers HR; Corson K; van Rijnsoever M; Elsaleh H. Int J Radiat Oncol Biol Phys 2004 Nov 1;60(3):871-8.

PURPOSE: We investigated the efficacy of hyperbaric oxygen therapy (HBOT) in the management of patients with radiation-induced late side effects, the majority of whom had failed previous interventions. METHODS AND MATERIALS: Of 105 eligible subjects, 30 had either died or were not contactable, leaving 75 who qualified for inclusion in this retrospective study. Patients answered a questionnaire documenting symptom severity before and after treatment (using Radiation Therapy Oncology Group criteria), duration of improvement, relapse incidence, and HBOT-related complications. RESULTS: The rate of participation was 60% (45/75). Improvement of principal presenting symptoms after HBOT was noted in 75% of head-and-neck, 100% of pelvic, and 57% of "other" subjects (median duration of response of 62, 72, and 68 weeks, respectively). Bone and bladder symptoms were most likely to benefit from HBOT (response rate, 81% and 83%, respectively). Fifty percent of subjects with soft tissue necrosis/mucous membrane side effects improved with HBOT. The low response rate of salivary (11%), neurologic (17%), laryngeal (17%), and upper gastrointestinal symptoms (22%) indicates that these were more resistant to HBOT. Relapse incidence was low (22%), and minor HBOT-related complications occurred in 31% of patients. CONCLUSION: Hyperbaric oxygen therapy is a safe and effective treatment modality offering durable relief in the management of radiation-induced osteoradionecrosis either alone or as an adjunctive treatment. Radiation soft tissue necrosis, cystitis, and proctitis also seemed to benefit from HBOT, but the present study did not have sufficient numbers to reliably predict long-term response

Non-randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema and tissue fibrosis after radiotherapy for early breast cancer.

Gothard L; Stanton A; MacLaren J; Lawrence D; Hall E; Mortimer P; Parkin E; Pritchard J; Risdall J; Sawyer R; Woods M; Yarnold Radiother Oncol 2004 Mar;70(3):217-24.

BACKGROUND: Radiation-induced arm lymphoedema is a common and distressing complication of curative treatment for early breast cancer. Hyperbaric oxygen (HBO(2)) therapy promotes healing in bone rendered ischaemic by radiotherapy, and may help some soft-tissue injuries too, but is untested in arm lymphoedema. METHODS: Twenty-one eligible research volunteers with a minimum 30% increase in arm volume in the years after axillary/supraclavicular radiotherapy (axillary surgery in 18/21 cases) were treated with HBO(2). The volunteers breathed 100% oxygen at 2.4 ATA for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The volume of the ipsilateral limb, measured opto-electronically by a perometer and expressed as a percentage of contralateral limb volume, was selected as the primary endpoint. A secondary endpoint was local lymph drainage expressed as fractional removal rate of radioisotopic tracer, measured using lymphoscintigraphy. RESULTS: Three out of 19 evaluable patients experienced >20% reduction in arm volume at 12 months. Six out of 13 evaluable patients experienced a >25% improvement in (99)Tc-nanocolloid clearance rate from the ipsilateral forearm measured by quantitative lymphoscintigraphy at 12 months. Overall, there was a statistically significant, but clinically modest, reduction in ipsilateral arm volume at 12 months follow-up compared with baseline (P = 0.005). The mean percentage reduction in arm volume from baseline at 12 months was 7.51. Moderate or marked lessening of induration in the irradiated breast, pectoral fold and/or supraclavicular fossa was recorded clinically in 8/15 evaluable patients. Twelve out of 19 evaluable patients volunteered that their arms felt softer, and six reported improvements in shoulder mobility at 12 months. No significant improvements were noted in patient self-assessments of quality of life. CONCLUSION: Interpretation is limited by the absence of a control group. However, measurement of limb volume by perometry is reportedly reliable, and lymphoscintigraphy is assumed to be operator-independent. Taking all data into account, there is sufficient evidence to justify a double-blind randomised controlled trial of hyperbaric oxygen in this group of patients.

Interventions for the physical aspects of sexual dysfunction in women following pelvic radiotherapy.

Denton AS; Maher EJ. Cochrane Database Syst Rev 2003;(1):CD003750.

BACKGROUND: Following pelvic radiotherapy (RT), a proportion of women experience problems related to sexual function, which are multifactorial in origin. The physical components relate to distortion of the perineum and vagina, which may occur as a result of surgery and/or radiotherapy and compromise sexual activity resulting in considerable distress. OBJECTIVES: The aim of this review was to evaluate the evidence for treatment options addressing the physical components of sexual dysfunction arising from pelvic radiotherapy as prevention or treatment of acute or late complications. SEARCH STRATEGY: The concepts used included synonyms for radiation therapy and brachytherapy and synonyms for the spectrum of physical aspects of sexual dysfunction in women. randomized. We searched the Cochrane Controlled Trials Register (CENTRAL), issue 1, 2002, MEDLINE 1966 to 2002, EMBASE 1980 to 2002, CANCERCD 1980 to 2002, Science Citation Index 1991 to 2002, CINAHL 1982 to 2002, as well as sources of grey literature. We also hand searched relevant textbooks and contacted experts in the field. SELECTION CRITERIA: Any study describing the therapeutic trial of a treatment to relieve the physical aspects of female sexual dysfunction which had developed following pelvic radiotherapy was considered. The quality of each study was then assessed by two reviewers independently to determine its suitability for inclusion in statistical analysis. DATA COLLECTION AND ANALYSIS: Thirty-two references met the inclusion criteria for the search but of these only four were suitable to be included for statistical analysis. MAIN RESULTS: The strongest evidence for benefit is the grade IC data in the topical oestrogens and benzydamine sections which describes the treatment of acute radiation vaginal changes. The use of vaginal dilators to prevent the development of vaginal stenosis is supported by grade IIC evidence. The value of hyperbaric oxygen therapy and surgical reconstruction is supported by the much weaker grade IIIC evidence in the form of case series. REVIEWER'S CONCLUSIONS: These findings reflect the quality of published data regarding interventions for this aspect of the management of radiation induced complications. Although there is grade IC evidence, these studies are not recent, the allocation concealment is unclear in the text, and overall there is a variable level of assessment of the response, emphasising the need for more studies to be conducted with improved designs to clarify the investigative process and support the final result.

A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: an evidence based approach.

Feldmeier JJ; Hampson NB. Undersea Hyperb Med 2002 Spring;29(1):4-30.

The treatment of delayed radiation injuries (soft tissue and bony radiation necrosis) is one of thirteen conditions approved by the Hyperbaric Oxygen Therapy Committee of the Undersea and Hyperbaric Medical Society as appropriate indications for hyperbaric oxygen (HBO2). This paper provides a systematic review of the literature reporting the results of HBO2 therapy in the treatment and/or prophylaxis of delayed radiation injury. Since the introduction of the concept of evidence based medicine, the medical community in general has set out to apply more critical and stringent standards in evaluating published support for therapeutic interventions. Evidence based medicine is designed to discover the best evidence available and apply it in daily practice for treatment of the individual patient. The preferred level of evidence is the randomized controlled trial, however, other evidence has merit as well. In this review, seventy-four publications are represented reporting results of applying HBO2 in the treatment or prevention of radiation injuries. These are appraised in an evidence-based fashion by applying three established systems of evaluation. All but seven of these publications report a positive result when HBO2 is delivered as treatment for or prevention of delayed radiation injury. These results are particularly impressive in the context of alternative interventions. Without HBO2, treatment often requires radical surgical intervention, which is likely to result in complications. Other alternatives including drug therapies are rarely reported, and for the most part have not been the subject of randomized controlled trials. Based on this review, HBO2 is recommended for delayed radiation injuries for soft tissue and bony injuries of most sites. Of note, an increasing body of evidence supports HBO2 for radiation-induced necrosis of the brain. For other radiation-induced neurological injuries, additional study is required before recommendations for routine hyperbaric therapy can be made.

Hyperbaric oxygen--an effective tool to treat radiation morbidity in prostate cancer.
Mayer R; Klemen H; Quehenberger F; Sankin O; Mayer E; Hackl A; Smolle-Juettner FM. Radiother Oncol 2001 Nov;61(2):151-6.

PURPOSE: We report the results of hyperbaric oxygen therapy (HBO) used in the treatment of radiation cystitis and proctitis following irradiation of prostate cancer. MATERIALS AND METHODS: Between June 1995 and March 2000, 18 men (median age 71 years) with radiation proctitis (n=7), cystitis (n=8), and combined proctitis/cystitis (n=3) underwent HBO therapy in a multiplace chamber for a median of 26 sessions (range 2-60). The treatment schedule (2.2-2.4 atmospheres absolute, 60 min bottom time, once-a-day, 7 days a week) was set at a lower limit of 20 sessions; the upper limit was left open to symptom-related adjustment. Prior to HBO treatment, RTOG/EORTC late genitourinal (GU) morbidity was Grade 2 (n=3), Grade 3 (n=6) or Grade 4 (n=2); modified RTOG/EORTC late gastrointestinal (GI) morbidity was either Grade 2 (n=4) or Grade 3 (n=6). RESULTS: Sixteen patients underwent an adequate number of sessions. RTOG/EORTC late GU as well as modified GI morbidity scores showed a significant improvement after HBO (GI, P=0.004; GU, P=0.004; exact Wilcoxon signed rank test); bleeding ceased in five out of five patients with proctitis and in six out of eight patients with cystitis; one of those two patients, in whom an ineffective treatment outcome was obtained, went on to have a cystectomy. CONCLUSIONS: HBO treatment seems to be an effective tool to treat those patients with late GI and GU morbidity when conventional treatment has led to unsatisfactory results. Particularly in patients with radiation cystitis, HBO should not be delayed too long, as in the case of extensive bladder shrinkage improvement is hard to achieve.