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Hyperbaric medicine includes two different medical fields: hyperbaric oxygenation (HBO) as emergency and intensive care, and diving medicine. Recent topics in hyperbaric therapy include radiation oncology and regenerative medicine. Of special interest are clinical studies of radiotherapy after HBO that were conducted at some institutes to evaluate its therapeutic effects for cancer patients. A few studies have shown that HBO improves memory disturbance following traumatic brain injury and hypoxic and ischemic events. There is a great possibility that HBO enhances the therapeutic effects of radiotherapy and potentiates regenerative medicine. Randomized controlled trials, however, have indicated the re-examination of its viable treatment effects in some conditions, including decompression illness, carbon monoxide poisoning, and serious soft tissue infection. As recent trends in the treatment of decompression illness have changed on the basis of clinical series, the laws related to diving and caisson work should be amended in the future.

Neuropathic pain (NPP) refers to the pain caused by primary or secondary injury or dysfunction of the peripheral or central nervous system, and usually requires multidisciplinary treatment. However, most pharmacological and non-pharmacological interventions can only temporarily and/or moderately improve pain-related symptoms, and they often produce unbearable adverse reactions or cause drug resistance. Hyperbaric oxygen (HBO2) therapy has been widely used in the clinical treatment of some diseases due to its advantages of safety, few side effects, no resistance, and non-invasiveness. In recent years, increasing numbers of basic and clinical studies have been conducted to investigate the efficacy and mechanism of HBO2 in the treatment of NPP, and great progress has been made in this field. In this paper, we briefly introduce the pathogenesis of NPP and therapeutic effects of HBO2 and summarize the mechanisms underlying the effects of HBO2 in treating NPP, which may provide reference for the clinical treatment of pain with HBO2., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

In hyperbaric oxygen therapy (HBOT), the subject is placed in a chamber containing 100% oxygen gas at a pressure of more than one atmosphere absolute. This treatment is used to hasten tissue recovery and improve its physiological aspects, by providing an increased supply of oxygen to the damaged tissue. In this review, we discuss the consequences of hypoxia, as well as the molecular and physiological processes that occur in subjects exposed to HBOT. We discuss the efficacy of HBOT in treating neurological conditions and neurodevelopmental disorders in both humans and animal models. We summarize by discussing the challenges in this field, and explore future directions that will allow the scientific community to better understand the molecular aspects and applications of HBOT for a wide variety of neurological conditions.

Background: To assess the arterial oxygen partial pressure (PaO2) at defined time points during preoxygenation and to compare high-flow heated humidified nasal oxygenation with standard preoxygenation using oxygen insufflation via a facemask for at least 5 minutes, before intubation during induction of general anesthesia., Methods: This randomized, single-blinded, prospective study will be conducted in patients undergoing head and neck surgery. After standard monitoring, the artery catheter at the radial artery or dorsalis pedis artery will be placed and arterial blood gas analysis (ABGA) for baseline values will be performed simultaneously. Each group will be subjected to 1 of 2 preoxygenation methods (high-flow nasal cannula or simple facemask) for 5 minutes, and ABGA will be performed twice. After confirming intubation, we will start mechanical ventilation and check the vital signs and perform the final ABGA., Discussion: This trial aims to examine the trajectory of PaO2 levels during the whole preoxygenation procedure and after intubation. We hypothesize that preoxygenation with the high-flow nasal cannula will be superior to that with the face mask., Study Registration: This trial was registered with the Clinical Trial Registry (NCT03896906; ClinicalTrials.gov).

Background and Objective: Pyogenic spinal infections are rare and potentially devastating, requiring prompt recognition and management. Parallel to the ever-increasing number of invasive spinal procedures, its incidence is on a steady rise, particularly in an expanding elderly population. The aim of this study was to evaluate the efficacy of hyperbaric oxygen (HBO 2 ) therapy in the treatment of this heterogeneous group of disorders. Materials and Methods: Nineteen patients who were referred to our center for HBO 2 with a clinical diagnosis of spinal infections (vertebral osteomyelitis, pyogenic spondylitis, spondylodiscitis, surgical site infection following spine surgery, epidural abscess) were retrospectively reviewed. Results: Infection resolution was adequately achieved in 12 of 13 patients (92.3%) on magnetic resonance imaging at the end of HBO 2 treatment or during the first month of follow-up. The mean follow-up period was 11 months (range 1 month to 3 years). Conclusions: This study suggests that HBO 2 therapy is efficacious in patients with pyogenic spinal infections complicated by primary therapy failure or by medical comorbidities that may impede the eradication of microbial infection and delay wound healing. HBO 2 therapy may be useful for reducing long hospital stays, repeated surgeries, and morbidities.

Study Design: Animal study., Objectives: To evaluate the efficacy of hyperbaric oxygen (HBO) therapy for spinal cord injury (SCI) in rats with different treatment course using diffusion tensor imaging (DTI)., Setting: Hospital in Fuzhou, China., Methods: Fifty adult Sprague-Dawley rats were grouped as: (A) sham-operated group (n = 10); (B) SCI without HBO therapy group (n = 10); (C) SCI with HBO therapy for 2 weeks (SCI+HBO 2W ) group (n = 10); (D) SCI with HBO therapy for 4 weeks (SCI+HBO 4W ) group (n = 10); (E) SCI with HBO therapy for 6 weeks (SCI+HBO 6W ) group (n = 10). Basso Beattie Bresnahan (BBB) scores and diffusion tensor imaging parameters including fractional anisotropy (FA), mean diffusivity (MD), radial diffusion (RD), and axial diffusion (AD) values in the injury epicenter, as well as 2 mm rostral and caudal to the injury epicenter were collected and analyzed 6 weeks post-injury., Results: Higher BBB score and FA values were found in the SCI+HBO 4W group than in the SCI and SCI+HBO 2W groups (all P < 0.05), whereas no significant differences of these metrics were observed between the SCI+HBO 4W and SCI+HBO 6W groups. MD and RD values of the SCI+HBO 4W group were significantly lower than those of the SCI group (all P < 0.01). FA values were positively correlated with BBB scores. MD and RD values were negatively correlated with BBB scores., Conclusion: DTI parameters, especially FA, could non-invasively and quantifiably evaluate the efficacy of HBO treatment for rats with SCI and 4 weeks may be the more appropriate treatment course.

Hyperbaric oxygen therapy (HBOT) is a treatment procedure that involves breathing 100% O 2 for a certain time and under a certain pressure. HBOT is commonly administrated as a primary or alternative therapy for different diseases such as infections. In this paper, we reviewed the general aspect of HBOT procedures, the mechanisms of antimicrobial effects and the application in the treatment of infections. Parts of the antimicrobial effects of HBOT are believed to result of reactive from the formation of reactive oxygen species (ROS). It is also said that HBOT enhances the antimicrobial effects of the immune system and has an additive or synergistic effect with certain antimicrobial agents. HBOT has been described as a useful procedure for different infections, particularly in deep and chronic infections such as necrotizing fasciitis, osteomyelitis, chronic soft tissue infections, and infective endocarditis. The anti-inflammation property of HBOT has demonstrated that it may play a significant role in decreasing tissue damage and infection expansion. Patients treated by HBOT need carful pre-examination and monitoring. If safety standards are strictly tracked, HBOT can be considered a suitable procedure with an apt rate of complication., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Chronic pain is one of the most common clinical presentations in the primary care settings. In the US, Fibromyalgia (FM) affects about 1-3% of adults and commonly occurs in adults between the ages of 40-50 years. FM causes widespread muscular pain and tenderness with hyperalgesia and allodynia and may be associated with other somatic complaints. Hyperbaric oxygen therapy (HBOT) has been utilized and has recently shown promising effects in the management of FM and other chronic pain disorders. In HBOT, the intermittent breathing of 100% oxygen in a pressurized chamber where the pressure is higher than 1 atmosphere absolute (ATA) has been utilized. HBOT exhibits a significant anti-inflammatory effect through reducing production of glial cells and inflammatory mediators which results in pain alleviation in different chronic pain conditions. HBOT can also influence neuroplasticity and affects the mitochondrial mechanisms resulting in functional brain changes. In addition to that, HBOT stimulates nitric oxide (NO) synthesis which helps in alleviating hyperalgesia and NO-dependent release of endogenous opioids which seemed to be the primary HBOT mechanism of antinociception. Moreover, aerobic exercise and meditative movement therapies (MMT) have gained attention for their role in pain alleviation through different anti-inflammatory and antioxidant mechanisms. In this review, we aim to elucidate the different mechanisms of HBOT and aerobic exercise in attenuating pain as adjuvant therapy in the multidisciplinary treatment strategy of chronic pain, and more particularly fibromyalgia., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Study Design: A controlled laboratory study., Objective: The aim of this study was to analyze the effectiveness of hyperbaric therapy (HT) using mild and moderate models of spinal cord injury (SCI)., Summary of Background Data: SCI can cause permanent impairment with socioeconomic consequences. The motor deficit occurs by two mechanisms: destruction of neuronal cells and local inflammatory response, resulting in hypoxia. HT acts by increasing oxygen in the injured area., Methods: Thoracic laminectomy was performed in 72 female Wistar rats. The MASCIS impactor was used at 12.5 mm (n = 35) and 25 mm (n = 35) of height to perform, respectively, mild and moderate SCI. Muscle strength was assessed through the Basso, Beattie, and Bresnahan scale (BBB) on days 1, 7, 14, 21, and 28 after SCI. The animals were randomized into five subgroups with seven animals each: (1) control group had SCI without HT; (2) HT 30 minutes after SCI; (3) HT 30 minutes after SCI and daily for 7 days; (4) HT 12 hours after SCI; and (5) HT 12 hours after SCI and daily for 7 days. HT was performed at 2.5 atm for 1 hour., Results: There was a linear relationship between injury severity and motor deficit until day 21, with similar BBB scores on day 28. A pattern of uniform lesions was observed in the mild SCI, with lower variation of BBB when compared with moderate SCI. All animals that underwent HT had significant improvement in motor function and histology when compared with control group. Regardless of the injury model, animals submitted to 7-day protocols had an early improvement in motor function and a smaller area of histological injury., Conclusion: The present study reported that the sooner HT is begun after mild and moderate SCI and the larger the number of sessions, the greater and earlier is the motor recovery and smaller is the tissue injury., Level of Evidence: N/A.

Overutilization of hyperbaric oxygen therapy (HBOT) is commonplace and primarily associated with outpatient wound care. While the number of hospitals providing HBOT is at an all-time high, the number of those willing to treat patients in immediate need is at an all-time low. Huge areas of the country, including major population areas, are now completely devoid of 24/7 HBOT availability and inpatient access. Purchasers of healthcare, including the Centers for Medicare and Medicaid Services, have become increasingly concerned to the point that several strategies have been introduced to constructively deal with this issue. This commentary serves as a counterpoint to concerns that one such approach, prior authorization of elective indications, adversely delays medically necessary care. The historical evolution of HBOT practice will be described to underscore how this problem has become so widespread and, to date, largely unchecked. It will also address the paradoxical national crisis of access for emergencies.

Background: High-altitude flight simulation familiarizes military trainees with the symptoms of hypoxia to prepare them for emergency situations. Decompression sickness (DCS) can occur as a result of these simulations. In cases when ground-level supplemental oxygen does not resolve symptoms, hyperbaric oxygen (HBO) therapy is indicated. Many military hyperbaric chambers have been closed because of cost reductions, necessitating partnerships with community hospitals to ensure access to treatment., Materials and Methods: This article describes the unique arrangement between a community hospital in Colorado and a military training site to treat DCS cases emergently. We gathered cost data from the community hospital to estimate and compare the cost of providing HBO therapy in the hospital versus a standalone chamber similar to the former military hyperbaric chamber., Results: Since the closure of the military hyperbaric chamber, the community hospital treated an estimated 50 patients with DCS requiring HBO therapy attributed to high-altitude flight simulation between October 2003 and April 2015. Cost to the institution providing HBO treatment varies widely on the basis of patient volume. Assuming a volume of five treatments, per-treatment cost at a standalone center is $95,380. In contrast, per-treatment cost at the hospital assuming a volume of 1,000 treatments commensurate with the hospital's ability to bill for other services is $698 per treatment., Conclusion: The cost analysis demonstrates that the per-treatment cost of operating a standalone HBO therapy center may be greater than 100 times that of operating a center at a community hospital, suggesting the arrangement is beneficial to the military., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

Competing Interests: The author of this paper declares no conflicts of interest exist with this submission.

As the title implies, much appears amiss with hyperbaric medicine. Long recognized for its life-saving, CNS-sparing,infection-fighting and tissue-salving attributes, its current application has been rightly called into question by a broad cross-section of health care delivery system stakeholders [1, 2, 3, 4, 5]. This paper will examine what lies behind the stunning loss of availability for a majority of the Federal Drug Administration-approved uses, arguably those for which patients have the most to gain. It will address overutilization in the context of an erosion of practice standards and widespread manipulation of the reimbursement process. It will make suggestions aimed at restoring its broader availability across the full extent of FDA-approved uses. Finally, it offers guidance to ensure that HBO₂ therapy is employed only when medically necessary by adoption of the drug administration "rights" principle, namely the right indication for the right patient at the right time and only for the right amount of time., Competing Interests: The author of this paper declares no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post-operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: Neuroinflammation plays an important role in secondary tissue damage after traumatic brain injury (TBI). Recently, the inflammasome-mediated inflammatory pathway has been observed in the inflammatory response of TBI. In this study, we investigated the influence of hyperbaric oxygen therapy (HBOT) on inflammasome activation after TBI., Methods: The experimental mice were randomly divided into 4 groups as follows: sham-operated normobaric air (21% O2 at one absolute atmosphere), HBOT only, TBI + normobaric air and TBI + HBOT. Following the evaluation of motor deficits and brain edema, the expression of inflammasome components and effectors was measured by qRT-PCR and Western blotting. Moreover, alterations in IL-1β, IL-18 and high-mobility group box 1 (HMGB1) were calculated by enzyme-linked immunosorbent assay at each time point after injury., Results: HBOT improved motor score and reduced brain edema. Furthermore, it suppressed protein expression of inflammasome components and reduced the levels of IL-1β and IL-18, accompanied by the reduction of HMGB1 in brain tissues and serum., Conclusion: These results suggest that HBOT may alleviate the inflammatory response after TBI by inhibiting the activation of inflammasome signaling., (© 2016 S. Karger AG, Basel.)

Traumatic brain injury (TBI) imparts a significant health burden in the United States, leaving many patients with chronic deficits. Improvement in clinical outcome following TBI has been hindered by a lack of treatments that have proven successful during phase III trials. Research remains active into a variety of non-pharmacologic, small molecule, endocrine and cell based therapies. Of particular focus in this review are the recent therapeutic avenues that have undergone clinical investigation and the mechanisms by which cell therapies may mediate recovery in severe TBI. Preclinical data show cell therapies to provide benefit when administered systemically or with transplantation to the site of injury. Increasingly, studies have shown that these cells are able to attenuate the inflammatory response to injury and stimulate production of neurotrophic factors. In animal models, beneficial effects on blood-brain barrier permeability, neuroprotection and neural repair through enhanced axonal remodeling have been observed. Clinical investigation with cell therapies for TBI remains ongoing., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Diabetic foot ulceration is a serious complication of diabetes mellitus worldwide and the most common cause of hospitalization in diabetic patients. The etiology of diabetic foot ulcerations is complex due to their multifactorial nature. Polyneuropathy plays an important role in the pathophysiology of diabetic foot ulceration. Proper adherence to standard treatment strategies and interdisciplinary cooperation can reduce the high rates of major amputations.

Objective: The aim was to investigate and define possible alterations in cerebral activity during prolonged hyperbaric oxygen exposure and decompression as compared to baseline activity., Methods: Thirty-two channel electroencephalography (EEG) was recorded with a Bluetooth EEG system in 11 subjects. A 20-min EEG recording was carried out under three different conditions: breathing air inside a hyperbaric chamber at sea level; breathing oxygen at a simulated depth of 18 msw; breathing air at sea level after decompression. Relative EEG power was estimated in frequency ranges., Results: During oxygen breathing, brain activity showed an early fast delta decrease in the posterior regions, with a synchronous and significant increase in alpha in the same regions. After decompression, the delta relative power decrease was uniformly distributed over the cerebral cortex until minute 8, and the alpha relative power was maximal in the posterior regions during the first 2 min., Conclusions: These results may be relevant for establishing a reference point in future studies on oxygen-sensitive subjects who reported problems during oxygen diving., Significance: Significant changes in EEG relative power suggest that it may be possible to define and recognize landmarks of oxygen-induced brain activity, which would be useful in the medical treatment of subjects reporting "oxygen-toxicity diving-related problems"., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

There is some evidence for the benefit of hyperbaric oxygen therapy in late radiation tissue injury (LRTI) affecting the head, neck and lower bowel, but there is little evidence for or against the benefit in other tissues (e.g. the breast) affected by LRTI. There is a need for large prospective trials including quality-of-life and cost-effectiveness studies, because hyperbaric oxygen therapy is becoming more popular.

Advances in the treatment of chronic wounds* have steadily occurred over the past decade and include the specialized use of dynamic compression therapy, implementation of moist wound care techniques, chronic lymphedema therapy, negative pressure wound therapy, arterial compression therapy and application of off-loading devices. General medical practitioners should recognize when timely patient referral to a comprehensive wound care center is indicated. The clinical practice of HBOT and its scientific basis has also advanced significantly during this same time period. HBOT is a therapeutic tool with many qualities that are unique to medical care and enable difficult and otherwise untreatable conditions to be safely and effectively managed. Level 1 evidence exists for HBOT and the therapeutic indications are growing. It is the responsibility of all practitioners to become informed about the modern principles and practice of HBOT. Clinicians should take the advice of Mark Twain: "Supposing is good but finding out is better." It is the responsibility of educational institutions and medical societies to become informed and actively engaged in hyperbaric medical care, education and research. This will benefit our patients as well as our systems of medical care. There is now ample access to hyperbaric oxygen facilities and expertise with the state. There is a growing need for HBOT services due to the rising incidence of obesity and diabetes combined with an aging demographic. Appropriate networks and patterns of referral have lagged behind this demand due to a generalized lack of understanding of the true risks, benefits and indications for HBOT. This review will hopefully begin to address this problem. Hyperbaric medicine is in an early phase of development. The current and future demand for clinical services will drive development of research and educational programs. Only through continued efforts for perform high quality research and education will the full potential of HBOT be realized. Much remains to be done. As systems for the delivery of healthcare enter an era of population management, the regenerative potential of hyperbaric therapies should improve quality of and reduce costs and enable us to meet the challenge of providing care for the growing population of chronic wound patients.

Hyperbaric oxygen therapy has a rich and diverse history, both in the United States and around the world. From its early uses in war to the building of bridges, and through many introductions to innovations in the medical community, it has been debated and modified until its ultimate acceptance in multiple areas of patient care. Numerous areas of patient care use hyperbaric therapy, from wound care to military applications, in both single monoplace chambers and multipatient settings in larger chambers. This article provides an overview on the history, trial and error, and modern development of hyperbaric oxygen in clinical care therapies in 21st century medicine and nursing.

Despite considerable advancements in the therapy of malignant glioma in recent years with modern radiation and surgical techniques, alkylating and antiangiogenic chemotherapy, as well as molecular-based treatment decisions, treatment outcomes are mostly unsatisfactory. Understandably, patients often ask for experimental, sometimes unusual therapeutic modalities and this should be integrated into the clinical practice. In addition to experimental therapeutic approaches based on novel drugs, viral agents, immunotherapy and radiation approaches, experimental procedures of interest for patients particularly encompass mechanical approaches with the aim at physically altering the tumor tissue by temperature, oxygenation or magnetization. These mechanical procedures are based on intuitive concepts and promise fewer side effects than other experimental approaches. In addition, the requirements for approval by medical device regulations in terms of proof of efficacy are generally less stringent. As a consequence approaches, such as hyperbaric oxygenation, hyperthermia and electric fields, which are often heavily advertised and in part reimbursed by health insurances, have been used for many years, often by centers not specialized in the treatment of brain tumor patients, although sound data from prospective controlled clinical trials that determine which patients in which situation may benefit, are generally lacking. In this review we review these clinical therapeutic approaches.

Hyperbaric Medicine studies the physiology and the treatment of pathologies in an environment with above-atmospheric pressure. Hyperbaric Oxygen Therapy, consists in administering 100% oxygen at pressures higher than atmospheric pressure (usually 2 to 3 times higher). This therapy is increasingly used in a wide range of clinical areas, treating both ambulatory and inpatients, including those critically ill. Nevertheless, it involves mechanisms sometimes poorly understood and somewhat complex facilities. This article aims to spread the word about Hyperbaric Medicine in Portugal, contribute to a better understanding of its physiological basis, and review its indications, risks and clinical utility.

Oxygen is one of the most commonly used therapeutic agents. Injudicious use of oxygen at high partial pressures (hyperoxia) for unproven indications, its known toxic potential, and the acknowledged roles of reactive oxygen species in tissue injury led to skepticism regarding its use. A large body of data indicates that hyperoxia exerts an extensive profile of physiologic and pharmacologic effects that improve tissue oxygenation, exert anti-inflammatory and antibacterial effects, and augment tissue repair mechanisms. These data set the rationale for the use of hyperoxia in a list of clinical conditions characterized by tissue hypoxia, infection, and consequential impaired tissue repair. Data on regional hemodynamic effects of hyperoxia and recent compelling evidence on its anti-inflammatory actions incited a surge of interest in the potential therapeutic effects of hyperoxia in myocardial revascularization and protection, in traumatic and nontraumatic ischemicanoxic brain insults, and in prevention of surgical site infections and in alleviation of septic and nonseptic local and systemic inflammatory responses. Although the margin of safety between effective and potentially toxic doses of oxygen is relatively narrow, the ability to carefully control its dose, meticulous adherence to currently accepted therapeutic protocols, and individually tailored treatment regimens make it a cost-effective safe drug.

Because clinicians require objectively demonstrable neurological deficits to confirm a diagnosis, the recognition of embolic events in the nervous system is generally restricted to the effects of ischemic necrosis produced by arterial occlusion. However, magnetic resonance imaging (MRI) has shown that lesser degrees of damage associated with small emboli are common, especially in the mid brain, and are usually clinically silent. They are frequently associated with atheromatous embolism in the elderly, but microembolic debris, such as fat, is common in the systemic venous return of healthy people and generally trapped in the microcirculation of the lung being removed by phagocytosis. However, pulmonary filtration may fail and microemboli may also pass through an atrial septal defect in so-called 'paradoxical' embolism. Studies of bubbles formed on decompression in diving have demonstrated the importance of pulmonary filtration in the protection of the nervous system and that filtration is size dependant, as small bubbles may escape entrapment. Fluid and even small solid emboli, arresting in or passing through the cerebral circulation, do not cause infarction, but disturb the blood-brain barrier inducing what has been termed the 'perivenous syndrome'. The nutrition of areas of the white matter of both the cerebral medulla and the spinal cord depends on long draining veins which have been shown to have surrounding capillary free zones. Because of the high oxygen extraction in the microcirculation of the gray matter of the central nervous system, the venous blood has low oxygen content. When this is reduced further by embolic events, tissue oxygenation may fall to critically low levels, leading to blood-brain barrier dysfunction, inflammation, demyelination and eventually, axonal damage. These are the hallmarks of the early lesions of multiple sclerosis where MR spectroscopy has also shown the presence of lactic acid. Significant elevation of the venous oxygen tension requires oxygen to be provided under hyperbaric conditions. Arterial tension is typically increased ten-fold breathing oxygen at 2 atmospheres absolute (ATA), but this results in only a 1.5-fold increase in the cerebral venous oxygen tension. The treatment of decompression sickness, and both animal and clinical studies, have confirmed the value of oxygen provided under hyperbaric conditions in the restoration and preservation of neurological function in the 'perivenous' syndrome.

Neuroprotective drugs have so far failed clinical trials, at high cost, and intravenous tissue plasminogen activator (i.v. tPA) remains the only FDA-approved acute stroke therapy. Hyperoxia, acting via multiple direct and indirect mechanisms, may be a powerful neuroprotective strategy to salvage acutely ischemic brain tissue and extend the time window for acute stroke treatment. Of the available oxygen delivery methods, hyperbaric oxygen therapy (HBO) appears to be the most potent, while even normobaric oxygen therapy (NBO) may be effective if started promptly after stroke onset. HBO has so far failed to show efficacy in three clinical trials. The failure of these trials is probably attributable to factors such as delayed time to therapy, inadequate sample size and use of excessive chamber pressures. Previous trials did not assess long-term benefit in patients with tissue reperfusion. In this modern era of stroke thrombolysis and advanced neuroimaging, oxygen therapy may have renewed significance. If applied within the first few hours after stroke onset or in patients with imaging evidence of salvageable brain tissue, oxygen therapy could be used to 'buy time' for the administration of thrombolytic or neuroprotective drugs. This article reviews the history and current rationale for using oxygen therapy in stroke, the mechanisms of action of HBO and the results of animal and human studies of hyperoxia in cerebrovascular diseases.

CO is likely to be the most common cause of poisoning worldwide and often results in persistent neuropathologic and cognitive sequelae. While the displacement of oxygen from hemoglobin by CO has overshadowed the myriad mechanisms by which CO causes injury, mere oxygen displacement has endured as the etiology of CO poisonings and perpetuated a cascade of misdiagnosis, misunderstandings and confusion regarding how and when to treat CO poisoning. Hyperbaric oxygen benefits the brain more than normobaric oxygen by, e.g. improving energy metabolism, preventing lipid peroxidation and decreasing neutrophil adherence. Randomized controlled trials have definitively shown hyperbaric oxygen as the only efficacious therapy for acute CO poisoning if delayed neurological sequelae are to be minimized. Normobaric oxygen should not be used between multiple hyperbaric oxygen treatments as this can contribute to toxicity. Hyperbaric oxygen seems to also have potential in the delayed treatment of CO poisoning using multiple treatments of low dose of oxygen; however, oxygen dosing issues are not yet fully understood for either acute or delayed treatment. It would behoove medical decision-makers to embrace this important tool and make it more accessible as well as helping to disseminate to the medical community what is now known from the available literature.

Objectives: This critical literature review examines historical and current investigations on the efficacy and mechanisms of hyperbaric oxygen (HBO) treatment in traumatic brain injury (TBI). Potential safety risks and oxygen toxicity, as well as HBO's future potential, are also discussed., Methods: Directed literature review., Results: Historically, cerebral vasoconstriction and increased oxygen availability were seen as the primary mechanisms of HBO in TBI. HBO now appears to be improving cerebral aerobic metabolism at a cellular level, namely, by enhancing damaged mitochondrial recovery. HBO given at the ideal treatment paradigm, 1.5 ATA for 60 minutes, does not appear to produce oxygen toxicity and is relatively safe., Discussion: The use of HBO in TBI remains controversial. Growing evidence, however, shows that HBO may be a potential treatment for patients with severe brain injury. Further investigations, including a multicenter prospective randomized clinical trial, will be required to definitively define the role of HBO in severe TBI.

Peripheral nerves are essential connections between the central nervous system and muscles, autonomic structures and sensory organs. Their injury is one of the major causes for severe and longstanding impairment in limb function. Acute peripheral nerve lesion has an important inflammatory component and is considered as ischemia-reperfusion (IR) injury. Surgical repair has been the standard of care in peripheral nerve lesion. It has reached optimal technical development but the end results still remain unpredictable and complete functional recovery is rare. Nevertheless, nerve repair is not primarily a mechanical problem and microsurgery is not the only key to success. Lately, there have been efforts to develop alternatives to nerve graft. Work has been carried out in basal lamina scaffolds, biologic and non-biologic structures in combination with neurotrophic factors and/or Schwann cells, tissues, immunosuppressive agents, growth factors, cell transplantation, principles of artificial sensory function, gene technology, gangliosides, implantation of microchips, hormones, electromagnetic fields and hyperbaric oxygenation (HBO). HBO appears to be a beneficial adjunctive treatment for surgical repair in the acute peripheral nerve lesion, when used at lower pressures and in a timely fashion (<6 hours).

Purpose: Recent data demonstrate that the mortality rate from carbon monoxide poisoning has declined over the past 2 decades. It is not known whether this decrease in mortality is reflective of the total burden of carbon monoxide poisoning. This study sought to examine trends in other potential indicators of the incidence of carbon monoxide poisoning in the United States., Basic Procedures: Published data from US poison control centers (PCCs) were used to calculate annual rates of calls regarding carbon monoxide exposures. Data on numbers of carbon monoxide-poisoned patients treated with hyperbaric oxygen (HBO) were used to calculate annual treatment rates. Trends in rates of carbon monoxide-related mortality, calls to PCCs, and HBO treatment were then compared., Main Findings: Contrary to the decline in carbon monoxide-related mortality from 1968 to 1998, rates of calls to PCCs significantly increased over the same period. Neither rates of PCC calls nor HBO treatment changed significantly from 1992 to 2002. The latter 2 measures were strongly correlated., Principal Conclusions: Although deaths from carbon monoxide poisoning have clearly decreased in the United States, other indicators of the incidence of the condition suggest that the total burden (fatal and nonfatal) may not have significantly changed. Efforts to prevent carbon monoxide poisoning should not be relaxed.

Background: Hyperbaric oxygen (HBO) therapy of cerebral ischemia has been evaluated in a number of human and animal studies; however, there is presently no consensus on its efficacy., Methods: We present a review of animal and human studies on HBO therapy of cerebral ischemia as well as present potential mechanisms of action of HBO., Results: Animal studies of HBO have shown promise by reducing infarct size and improving neurologic outcome. HBO has also been shown to inhibit inflammation and apoptosis after cerebral ischemia. Early reports in humans also suggested benefit in stroke patients treated with HBO. Recent randomized, controlled human studies, however, have not shown benefit, although all were limited by small sample size. Important differences between animal and human studies suggest HBO might be more effective in stroke within the first few hours and at a pressure of 2-3 ATA., Conclusions: The clinical usefulness of HBO in the treatment of cerebral ischemia is not yet certain. Attention to emerging pathophysiologic data should be taken into consideration in design of any future clinical trials of HBO in acute ischemic stroke., (2005 S. Karger AG, Basel)

Hyperbaric medicine is the fascinating use of barometric pressure for delivering increased oxygen dissolved in plasma to body tissues. Hyperbaric oxygen therapy (HOT) or hyperbaric oxygen (HBO) involves intermittent inhalation of 100% oxygen under a pressure exceeding that of the atmosphere, that is greater than 1 atmosphere absolute (ATA). Therapy is given in special therapeutic chambers which were earlier used primarily to treat illnesses of deep sea divers. There is recently a renewed interest in this field all over the world. Acute traumatic wounds, crush injuries, burns, gas gangrene and compartment syndrome are indications where addition of hyperbaric oxygen may be life and limb saving. Patients who are suffering with non-healing ulcers, decubitus ulcers (bed sores) and all late sequelae of radiation therapy are also benefited with HBO therapy. Acute hearing loss and many neurological illnesses are also now known to possibly benefit from hyperbaric oxygen therapy. This article aims to give a brief overview of the rationale, existing trends and applications of this therapy.

We envisage that hyperbaric oxygen (HBO) would ameliorate islet anoxia, preventing early graft failure. Thus, treatment of HBO to diabetic recipients should improve the outcome of islet transplantation. We tested this hypothesis by syngeneically transplanting insufficient number of islets (150 islets) into streptozotocin-diabetic C57BL/6 mice, each followed by HBO (2.4 ATA, 100% O2) therapy for 1.5 h from day 0 to 28, once daily (group A) or twice daily (group B), or from day 5 to 28, once daily (group C) or twice daily (group D), 6 days/week. Recipients without HBO treatment served as controls. At day 28 after transplantation, groups B, C, and D gained weight and had lower blood glucose compared with their baseline values. In addition, groups B and D had higher insulin content of the graft than the controls. To determine the optimal timing of HBO therapy, groups B and D were compared with recipients treated with HBO twice daily, 6 days/week, from day -14 to 0 (group E) and from day -14 to 28 (group F). At day 28 after transplantation, groups B, D, E, and F had significantly lower blood glucose than their individual baseline values and higher insulin content of the graft than controls. But only group F had more beta-cell mass of the graft than controls. These findings lend credence to the expectation that peritransplant application of adequate frequency of HBO to diabetic recipients would enhance the performance and growth of the islet graft, resulting in an improvement of the outcome of the transplantation.

Novel therapies for the next decade include hyperbaric oxygen, nitric oxide, and extracorporeal membrane oxygenation. Hyperbaric oxygen delivers oxygen at a pressure greater than one atmosphere and has been used in diseases ranging from decompression sickness to carbon monoxide poisoning. Inhaled nitric oxide, a potent vasodilator, has been used in the acute respiratory distress syndrome and for the diagnosis and treatment of pulmonary hypertension. Extracorporeal membrane oxygenation (ECMO) has been used to provide cardiopulmonary bypass support, particularly in the pediatric and neonatal population.