The appropriate indications for HBO2T are controversial and evolving. Practitioners in this area are in a unique position. Unlike most branches of medicine, hyperbaric physicians do not deal with a range of disorders within a defined body system (e.g., cardiology), nor are they masters of a therapy specifically designed for a single group of disorders (e.g., radiotherapy). Inevitably, the encroachment of hyperbaric physicians into other medical fields generates suspicion from specialist practitioners in those fields. At the same time this relatively benign therapy, the prescription and delivery of which requires no medical license, attracts both charlatans and well-motivated proselytizers who tout the benefits of oxygen for a plethora of chronic incurable diseases. This battle on two fronts has meant that mainstream hyperbaric physicians have been careful to claim effectiveness only for those conditions where there is a reasonable body of supporting evidence. In 1977, the UHMS systematically examined the claims for the routine use of HBO2T in more than 100 disorders and found sufficient evidence to support routine use in only 12. The Hyperbaric Oxygen Therapy Committee of that organization has continued to update this list periodically with an increasingly formalized system of appraisal for new indications and emerging evidence (Table e52–1). Around the world, other relevant medical organizations have generally taken a similar approach, although indications vary considerably—particularly those recommended by hyperbaric medical societies in Russia and China where HBO2T has gained much wider support than in the United States, Europe, and Australasia. Recently, several Cochrane reviews have examined the randomized trial evidence for many putative indications, and attempts have been made to examine the cost-effectiveness of HBO2T across a range of conditions. Table e52–2 is a synthesis of these two approaches and lists the estimated cost of attaining health outcomes with the use of HBO2T. Any savings associated with alternative treatment strategies avoided as a result of HBO2T have not been taken into account in these estimates (e.g., the avoidance of lower leg amputation in diabetic foot ulcers). Following are short reviews of several important indications that are accepted by the UHMS.
Late Radiation Tissue Injury
Radiotherapy is a well-established treatment for suitable malignancies. In the United States alone, approximately 300,000 individuals annually will become long-term survivors of cancer treated by irradiation. Serious radiation-related complications developing months or years after treatment [late radiation tissue injury (LRTI)] will significantly affect between 5 and 15% of those long-term survivors, although incidence varies widely with dose, age, and site. LRTI is most common in the head and neck, chest wall, breast, and pelvis.
Pathology and Clinical Course
With time, tissues undergo a progressive deterioration characterized by a reduction in the density of small blood vessels (reduced vascularity) and the replacement of normal tissue with dense fibrous tissue (fibrosis). Ultimately, and often triggered by a further physical insult such as surgery or infection, there may be insufficient oxygen to sustain normal function, and the tissue becomes necrotic (radiation necrosis). LRTI may be life-threatening and significantly reduce quality of life. Historically, the management of these injuries has been unsatisfactory. Conservative treatment is usually restricted to symptom management, while definitive treatment traditionally entails surgery to remove the affected part and extensive repair. Surgical intervention in an irradiated field is often disfiguring and associated with an increased incidence of delayed healing, breakdown of a surgical wound, or infection. HBO2T may act by several mechanisms to improve this situation, including edema reduction, vasculogenesis, and enhancement of macrophage activity (Fig. e52-3). The intermittent application of HBO2 is the only intervention shown to increase the microvascular density in irradiated tissue.
The typical course of HBO2T consists of 30 once-daily compressions to 2–2.4 ATA for 1.5 to 2 hours each session. This course is often bracketed around surgical intervention if required. While HBO2T has been used for LRTI since at least 1975, most clinical studies have been limited to small case series or individual case reports. In a recent semi-quantitative review, Feldmeier and Hampson located 71 such reports involving a total of 1193 patients across eight different tissues. There were clinically significant improvements in the majority of patients and only 7 of 71 reports indicated a generally poor response to HBO2T. A recent Cochrane systematic review with meta-analysis included six randomized trials published since 1985 and drew the following conclusions (see Table e52–2 for numbers needed to treat): HBO2T improves healing in radiation proctitis [relative risk (RR) of healing with HBO2T 2.7, 95% confidence interval (CI) 1.2–6] and following hemimandibulectomy and reconstruction of the mandible (RR 1.4, CI 1.1–1.8); HBO2T improves the probability of achieving mucosal coverage (RR 1.4, CI 1.2–1.6) and the restoration of bony continuity with osteoradionecrosis (ORN) (RR 1.4, CI 1.1–1.8); HBO2T prevents the development of ORN following tooth extraction from a radiation field (RR 1.4, CI 1.08–1.7); and reduces the risk of wound dehiscence following grafts and flaps in the head and neck (RR 4.2, CI 1.1–16.8). Conversely, there was no evidence of benefit in established radiation brachial plexus lesions or brain injury.
A problem wound is any cutaneous ulceration that requires a prolonged time to heal, does not heal, or recurs. In general, wounds referred to hyperbaric facilities are those where sustained attempts to heal by other means have failed. Problem wounds are common and constitute a significant health problem. It has been estimated that 1% of the population of industrialized countries will experience a leg ulcer at some time. The global cost of chronic wound care may be as high as $25 billion US per year.
Pathology and Clinical Course
By definition, chronic wounds are indolent or progressive and resistant to the wide array of treatments applied. While there are many contributing factors, most commonly these wounds arise in association with one or more comorbidities such as diabetes, peripheral venous or arterial disease, or prolonged pressure (decubitus ulcers). First-line treatments are aimed at correction of the underlying pathology (e.g., vascular reconstruction, compression bandaging, or normalization of blood glucose level) and HBO2T is an adjunctive therapy that may be added to good general wound care practice in order to maximize the chance of healing.
For most indolent wounds hypoxia is a major contributor to failure to heal. Many guidelines to patient selection for HBO2T include the interpretation of transcutaneous oxygen tensions around the wound while breathing air and oxygen at pressure (Fig. e52-4). Wound healing is a complex and incompletely understood process. While it appears that in acute wounds healing is stimulated by the initial hypoxia, low pH, and high lactate concentrations found in freshly injured tissue, some elements of tissue repair are extremely oxygen dependent, for example, collagen elaboration and deposition by fibroblasts, and bacterial killing by macrophages. In this complicated interaction between wound hypoxia and peri-wound oxygenation, successful healing relies on adequate tissue oxygenation in the area surrounding the fresh wound. Certainly, wounds that lie in hypoxic tissue beds are those that most often display poor or absent healing. Some causes of tissue hypoxia will be reversible with HBO2T, while some will not (e.g., in the presence of severe large vessel disease). When tissue hypoxia can be overcome by a high driving pressure of oxygen in the arterial blood, this can be demonstrated by measuring the tissue partial pressure of oxygen using an implantable oxygen electrode or more commonly, a modified transcutaneous Clarke electrode.
Suitability for hyperbaric oxygen therapy (HBO2T) guided by transcutaneous oximetry around the wound bed.
*In diabetic patients <50 mmHg may be more appropriate. PtcO2, transcutaneous oxygen pressure.
The intermittent presentation of oxygen to those hypoxic tissues facilitates a resumption of healing (Fig. e52-3). As discussed above, these short exposures to high oxygen tensions have long-lasting effects (at least 24 hours) on a wide range of healing processes. The result is a gradual improvement in oxygen tension around the wound that reaches a plateau in experimental studies at about 20 treatments over 4 weeks. Improvements in oxygenation are associated with an eight- to ninefold increase in vascular density over both normobaric oxygen and air-breathing controls.
The typical course of HBO2T consists of 20 to 30 once-daily compressions to 2–2.4 ATA for 1.5 to 2 hours each session, but is highly dependent on the clinical response. There are many case series in the literature supporting the use of HBO2T for a wide range of problem wounds. Both retrospective and prospective cohort studies suggest that 6 months after a course of therapy about 70% of indolent ulcers will be healed or nearly so. Often the mean period such ulcers have been present is many months or years, suggesting that the application of HBO2T has a profound effect, either primarily or as a facilitator of other strategies. A Cochrane review included five randomized controlled trials (RCTs) and concluded that HBO2T reduces the rate of major amputation in people who have chronic foot ulcers as a result of diabetes [the RR of amputation with HBO2T was 0.31 (95% CI 0.13–0.71) and suggests the number needed to receive HBO2T to avoid one major amputation is 4 (95% CI 3–11)]. Randomized data on wound healing are notably lacking. Only one small trial reported this outcome and although there was a trend toward better outcomes with HBO2T, the result is not statistically convincing (78% healed with HBO2T versus 44% with sham).
Carbon Monoxide Poisoning
Carbon monoxide (CO) is a colorless, odorless gas formed during incomplete hydrocarbon combustion. While CO is an essential endogenous neurotransmitter linked to NO metabolism and activity, it is also a leading cause of poisoning death and in the United States alone, results in more than 50,000 emergency department visits per year and about 2000 deaths. While there are large variations from country to country, about half of nonlethal exposures are due to self-harm. Accidental poisoning is commonly associated with defective or improperly installed heaters, house fires, and industrial exposures. The motor vehicle is by far the most common source of intentional poisoning.
Pathology and Clinical Course
The pathophysiology of carbon monoxide exposure is incompletely understood. CO binds to hemoglobin with an affinity more than 200 times that of oxygen, and this not only directly reduces the oxygen-carrying capacity of blood, but further promotes tissue hypoxia by shifting the oxyhemoglobin dissociation curve to the left. CO is also an anesthetic agent that inhibits evoked responses and narcotizes experimental animals in a dose-dependent manner. The associated loss of airway patency together with reduced oxygen carriage in blood may cause death from acute arterial hypoxia in severe poisoning. CO may also cause harm by other mechanisms including direct disruption of cellular oxidative processes, binding to myoglobin and hepatic cytochromes, and peroxidation of brain lipids.
The brain and heart are the most sensitive target organs due to their high blood flow, poor tolerance of hypoxia, and high oxygen requirements. Minor exposure may be asymptomatic or present with vague constitutional symptoms such as headache, lethargy, and nausea, while higher doses may present with poor concentration and cognition, short-term memory loss, confusion, seizures, and loss of consciousness. While carboxyhemoglobin (COHb) levels on admission do not necessarily reflect the severity or the prognosis of CO poisoning, cardiorespiratory arrest carries a very poor prognosis. Over the longer term, surviving patients commonly have neuropsychological sequelae that may present days to months after poisoning. Motor disturbances, peripheral neuropathy, hearing loss, vestibular abnormalities, dementia, and psychosis have all been reported. Risk factors for poor outcome are age >35 years, exposure for >24 hours, acidosis, and loss of consciousness.
The typical course of HBO2T consists of two to three compressions to 2–2.4 ATA for 1.5 to 2 hours each session. It is common for the first two compressions to be delivered within 24 hours of the exposure. CO poisoning is one of the longest-standing indications for HBO2T—based largely on the obvious connection between exposure, tissue hypoxia, and the ability of HBO2T rapidly to overcome hypoxemia. CO is eliminated rapidly via the lungs on application of HBO2T, with a half-life of about 21 minutes at 2.0 ATA versus 5.5 hours breathing air and 71 minutes breathing oxygen at sea level. In practice, however, it seems unlikely that HBO2T can be delivered in time to prevent either acute hypoxic death or irreversible global cerebral hypoxic injury. If HBO2T is beneficial in CO poisoning, it must reduce the likelihood of persisting and/or delayed neurocognitive deficit through a mechanism other than the simple reversal of arterial hypoxia due to high levels of COHb. The difficulty in accurately assessing neurocognitive deficit has been one of the primary sources of controversy surrounding the clinical evidence in this area. To date there have been six randomized controlled trials of HBO2T for CO poisoning, although only four have been reported in full. While a Cochrane review suggested that overall there is insufficient evidence to confirm a beneficial effect of HBO2T on the chance of persisting neurocognitive deficit following poisoning [34% of patients treated with oxygen at 1 atmosphere versus 29%, of those treated with HBO2T, odds ratio (OR) 0.78; 95% CI 0.54–1.1], this may have more to do with poor reporting and inadequate follow-up than with evidence that HBO2T is not effective. The interpretation of the literature has much to do with how one defines neurocognitive deficit. In the most methodologically rigorous of these studies (Weaver et al.), a professionally administered battery of validated neuropsychological tests and a definition based on the deviation of individual subtest scores from the age-adjusted normal values was employed; if the patient complained of memory, attention, or concentration difficulties, the required decrement was decreased. Using this approach, 6 weeks after poisoning, 46% of patients treated with normobaric oxygen alone had cognitive sequelae compared to 25% of those who received HBO2T [p = .007, number needed to treat (NNT) 5, 95% CI 3–16]. At 12 months the difference remained significant (32% versus 18%, p = .04, NNT 7, 95% CI 4–124) despite considerable loss to follow-up.
On this basis, HBO2T remains widely advocated for the routine treatment of patients with moderate to severe poisoning—in particular in those older than 35 years, presenting with a metabolic acidosis on arterial blood-gas analysis, exposed for lengthy periods or with a history of unconsciousness.