What can Hyperbaric Oxygen Therapy (HBOT) be used for?
Scuba divers suffering from decompression illness (DCI)
Air or gas embolism
Carbon monoxide poisoning and smoke inhalation
Clostridial Myonecrosis (Gas gangrene)
Enhancement of healing in selected problem wounds
Skin grafts and flaps (compromised)
Crush injury, compartment Syndrome and other acute traumatic ischaemias
Necrotising soft tissue infections (subcutaneous tissue, muscle, fascia)
Adjunctive hyperbaric oxygen in intracranial abscess
Radiation tissue damage (Osteoradionecrosis)
Exceptional blood loss (Anaemia)
Central Retinal Artery Occlusion
Decompression Sickness Decompression sickness (DCS) refers to symptoms caused by blocked blood supply, damage from direct mechanical effects, or later biochemical actions from suspected bubbles evolving from inert gas dissolved in blood or tissues when atmospheric pressure decreases too rapidly. DCS can occur after scuba diving, ascent with flying, or hypobaric or hyperbaric exposure.
DCS can be broken down into the following 3 types:
Type I involves musculoskeletal, skin, and lymphatic tissue, and often has accompanying fatigue.
Type II includes neurologic systems (either CNS or peripheral), cardiorespiratory, audiovestibular, and shock.
Type III DCS describes a syndrome that presents with symptoms that progress to a spinal deficit that may be refractory to recompression.
The bubbles causing DCS also can injure vessel endothelium, which leads to platelet aggregation, denatured lipoproteins, and activation of leukocytes, causing capillary leaks and proinflammatory events.
Hyperbaric oxygen therapy (HBOT) is used to diminish the size of the bubbles, not simply through pressure, but also by using an oxygen gradient. According to Boyle's law, the volume of the bubble becomes smaller as pressure increases. With a change in 1.8 ATA, this is only about 30%. The bubble causing DCS is thought to be composed of nitrogen. When a tissue compartment is at equilibrium and then ascends to a decreased atmospheric pressure, nitrogen seeps out of blood, tissue, or both, causing a bubble. During HBOT, the patient breathes 100% oxygen, creating oxygen-rich, nitrogen-poor blood. This creates a gradient of nitrogen between the blood and the bubble, causing nitrogen to efflux from the bubble into the bloodstream, which, in effect, makes the bubble smaller.
The treatment of choice is recompression. Although treatment as soon as possible has the greatest success, recompression is still the definitive treatment, and no exclusionary time from symptom onset has been established. DCS Type I can be treated using the US Navy Treatment Table 5: 60 fsw for two 20-min periods, with a slow decompression to 30 fsw for another 20 minutes. For DCS types I, II, and III, the US Navy Treatment Table 6 is a recommended treatment protocol. Patients are placed at 60 fsw (2.8 ATA) for at least three 20-min intervals and then are slowly decompressed to 30 fsw. They remain there for at least another 2.5 hours. The time a patient is kept at 60 or 30 fsw can be extended depending on the patient's symptom response to therapy.
Air embolism refers to bubbles in the arterial or venous circulation. Venous bubbles can result from compressed gas diving (such as scuba) but are often filtered through the pulmonary capillary bed. If a large volume of bubbles is noted, they may overwhelm the pulmonary filter and enter the arterial circulation. Arterial gas emboli (AGE) can also result from pulmonary barotrauma or accidental intravenous air injection or some surgical procedures. Symptoms usually occur within seconds to minutes of the event and can include loss of consciousness, confusion, neurological deficits, cardiac arrhythmias, or cardiac arrest.
The treatment of choice is recompression therapy. Gas embolism used to be treated with US Navy Treatment Table 6A, which required a pressure of 6 ATA. The rationale was that the larger volume of gas warranted increased pressure to force bubble redistribution or elimination. No conclusive evidence shows that this offers superior treatment to the US Navy Treatment Table 6 for most cases; however, if complete relief is not achieved after initial recompression, deeper recompression may be needed.
Carbon Monoxide Poisoning
Carbon monoxide (CO) poisoning, whether intentional or accidental, occurs when one inhales the colorless and odorless carbon monoxide gas. Despite improved awareness and sensory alarms, multiple deaths occur each year.
CO binds to hemoglobin with 200 times the affinity of oxygen. CO also shifts the oxygen dissociation curve to the left (the Haldane effect), which decreases oxygen release to tissues. CO can also bind cytochrome oxidase aa3/C and myoglobin. Reperfusion injury can occur when free radicals and lipid peroxidation are produced.
The treatment of CO poisoning with hyperbaric oxygen therapy (HBOT) is based upon the theory that oxygen competitively displaces CO from hemoglobin. While breathing room air, this process takes about 300 minutes. While on a 100% oxygen nonrebreather mask, this time is reduced to about 90 minutes; with HBOT, the time is shortened to 32 minutes. HBOT (but not normobaric oxygen) restores cytochrome oxidase aa3/C36 and helps to prevent lipid peroxidation. HBOT is also used to help prevent the delayed neurologic sequelae (DNS); treatment instituted sooner is more effective. Multiple papers describe controversial methods and conclusions about the use of HBOT for CO poisoning.
Patients with CO poisoning can present with myriad symptoms that they may not initially attribute to CO poisoning, as CO is considered the "great imitator" of other illnesses. Presentation can include flulike symptoms such as headache, visual changes, dizziness, and nausea. More serious manifestations include loss of consciousness, seizures, chest pain, ECG changes, tachycardia, and mild to severe acidosis.
Candidates for HBOT are those who present with morbidity and mortality risks that include pregnancy and cardiovascular dysfunction and those who manifest signs of serious intoxication, such as unconsciousness (no matter how long a period), neurologic signs, or severe acidosis. CO-hemoglobin (Hgb) level usually does not correlate well with symptoms or outcome; many patients with CO-Hgb levels of 25-30% are treated.
Pregnant females often have a CO level that is 10-15% lower than the fetus. Fetal Hgb not only has a higher affinity for CO but also has a left-shifted oxygen dissociation curve compared with adult hemoglobin. Exposure to CO causes an even farther leftward shift, in both adult and fetal hemoglobin, and decreased oxygen release from maternal blood to fetal blood and from fetal blood to fetal tissues. Pregnant patients with CO-Hgb levels greater than 10% should be treated with HBOT.
HBOT is administered at 2.5-3 ATA for periods of 60-100 minutes. Depending on patient presentation and response, 1-5 treatments are recommended.
For gas gangrene or spreading clostridial cellulitis with systemic toxicity the preferred treatment is a combination of hyperbaric oxygen (HBO2), surgery, and antibiotics.
Gas gangrene is an acute, rapidly progressive, non-pyogenic, invasive clostridial infection of the muscles, characterized by profound toxaemia, extensive oedema, massive death of tissue, and a variable degree of gas production. Gas gangrene is either an endogenous infection, caused by contamination from a clostridial focus in the body, or an exogenous infection, mostly in patients with compound and/or complicated fractures with extensive soft tissue injuries after street accidents. The infection is caused by anaerobic, spore forming, Gram positive encapsulated bacilli of the genus clostridium. More than 150 species of clostridium have been recognized but the most commonly isolated is C. perfringens type A (95%) either alone or in combination with other pathogenic clostridia.
The essential role of alpha-toxin in the pathogenesis of gas gangrene was recently confirmed by Williamson and Titball, who developed a genetically engineered vaccine against alpha-toxin. Immunization with the C-Domain of a-toxin proved to be of value in animal experiments. Clostridium perfringens is not a strict anaerobe; it may grow freely in O2 tensions of up to 30 mmHg and in a restricted manner in O2 tensions up to 70 mmHg.
The key to understanding the pathophysiology of gas gangrene is to approach it as a clinical concept, rather than a definitive bacteriologic or pathologic entity.
For the induction of gas gangrene, two conditions have to be fulfilled:
1. The presence of clostridial spores and
2. An area of lowered oxidation reduction potential caused by circulatory failure in a local area or by extensive soft tissue damage and necrotic muscle tissue. This condition results in an area with a low O2 tension where clostridial spores can develop into the vegetative form.
More than 20 different clostridial exotoxins have been identified, nine of which are implicated in the local and systemic changes seen in gas gangrene; alpha toxin, theta toxin, kappa toxin, mu toxin, nu toxin, fibrinolysin, neuraminidase, "circulating factor," and "bursting factor."
The most prevalent is the O2 stable lecithinase C, alpha toxin, which is haemolytic and tissue necrotizing. It destroys platelets and polymorphnuclear leukocytes and causes widespread capillary damage and is often lethal.
The other toxins are ancillary to the alpha toxin, which gives rise to haemoglobinuria, aemolysis, jaundice, anaemia, tissue necrosis, renal failure, and serious systemic effects such as cardiotoxicity and brain dysfunction. The other exotoxins are synergistic and enhance the rapid spread of infection by destroying, liquefying, and dissecting healthy tissue. The clostridial organisms surround themselves with toxins. Local host defense mechanisms are abolished when the toxin production is sufficiently high. This results in fulminating tissue destruction and further clostridial growth. Alpha toxin can be fixed to susceptible skin cells in 20-30 min, is detoxified within 2 hours after its elaboration, and causes active immunity with production of a specific antitoxin. The infection, however, is so progressive with continuous production of alpha toxin that the patient dies before any immunity can develop.
The action of HBOT on clostridia (and other anaerobes) is based on the formation of O2 free radicals in the relative absence of free radical degrading enzymes, such as superoxide dismutases, catalases, and peroxidases. Van Unnik showed that an O2 tension of 250 mmHg is necessary to stop alpha toxin production. Although it does not kill all clostridia, it is bacteriostatic both in vivo and in vitro. Tissue O2 measurements made have shown that treatment with HBO2 at 3.0 atm abs is required to achieve tissue partial pressures above 300 mmHg.
If further toxin elaboration is prevented by the addition of hyperbaric oxygen, a very sick patient can rapidly be made non-toxic.
The diagnosis of clostridial myonecrosis is based primarily on clinical data, supported by the demonstration of Gram positive rods from the fluids of the involved tissues as well as a virtual absence of leukocytes. A leukocytosis indicates a mixed infection.
The onset of gas gangrene may occur between 1 and 6 hours after injury or an operation and begins with severe and sudden pain in the infected area before the clinical signs appear. This seemingly disproportionate pain in a clinically still normal area must make the clinician highly suspicious for a developing gas gangrene, especially after trauma or an operation. The body temperature is initially normal but than rises very quickly. The skin overlying the wound in the early phases appears shiny and tense and then becomes dusky and progresses to a bronze discoloration. The infection can advance at a rate of 6 inches per hour. Any delay in recognition or treatment may be fatal. Haemorrhagic bullae or vesicles may also be noted. A thin, sero-sanguinolent exudate with a sickly, sweet odour is present. Swelling and oedema of the infected area is pronounced. The muscles appear dark red to black or greenish. They are noncontractile, and do not bleed when cut.
The tissue gas seen on radiographs appears as feather like figures between muscle fibers and is an early and highly characteristic sign of clostridial myonecrosis. Crepitus is usually present as well.
The acute problem in gas gangrene is not normal tissue or already necrotic tissue, but the rapidly advancing phlegmon in between, which is caused by the continuous production of alpha toxin in infected but still viable tissue. It is essential to stop alpha toxin production as soon as possible and to continue therapy until the advance of the disease process has been clearly arrested. Since van Unnik showed that a tissue PO2 of 250 mmHg is necessary to stop toxin production completely, the only way to achieve this is to start hyperbaric oxygen therapy as soon as possible.
A minimum of three to four HBOT treatments is necessary for this response. Treatment starts on the basis of the clinical picture and the positive Gram stained smear of the wound fluid (without leukocytes). HBOT treatment stops alpha toxin production and inhibits bacterial growth thus enabling the body to utilize its own host defense mechanisms.
Although a three pronged approach consisting of HBO2, surgery, and antibiotics is essential in treating gas gangrene, initial surgery can be restricted to opening of the wound. An initial fasciotomy may be undertaken, but lengthy and extensive procedures in these very ill patients can usually be postponed, depending on how rapidly HBOT therapy can be initiated. Debridement of necrotic tissue can be performed between HBOT treatments and should be delayed until clear demarcation between dead and viable tissues can be seen.
Major retrospective clinical studies indicate that the lowest morbidity and mortality are achieved with initial conservative surgery and rapid initiation of HBOT therapy. Results decline progressively when HBOT therapy is delayed. Early aggressive surgery and delayed HBOT treatment lead to a significantly higher mortality and morbidity than when HBOT is administered promptly.
In experimental monomicrobial gas gangrene, the combination therapy of surgery and HBOT started 45 min after the inoculation of bacteria, reduced mortality to 13% compared with 38% with surgery alone. The combination therapy appeared to be especially effective in wound healing and in prevention of morbidity compared with surgical debridement alone. The effectiveness of the combination therapy was strongly time dependent.
The advantages of early HBO2 treatment are that:
1. It is life saving because less heroic surgery needs to be performed in gravely ill patients and the cessation of alpha toxin production is rapid.
2. It is limb and tissue saving because no major amputations or excisions are done prematurely (except opening of wounds). It clarifies the demarcation, so that within 24-30 hours there is a clear distinction between dead and still living tissue. In this way, both the number and the extent of amputations are reduced.
Enhancement of Healing in Selected Problem Wounds
Normal wound healing proceeds through stages of hemostasis, removal of infectious agents, resolution of the inflammatory response, reestablishment of a connective tissue matrix, angiogenesis, and resurfacing. Problem (or chronic) wounds are those which do not proceed completely through this process because of any number of local and systemic host factors. For this reason, chronic wounds are often categorized as diabetic wounds, venous stasis ulcers, arterial ulcers, or pressure ulcers.
Wounds that fail to heal are typically hypoxic. Multiple components of the wound healing process are affected by oxygen concentration or gradients, which explains why hyperbaric oxygen therapy (HBOT) can be an effective therapy to treat chronic wounds. Angiogenesis occurs in response to high oxygen concentration. This is likely a multifactorial effect of HBOT. First, fibroblast proliferation and collagen synthesis are oxygen dependent, and collagen is the foundational matrix for angiogenesis. In addition, HBOT likely stimulates growth factors involving angiogenesis and other mediators of the wound healing process. Hyperbaric oxygen also has been shown to have direct and indirect antimicrobial activity; in particular, it increases intracellular leukocyte killing.
Diabetic lower extremity ulcers have been the focus of most wound research in hyperbaric medicine, since the etiology of these wounds is multifactorial, and HBOT can address many of these factors. Several randomized controlled clinical trials have studied HBOT for the treatment of diabetic lower extremity wounds. Additionally, many more prospective, noncontrolled clinical trials and retrospective trials have been completed. Based on the body of evidence, major insurance carriers around the world now endorse the use of HBOT for the treatment of diabetic lower extremity wounds that show evidence of deep soft tissue infection, osteomyelitis, or gangrene. HBOT has been shown to reduce the amputation rate in patients with diabetic ulcers as well.
In an effort to select patients appropriately for HBOT, various objective vascular evaluation methods have been used, including transcutaneous oximetry, capillary perfusion pressure, laser Doppler, and other types of vascular studies. Debate is ongoing regarding which method provides the most reliable data and whether these methods are more useful than other clinical markers of wound failure.
Note that HBOT should be used in conjunction with a complete wound healing care plan. As with all chronic wounds, other underlying host factors (eg, large vessel disease, glycemic control, nutrition, infection, presence of necrotic tissue, offloading) must be simultaneously addressed in order to have the highest chance of successful healing and functional capacity.
Because the goals of HBOT for wound healing include cellular proliferation and angiogenesis, HBOT is generally performed daily for a minimum of 30 treatments. Treatment is generally at 2 to 2.4 ATA for a total of 90 minutes of 100% oxygen breathing time. Based on the response to therapy, extended courses of therapy may be indicated.
Compromised Skin Grafts and Flaps
Most skin grafts and flaps in normal hosts heal well. In patients with compromised circulation, this may not be the case. Patients with diabetes or vasculopathy from another etiology and patients who have irradiated tissue are particularly subject to flap or graft compromise. In these patients, hyperbaric oxygen therapy (HBOT) has been shown to be useful. Unfortunately, if patients are not identified early, the initial flap or graft may be lost. Even in such cases, patients can significantly benefit from HBOT to prepare the wound bed for another graft or flap procedure; the procedure then has a higher chance of success following HBOT.
Over 30 animal studies have shown efficacy of HBOT in preserving both pedicled and free flaps in multiple models. These models looked at arterial, venous, and combined insults in addition to irradiated tissues. While improvement was observed regardless of the type of vascular defect, those with arterial insufficiency and radiation injury showed the greatest improvement.
Human case studies showing benefit of hyperbaric treatment for flap survival were first reported in 1966. A controlled clinical trial showing improved survival of split skin grafts followed shortly thereafter. This was corroborated by a later clinical trial. Additionally, evidence exists of benefit for flaps in post-irradiated tissue in human subjects.
As the underlying pathophysiology of all compromised grafts and flaps is hypoxia, HBOT benefits patients by reducing the oxygen deficit. A unique mechanism of action of HBOT for preserving compromised flaps is the possibility of closing arteriovenous shunts. Additionally, the same mechanisms of action that improve wound healing, namely, improved fibroblast and collagen synthesis11 and angiogenesis,10 also are likely to benefit a compromised graft or flap.
The current standard for HBOT to treat a compromised graft or flap includes twice daily treatment until the graft or flap appears viable and then once per day until completely healed. The initiation of HBOT should be expedited. In general, benefit should be seen by 20 treatments; if it is not, continuation of therapy should be reviewed. However, the cost of creating a complex flap is high, which makes HBOT cost-effective for this diagnosis. Of course, patients with compromised flaps need surgical attention to the arterial and venous supply, appropriate local management, and maximization of medical support.
Crush Injury and Compartment Syndrome
Acute peripheral traumatic ischemia includes those injuries that are caused by trauma that leads to ischemia and edema; a gradient of injury exists. This category contains crush injuries as well as compartment syndrome. Crush injuries often result in poor outcome because of the body's attempt to manage the primary injury. The body then develops more injury due to the reperfusion response. Injuries are graded using definite points on a severity scale. The commonly referenced system is the Gustilo classification, but other classification scales are available.
The benefits of hyperbaric oxygen therapy (HBOT) for this indication include hyperoxygenation by increasing oxygen within the plasma. HBOT also induces a reduction in blood flow that allows capillaries to resorb extra fluid, resulting in decreased edema. As a gradient of oxygenation is based on blood flow, oxygen tissue tensions can be returned, allowing for the host defenses to properly function. Animal studies suggest that a decreased neutrophil adherence to ischemic venules is observed with elevated oxygen pressures (2.5 ATA). Reperfusion injury is diminished, as HBOT generates scavengers to destroy oxygen radicals.
Compartment syndrome also is a continuum of injury that occurs when compartment pressures exceed the capillary perfusion pressures. The extent to which the injury has affected tissues is unclear, even after surgical intervention. HBOT is not recommended during the "suspected" stage of injury, when compartment syndrome is not yet present but may be impending. HBOT is beneficial during the impending stage, when objective signs are noted (pain, weakness, pain with passive stretch, tense compartment). With these signs, even if surgery is not elected because of compartment pressures or patient stability, HBOT is indicated. Once the patient has undergone fasciotomy, HBOT can be used to help decrease morbidity.
HBOT should be started as soon as is feasible, ideally within 4-6 hours from time of injury. After emergent surgical intervention, the patient should undergo HBOT at 2-2.5 ATA for 60-90 minutes. For the next 2-3 days, perform HBOT 3 times daily, then twice daily for 2-3 days, and then daily for the next 2-3 days.
Necrotizing Soft Tissue Infections
These infections may be single aerobic or anaerobic but are more often mixed infections that often occur as a result of trauma, surgical wounds, or foreign bodies, including subcutaneous and muscular injection of contaminated street drugs. They are often seen in compromised hosts who have diabetes or a vasculopathy of another type. These infections are named based on their clinical presentation and include necrotizing fasciitis, clostridial and nonclostridial myonecrosis, and Fournier gangrene.
Regardless of the depth of the tissue invasion, these infections have similar pathophysiology that includes local tissue hypoxia, which is exacerbated by a secondary occlusive endarteritis.63 Intravascular sequestration of leukocytes is common in these types of infections, mediated by toxins from specific organisms.64 Clostridial theta toxin appears to be one such mediator. All of these factors together foster an environment for facultative organisms to continue to consume remaining oxygen, and this promotes growth of anaerobes.
The cornerstones of therapy are wide surgical debridement and aggressive antibiotic therapy. Hyperbaric oxygen therapy (HBOT) is used adjunctively with these measures, as it offers several mechanisms of action to control the infection and reduce tissue loss. First, HBOT is toxic to anaerobic bacteria. Next, HBOT improves polymorphonuclear function and bacterial clearance. Based on results of work related to CO poisoning, HBOT may decrease neutrophil adherence based on inhibition of beta-2 integrin function. Further investigation is needed to see if this mechanism is at work in necrotizing infections as well. In the case of clostridial myonecrosis, HBOT can stop the production of the alpha toxin. Finally, limited evidence indicates that HBOT may facilitate antibiotic penetration or action in several classes of antibiotics, including aminoglycosides, cephalosporins, sulfonamides and amphotericin.
Multiple clinical studies suggest that HBOT is efficacious in the treatment of necrotizing soft tissue infections. These include case series, retrospective and prospective studies, and non-randomized clinical trials. They suggest significant reductions in mortality and morbidity. The reduction in mortality was remarkably similar in 2 studies: 34% (untreated) vs. 11.9% (treated) in one study; 38% (untreated) vs. 12.5% (treated) in the other. In another study, the treated group had more patients with diabetes and more patients in shock and still had significantly less mortality (23%) than the untreated group (66%). Clinical studies involving patients with Fournier gangrene treated with HBOT bear similar results.
Initial HBOT is aggressively performed at least twice per day in coordination with surgical debridement. Typically, a treatment pressure ranging from 2.0-2.5 ATA is adequate. However, in the specific case of clostridial myonecrosis, 3 ATA is often used to ensure adequate tissue oxygen tensions to stop alpha toxin production. For the same reason, HBOT should be initiated as quickly as possible in this circumstance and performed 3 times in the first 24 h if at all feasible.
The disorders considered in treatment of intracranial abscesses (ICA) include subdural and epidural empyema as well as cerebral abscess. Studies from around the world have reviewed mortality from ICA with a resulting mortality of about 20%. HBOT has multiple mechanisms that make it useful as an adjunctive therapy for ICA.
HBOT induces high oxygen tensions in tissue, which helps to prevent anaerobic bacterial growth, including organisms commonly found in ICA. HBOT can also help reduce increased intracranial pressure (ICP) and its effects are proposed to be more pronounced with perifocal brain swelling. As discussed earlier, HBOT can enhance host immune systems and the treatment of osteomyelitis. Candidates for adjunctive HBOT are patients who have multiple abscesses, who have an abscess that is in a deep or dominant location, whose immune systems are compromised, in whom surgery is contraindicated, who are poor candidates for surgery, and who exhibit inadequate response despite standard surgical and antibiotic treatment.
HBOT is administered at 2.0-2.5 ATA for 60-90 minutes per treatment. HBOT may be 1-2 sessions per day. The optimized number of treatments has not been determined.
Delayed Radiation Injury
Radiation therapy causes acute, subacute, and delayed injuries. Acute and subacute injuries are generally self-limited. However, delayed injuries are often much more difficult to treat and may appear anywhere from 6 months to years after treatment. They generally are seen after a minimum dose of 6000 cGy. While uncommon, these injuries can cause devastating chronic debilitation to patients. Notably, they can be quiescent until an invasive procedure is performed in the radiation field. Injuries are generally divided into soft tissue versus hard tissue injury (osteoradionecrosis [ORN]).
While the exact mechanism of delayed radiation injury is still being elucidated, the generally accepted explanation is that an obliterative endarteritis and tissue hypoxia lead to secondary fibrosis.79 Hyperbaric oxygen therapy (HBOT) was first used to treat ORN of the mandible. Based on the foundational clinical research of Marx,80 multiple subsequent studies supported its use. The success of HBOT in treating ORN then led to its use in soft tissue radionecrosis as well.
Marx demonstrated conclusively that ORN is primarily an avascular aseptic necrosis rather than the result of infection.80 He developed a staging system for classifying and planning treatment,81 which is largely accepted throughout the oromaxillofacial surgery community.
Stage I - Exposed alveolar bone: The patient receives 30 HBOT treatments and then is reassessed for bone exposure, granulation, and resorption of nonviable bone. If response is favorable, an additional 10 treatments may be considered.
Stage II - A patient who formerly was Stage I with incomplete response or failure to respond: Perform transoral sequestrectomy with primary wound closure followed by an additional 10 treatments.
Stage III - A patient who fails stage II or has an orocutaneous fistula, pathologic fracture, or resorption to the inferior border of the mandible: The patient receives 30 treatments, transcutaneous mandibular resection, wound closure, and mandibular fixation, followed by an additional 10 postoperative treatments.
Stage IIIR - Mandibular reconstruction 10 weeks after successful resolution of mandibular ORN: The patient receives 10 additional postoperative HBOT treatments.
The cornerstone of therapy is to begin and complete (if possible) HBOT prior to any surgical intervention and then to resume HBOT as soon as possible after surgery. Only in this way is adequate time allowed for angiogenesis to support postoperative healing. For patients with a history of significant radiation exposure, but no exposed bone, who require oral surgery, many practitioners suggest 20 HBOT treatments prior to surgery and 10 treatments immediately following surgery. Feldmeier has published an excellent review of this literature.
Soft tissue radionecrosis
While soft tissue radionecrosis also is rare, it causes significant morbidity, depending on the site of injury. All of these injuries lead to significant local pain. Both radiation cystitis and radiation proctitis can result in severe blood loss with symptomatic anemia, and radiation cystitis may cause obstructive uropathy secondary to fibrosis and blood clot formation. Radionecrosis of the neck and larynx can lead to dysphagia and respiratory obstruction. Irradiated skin develops painful, necrotic wounds that do not heal with standard wound healing care plans.
For each of these subpopulations of soft tissue radionecrosis, published case series and prospective, nonrandomized clinical trials corroborate one another, providing a degree of external validity. Larger studies are warranted. A national registry is currently being evaluated, from which more powerful conclusions may be forthcoming. Currently, the largest group of reported patients treated with HBOT for soft tissue radionecrosis are those with radiation cystitis. At least 15 publications, representing almost 200 patients, report a combined success rate in the 80% range. The 2 largest studies were published by Bevers and Chong.
HBOT and carcinogenesis
Practitioners and patients are often concerned that HBOT may foster recurrence of malignancy or promote the growth of an existing tumor. This is largely because of the known angiogenic effective of HBOT. Feldmeier has reviewed this subject extensively. Malignant angiogenesis appears to follow a different pathway than angiogenesis related to wound healing. His review of the literature suggests that the risk is low.
Refractory osteomyelitis is defined as acute or chronic osteomyelitis that is not cured after appropriate interventions. More often than not, refractory osteomyelitis is seen in patients whose systems are compromised. This condition often results in nonhealing wounds, sinus tracts, and, in the worst case, more aggressive infections that require amputation.
Mader and Niinikoski showed that hyperbaric oxygen therapy (HBOT) is capable of elevating oxygen tension in infected bone to normal or above normal levels. Since polymorphonuclear (PMN) function requires adequate oxygen concentration, this is a significant mechanism by which HBOT helps to control osteomyelitis, as demonstrated by Mader in the same study.
A unique mechanism by which HBOT is beneficial in osteomyelitis is in promoting osteoclast function. The resorption of necrotic bone by osteoclasts is oxygen-dependent. This has best been demonstrated in animal models of osteomyelitis.
Additionally, as previously mentioned, HBOT facilitates the penetration or function of antibiotic drugs. Other properties of HBOT previously discussed, such as neovascularization and blunting the inflammatory response, likely provide additional benefit.
Convincing animal evidence supports the use of HBOT in the treatment of osteomyelitis. Clinical studies are somewhat problematic, however, because osteomyelitis has so many different presentations that comparisons become difficult. This is compounded by the small study sizes found in the literature; however, these do suggest benefit of HBOT for refractory osteomyelitis in humans.
One specific subset of osteomyelitis that merits special attention is malignant otitis externa. This progressive pseudomonal osteomyelitis of the ear canal can spread to the skull base and become fatal. Davis et al published a study of 17 patients with malignant otitis externa, all of whom showed dramatic improvement with the addition of HBOT to standard surgical debridement and antibiotic therapy.
Thermal burns present a multifactorial tissue injury that culminates in a marked inflammatory response with vascular derangement from activated platelets and white cell adhesion with resultant edema, hypoxia, and vulnerability to severe infection. Poor white cell function caused by the local environment exacerbates this problem. Hyperbaric oxygen therapy (HBOT) addresses each of these pathophysiological derangements, and can, therefore, make a significant difference in patient outcomes. These mechanisms of action have been discussed above.
Multiple animal studies support the utility of HBOT for treatment of thermal burns. Human studies ranging from case series to randomized clinical trials have supported the potential benefit of HBOT in burn treatment. These include a small randomized study by Hart that demonstrated improved healing and decreased mortality. Niezgoda90 showed increased healing in a standardized human burn model. In a series of publications, Cianci suggests significant reduction in length of hospital stay, need for surgery, and cost.
Because of the goals of therapy, HBOT is begun as soon as possible after injury, with a goal of 3 treatments within the first 24 hours and then twice daily. Length of treatment depends on the clinical impairment of the patient and the extent of and response to grafting. Special attention must be given to fluid management and chamber and patient temperature to avoid undue physiologic stress to the patient as well as potential complications of treatment (ie, oxygen toxicity).
Patients who develop exceptional anemia have lost significant oxygen carrying capacity in the blood. These patients become candidates for hyperbaric oxygen therapy (HBOT) when they are unable to receive blood products because of religious or medical reasons. The major oxygen carrier in human blood is hemoglobin, transporting 1.34 mL of oxygen per gram. Borema performed an experiment in the 1960s in which exsanguinated pigs (who had only plasma in their vasculature) were able to sustain life under hyperbaric conditions.
The body generally uses 5-6 vol% (mL of O2 per 100 mL of blood); under 3 ATA, 6 vol% of molecular oxygen can be dissolved into the plasma. The CNS and cardiovascular systems are the two most oxygen-sensitive systems in the human body. Oxygen debt is one way of determining a patient's need to start or continue HBOT. A cumulative oxygen debt is the time integral of the volume of oxygen consumption (VO2) measured during and after shock insult minus the baseline VO2 required during the same time interval. Patients who have a debt >33 L/m2 do not survive, whereas patients with debts =9 usually recover.
HBOT is administered at 2-3 ATA for periods of up to 4 hours per treatment. As many as 3-4 sessions a day may be necessary, depending on a patient's clinical picture. Treatments should continue until the patient can receive blood products, no longer demonstrates end stage organ failure, or no longer has a calculated oxygen debt.
Central Retinal Artery Occlusion
Central retinal artery occlusion (CRAO) is a sudden, painless loss of vision; this is the most recently approved indication by the Undersea and Hyperbaric Medicine Society (UHMS) for HBOT. CRAO is caused by the obstruction of the central retinal artery and, although an infrequent cause of visual loss, leads to permanent visual loss. Current treatment for CRAO consists of attempts to lower intraocular pressure and movement of a potential embolus downstream, ocular massage, anterior chamber paracentesis, and medications (both eye drops and oral); most modalities have proven inefficacious.
A small study by Hertzog et al evaluated HBOT with CRAO. Patients were divided into groups based on time of onset of CRAO to HBOT. The study noted that HBOT was most useful in preserving vision if instituted within 8 hours. Another retrospective study published by Beiran compared patients from a facility where HBOT was available to a facility that did not have HBOT. The patients who received HBOT demonstrated visual improvement (82% HBOT vs 29.7% control).
Patient selection for HBOT should meet the following criteria: <24 hours of painless vision loss; no history of flashes or floaters prior to vision loss; visual acuity 20/200 or worse, even with pinhole testing; age >40 years; and no recent eye surgery or trauma. Visual improvement has been reported even with delay of HBOT.
HBOT is administered at 2 ATA on 100% oxygen. If no response is noted, pressure should be increased to 2.8 ATA. If vision is still not improved after 20 minutes, US Navy treatment Table 6 is indicated. If vision is improved, continue at treatment depth for 90 minutes bid. Continue daily bid compression until resulting in 3 days without visual improvement. If the patient responds to 100% oxygen via nonrebreather (NRB) mask itself, HBOT is not needed, and the patient should be maintained on surface 100% oxygen for 12 hours.