For Physicians

Lisa St. John, Clinic Director

Bay Area Hyperbarics

(full video segment - 30 min. duration)

What is Hyperbaric Oxygen Therapy?

Hyperbaric Oxygen Therapy is a treatment that uses pure oxygen under pressure to speed and enhance the body's natural ability to heal. It delivers 100% oxygen at a greater than atmospheric pressure in a certified hyperbaric chamber. Oxygen is a necessary part of cellular life. Hyperbaric oxygen dissolves 400 times more oxygen molecules into the plasma. This process increases oxygen to damaged areas and regrows microvasculature. Hyperbarics has been proven to stimulate osetoblastic and fibroblastic proliferation and angiogenesis, increase collagen tissue matrix, and kill bacteria. Hyperbaric oxygen enhances the body's natural healing process.

The hyperbaric treatment is both non-invasive and painless. A patient undergoing Hyperbarics spends a prescribed amount of time sitting or reclining in one of our private, cylindrical, body-length hyperbaric chambers where pure oxygen is administered and atmospheric pressure is controlled under meticulous conditions. The dosage, which includes pressure, time, and frequency of treatment, is suited to each patient's specific diagnosis. Hyperbarics requires a physician's prescription. During the treatment, a patient can watch movies, listen to music, meditate, or sleep.

Hyperbaric Oxygen Therapy is a Medicare, U.S. Food and Drug Administration (FDA), and American Medical Association (AMA) approved treatment used to treat numerous health conditions, diseases, and illnesses. It uses pure oxygen to speed and enhance the body's natural ability to heal. It has been around for 50+ years as an accepted and effective treatment for many conditions, diseases, illnesses, and health problems. It is safe and effective.

Conditions and diagnoses treated by hyperbarics that are typically covered by health insurance:

Conditions related to cancer treatments and radiation damage
Infections in tissue, muscle, bone or skin, and/or drug resistant infections
Sores and gangrene that will not heal or that are related to diabetes
Surgical sites with grafts or flaps
Bones and/or tissue that are difficult to heal
Acute severe problems from accidents (e.g. compartment syndrome, or crushed leg, arm, fingers)
Conditions such as decompression sickness, anemia, burns, carbon monoxide poisoning, or emboli from air or gas
Reattachment of limbs
Cerebral edema

Medicare Approved Conditions for Hyperbarics (reimbursable):

Acute carbon monoxide intoxication
Decompression illness
Gas embolism
Gas gangrene
Acute traumatic peripheral ischemia. HBO therapy is a valuable adjunctive treatment to be used in combination with accepted standard therapeutic measures when loss of function, limb, or life is threatened.
Crush injuries and suturing of severed limbs. As in the previous conditions, HBO therapy would be an adjunctive treatment when loss of function, limb, or life is threatened.
Progressive necrotizing infections (necrotizing fasciitis)
Acute peripheral arterial insufficiency
Treatment of compromised skin grafts
Chronic refractory osteomyelitis, unresponsive to conventional medical and surgical management
Osteoradionecrosis as an adjunct to conventional treatment
Soft tissue radionecrosis as an adjunct to conventional treatment
Cyanide poisoning
Actinomycosis, only as an adjunct to conventional therapy when the disease process is refractory to antibiotics and surgical treatment.

Other Treatable Conditions:

Skin and other infections
Wounds not covered by Medicare
Diabetes
Sudden blindness or deafness
Eye conditions (such as macular edema)
Perineal Crohn's Disease
Sickle Cell Disease with Crisis
Peripheral Vascular Disease
Scleroderma
Stroke rehabilitation
Traumatic brain injury
Cerebral Palsy
Athletic injury
Lyme Disease
Autism
Closed head injury
Coma
Cerebral Edema
Migraine/Cluster Headache
Spinal cord injury
Multiple Sclerosis (certain aspects)
Macular Degneration
Reflex Sympathetic Dystrophy and other neurological disorders
Chronic fatigue symptoms
Orthopedic problems-sprains/strains chronic or acute/fractures non-healing
Myocardial problems
Liver detoxification enhancement
Colon disorders
Ulcerative Colitis
Chronic pain

Contraindications

Absolute Contraindications

Doxorubicin (Adriamycin®) – Upton and co-workers (30), while investigating the possible use of hyperbaric oxygen among other non-surgical “antidotes” for tissue damage caused by extravasation of doxorubicin, found that this chemotherapeutic drug produced an 87% mortality rate in rats when combined with HBO. Presumably this was due to cardiac toxicity. The animals were on a b.i.d. treatment schedule, but even when shifted to a once-a-day regimen, there was no significant decrease in mortality. Doxorubicin is probably inactivated and cleared from the tissues in about 24 hours. However, to be prudent, it would be wise to wait at least two to three days after the last dose of doxorubicin before initiating hyperbaric oxygen treatment. HBO has been used safely to aid in healing tissue necrosis secondary to doxorubicin extravasation, but chamber treatment was given after treatment with the drug had been halted.

Mafenide Acetate (Sulfamylon®) – This antibacterial drug was first synthesized in Germany, but later developed into a useful topical agent by Pruitt and his colleagues at the Brook Army Burn Center in San Antonio, Texas. It was found to be effective in suppressing bacterial infection in burn wounds and superseded silver nitrate therapy. Mafenide, however, is a carbonic anhydrase inhibitor which tends to promote a CO₂ buildup, causing a peripheral vasodilatation. When this is coupled with the central vasoconstriction caused by HBO, the results are worse than when using either agent alone. If a burn patient is referred for hyperbaric therapy, all the mafenide cream must be carefully removed by showering or tubbing before putting the patient in the chamber. Silver sulfadiazine (Silvadene®) may be substituted quite effectively and it is safe for concomitant use with HBO.

Untreated Pneumothorax – Untreated pneumothorax is considered an absolute contraindication to hyperbaric treatment, as there is always a concern that if it becomes a tension pneumothorax while the patient is in the chamber, it will render decompression hazardous or potentially life threatening. Since there is no guaranteeing that a pneumothorax will not continue to enlarge at pressure or be transformed into a tension pneumothorax, a chest tube should always be inserted for control, before the patient is placed in the chamber. It is highly advisable to obtain a chest roentgenogram after placement, or attempted placement, of a subclavian line, before the patient is submitted to HBO. If the patient does not develop a pneumothorax at pressure, any preexisting pneumothorax will be made smaller when the patient breathes oxygen at treatment depth. The pneumothorax diminishes in size as the nitrogen present is rapidly eliminated secondary to oxygen breathing. Under such circumstances, the pneumothorax will be smaller when the patient is removed from the chamber. A one-liter pneumothorax, present just before decompression, however, will assume a 2.5 liter volume on reading the surface from 2.5 atmospheres absolute.

Rationale of Hyperbarics for the following Medicare Approved Conditions:

Air or Gas Embolism
Anemia
Burns
Carbon Monoxide Poisoning
Compartment Syndromes (skeletal muscle)
Crush Injuries
Decompression Sickness
Intracranial Abscess
       Cerebral Abscess
       Subdural Empyema
       Epidual Empyema
Ischemic Injury
Flaps
Gangrene
       Clostridial Myositis
       Clostridial Myonecrosis (gas gangrene)
       Clostridial Cellulitis
Grafts
Necrotizing Soft Tissue Infections
Osteomyelitis
Radiation Injuries (soft tissue and bony necrosis)
Ulcers
       Venous Stasis Ulcers
       Pressure Ulcers
       Arterial Insufficiency Ulcers
Wounds
       Non-Healing Wounds
       Diabetic Non-Healing Wounds

More Information for Physicians

Carcinogenesis—Concerns Related to Potential Cancer Growth Enhancement

The following are excerpts from Hyperbaric Oxygen 2003: Indications and Results, The Hyperbaric Oxygen Therapy Committee Report by John J. Feldmeier, D.O., Chairman and Editor. Copyright 2003, Undersea and Hyperbaric Medical Society, Inc. Visit: www.uhms.org.

Hyperbaric Oxygen: Definition back to top

Hyperbaric oxygen (HB₂O) is a treatment, in which a patient breathes 100% pure oxygen intermittently while inside a treatment chamber at a pressure higher than sea level pressure (i.e., >1 atmosphere absolute; atm abs). It can be viewed as the new application of an old, established technology to help resolve certain recalcitrant, expensive, or otherwise hopeless medical problems. In certain circumstances, it represents the primary treatment modality while in others it is an adjunct to surgical or pharmacologic interventions.

Treatment can be carried out in either a mono- or multiplace chamber. The former accommodates a single patient; the entire chamber is pressurized with 100% pure oxygen, and the patient breathes the ambient chamber oxygen directly (or the patient breathes 100% pure oxygen via a mask or hood while in the chamber). The latter holds two or more people (patient, observers, and/or support personnel); the chamber is pressurized with compressed air while the patients breathe 100% oxygen via masks, head hoods, or endotracheal tubes. According to the UHMS (Undersea and Hyperbaric Medical Society) definition and the determination of Medicare and other third party carriers, breathing 100% oxygen at 1 atmosphere of pressure or exposing isolated parts of the body to 100% oxygen does not constitute HBO₂ therapy. The patient must receive the oxygen by inhalation within a pressurized chamber. Current information indicates that pressurization should be to 1.4 atm abs or higher.¹

Acceptance (Addition) of New Indications for Hyperbaric Oxygen Therapy back to top

New indications for HBO₂ therapy are considered for acceptance at the meeting of the Hyperbaric Oxygen Committee during the annual meeting of the Undersea and Hyperbaric Medical Society. This consideration can be initiated from within the Committee itself or may result in response to a written report by a non-committee member. When a new indication is considered for acceptance, a position paper is written. The information must summarize the in vitro, in vivo, and clinical aspects of the new indication for HBO₂ therapy. Two members of the Hyperbaric Oxygen Committee review the position paper and each writes a critique. The position paper and critiques are presented to the Hyperbaric Oxygen Committee. A consensus of the Hyperbaric Oxygen Committee is required for recommending the indication be moved into the approved category. If the Committee determines that a new condition merits approval, it makes this recommendation to the Executive Committee of the Society which ultimately votes to approve or disapprove the new indication.¹

Air or Gas Embolism back to top
Richard E. Moon, M.D.

Gas embolism occurs when gas bubbles enter arteries or veins. Arterial gas embolism (AGE) was classically described during submarine escape training, in which pulmonary barotraumas occurred during free ascent after breathing compressed gas at depth. Pulmonary barotrauma and gas embolism due to breath holding can occur after an ascent of as little as one meter. AGE has been attributed to normal ascent in divers with lung pathology such as bullous disease and asthma. Pulmonary barotrauma can also occur as a result of blast injury in or out of water, mechanical ventilation, penetrating chest trauma, chest tube placement, and bronchoscopy.

HBO₂ to treat gas embolism remains the definitive treatment for gas embolism. Indications for treatment include neurological manifestations or cardiovascular instability. A review of 597 published cases of arterial gas embolism reveals superior outcomes with the use of HBO₂ compared to non-recompression treatment. HBO₂ treatment is not required for asymptomatic VGE, however it can effect clinical improvement in patients with secondary pulmonary edema. Gas bubbles have been known to persist for several days and there are many reports noting success when HBO₂ treatments were begun after delays of hours to days. A trial of HBO₂ therapy may be indicated even for those patients coming to a hyperbaric unit after a significant delay following the inciting event. Because of the tendency for patients with AGE to deteriorate after apparent recovery, early HBO₂ is recommended even for patients who appear to have spontaneously recovered. One author has suggested that the presence or absence of air detectable by brain computed tomography should be used as a criterion for HBO₂ therapy. However, timely administration of HBO₂ usually causes some clinical improvement, even in the absence of demonstrable air. Performing brain imaging usually delays the initiation of appropriate HBO₂ treatment and rarely serves a useful clinical purpose.

In patients with AGE caused by pulmonary barotrauma there may be a coexisting pneumothorax, which could develop into tension pneumothorax during chamber decompression. Therefore, if the patient will be treated in a monoplace chamber, placement of a chest tube prior to HBO₂ is recommended. For multiplace chamber treatment careful monitoring is a feasible option. Coexisting pneumomediastinum does not generally require any specific therapy, and will usually resolve during HBO₂.¹

Exceptional Anemia back to top
Keith Van Meter, M.D., FACEP

Patients who have marked loss of red blood cell mass by hemorrhage, hemolysis, or aplasia run the risk of lacking adequate oxygen carrying capacity by blood. The more quickly the severe anemia develops, the less tolerant the patient may be of the insult.

Hemoglobin (Hgb), a powerful carrier for oxygen, transports 1.34 ml of oxygen per gram. The amount of oxygen that will dissolve in one milliliter of plasma is 0.003 ml per mmHg of the partial pressure of oxygen (O₂) in inhaled gas. CaO₂ and CvO₂ respectively represent the arterial or venous content of oxygen in blood.

On the average, the body extracts 5 to 6 ml of O₂ for every 100 ml of blood that sweeps through the microvasculature of most organ systems. Physiologic normal levels of Hgb readily supply tissue oxygen extraction rates of 5 to 6 volume percent. As Hgb drops to 6 g/dL, oxygen delivery, to offset these baseline oxygen extraction rates, becomes problematic and is clearly inadequate at Hgb levels below 3.6 g/dL.

Accumulative oxygen debt is defined as the time integral of the VO₂ measured during and after shock insult minus the baseline VO₂ required during the same time interval. Clinical research in evaluation of patients with severe hemorrhage, demonstrates no chance of survival if the accumulative oxygen debt exceeds 33 L/m2. Multiorgan failure (MOF) occurs if the accumulative oxygen debt exceeds 22 L/m2. All patients who have an accumulative oxygen debt of 9 L/m2 survive without residual disability.¹

Thermal Burns back to top
Paul Cianci, M.D. and J. Benjamin Slade, Jr., M.D.

Severe thermal injury is one of the most devastating physical and psychological injuries a person can suffer. In the United States, more than 2 million burn injuries require medical attention each year, resulting in 14,000 deaths. About 75,000 patients require hospitalization each year, and 25,000 of those remain hospitalized for more than 2 months. The most common mechanisms of burn injury are flame and scalding, and the upper extremity, head and neck are the most common body areas involved.

The average cost of care for a critically burned patient in 1992 ranged from $23,000 to $34,000. Adjusting for 10% inflation/year, current average cost would range from $60,000 to $88,000. According to the executive director of the American Burn Association, for patients who survive 60% total body surface area burns (TBSA), charges for the hospital stay alone, not including operating room time, surgeons bill, artificial skin, rehabilitation, and other costs, averages $400,000 (in 2003 U.S. dollars). These costs can reach $500,000 for burns over 80% TBSA. During 1997-98, in a northern California regional burn center, hospital costs for 20 burn patients averaged $253,000 (range $1,100 to $1.5 million) per patient. This includes the cost of hyperbaric oxygen (HBO₂) which averaged $6,360 (range $1,000 to $27,500) per patient.

The burn wound is a complex, dynamic injury characterized by a zone of coagulation (or complete capillary occlusion), surrounded by an area of stasis, and bordered by an area of erythema. The zone of coagulation may increase by a factor of 10 during the first 48 hours after injury. Ischemic necrosis quickly follows. Hematological changes, including platelet microthrombi and hemoconcentration, occur in the postcapillary venules. Edema formation is rapid in the area of injury but also develops in distant, uninjured tissue. There are concurrent changes occurring in the distant microvasculature where red cell aggregation, white cell adhesion to venular walls, and platelet thromboemboli occur. Inflammatory mediators are elaborated locally in part from activated platelets, macrophages, and leukocytes, contribute to localand systemic hyperpermeability of the microcirculation and appear histologically as gaps in the venular and capillary endothelium. This progressive process may extend damage dramatically during the early days after injury. The continuing tissue damage in thermal injury is due to the failure of the surrounding tissue to supply borderline cells with oxygen and nutrients necessary to sustain viability. The impediment of circulation below the injury leads to desiccation, as fluid cannot be supplied via the thrombosed or obstructed capillaries. Topical agents and dressings may reduce but do not prevent desiccation of the burn wound and the inexorable progression of injury to deeper layers.

Infection remains the leading overall cause of death from burns. Susceptibility to infection is greatly increased due to the loss of the integumentary barrier to bacterial invasion, the ideal substrate present in the burn wound, and the compromised or obstructed microvasculature which prevents humoral and cellular elements from reaching the injured tissue. Additionally, the immune system is seriously affected, demonstrating decreased levels of immunoglobulins and serious perturbations of polymorphonuclear leukocyte (PMNL) function including a reduction in chemotaxis, phagocytosis, and diminished killing ability, resulting in increased morbidity and mortality. Regeneration cannot take place until equilibrium is reached; hence, healing is retarded. Prolongation of the healing process may lead to excessive scarring. Hypertrophic scars are seen in only 4% of cases requiring 10 days to heal, but up to 40% of cases requiring longer than 21 days to heal. Therapy of burns, therefore, must by directed to minimizing edema, preserving marginally viable tissue, enhancement of host defenses, and promoting wound closure. Adjunctive Hyperbaric Oxygen Therapy can benefit each of these problems directly, and shows promise in the treatment of inhalation injury. The more extensive the burn injury, the higher the incidence of an inhalation injury and pulmonary injury caused by smoke inhalation is the primary cause of fire-related deaths. The airway injury can be worsened by a variety of chemical pyrolysis products, depending on the material burned.¹

Summary
Current data show that Hyperbaric Oxygen Therapy, when used as an adjunct in a comprehensive program of burn care, can significantly improve morbidity and mortality, reduce length of hospital stay, and lesson the need for surgery. It has been demonstrated to be safe in the hands of those thoroughly trained in rendering Hyperbaric Oxygen Therapy in the critical care setting and with appropriate monitoring precautions. Careful patient selection and screening is mandatory.

Carbon Monoxide Poisoning back to top
Stephen R. Thom, M.D., Ph.D., FACEP and Lindell K. Weaver, M.D., FACP, FCCP, FCCM

The injuries caused by carbon monoxide (CO) traditionally have been viewed as due to a hypoxic stress mediated by an elevated carboxyhemoglobin (COHb) level. The two organ systems most susceptible to injury from CO are the cardiovascular and central nervous systems. Human and animal data indicate that major cardiac injury is due primarily to CO-induced hypoxic stress. However, the COHb level does not correlate well with the development of neurological injuries. Recent investigations have established that systemic oxidative stress can arise from exposure to CO and that perivascular and neuronal injuries arise by mechanisms other than hypoxia. Neuropathology seems to be due to a complex cascade of biochemical events involving several pathophysiologic processes.

Administration of supplemental oxygen is the cornerstone of treatment of CO poisoning. Oxygen inhalation will hasten disassociation of CO from hemoglobin dissociation to occur at a rate greater than that achievable by breathing pure oxygen at sea-level pressure. Additionally, HBO2, but not ambient pressure oxygen treatment, has several actions which have been demonstrated in animal models to be beneficial in ameliorating pathophysiologic events associated with central nervous system (CNS) injuries mediated by CO. These include an improvement in mitochondrial oxidative processes, inhibition of lipid peroxidation, and impairment of leukocyte adhesion to injured microvasculature. Animals poisoned with CO and treated with HBO2 have been found to have more rapid improvement in cardiovascular status, lower mortality, and lower incidence of neurological sequelae.

Since 1960, the clinical use of HBO2 for CO poisoning has occurred with increasing frequency. Over 2,500 CO-intoxicated patients were treated in North American hyperbaric chambers in 1992. However, this is only a small fraction of those poisoned with CO. Extrapolation of data from a 1994 survey across three western states projected that over 4,000 CO-poisoned patients are evaluated in emergency departments annually in the United States. In reported series, clinical recovery among patients treated with HBO2 appears to be improved beyond that expected with ambient pressure supplemental oxygen therapy. This has been observed both in terms of mortality and neurologic morbidity. This research found that the optimal benefit from HBO2 occurs in those treated with the delay after exposure and that repeat treatments may yield a better outcome than just a single treatment in selected patients.¹

Skeletal Muscle-Compartment Syndromes back to top
Michael B. Strauss, M.D., FACS, AAOS, ABPM/UHM

Crush injuries are directly associated with trauma while skeletal muscle compartment syndromes arise from ischemia, venous outflow obstruction, exertion, external compression as well as trauma. They have the following in common: 1) Ischemia and hypoxia at the injury site, 2) A gradient of injury, and 3) The potential for self-perpetuation of the injury. Management of the most severe presentations of these conditions almost always requires surgery. Hyperbaric oxygen (HBO2) is an effective intervention that counteracts the pathophysiological events which occur with these conditions. Studies show statistically significant reductions in the loss of muscle function, metabolites associated with muscle injury, edema, and muscle necrosis when HBO2 is used in crush injury, compartment syndrome models (1-6). Consequently, HBO2 should be used as a therapeutic adjunct for these conditions when their severity makes expectations of complications and/or less than optimal outcomes likely with usual surgical and medical interventions. Hyperbaric oxygen also should be considered for several conditions with related pathophysiology, namely, burns, threatened flaps, grafts and replantations, and frost bite.¹

Crush Injuries back to top
Michael B. Strauss, M.D., FACS, AAOS, ABPM/UHM

Decompression Sickness back to top
Richard E. Moon, M.D.

Decompression sickness (“bends,” DCS) arises from the generation of bubbles of inert gas in the tissue and/or blood in volumes sufficient to interfere with organ function, caused by rapid decompression during ascent from diving, flying, or a hyperbaric/hypobaric chamber. Bubble formation occurs when the speed of decompression exceeds the rate at which diffusion and perfusion reduce the tissue inert gas partial pressure. The resulting clinical manifestations include joint pains (limb bends), cutaneous eruptions or rashes (skin bends), neurological dysfunction (peripheral or central nervous system bends), cardiorespiratory symptoms and pulmonary edema (chokes), shock and death. Several mechanisms have been hypothesized by which bubbles may exert their deleterious effects. These include direct mechanical disruption of tissue, occlusion of blood flow, platelet deposition and activation of the coagulation cascade, endothelial dysfunction, and capillary leakage, complement activation, and leukocyte-endothelial interaction.

The diagnosis of DCS is made on the basis of signs and/or symptoms after a dive or altitude exposure. Manifestations most commonly include paresthesias, hypesthesia, joint pain, skin rash, and malaise. More serious signs and symptoms include motor weakness, ataxia, dyspnea, urethral and anal sphincter dysfunction, shock and death.

Chest radiography prior to HBO2 treatment in selected cases may be useful to exclude pneumothorax (which may require tube thoracostomy placement before recompression) and to exclude causes unrelated to diving for which treatment other than HBO2 would be appropriate (e.g. herniated disc). However, imagining studies are generally not helpful, and should not be relied upon to confirm the diagnosis of DCS or be used in deciding whether a patient with suspected DCS needs HBO2.

In addition to general supportive measures, included fluid resuscitation, airway protection, and blood pressure maintenance, the definitive treatment of decompression sickness is compression to suitable pressures greater than sea level. Improvement of decompression sickness symptoms as a result of compression was first noted in the Nineteenth Century. Recompression was first reported as a specific treatment for that purpose in 1896. Oxygen breathing was observed to improve the signs of decompression sickness in animals. The use of oxygen with pressure to accelerate gas diffusion and bubble resolution in humans was first suggested in 1897 and eventually tested in human DCS and recommended for the treatment of divers. The rationale for treatment with hyperbaric oxygen (HBO2) includes immediate reduction in bubble volume, increasing the diffusion gradient for inert gas from the bubble into the surrounding tissue, oxygenation of ischemic tissue and reduction of CNS edema. It is also likely that HBO2 has other beneficial pharmacological effects, such as a reduction in neutrophil adhesion to the capillary endothelium. The efficacy of administration of oxygen at increased ambient pressure (hyperbaric oxygen, HBO2) is widely accepted, and HBO2 is the mainstay of treatment for this disease.¹

Intracranial Abscess back to top
Reviewed by Irving Jacoby, M.D., FACEP

The term “intracranial abscess” (ICA) includes the following disorders: cerebral abscess, subdural empyema and epidural empyema. These disorders share many diagnostic as well as therapeutic similarities, and frequently, very similar pathophysiologic origins.

The overall mortality described in six case series of ICA from different countries during the years 1981-1986 ranged from 10 to 36%, with a summed death rate of 22%. During the years 1987-1993, the mortality may have decreased slightly, with a summed death of 18%. From the total of these 21 studies, the average mortality still remains at 20%. This is confirmed in the recent literature.

Because of improving mortality, there is a general trend toward a more conservative therapeutic approach in the management of ICA patients. This is reflected in the current international literature. However, patients with certain conditions and complications still pose major therapeutic problems. These include patients with: (1) multiple abscesses, (b) abscess in a deep or dominant location, (c) immune compromise, and (d) no response or further deterioration in spite of standard surgical and antibiotic treatment.

Preliminary experience using adjunctive HBO2 to treat patients with ICA has been favorable. To date, 48 such patients have been treated with 2% mortality. These include 16 consecutive patients reported in a series from Germany, 18 patients treated in Austria, 8 patients treated in France (4 with brain abscess; 4 with subdural and epidural empyema), and an additional 6 patients treated under the same conditions in several centers in the United States. The single death to date occurred in a patient with epidural empyema who had suffered hemispheric venous infarction from superior longitudinal sinus thrombosis prior to referral for Hyperbaric Oxygen Therapy.

Adjunct HBO2 should be considered under the following conditions:

Multiple abscesses
Abscesses in a deep or dominant location
Compromised host
In situations where surgery is contraindicated or where the patient is a poor surgical risk
No response or further deterioration in spite of standard surgical (e.g. 1-2 needle aspirates) and antibiotic treatment.

The low mortality of ICA patients treated with HBO2 as adjunct therapy is very encouraging. However, only a limited number of cases have been reported to date. In an attempt to collect information on a larger population of treated patients such that valid statistical comparisons can be made, the UHMS Therapy HBO2Committee is collecting case reports on additional such patients. It is requested that the critical parameters of the case and the results of treatment should be forwarded to the Chairman of the Committee at the address listed in the front of this Report. A specific questionnaire will then be forwarded to the treating physician to ensure that the necessary information regarding the case will be recorded.¹

Ischemic Injury back to top
Michael B. Strauss, M.D., FACS, AAOS, ABPM/UHM

Skin Flaps back to top
William A. Zamboni, M.D., FACS and Himansu R. Shah, M.D.

Hyperbaric oxygen (HBO2) therapy is neither necessary nor recommended for the support of normal, uncompromised skin grafts and flaps. However, in tissue compromised by irradiation or other cases where there is decreased perfusion or hypoxia, HBO2 has been shown to be extremely useful in flap salvage. Hyperbaric oxygen can help maximize the viability of the compromised tissue thereby reducing the need for regrafting or repeat flap procedures. A number of studies have shown the efficacy of HBO2 on enhancement of flap and graft survival in a variety of experimental and clinical situations.¹

Clostridial Myositis back to top
Dirk J. Bakker, M.D.

For clostridial myositis and myonecrosis (gas gangrene) or spreading clostridial cellulitis with systemic toxicity (or a presumptive diagnosis of either) the preferred treatment is a combination of hyperbaric oxygen (HBO2), surgery, and antibiotics.

Clostridial myositis with myonecrosis or gas gangrene is an acute, rapidly progressive, non-pyogenic, invasive clostridial infection of the muscles, characterized by profound toxemia, extensive edema, massive death of issue, and a variable degree of gas production.

Gas gangrene is either an endogenous infection, caused by contamination from a clostridial focus in the body (such as the bowel), 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 (95%) either alone or in combination with other pathogenic clostridia, C. novyi (8%), C. septicum (4%), and C. histolyticum, C. fallax, and C. sordelli (1% or less of the infections).

A further subdivision can be made in clostridia that are toxogenic, i.e., C. perfringens, C. septicum, C. novyi, and clostridia that are believed to be only proteolytic, i.e., C. histolyticum, C. bifermentans, C. sporogenes, and C. fallax, which augment an infection by their proteolytic capabilities but do not cause the classical gas gangrene syndrome. C. tertium, C. sphenoides, and C. sordelli can be considered as contaminants. It is not known if and what these microorganisms add to the disease process. The essential role of alpha-toxin in the pathogenesis of gas gangrene was confirmed by Williamson and Titball, who developed a genetically engineered vaccine against alpha-toxin. This vaccine 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 30mmHg and in a restricted manner in tensions up to 70mmHg.

The complete genome sequence of C. perfringens has been published recently.

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.¹

Clostridial Myonecrosis (gas gangrene) back to top
Dirk J. Bakker, M.D.

Clostridium perfringens is not a strict anaerobe; it may grow freely in O2 tensions of up to 30mmHg and in a restricted manner in tensions up to 70mmHg.

The complete genome sequence of C. perfringens has been published recently.

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.

Clostridial Cellulitis back to top
Dirk J. Bakker, M.D.

Clostridium perfringens is not a strict anaerobe; it may grow freely in O2 tensions of up to 30mmHg and in a restricted manner in tensions up to 70mmHg.

The complete genome sequence of C. perfringens has been published recently.

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.

Skin Grafts back to top
William A. Zamboni, M.D., FACS and Himansu R. Shah, M.D.

Necrotizing Soft Tissue Infections back to top
Michael Lepawsky, B.A., M.D., CCFP(C), FCFP

Hyperbaric Oxygen Therapy is an accepted adjunct to surgical and antibiotic treatment for necrotizing soft tissue infections. Such conditions may result from a single or a mixed population of organisms. They may be aerobic or anaerobic. Some necrotizing infections appear to be the result of a synergistic combination of organisms. Such infections appear in a wide variety of clinical settings, particularly after trauma, surgical wounding, and/or around foreign bodies. The host is frequently compromised in some way, often with diabetes, vasculopathy, or both. Infections typically cause local tissue hypoxia (1) and, in the case of necrotizing infections, this is exacerbated by an infection-induced occlusive endarteritis (2). Additionally, both toxin effect and intravascular sequestration of leukocytes occur in the presence of certain organisms associated with necrotizing soft tissue infections, resulting in a paucity of polymorphonuclear leukocytes (PMNs) neutrophils at the site of infection (3).

Hypoxic conditions profoundly impair PMN function (4). As a local infection develops, metabolism by facultative organisms further depletes the oxygen that is available. This action, as well as the accumulation of metabolic products, lowers the oxidation-reduction potential (Eh). Conditions are thereby improved for the growth of anaerobic bacteria. Metabolism by the mixed aerobic and anaerobic flora decreases the Eh and tissue oxygen levels further and the infectious process accelerates. These changes serve to promote the growth of even more fastidious organisms.

Discernible quantities of tissue gas may be produced in many mixed flora infections. Although carbon dioxide (CO2) is one of the end products of aerobic metabolism, it is readily dissipated and cleared by the body, rarely accumulating in tissues. Incomplete oxidation of substrates by facultative and anaerobic bacteria can result in the production of less soluble gases such as H2, H2S, and CH4, which do accumulate in tissues. The presence of these gases indicates rapid bacterial multiplication at a low Eh.

The principal treatments for necrotizing soft tissue infections are surgical debridement and administrations of systemic antibiotics. Hyperbaric oxygen (HBO2) is recommended as an adjunct only in those settings where mortality and morbidity are expected to be high despite aggressive standard treatment. HBO2 has been used in the past because of its anticipated benefits in abating the synergistic interaction present in mixed infections. The improved tissue oxygen tension will adversely affect anaerobic bacterial growth by direct toxic mechanisms, as well as by increasing tissue Eh (5-8). Investigators have also shown that obligate anaerobic bacteria can inhibit PMN phagocytosis of facultative organisms (9-11). Hyperbaric oxygen should also ameliorate these effects since improved oxygenation can improve PMN function (12,13) and bacterial clearance (14,15). It has recently been suggested that the rapidity of Streptococcal and Clostridial tissue necrosis was the consequence of leukocyte-endothelial interactions, leading to progressive vascular insufficiency and ischemic necrosis (16). Bryant and co-workers have demonstrated that Clostridial theta toxin and streptolycin O, nearly identical thiol-activated cytolysins, up-regulate endothelial adherence molecules (E-selectin, platelet activating factor, and ICAM-1) as well as the granulocyte adherence molecule CD18b/CD18 (17,18). In vitro, this interaction results in adherence of PMNs to endothelium and after, several hours, cytotoxicity of endothelial cell monolayers (19). HBO2 has been shown to decrease neutrophil adherence by selective inhibition of beta-2 integrin function, preventing persistent PMN adherence to the endothelium in a carbon monoxide injury model (20). Additional work is needed to demonstrate a similar mechanism action in necrotizing wounds. Mechanistic studies such as those described above support the benefits of HBO2 described in clinical reports below.¹

Refractory Osteomyelitis back to top
Brett B. Hart, M.D.

Refractory osteomyelitis is chronic osteomyelitis that persists or recurs after appropriate interventions have been performed or where an acute osteomyelitis does not respond to accepted management techniques (1). Patients with refractory osteomyelitis frequently suffer from coexisting local and systemic factors that compromise their responsiveness to infection. Hyperbaric oxygen (HBO2), when combined with appropriate antibiotics, nutritional support, surgical debridement and reconstruction, provides a useful clinical adjunct in the management of refractory bone infections. Overall, the addition of HBO2 therapy to the clinical management of previously refractory osteomyelitis produces infection arrest rates in approximately 80% of cases.

Initial evidence for this therapeutic benefit stemmed from reports collected during the 1960s, in which difficult cases of osteomyelitis were successfully treated by the addition of HBO2 therapy (2-5). A series of controlled animal studies subsequently confirmed the perceived clinical benefit of HBO2 (6-9). More recently, in vitro and in vivo studies have revealed specific mechanisms of action that explain the benefits seen with HBO2 treatment of refractory osteomyelitis. Common to each mechanism is the generation of normal to elevated tissue oxygen tensions in infected bone. Mader and Niinikoski demonstrated that the decreased oxygen tensions typically associated with infected bone can be elevated to normal or above normal while breathing 100% oxygen in a hyperbaric chamber (10). Such elevations have important consequences for the hypoxic milieu of osteomyelitic tissues.¹

Delayed Radiation Injury (soft tissue and bony necrosis) back to top
John J. Feldmeier, D.O. and Luis A. Matos, M.D.

Radiation injuries should be differentiated as acute, sub-acute or delayed complications (1). Acute injuries are due to direct cellular toxicity caused by free radical-mediated damage to cellular DNA and are usually self-limited and treated symptomatically. However, they can be very debilitating during their duration. Sub-acute injuries are typically identifiable in only a few organ systems, e.g. radiation pneumonitis following the treatment of lung cancer with an onset typically 2 to 3 months after completion of irradiation. These, too, are generally self-limited but occasionally evolve to become delayed injuries. Delayed radiation complications are typically seen after a latent period of six months or more and may develop many years after the radiation exposure. Often, they are precipitated by an additional tissue insult such as surgery within the radiation field. Although the etiology of delayed injuries may vary somewhat among organ systems, the hallmark of delayed radiation injury is endarteritis with tissue hypoxia and secondary fibrosis (2). Recently, it has become apparent that the evolution of radiation injury is a continuum of events rather than several discrete occurrences (3-5). The elaboration of fibrogenic cytokines begins at the time of irradiation. This recognition may permit the development of predictive assays to identify those patients at high risk for radiation injury prior to its manifestation and permit prophylactic intervention prior to its expression. Such intervention might include Hyperbaric Oxygen Therapy.

Hyperbaric oxygen (HBO2) has been utilized effectively for manifest chronic radiation injuries for many years. The site to which it has been applied for the longest period of time and with the most publications supporting its application is the mandible (6-24). The success in treating mandibular osteoradionecrosis has led researchers to apply HBO2 to radiation injuries at other sites involving other organ systems.

Hyperbaric oxygen has been shown to induce neovascularization and increased cellularity in irradiated and other hypoxic tissues. Marx and co-workers have shown in both an animal experimental model and with serial transcutaneous oxygen measurements in clinical subjects that HBO2 does increase vascular density and resultant tissue oxygen content (16,20,25). Feldmeier and colleagues have shown with several assays in an animal model that tissue fibrosis can also be reduced with the application of HBO2 given in a prophylactic mode (26,27). Marx had previously established the principle of prophylactic intervention in the setting of tooth extractions and alveoloplasty from heavily irradiated mandibles (28). Dental extractions or other surgical procedures are fraught with high complication rates when done in heavily irradiated tissues without the benefit of preoperative HBO2 therapy (29-33).¹

Enhancement of healing in selected problem wounds back to top
Robert A. Warriner III, M.D., FACA, FCCP, CWS and Harriet W. Hopf, M.D.

Problem wounds represent a significant and growing challenge to our healthcare system. The incidence and prevalence of these wounds are increasing in the population resulting in growing utilization of healthcare resources and dollars expended. Venous leg ulcers represent the most common lower extremity wound seen in ambulatory wound care centers with recurrences frequent and outcomes often less than satisfactory. Pressure ulcers are common in patients in long term institutional care settings adding significant increases in cost, disability, and liability. Foot ulcers in patients with diabetes contribute to over half of lower extremity amputations in the United States in a group at risk representing only 3 percent of the population. In response to this challenge specialized programs have emerged designed to identify and manage these patients using a variety of new technology to improve outcomes. Hyperbaric oxygen treatment has been increasingly utilized in an adjunctive role in many of these patients coinciding with optimized patient and local wound care.¹

Hypoxia in Wound Healing Failure back to top

Normal wound healing proceeds through an orderly sequence of steps involving control of contamination and infection, resolution of inflammation, regeneration of the connective tissue matrix, angiogenesis, and resurfacing. Several of these steps are critically dependent upon adequate perfusion and oxygen availability. The end result of this process is sustained restoration of anatomical continuity and functional integrity. Problem or chronic wounds are wounds that have failed to proceed through this orderly sequence of events and have failed to establish a sustained anatomic and functional result. This failure of wound healing is usually the result of one or more local wound or systemic host factors inhibiting the normal tissue response to injury. These factors include persistent infection, malperfusion and hypoxia, cellular failure, and unrelieved pressure or recurrent trauma.

The hypoxic nature of all wounds has been demonstrated, and the hypoxia, when pathologically increased, has correlated with impaired wound healing and increased rates of wound infection. Local oxygen tensions in the vicinity of the wound are approximately half the values observed in normal, non-wounded tissue. The rate at which normal wounds heal has been shown to be oxygen dependent. Fibroblast replication, collagen deposition, angiogenesis, resistance to infection, and intracellular leukocyte bacterial killing are oxygen sensitive responses essential to normal wound healing. However, if the periwound tissue is normally perfused, steep oxygen gradients from the periphery to the hypoxic wound center support a normal wound healing response.¹

Physiology of Hyperbaric Oxygenation of Wounds back to top

Regardless of the primary etiology of problem wounds, a basic pathway to non-healing is the interplay between tissue hypoperfusion, resulting hypoxia, and infection. A large body of evidence exists which demonstrates that intermittent oxygenation of hypoperfused wound beds, a process only achievable in selected patients by exposing them to hyperbaric oxygen treatment, mitigates many of these impediments and sets into motion a cascade of events that leads to wound healing. Hyperbaric oxygenation is achieved when a patient breathes 100% oxygen at an evaluated atmospheric pressure. Physiologically, this produces a directly proportional increase in the plasma volume fraction of transported oxygen that is readily available for cellular metabolism. Arterial PO2 elevations to 1500 mmHg or greater are achieved with 2 to 2.5 atm abs with soft tissue and muscles PO2 levels elevated correspondingly. Oxygen diffusion varies in a direct linear relationship to the increased partial pressure of oxygen present in the circulating plasma caused by Hyperbaric Oxygen Therapy. This significant level of hyperoxygenation allows for the reversal of localized tissue hypoxia, which may be secondary to ischemia or to other local factors within the compromised tissue.¹

Diabetic Lower Extremity Wounds, the Prototype Hypoxic Wound back to top

Lower extremity ulcers and amputations are an increasing problem for people with diabetes. Up to 6 per cent of all hospitalizations for diabetics include a lower extremity ulcer as a discharge diagnosis. When present, an ulcer increased hospital length of stay by an average of 59% compared to diabetics admitted without lower extremity ulcers. Finally, once an amputation occurs, nine to 20% of diabetic patients will experience an ipsilateral or contralateral amputation within 12 months and 28-52% within five years. The cost of care for a new diabetic foot ulcer has been calculated to be $27,987 in the two years following diagnosis.

The pathophysiology of diabetic foot ulceration, faulty healing, and lower extremity limb loss has been well described. It involves the progressive development of a sensory, motor, and autonomic neuropathy leading to loss of protective sensation, deformity increasing plantar foot pressures, and alternations in autoregulation of dermal blood flow. Diabetics show earlier development and progression of lower extremity peripheral arterial occlusive disease with a predilection for the trifurcation level vessels just distal to the knee. Impaired host immune response to infection and possible cellular dysfunction all contribute to the clinical outcomes described above.

Management, likewise, has been extensively described and includes careful attention to identification and management of infection, aggressive surgical debridement, evaluation and correction of vascular insufficiency ambulatory off-loading, and glycemic control. While a full discussion of these interventions is beyond the scope of this review, they form the basis of effective diabetic foot ulcer management and must be applied consistently if adjunctive interventions are to provide an additive value. Other interventions have recently been advocated including topical application of a recombinant human platelet derived growth factor (PDGF-BB, becaplermin), bioengineered human monolayer fibroblast grafts and bilayer fibroblast and keratinocyte grafts, and negative pressure wound therapy (wound vac). Clearly, regardless of the interventions applied, limb salvage rates improve when care is applied in a multidisciplinary setting using comprehensive protocols for care.

Local wound hypoxia plays a pivotal role in diabetic wound healing failure and limb loss as evidence by the report by Pecoraro that when periwound PtcO2 values were below 20 mmHg they were associated with a 39 fold increased risk of primary healing failure. While aggressive distal lower extremity bypass grafting and lower extremity angioplasty have contributed to increased wound healing and limb salvage rates, technical grafting success does not necessarily equate with limb salvage. Hyperbaric oxygen treatment offers an intriguing opportunity to maximize oxygen delivery in the setting of minimal or insufficiently corrected blood flow.¹

Clinical Experience with HBO2 in Diabetic Lower Extremity Wounds back to top

On August 30, 2002, the Center for Medicare and Medicaid Services announced in CAG-00060N, Coverage Decision Memorandum for Hyperbaric Oxygen Therapy in the Treatment of Hypoxic Wounds and Diabetic Wounds of the Lower Extremities and in Transmittal AB-02-183 Program Memorandum for Intermediaries/Carriers its decision to cover treatment of diabetic wounds of the lower extremities with hyperbaric oxygen effective April 1, 2003, in patients meeting the following criteria:

Patient has type 1 or 2 diabetes and has a lower extremity wound that is due to diabetes;
Patient has a wound classified as Wagner grade III or higher;
Patient has failed an adequate course of standard wound therapy (defined as 30 days of standard treatment including assessment and correction of vascular abnormalities, optimization of nutritional status and glucose control, debridement, moist wound dressing, off-loading, and treatment of infection).¹

Other Potentially Hypoxic Wounds back to top

Venous Stasis Ulcers: Compression therapy with multilayer external compression bandaging techniques remains the mainstay of management of venous stasis ulcers of the lower extremity. Recent evidence suggests that bioengineered tissue grafts used in combination with standard compression bandaging techniques may shorten time to healing. While one prospective, blinded, randomized clinical trial of hyperbaric oxygen treatment in leg ulcers of undefined etiology showed a statistically greater reduction in wound size at six weeks compared to control wounds, hyperbaric oxygen treatment is not indicated in the primary management of venous stasis ulcers of the lower extremities. Hyperbaric oxygen may be required to support skin grafting in patients with concomitant peripheral arterial occlusive disease and hypoxia not corrected by control of edema.

Pressure Ulcers: The management of decubitus ulcers has been well described elsewhere and emphasizes pressure relief, surgical debridement, treatment of infection, nutritional support, and surgical closure for large ulcers. Other interventions such as negative pressure wound therapy (wound vac) may be beneficial. Hyperbaric oxygen treatment is not indicated in routine decubitus ulcer management. It may be necessary for support of skin grafts or flaps showing evidence of ischemic failure, when the ulcer develops in the field of previous radiation treatment for pelvic or perineal malignancies, or when progressive necrotizing soft tissue infection or refractory osteomyelitis is present.

Arterial Insufficiency Ulcers: The primary treatment of refractory ischemic wounds of the lower extremities is improvement in blood flow by angioplasty or surgical revascularization. However, hyperbaric oxygen treatment may be of benefit in those cases where persistent hypoxia remains after attempts at increasing blood flow or when wound failure continues despite maximum revascularization. Hyperbaric oxygen treatment may also be required in support of skin grafting in this setting.¹

Concerns Related to Potential Carcinogenesis or Cancer Growth Enhancement back to top
John J. Feldmeier, D.O. and Luis A. Matos, M.D.

A frequently expressed concern by those considering hyperbaric oxygen for a patient with radiation injury is the fear that hyperbaric oxygen will somehow accelerate malignant growth or cause a dorminant malignancy to be re-activated. In Marx's very large group of patients treated with HBO2 for radiation injury of the mandible, there was no increased likelihood of tumor recurrence or second tumor development. In 1994, Feldmeier and his colleagues reviewed the available literature related to this issue. An overwhelming majority of both clinical reports and animal studies reviewed in this paper showed no enhancement of cancer growth. A small number of reports actually showed a decrease in growth or rates of metastases. Feldmeier updated this material for the Consensus Conference held in 2001 jointly sponsored by the European Society of Therapeutic Radiology and Oncology (ESTRO) and the European Committee for Hyperbaric Medicine (ECHM). In this update, Feldmeier emphasized the differences known in tumor and wound healing angiogenesis with similar but distinct processes operative in each case. He also showed that there are significant differences in the growth and inhibition factors, which modulate angiogenesis, in both circumstances. He summarized the literature demonstrating that tumors which are hypoxic are less responsive to treatment, less subject to death by apoptosis and more prone to aggressive growth and lethal metastases. Most experienced practitioners of hyperbaric oxygen no longer fear that hyperbaric oxygen will promote malignant growth. An even more recent review has been accepted for publication in Undersea and Hyperbaric Medicine.¹

¹ Hyperbaric Oxygen 2003: Indications and Results, The Hyperbaric Oxygen Therapy Committee Report by John J. Feldmeier, D.O., Chairman and Editor. Copyright 2003, Undersea and Hyperbaric Medical Society, Inc., Kensington, MD.