Paul Nicholson, MD, Clinical Instructor, Department of Emergency Medicine, Wexner Medical Center, The Ohio State University, Columbus

Christopher San Miguel, MD, Assistant Professor of Emergency Medicine, Wexner Medical Center, The Ohio State University, Columbus

Colin G. Kaide, MD, FACEP, FAAEM, Associate Professor of Emergency Medicine, Specialist in Hyperbaric Medicine, Wexner Medical Center, The Ohio State University, Columbus


Heather Murphy-Lavoie, MD, FACEP, FUHM, Associate Professor, Section of Emergency Medicine, Associate Program Director, LSU Undersea and Hyperbaric Medicine Fellowship, Louisiana State University, New Orleans

A thorough understanding of the gas laws is necessary to explain the mechanics of HBO2. Dalton’s law states that in a mixture of non-reacting gases, the total pressure is equal to the sum of the partial pressures of each of the individual gases.2,3 The air in the Earth’s atmosphere is composed of 21% oxygen, 78% nitrogen, and 1% trace gases. Henry’s law states that the amount of a given gas that dissolves in a volume of liquid is directly proportional to the pressure exerted on the surface of the liquid.2,4 This means that as the partial pressure of a gas above a liquid increases, the amount of that gas that dissolves in the liquid also increases. Conversely, if the partial pressure of the gas is decreased, then some of the dissolved gas must come out of the solution and return to the gaseous state.

Hyperbaric oxygen therapy works by dramatically increasing the amount of oxygen dissolved in the plasma as a result of the laws described previously. Under normal conditions, the amount of dissolved oxygen is negligible — only 0.3 mL of oxygen per 100 mL of blood, known as volumes percent (vol%). Under hyperbaric conditions with 100% oxygen and 3.0 ATA, the dissolved oxygen can reach 6 vol%. (See Table 1.) This high level of dissolved oxygen is enough to sustain the basal metabolic functions in the complete absence of any hemoglobin. It also allows for delivery of oxygen to hypoxic tissues even if they are inaccessible to red cells.

Table 1. Oxygen Content: Arterial (CaO2)

CaO2 = oxygen carried by hemoglobin (HgB) + oxygen dissolved in plasma

CaO2 = (HgB × % saturation × 1.34) + (PaO2 × 0.003)

Normobaric Oxygen (FiO2 = 21% at 1 ATA)

CaO2 = 21% × 100% × 1.34 + 100 mmHg (0.003)

CaO2 = 20 volumes %* + 0.3 volumes%*

Hyperbaric Oxygen (FiO2 = 100% at 3 ATA)

CaO2 = HgB × 100% × 1.34 + 2,000 mmHg (0.003)

CaO2 = 20 volumes %* + 6 volumes%*

*Volumes% of oxygen is mL of oxygen per 100 mL of blood

HBO also acts on gas bubbles by compressing them and decreasing their volume per Boyle’s law, which states that the volume of a gas is inversely proportional to the pressure exerted upon that gas.4 (See Figure 2.) This reduction in gas bubble size becomes important when treating patients with air-gas embolism or decompression sickness.

Figure 2. Bubble Size Under Pressure

Bubble size

Image courtesy of Colin Kaide, MD

Indications and Contraindications

In 1976, the UHMS established and tasked the Hyperbaric Oxygen Therapy Committee to oversee the development of an evidence-based list of indications for the use of HBO. There are currently 14 indications. (See Table 2.) Of these, five lend themselves naturally to application in emergency medicine.5,6 There are only two absolute contraindications to HBO2: untreated pneumothorax and use of doxorubicin within the past seven days. Relative contraindications include chronic obstructive pulmonary disease (COPD), pulmonary blebs, upper respiratory or sinus infections, recent ear or thoracic surgery, and claustrophobia. It should be noted that the use of HBO2 in emergency situations should not be precluded by these relative contra-indications when it is considered the primary or only possible effective treatment modality.

Table 2. Approved Indications for Hyperbaric Therapy

Non-emergency Indications

• Arterial insufficiencies (enhancement of healing in selected problem wounds)

• Exceptional blood loss (anemia)

• Intracranial abscess

• Osteomyelitis (refractory)

• Delayed radiation injury (soft tissue and bony necrosis)

• Compromised skin grafts and flaps

• Thermal burn injury

• Idiopathic sudden sensorineural hearing loss

Emergency Indications

• Air or gas embolism

• Carbon monoxide poisoning

• Clostridial myositis and myonecrosis (gas gangrene)

• Crush injury, compartment syndrome, and other acute traumatic ischemias

• Decompression sickness

• Necrotizing soft tissue infections

• Arterial insufficiencies (central retinal artery occlusion)

Emergency Applications of Hyperbaric Oxygen

Air-gas Embolism

Air-gas embolism (AGE) occurs when air bubbles are introduced into the circulatory system. This can occur as a result of a variety of causes. The most clinically relevant examples include dive-related accidents and complications of a medical procedure. Air bubbles produce injury by multiple mechanisms. The most obvious problem is occlusion of blood flow. However, this does not account for all the problems caused by AGE. Bubbles injure the endothelium of blood vessels, causing an inflammatory cascade and further obstruction.7 Additionally, when the mechanical obstruction caused by the bubble is relieved, a reperfusion-type injury may be incited. Air-gas embolism can be broken down into three major categories: arterial, venous, and paradoxical AGE.

Arterial Air-gas Embolism

Arterial air-gas embolism occurs when a gas bubble enters the arterial circulation. The ultimate consequences of an arterial AGE depend on the organ or organs affected and how well they tolerate an acute vascular occlusion. Emboli that become lodged in the coronary arteries can precipitate acute coronary syndrome (ACS). Air that enters the carotid arteries and subsequently the brain causes cerebral air-gas embolism (CAGE). (See Figure 3.) CAGE can manifest with the symptoms of an ischemic stroke, such as motor or sensory deficits, altered mental status, seizures, and coma.8

Figure 3. Bubbles in Cerebral Vasculature

Bubbles in cerebral vasculature

Image courtesy of Colin Kaide, MD

One of the most common causes of AGE is scuba diving accidents. Normally, when divers are ascending, they will breathe in and out. This allows the expanding gas a method of escape. However, if a diver holds his or her breath during ascent, the expanding gas has nowhere to go. It will continue to expand until it exceeds the maximum lung volume, causing lung injury. Possible injuries include pneumothorax, pneumomediastinum, and gas entering the cardiovascular system leading to AGE. (See Figure 4.) If the gas enters the pulmonary venous system or the systemic arterial system, it will result in arterial air embolism.7

Figure 4. Air Embolism in Ascending Diver

Air embolism in ascending diver

Image courtesy of Colin Kaide, MD

The only proven definitive treatment for arterial AGE is HBO2.7,9,10,11,12 Rapid recognition of this clinical entity is critical. Any diver who is unconscious when surfacing or who quickly deteriorates should be presumed to have AGE until proven otherwise and efforts should be made to initiate HBO2. While awaiting HBO2, the patient should be placed on 100% oxygen by non-rebreather to treat hypoxia and reduce bubble size. It reduces bubble size by creating a diffusion gradient that favors the movement of inert gasses such as nitrogen out of the bubble and back into the plasma.7,9,10,11,12

The current HBO2 regimen recommended by the UHMS for arterial AGE is the U.S. Navy Treatment protocol. This involves compression between 2.0 ATA to 2.82 ATA with at least 60 minutes spent at 2.82 ATA at 100% oxygen. The protocol calls for a total treatment duration of 290 minutes. Some patients may require time extensions at the higher or lower pressures or additional treatments in the hyperbaric chamber to facilitate more complete resolution of symptoms.

Venous Air-gas Embolism

Venous air-gas embolism occurs when air is introduced into the venous side of the circulation. Only large acute venous air emboli are of clinical consequence because of the filtering action of the lung.10 A large volume of air delivered to the venous system over a short period of time can cause serious issues, including cardiovascular collapse and death. A large air bubble can travel through the venous circulation and become lodged in the right ventricle, causing right ventricular outflow tract obstruction, or can continue on to the pulmonary vasculature and lead to increased pulmonary vascular resistance. Ultimately, this leads to decreased preload and, therefore, decreased stroke volume from the left ventricle. It is estimated that venous air-gas emboli between 100-300 mL are sufficient to cause immediate cardiac arrest.7,13,14

The first maneuver that should be undertaken by the emergency provider is to place the patient in the left-lateral decubitus position. The theoretical benefit of this action is to trap the air in the right ventricle and reduce the risk of the bubble traveling to the lungs. Oxygen therapy and hemodynamic support also are indicated. Typically, these patients will have a distribution of the air bubble to the lungs prior to receiving any treatment. If the patient remains symptomatic or develops pulmonary edema, HBO2 can be considered as an adjunctive therapy. In the rare case of a known air bubble trapped in the right ventricle, needle aspiration can serve as a definitive treatment.7,15

Paradoxical Air-gas Embolism

Paradoxical air-gas emboli occur when an air bubble that originated on the venous side of the circulation crosses over to the arterial side. This generally occurs by way of a patent foramen ovale (PFO) but also can occur as a result of intra-pulmonary shunts, arteriovenous fistulas/malformations, atrial septal defects, and ventricular septal defects. Approximately 30% of the otherwise normal population has a PFO.16 When air from the venous system is present in a large enough quantity, increased pressures in the right ventricular outflow tract can force air from the right side of the heart to the left via a PFO. Treatment of paradoxical AGE is similar to that described earlier for arterial AGE.

Carbon Monoxide Poisoning

Carbon monoxide (CO) poisoning is the most common cause of unintentional death by poisoning in the United States and is responsible for approximately 15,000 ED visits and 500 deaths annually. CO causes cellular damage by a number of mechanisms, including tissue hypoxia and direct toxicity. CO has an affinity for hemoglobin (HgB) that is 240 times greater than that of oxygen. Binding of HgB by CO also causes a leftward shift of the oxyhemoglobin dissociation curve, known as the Haldane effect. In effect, this both reduces the oxygen-carrying capacity of HgB and makes it more difficult for HgB to deliver the oxygen it is able to carry. CO also interferes with oxidative phosphorylation by inhibiting cytochromes and triphosphopyridine nucleotide reductase.17 Additionally, CO causes oxidative stress and, therefore, the production of free radicals that directly damage cells.18,19

The signs and symptoms of CO poisoning vary depending on the degree of exposure. At lower levels of carboxyhemoglobin (COHgB), patients typically will complain of headache, nausea, and dizziness. As levels increase, patients can progress to confusion, syncope, decreased level of consciousness, and coma.20,21,22 Alterations in vital signs also may be observed. Tachycardia and tachypnea may develop in response to hypoxia. This can progress to bradycardia, hypotension, and decreased respiration in advanced stages. Ultimately, if the exposure is severe enough, CO poisoning can be fatal.

Certain populations are particularly at risk for bad outcomes due to CO poisoning. The very young and very old have minimal reserves to deal with hypoxic insults compared to the healthy adult population. Patients with coronary artery disease are at increased risk of ACS due to myocardial hypoxia.23 Those with underlying pulmonary or vascular disease are at increased risk for similar reasons. Pregnant women also represent a vulnerable population. Fetal hemoglobin has an even higher affinity for CO than does adult hemoglobin. Fetal hemoglobin also has a left shift oxygen dissociation curve compared to adult hemoglobin. This can cause fetal CO levels to become dangerously high and lead to intrauterine fetal demise.

Apart from acute CO poisoning, there are three distinct injury patterns associated with CO poisoning: cardiovascular sequelae, delayed neurologic sequelae (DNS), and chronic CO poisoning. Patients who have had moderate to severe CO exposures are at risk for cardiovascular complications, including cardiomyopathy and myocardial infarction.24 A significant percentage of patients (up to 40%) will develop some sort of delayed neurologic sequelae that can present as cognitive or focal neurologic deficits, personality changes, and movement disorders. The time of onset is variable, usually occurring within a few weeks but may occur years later. These neurologic symptoms often last years and may be permanent in some cases.25,26,27 Chronic CO poisoning is perhaps the most challenging to diagnose, as patients present after long-term exposure to low levels of CO and have vague, nonspecific complaints. Symptoms can manifest as headache, dizziness, anorexia, weight loss, personality changes, impaired sleep, nystagmus, myoclonus, and weakness, among others.28,29

The diagnosis of CO poisoning is often challenging and can be missed easily, as the presentation can be subtle and nonspecific.20 A thorough history and physical exam is paramount. CO poisoning should be on the differential for patients presenting with headache, nausea, dizziness, altered mental status, and/or syncope.

CO poisoning also should be considered when more than one person living or working in close proximity presents with similar symptoms. This is especially true in winter months when people are more likely to be using propane tanks, gas heaters, and other appliances that produce CO. Although CO can cause virus-like symptoms, it is important to remember that CO-poisoned patients will present in parallel, whereas patients with a viral illness tend to present serially.

When CO exposure is suspected, the COHgB level can be tested. The preferred test is a venous COHgB level.30 While there is a correlation between severity of symptoms and measured COHgB level, the level cannot predict the degree and nature of the patient’s symptoms accurately. Levels between 3-10% tend to cause minor symptoms, 25-40% moderate symptoms, and 40-50% severe symptoms. Interestingly, heavy smokers can have CO levels of up to 13% and remain asymptomatic.31,20 Although venous COHgB levels are highly accurate and crucial in diagnosis, it is possible for a patient’s level to be inconclusive or even negative, especially if the patient has been removed from the source for a prolonged period of time. If suspicion for CO poisoning remains high, even after a normal venous COHgB, the suspected source should be tested. This may mean sending police, emergency medical services, fire personnel, or the local gas company to the site.

Treatment first involves removal of the patient from the source of CO. Once this is accomplished, the patient should be treated with supplemental oxygen at the highest level possible. This typically is achieved using a non-rebreather (NRB) mask at 15 L/min. This allows for an FiO2 of approximately 63%. Ideally, the patient would breathe 100% oxygen. Unfortunately, other than HBO2, this is only possible with an anesthesia circuit in the operating room (OR).32 One alternative method (borrowed from rapid-sequence intubation) to maximize FiO2 delivered with an NRB mask is to turn the knob on the oxygen delivery source to flush (all the way up until the knob stops turning). This can deliver close to 50 L/min. Adding a nasal cannula under the NRB mask and setting it to 15 L/min can help supplement the oxygen, and together they can deliver an FiO2 of about 90%. At sea level at an FiO2 of 21%, the half-life of COHgB is about 300 minutes. At 100% FiO2, the half-life is reduced to about 90 minutes.

With the use of HBO2 at an FiO2 of 100% and 3 ATA, it is possible to reduce the half-life of COHgB to less than 30 minutes.33 In animal studies, researchers have also shown that HBO2 can promote the dissociation from cytochrome c oxidase and perhaps blunt some of the direct cellular toxicity that is associated with CO.34,35,36

Despite the face validity and existing evidence of HBO2 in CO poisoning, there is debate in the scientific community regarding its efficacy and whether there is any true, acute benefit over oxygen delivered under normobaric conditions. In fact, some of the strongest evidence supports HBO2’s role in preventing chronic symptoms. A double-blind, randomized, controlled trial showed that HBO2 reduced the occurrence of delayed neurological sequelae at six weeks and 12 months post poisoning.37 A delve into the literature is beyond the scope of this article; however, the UHMS does recommend HBO2 for patients presenting with transient or prolonged unconsciousness, cardiovascular dysfunction, neurologic signs, or severe acidosis.38

Because the potential harms are relatively low and the balance of evidence suggests that the potential benefits are high, most experts in the field recommend HBO2 in selected patient populations. We would suggest using HBO2 in patients who meet the criteria listed by the UHMS, as well as pregnant women with a COHgB level above 15% or signs of fetal distress, and patients who exhibit persistant symptoms despite normobaric therapy.

Currently, there is no single accepted HBO2 protocol for CO poisoning. Protocols generally range from a single treatment at 2.8 to 3.0 ATA to multiple treatments at varying pressures.

Decompression Sickness

Decompression sickness (DCS) develops when inert gases, mainly nitrogen, precipitate out of solution and collect in the cardiovascular system or tissues in sufficient quantity to impair organ function.2,3,4,39,40,41,42,43 This generally occurs when a scuba diver makes too rapid an ascent, dives too deep, or stays at depth for too long.39

When a diver descends below the surface, the pressure he or she feels is equal to the column of water above the diver in addition to the column of air above the water. This pressure is the atmospheres absolute or ATA. Every 33 feet or 10 m is equal to 1 atm. Therefore, at a depth of 33 feet below water at sea level, the diver experiences a pressure of 2 ATA.

The increase in pressure makes it more difficult for the diver to breathe. Diving equipment is designed to address this issue by increasing the pressure of delivered air. This rise in overall pressure of gas means a proportional rise in the partial pressure of each component gas. As the partial pressure of the inspired gases increases, the amount of each of these gases that dissolves into the blood increases as a result of Henry’s law. This means that as the diver dives deeper, more nitrogen is dissolved in the blood in a process known as on-gassing. The reverse occurs during ascent in a process known as off-gassing. As the diver surfaces, nitrogen moves down the concentration gradient from the tissues, to the blood, and out the lungs.39,40

During a proper ascent, nitrogen will remain in solution as it moves down its concentration gradient until it is expired via the lungs. If the diver ascends too rapidly or accumulates too much nitrogen “debt” by diving too deep for too long a period of time, the nitrogen will not be able to be removed fast enough by the lungs and will return to the gaseous phase in the tissues or bloodstream. This is the mechanism that underlies the pathophysiology seen in decompression sickness.3,39,40,41

Flying in a commercial airplane shortly after ascent also can lead to decompression sickness. Most of these aircraft are pressurized to the pressure felt at 8,000 feet. This is equivalent to approximately 0.73 atm. This rapid decrease in pressure can further facilitate nitrogen bubble formation from dissolved gas that otherwise was not a problem.39,40,42 In some of the newer airplanes and most private aircraft, this does not represent a significant risk as the aircraft are pressurized to sea level or 1 atm.

Decompression sickness is diagnosed by history and physical exam; there is no laboratory or imaging test to aid in diagnosis. Most patients with DCS will develop symptoms within one to three hours of surfacing from their dive.41 Patients are unlikely to manifest initial symptoms after 24 hours unless they take a commercial flight.40 It is important for the clinician to elicit a thorough dive history, including the depth, time at that depth, and how the diver ascended. DCS is most likely to occur in scuba dives.39,40 The most common complaint is joint pain, but patients also may complain of shortness of breath, chest pain, lightheadedness, confusion, or other neurological issues. The physical exam may reveal signs of pneumothorax, subcutaneous emphysema, neurologic deficits, and rash. Cutis marmorata is a marbled, pruritic rash specific to DCS that frequently can be seen on physical exam.3 (See Figure 5.)

Figure 5. Cutis Marmorata

Cutis marmorata

Source: Creative Commons

Decompression sickness is broken down into two categories: type 1 and type 2. Type 1 is mild and is characterized by joint pain, generalized pain, fatigue, pitting edema, pruritus, and rash.2,39,41 When the joints primarily are involved, the illness colloquially is known as “the bends.” Type 2 DCS is more serious. This involves CNS dysfunction, cardiopulmonary dysfunction, or onset of type 1 symptoms while still submerged.2,39 CNS involvement can manifest as altered mental status, focal neurologic deficits, syncope, and seizure. When ataxia is present, the illness often is referred to as “the staggers.” Cardiac symptoms are varied but can lead to lightheadedness and, in severe cases, cardiogenic shock. Pulmonary symptoms include cough, dyspnea, and respiratory distress and may be referred to as “the chokes.”2,39,41

Patients who have surfaced from a dive recently and who present with signs and symptoms consistent with DCS should be given supplemental oxygen at the highest possible concentration and should undergo HBO2.4 Even though they may present with only mild DCS type 1, they may have subtle signs of DCS type 2 and can progress to severe type 2 over time. Patients often will have dramatic improvement with just supplemental oxygen; however, it is important for the clinician to remember that these patients still should receive HBO2, as symptoms may recur. If a patient requires transfer, the preferred method is by ground. If air transport is necessary, the aircraft should be pressurized to sea level or should fly below 300 m.2,4

Necrotizing Soft Tissue Infections

Necrotizing soft tissue infections are a group of rapidly progressive, life-threatening, soft tissue infections. This section will discuss the role of HBO2 in the treatment of necrotizing fasciitis, clostridial gas gangrene, and, briefly, mucormycosis.

The mechanisms by which HBO2 are thought to work are essentially the same for all of these necrotizing soft tissue infections. HBO2 enhances granulocyte-killing activity by facilitating the generation of superoxide, peroxide, and hydroxyl radicals.44 HBO2 decreases the amount of hypo-perfused tissue susceptible to infection.45 Additionally, this improves tissue repair. It is well known that poorly vascularized, ischemic tissue results in a severely impaired capacity to heal. Promotion of wound closure by restoring oxygen to ischemic tissues is important in preventing further infection.46 Certain antibiotics, such as vancomycin, show decreased activity in hypoxic environments. HBO2 potentially can restore normoxia and, therefore, normal antibiotic function.47,48 The growth of anaerobic bacteria is suppressed in the oxygen-rich environment supplied by HBO2, as they lack the ability to defend against toxic oxygen species. Other mechanisms specific to a particular infection will be discussed in the context of that infection.

Necrotizing Fasciitis

Necrotizing fasciitis (NF) is a deep-seated soft tissue infection that involves the fascia and subcutaneous tissue. A related condition known as necrotizing myositis primarily involves necrosis of muscle tissue. Distinguishing between these two entities is difficult because both tend to involve the fascia and muscle and the difference is unlikely to be clinically relevant; therefore, this section will refer to both as NF. In this condition, bacteria spread rapidly and cause extensive tissue damage through the release of exotoxins and proteases that degrade fat and extracellular matrix.49 NF is relatively rare, with approximately 500 to 1,500 cases in the United States per year, but it has a mortality rate of 20-40%.50,51 Those who survive often have significant morbidity, as they frequently require multiple debridements and sometimes amputations.

Initially, NF was categorized in two distinct patterns of disease, but recently, some experts in the field added a third designation.52 Type I NF occurs in patients who have impaired immune function. This includes patients with uncontrolled diabetes, peripheral vascular disease, malnutrition, or any other cause of immune compromise. Typically there is an inciting event, such as a wound caused by trauma, surgery, an animal bite, needle puncture, or pressure ulcer. Type I NF is polymicrobial and is composed of both aerobic and anaerobic bacteria. Fournier gangrene is a subset of NF type I that involves the perineum and anterior abdominal wall. This is also polymicrobial and usually includes enteric organisms.

Type II NF is monomicrobial and classically is caused by Group A Streptococcus; however, there have been increasing reports of cases caused by methicillin-resistant Staphylococcus aureus (MRSA).53 Type II NF can occur in otherwise healthy individuals with only minimal predisposing factors such as a minor trauma. In many cases, no obvious inciting event or portal of bacterial entry can be identified.54,55

Type III NF is a monomicrobial infection caused by Vibrio vulnificus. This infection is seen in the setting of traumatic injury in warm salt water. This category is less accepted among the scientific community, as it represents a small number of patients with an already rare disease.56

The primary treatment modalities for NF are early surgical debridement and broad-spectrum antibiotics. Early, aggressive surgical debridement is the most important therapy, as the source must be controlled. Frequently, patients require multiple debridements in the first 24 hours.57 A common antibiotic regimen includes vancomycin, pipercillin-tazobactam, and clindamycin. This provides coverage for Gram-positives, Gram-negatives, and anaerobes. Clindamycin is added to inhibit the production and release of bacterial exotoxins, and in fact should be the first antibiotic administered.

HBO2 is an adjunctive therapy in NF. Surgical debridement and, to a lesser extent, antibiotics should never be delayed for HBO2.50,58 Currently, there are no large, randomized controlled trials that clearly demonstrate the effectiveness of HBO2 in NF. However, there are multiple small clinical reports and retrospective analyses that report benefit. Based on the data accumulated so far, there seems to be a trend toward decreased mortality and number of debridements required in patients who received HBO2. Therefore, it is reasonable to recommend HBO2 as adjunctive therapy after aggressive surgical debridement. If there is a substantial time delay in going to the OR, HBO2 may be initiated before surgery if the treatment does not further delay debridement. If a patient is at a hospital without HBO2, surgical management should take priority, and transfer to an HBO2 center should be considered after the patient is stabilized.

Clostridial Gas Gangrene

Gas gangrene is a rapidly progressive infection of muscle tissue due to bacteria of the genus Clostridium. It is another relatively rare condition that causes approximately 1,000 to 3,000 cases per year in the United States.59 The most commonly isolated organism is Clostridium perfringens.60 This is a Gram-positive, spore-forming anaerobic bacteria that is found commonly in the soil and mammalian gastrointestinal tract. Gas gangrene occurs when there is direct inoculation of clostridia into an ischemic traumatic wound. Because clostridia are anaerobic, they thrive on a relatively hypoxic tissue environment.

While in this hypoxic environment, clostridia produce a number of exotoxins that work to break down connective tissue, lyse blood components, cause tissue necrosis, and produce systemic effects such as septic shock. The most important known toxin is a phospholipase C known as alpha toxin. Alpha toxin is responsible chiefly for degradation of cell membranes and liquefactive necrosis. In fact, without alpha toxin, Clostridium loses all virulence.61

The condition is characterized by pain around the infection site that is out of proportion to the visible wound. Rapid extension and tissue destruction then ensues. The affected area can spread at rates of up to 15 cm/h.62 Blebs and bullae formation are common. Gas and crepitus often can be felt on physical exam, and a “sickly sweet” odor can be detected from the wound drainage. Vital sign abnormalities include fever, tachycardia out of proportion, and hypotension as a late and ominous finding. Alterations in cognition also are common, ranging from a lack of concern similar to la belle indifference to a sense of impending doom.

Diagnosis in the ED can be made presumptively based on history and clinical signs and symptoms. Imaging with plain radiographs may demonstrate gas in the soft tissue. Computed tomography (CT) is more sensitive and specific and can determine the extent of the infection as well as gas within the tissue. However, the emergency physician should not delay therapy to obtain CT imaging, nor should the diagnosis hinge on identification of gas on examination or imaging. In at least half of cases, gas is not demonstrable at all.

Thus far, there have been no randomized controlled trials to compare standard therapy with aggressive surgical debridement and antibiotics to standard therapy plus HBO2. However, there is such a large body of evidence to support its use that HBO2 should be considered an integral part of the management of clostridial gas gangrene.

In gas gangrene, HBO2 is thought to work by inhibition of alpha toxin production. The clinical syndrome observed in this infection is not due to direct spread of bacteria or fulminant sepsis, but is the result of elaboration of exotoxins. As stated previously, alpha toxin is essential to this process. Alpha toxin is cleared from the body within two hours of production, and at a PO2 of 250 mmHg, alpha toxin production is completely inhibited.63 This tissue PO2 is easily achievable with HBO2. Additionally, because clostridia are anaerobic, bacterial growth is also inhibited with HBO2.

Unlike with NF, in the setting of gas gangrene HBO2 should be started before surgical debridement when possible. Patients who are unstable or systemically ill are especially likely to benefit from HBO2. Those who are too sick to go to the OR could be resuscitated with bedside fasciotomies, followed by immediate HBO treatment. Definitive operative management then can be performed. HBO2 can continue to be used until improvement is seen. If the patient is not at an HBO2 center, transfer is recommended when possible. The condition of the patient, available resources, and transfer time should be taken into account when making a decision either to transfer immediately or after initial surgical debridement.


Mucormycosis is another invasive, life-threatening infection; however, this disease is caused by molds of the order Mucorales. These fungi have a predilection for blood vessels and cause significant tissue infarction and necrosis. Mucormycosis is quite rare and tends to occur in patients who are immunocompromised. Risk factors include poorly controlled diabetes mellitus, neutropenia, malignancies, transplants, burns, chronic renal failure, and the use of immunosuppressive and deferoxamine therapy.64,65

The most common, and frequently fatal, presentation is an infection of the sinuses, oral cavity, nasal passages, and brain known as rhinocerebral mucormycosis. Definitive diagnosis depends on tissue histopathology, but this should not delay management. As with necrotizing fasciitis and gas gangrene, early aggressive therapy is of the essence. The current mainstay of treatment is surgical debridement and antifungal therapy with amphotericin.

Although no large randomized trials have been performed, and likely never will be, HBO2 should be used as an adjunct in the treatment of mucormycosis. There is a small but compelling body of evidence to support its use in conjunction with standard therapies. We would recommend using HBO2 in a similar fashion as in necrotizing fasciitis, after initial surgical debridement.

Arterial Insufficiencies

Central Retinal Artery Occlusion. Central retinal artery occlusion (CRAO) is a serious ophthalmologic emergency requiring rapid recognition, as irreversible vision loss can occur within 90 minutes of onset. The incidence of CRAO is estimated to be around 1/100,000 persons, with one study showing that 80% of the patients presented with visual acuity worse than 20/400.66 Risk factors include hypertension, carotid artery disease, diabetes mellitus, cardiac disease (especially atrial fibrillation and valvular disease), vasculitis, temporal arteritis, and sickle cell disease.

Reports vary, but as much as 50% of the general population has an anatomical variation with the presence of an additional artery called the cilioretinal artery. It supplies the macula, where the highest number of photoreceptors live. Since this artery is not a branch of the central retinal artery, the macula may remain perfused in these patients who develop CRAO. This might allow for preservation of the most important part of the visual field (macular sparing).68

CRAO represents an acute ischemic insult to the retina. The usual presentation of CRAO is sudden, rapidly evolving (20 to 30 seconds), painless, mostly complete (with or without macular sparing), monocular vision loss with an afferent pupillary defect. Because of the embolic nature of CRAO, a workup for stroke risk factors, such as electrocardiograms, echocardiogram, carotid Doppler, and a hypercoagulable workup, should be pursued.67

The outcome of CRAO depends on which vessel is occluded and the degree of occlusion, but also on the time frame from onset to when oxygen can be delivered to the ocular tissues. The retinal circulation supplies the inner retinal layers (ganglion cell layer and inner nuclear layer). Under hyperbaric conditions, enough oxygen can be delivered to this tissue via diffusion from the choroidal circulation to allow for return of function.68,69

Traditionally, CRAO has been treated with ocular massage, anterior chamber paracentesis, and medications used to lower intraocular pressure. The theory is that these methods aim to help move an embolus more distally in the occluded vessel and allow for more flow to a larger area of tissue. These treatment modalities have been relatively unsuccessful.70,71,72 More recent treatments have included attempts to remove the embolus surgically and the use of intra-arterial tPA. These modalities have had variable success with an overlying theme that earlier intervention has a higher chance of success.

HBO2 represents a promising, novel treatment modality that may succeed where others have failed to show consistent results. Over the last 52 years, 887 patients with CRAO were treated with HBO (published in 39 publications). In these retrospective case-controlled series, 64% showed improvement.73

A 2016 retrospective study of 129 patients showed a significant improvement in the best corrected visual acuity in a majority of the patients as long as they had not yet developed a cherry red spot (CRS) on fundoscopic exam, as this served as a marker for irreversible anoxic retinal damage. Treatment was given in 2 to 2.4 ATA, 100% oxygen, 90-minute sessions, three times in the first 24 hours and once daily thereafter. Treatment was discontinued when no further improvement in best corrected visual acuity was observed in two consecutive treatments. Improvement was seen in 86% without a CRS as compared to 57.6% of those with a CRS, demonstrating that initial retinal findings were a better predictor of HBO2 success than absolute duration of symptoms.74

HBO2 is safe with a very low side-effect profile. The timing of initiation of HBO2 therapy and, more importantly, the condition of the retina, is critical in CRAO. The use of HBO2 in CRAO is supported by Level IIb evidence with fair to good retrospective case series evidence to support its use when it is started shortly after onset of vision loss and in the absence of irreversible retinal ischemia (CRS). Prospective, randomized trials still are lacking, but this should not dissuade its use in the right patients, as no better treatment is yet proven.

Crush Injuries

Crush injuries are complex, not only in their effect on multiple types of tissues with varying degrees of injuries, but also in the pathophysiology of their healing. Even after the setting of bones, debridement of nonviable tissue, anastomosis of major vessels, and potential skin closure, the wound is just beginning to enter the stages of a vicious cycle of tissue ischemia and edema.75 As suboptimally perfused tissues become more hypoxic, cellular death causes extravasation of fluids and worsening edema. The worsening edema increases interstitial pressures and increases the space from capillaries to functioning cells, further inhibiting perfusion. These processes lead to the frequent need for subsequent surgical intervention, such as debridement, tissue and skin flaps, and amputation. Similar physiology is observed in skeletal muscle compartment syndrome (SMCS) in which edema or bleeding causes increased compartment pressures, which beget more inflammation and worsening edema. HBO2 serves to break this cycle in both processes. In crush injuries, it allows for more complete and uncomplicated wound healing.75 In the incipient stage of SMCS, HBO2 can be used to prevent the progression to an established phase, which necessitates surgical intervention.76

The most obvious mechanism by which HBO2 affects these processes is through the oxygen-rich environment created during the treatment sessions. As discussed above, HBO2 can provide sufficient partial pressure of oxygen to oxygenate tissues and allow for aerobic cellular functions even without accounting for oxygen bound to hemoglobin.75 Tissues that are not accessible to hemoglobin, either through damage to capillary networks or increasing interstitial edema, still can be perfused via HBO2. HBO2 also directly reduces edema via the body’s natural response to hyperoxia, vasoconstriction. Vasoconstriction during an HBO session can reduce blood flow by 20%.75 Since resorption of edema in the capillaries remains steady, this results in a 20% reduction in edema. HBO2 also promotes wound healing by inhibiting the proliferation of anaerobic behavior by nature of the oxygenated environment it creates in the wound. Finally, HBO2 limits the damage from oxygen radical species through several biochemical mechanisms.

More than 600 case reports have been published describing the use of HBO2 in crush injuries, with 80% showing positive results.76 However, most of these described the effectiveness of HBO2 in subjective terms. Authors of a 2005 evidence-based guideline looked at nine studies that included 150 patients. They concluded that HBO2 is not harmful and may be beneficial in patients with crush injury if used early in care.77

Despite strong logical arguments for the use of HBO2 in the treatment of crush injuries, there is a relative paucity of evidence in this area. Research supporting its use largely is composed of limited retrospective analyses.78 The only randomized prospective trial to date had a total of 36 participants, half of whom received six days of twice-daily HBO2 sessions started within 24 hours of initial surgical management, and half of whom received sham HBO2 sessions at the same rate.79 Complete wound healing was observed in 17 of 18 patients receiving HBO2, compared to 10 of 18 in the control group. HBO2 also required statistically fewer revision procedures. Interestingly, there was no difference in hospitalization time between the two groups. Despite limited evidence, based on the strength of the logic of the proposed benefit as well as few potential harms, we believe HBO2 should be strongly considered as adjuvant therapy for crush injuries immediately following primary surgical treatment.

Future Considerations

Each year, almost 2 million people in the United States suffer a traumatic brain injury (TBI) severe enough to warrant a visit to the ED. Almost one-quarter are hospitalized and about 10% die from their injuries.80 The morbidity from TBI can be devastating, with more than 5 million Americans living with long-term disability from their injuries.81

After the initial traumatic injury, secondary injury frequently develops over the next 24 hours, often from ischemia due to altered cerebral blood flow and resultant cellular injury and death. Hyperbaric oxygen therapy has the potential to deliver large amounts of oxygen to ischemic tissue and has been considered as a potential therapy, yet it has remained inadequately studied, with mixed results in the limited data available.81 As such, a large National Institute of Neurological Disorders and Stroke-sponsored study is planned to begin this year. The Hyperbaric Oxygen Brain Injury Treatment (HOBIT) trial is a Phase II trial that aims to enroll 200 patients across 15 participating U.S. academic centers.81

Although not without controversy, nearly 50 years of preclinical and clinical research has shown the potential efficacy of HBO2 in reducing the clinical sequelae of TBI. It is hoped that this large controlled trial will demonstrate HBO2 as a viable way improve outcomes in TBI patients.


Hyperbaric oxygen therapy involves the exposure of the entire body to 100% oxygen at pressures in the 2-3 ATA range. Its emergency applications include treatment of air-gas embolism, carbon monoxide poisoning, decompression sickness, necrotizing soft tissue infections, and acute ischemic states. Emergency physicians should be aware of HBO2 and its uses in the context of these settings. Understanding how and when to use HBO2 has the potential to save lives and reduce morbidity in extremely morbid conditions.


  1. Weaver L, ed. Undersea and Hyperbaric Medical Society. Hyperbaric Oxygen Therapy Indications, 13th edition. Best Publishing Company, 2014.
  2. Schockley LW. Chapter 141: Scuba Diving and Dysbarism. In: Marx JA, Hockberger RS, Walls RM. Rosen’s Emergency Medicine: Concepts and Clinical Practice, 6th ed. St. Louis: 2006.
  3. Kindwall EP, Wheelan HT. Hyperbaric Medicine Practice, 3rd ed. Flagstaff, AZ: Best Publishing Company; 2008.
  4. Tetzlaff K, Shank ES, Muth CM. Evaluation and management of decompression illness — an intensivist’s perspective. Intensive Care Med 2003;29:2128-2136.
  5. Kindwall E. A History of Hyperbaric Medicine. In: Kindwall EP, Wheelan HT, eds. Hyperbaric Medicine Practice, 3rd ed. Flagstaff, AZ: Best Publishing Company; 2008.
  6. Weaver L, ed. Undersea and Hyperbaric Medical Society. Hyperbaric Oxygen Therapy Indications, 13th edition. Best Publishing Company, 2014.
  7. Kindwall EP. Gas Embolism. In: Kindwall EP, Wheelan HT, eds. Hyperbaric Medicine Practice, 3rd ed. Flagstaff, AZ: Best Publishing Company; 2008.
  8. Smith RM, Van Hoesen KB, Neuman TS. Arterial gas embolism and hemoconcentration. J Emerg Med 1994;12:147-153.
  9. Muth CM, Shank ES. Gas embolism. N Engl J Med 2000;342:476-482.
  10. Van Allen CM, Hrdina LS, Clark J. Air embolism from the pulmonary vein. Arch Surg 1929;19:567-599.
  11. Smith RM, Van Hoesen KB, Neuman TS. Arterial gas embolism and hemoconcentration. J Emerg Med 1994;12:147-153.
  12. Moon RE. Treatment of Decompression Illness. In: Bove AA, ed. Bove and Davis’ Diving Medicine, 4th ed. Philadelphia: Saunders; 2004.
  13. Durant TM, Long J, Oppenheimer MJ. Pulmonary (venous) air embolism. Am Heart J 1947;33:269-281.
  14. Palmon SC, Moore LE, Lundberg J, Toung T. Venous air embolism: A review. J Clin Anesth 1997;9:251-257.
  15. Francis TJ, Mitchell SJ. Pathophysiology of Decompression Sickness. In: Bove AA, ed. Bove and Davis’ Diving Medicine, 4th ed. Philadelphia: Saunders; 2004.
  16. Lynch JJ, Schuchard GH, Gross CM, Wann LS. Prevalence of right-to-left atrial shunting in a healthy population: Detection by Valsalva maneuver contrast echocardiography. Am J Cardiol 1984;53:1478-1480.
  17. Hardy KR, Thom SR. Pathophysiology and treatment of carbon monoxide poisoning. J Toxicol Clin Toxicol 1994;32:613-629.
  18. Penney DG. Acute carbon monoxide poisoning: Animal models: A review. Toxicology 1990;62:123-160.
  19. Thom SR. Dehydrogenase conversion to oxidase and lipid peroxidation in brain after carbon monoxide poisoning. J Appl Physiol 1992;73:1584-1589.
  20. Ernst A, Zibrak JD. Carbon monoxide poisoning. N Engl J Med 1998;339:1603-1608.
  21. Ely EW, Moorehead B, Haponik EF. Warehouse workers’ headache: Emergency evaluation and management of 30 patients with carbon monoxide poisoning. Am J Med 1995;98:145-155.
  22. Burney RE, Wu SC, Nemiroff MJ. Mass carbon monoxide poisoning: Clinical effects and results of treatment in 184 victims. Ann Emerg Med 1982;11:394-399.
  23. Williams J, Lewis RW 2nd, Kealey GP. Carbon monoxide poisoning and myocardial ischemia in patients with burns. J Burn Care Rehabil 1992;13:210-213.
  24. Satran MD, Henry CR, Adkinson C, et al. Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol 2005;45:1513-1516.
  25. Thom SR, Taber RL, Mendiguren II, et al. Delayed neurolopsychologic sequelae after carbon monoxide poisoning: Prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995;25:474-480.
  26. Choi IS. Delayed neurologic sequelae in carbon monoxide intoxication. Arch Neurol 1983;40:433-435.
  27. Kwon OY, Chung SP, Ha YR, Kim SW. Delayed postanoxic encephalopathy after carbon monoxide poisoning. Emerg Med J 2004;21:250-251.
  28. Katz MD. Carbon monoxide asphyxia: A common clinical entity. Can Med Assoc J 1958;78:182-186.
  29. Gilbert GJ, Glaser GH. Neurologic manifestations of chronic carbon monoxide poisoning. N Engl J Med 1959;261:1217-1220.
  30. Touger M, Gallagher EJ, Tyrell J. Relationship between venous and arterial carboxyhemoglobin levels in patients with suspected carbon monoxide poisoning. Ann Emerg Med 1995;25:481-483.
  31. Hee J, Callais F, Momas I, et al. Smokers’ behaviour and exposure according to cigarette yield and smoking experience. Pharmacol Biochem Behav 1995;52:195-203.
  32. Walls RM, Luten RC, Murphy MF, Schneider RE, eds. Manual of Emergency Airway Management, 2nd ed. Philadelphia: Lippincott, Williams & Wilkins; 2004.
  33. Pace N, Strajman E, Walker E. Acceleration of carbon monoxide elimination in man by high pressure oxygen. Science 1950;111:652-654.
  34. Thom SR. Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. Toxicol Appl Pharmacol 1990;105:340-344.
  35. Brown SD, Piantadosi CA. Recovery of energy metabolism in rat brain after carbon monoxide hypoxia. J Clin Invest 1992;89:666-672.
  36. Thom SR. Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. Toxicol Appl Pharmacol 1993;123:248-256.
  37. Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med 2002;347:1057-1067.
  38. Feldmeier JJ, chairman and editor. Hyperbaric Oxygen 2003: Indications and Results: The Hyperbaric Oxygen Therapy Committee Report. Dunkirk, MD: Undersea and Hyperbaric Medical Society; 2003.
  39. Bookspan J. Diving Physiology in Plain English. Kensington, MD: Undersea and Hyperbaric Medical Society, Inc.; 1995.
  40. Bove A. Bove and Davis’ Diving Medicine, 4th ed. Philadelphia, PA: Saunders; 2004.
  41. Freiberger, JJ, Lyman, SJ, Denoble PJ, et al. Consensus factors used by experts in the diagnosis of decompression illness. Aviat Space Environ Med 2004;75:1023-1028.
  42. Freiberger JJ, Denoble PJ, Pieper CF, et al. The relative risk of decompression sickness during and after air travel following diving. Aviat Space Environ Med 2002;73:980-984.
  43. Moon RE. Treatment of diving emergencies. Crit Care Clin 1999;15:429-456.
  44. Babior B. Oxygen-dependent microbial killing by phagocytes (first of two parts). N Engl J Med 1978;298:659-668.
  45. Jonsson K, Hunt TK, Mathes SJ. Oxygen as an isolated variable influences resistance to infection. Ann Surg 1988;208:783-787.
  46. Kivisaari J, Niinikoski J. Effects of hyperbaric oxygenation and prolonged hypoxia on the healing of open wounds. Acta Chir Scand 1975;141:14-19.
  47. Norden CW, Shaffer M. Treatment of experimental chronic osteomyelitis due to Staphylococcus aureus with vancomycin and rifampin. J Infect Dis 1983;147:352-357.
  48. Smith J, Lewin C. Chemistry and mechanisms of action of the quinolone antibacterials. In: Andriole V, ed. The Quinolones. New York: Academic Press; 1988:23-82.
  49. Mandell GL, Bennett JE, et al. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. New York: Churchill-Livingston; 2005.
  50. Jallali WS, Withey S, Butler PE. Hyperbaric oxygen as adjuvant therapy in the management of necrotizing fasciitis. Am J Surg 2005;189:462-466.
  51. Levine EG, Manders SM. Life-threatening necrotizing fasciitis. Clin Dermatol 2005;23:144-147.
  52. Sarani B, Strong M, Pascual J, Scwab CW. Necrotizing fasciitis: Current concepts and review of the literature. J Am Coll Surg 2009;208:279-288.
  53. Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med 2005;352:1445-1453.
  54. Childers BJ, Potyondy LD, Nachreiner R, et al. Necrotizing fasciitis: A fourteen-year retrospective study of 163 consecutive patients. Am Surg 2002;68:109-116.
  55. McHenry CR, Brandt CP, Piotrowski JJ, et al. Idiopathic necrotizing fasciitis: Recognition, incidence, and outcome of therapy. Am Surg 1994;60:490-494.
  56. Hau V, Ho C. Necrotising fasciitis caused by Vibrio vulnificus in the lower limb following exposure to seafood on the hand. Hong Kong Med J 2011;17:335-337.
  57. Bakker D. Selected aerobic and anaerobic soft tissue infections. In: Kindwall E, Whelan H, eds. Hyperbaric Medicine Practice. Flagstaff (AZ): Best Publishing Co.; 2004:575-601.
  58. Jallali N. Necrotising fasciitis: Its aetiology, diagnosis and management. J Wound Care 2003;12:297-300.
  59. Hart G, Lamb R, Strauss M. Gas gangrene. J Trauma 1983;23:991-1000.
  60. Heimbach R. Gas Gangrene. In: Kindwall E, Whelan H, eds. Hyperbaric Medicine Practice. Flagstaff (AZ): Best Publishing Co., 2004:549-565.
  61. Awad MM, Bryant AE, Stevens D, et al. Virulence studies on chromosomal alpha-toxin and theta-toxin mutants constructed by allelic exchange provide genetic evidence for the essential role of alpha-toxin in Clostridium perfringens-mediated gas gangrene. Mol Microbiol 1995;15:191-202.
  62. Bakker D. Clostridial myonecrosis (gas gangrene). In: Feldmeier J, ed. Hyperbaric Oxygen Therapy Committee Report 2003. Dunkirk (France): Undersea and Hyperbaric Medical Society; 2003:19-25.
  63. Van Unnik A. Inhibition of toxin production in Clostridium perfringens in vitro by hyperbaric oxygen. Antonie Leeuwenhoek Microbiology 1965;31:181-186.
  64. Kontoyiannis DP, Lewis RE. Invasive zygomycosis: Update on pathogenesis, clinical manifestations, and management. Infect Dis Clin North Am 2006;20:581-607.
  65. John BV, Chamilos G, Kontoyiannis DP. Hyperbaric oxygen as an adjunctive treatment for zygomycosis. Clin Microbiol Infect 2005;11:515-517.
  66. Varma DD, Cugati S, Lee AW, Chen CS. A review of central retinal artery occlusion: Clinical presentation and management. Eye 2013;27:688-697.
  67. Murphy-Lavoie H, LeGros TL. Central Retinal Artery Occlusion. In: Whelan HT, Kindwall EP, ed. Hyperbaric Medicine Practice. 4th ed. Flagstaff, ZA: Best Publishing Company; 2017.
  68. Patz A. Oxygen inhalation in retinal arterial occlusion; a preliminary report. Am J Ophthalmol 1955;40:789-795.
  69. Li HK, Dejean BJ, Tang RA. Reversal of visual loss with hyperbaricoxygen treatment in a patient with Susac syndrome. Ophthalmology 1996:103:2091-2098.
  70. Murphy-Lavoie H. Central retinal artery occlusion treated with oxygen: A literature review and treatment algorithm. Undersea & Hyperbaric Medicine 2012;39:943.
  71. Neubauer AS, Mueller AJ, Schriever S, et al. [Minimally invasive therapy for clinically complete central retinal artery occlusion — results and meta-analysis of literature.] Klin Monbl Augenheilkd 2000;217:30-36.
  72. Duker JS, Brown GC. Recovery following acute obstruction of the retinal and choroidal circulations. Retina 1988;8:257-260.
  73. Murphy-Lavoie H, LeGros T, Butler FK, Jain K. Hyperbaric oxygen therapy and ophthalmology. In: Jain KK, ed. Jain Textbook of Hyperbaric Medicine, 6th ed. Springer Publishing; 2016.
  74. Hadanny A, Maliar A, Fishlev G, et al. Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen. Clin Ophthalmol 2017;11:115-125.
  75. Weaver L, ed. Hyperbaric Oxygen Therapy Indications. 13th ed. Flagstaff, AZ: Best Publishing Company; 2014.
  76. Strauss MB, Lu LQ. The Roles of Hyperbaric Oxygen in Crush Injury and Other Traumatic Ischemias. In: Whelan HT, Kindwall EP. Hyperbaric Medicine Practice, 4th ed. Flagstaff, AZ: Best Publishing Company; 2017.
  77. Garcia-Covarrubias L, McSwain N, Van Meter K, Bell RM. Adjuvant hyperbaric oxygen therapy in the management of crush injury and traumatic ischemia: An evidence-based approach. Am Surg 2005;71:144-151.
  78. Dougherty JE. The role of hyperbaric oxygen therapy in crush injuries. Crit Care Nurs Q 2013;36:299-309.
  79. Bouachour G, Cronier P, Gouello J, et al. Hyperbaric oxygen therapy in the management of crush injuries: A randomized double-blind placebo-controlled clinical trial. J Trauma 1996;41:333-339.
  80. Centers for Disease Control and Prevention. Report to Congress on Traumatic Brain Injury in the United States: Epidemiology and Rehabilitation. National Center for Injury Prevention and Control; Division of Unintentional Injury Prevention: Atlanta; 2015.
  81. Daly S, Thorpe M, Rockswold S, et al. Hyperbaric oxygen therapy in the treatment of acute severe traumatic brain injury: A systematic review. J Neurotrauma 2018;35:623-629.