Arterial Gas Embolism and Decompression Sickness

Among the earliest application of hyperbaric therapy was to treat disorders related to gas bubbles in the body. Compressed air construction work required exposure to elevated ambient pressure within compartments (caissons) for many hours to excavate tunnels or bridge foundations in muddy soil that otherwise would flood. In the 19th century, workers were noted to frequently experience joint pains, limb paralysis, or pulmonary compromise when they returned to ambient pressure. This condition—decompression sickness (DCS), caisson disease, or bends—was later attributed to nitrogen bubbles in the body, and recompression was found to relieve symptoms. The mechanism, based purely on Boyle’s law, with reduction of gas bubble volume due to pressure, was later improved by adding supplemental oxygen to hasten inert gas diffusion out of the body. Similar observations were made at later times for scuba divers, who are also prone to develop arterial gas embolism (AGE) due to pulmonary overpressurization on decompression.

Iatrogenic AGE has been reported in association with cardiovascular, obstetric/gynecologic, neurosurgical, and orthopedic procedures and generally whenever disruption of a vascular wall occurs. Nonsurgical processes reported to cause AGE include overexpansion during mechanical ventilation, hemodialysis, and after accidental opening of central venous catheters.⁴

Treatment of gas bubble disorders includes standard support of airway, breathing, and circulation plus prompt application of HBO₂. Gas bubbles have been reported to persist for several days, and although delays should be avoided, HBO₂ may be beneficial even when begun after long delays.^5–9 Controlled animal trials support efficacy of HBO₂, but randomized clinical trials have not been done.¹⁰ In their review of 27 case series, Moon and Gorman described substantial benefit with HBO₂ treatment—78% of 441 cases receiving HBO₂ fully recovered and 4.5 % died, whereas only 26% of 74 cases not undergoing HBO₂ treatment fully recovered and 52% died.⁴

Mechanisms of action of HBO₂ in AGE and DCS treatment include reduction of gas according to Boyle’s law, hyperoxygenation to hasten inert gas diffusion, and an additional effect related to inhibition of leukocyte adherence to injured endothelium. Endothelial dysfunction occurs in association with mechanical interactions of bubbles at vessel walls and lumen occlusion.^11–15 Neutrophil activation and perivascular adherence occur and are associated with functional deficits post decompression.^16,4,17 Animals depleted of leukocytes before experimental cerebral air embolism suffer less severe reduction of cerebral blood flow and better neurologic outcome.¹⁸ HBO₂ has been shown to temporarily inhibit human β₂-integrin adhesion function.¹⁹ Inhibition of neutrophil β₂-integrin adhesion by HBO₂ has been described in a number of animal models including skeletal muscle ischemia-reperfusion, cerebral ischemia-reperfusion, pulmonary smoke inhalation injury, and brain injury after carbon monoxide (CO) poisoning.^20–23 The mechanism for this effect involves S-nitrosylation of cytoskeletal β-actin, which impedes the coordinated cell-surface β₂-integrin migration required for firm adherence.²⁴

Carbon Monoxide Poisoning

Carbon monoxide is the leading cause of injury and death by poisoning in the world.²⁵ The affinity of CO for hemoglobin, to form carboxyhemoglobin (COHb), is more than 200-fold greater than that of O₂. CO-mediated hypoxic stress is a primary insult, but COHb values correlate poorly with clinical outcome.* Pathologic mechanisms, in addition to elevations of COHb, include intravascular platelet-leukocyte aggregation, leukocyte-mediated oxidative injury to brain, excessive release of excitatory amino acids such as glutamate, impaired mitochondrial oxidative phosphorylation, and possible myocardial calcium overload.^† Survivors of acute CO poisoning are at risk for developing delayed neurologic sequelae (DNS) that include cognitive deficits, memory loss, dementia, parkinsonism, paralysis, chorea, cortical blindness, psychosis, personality changes, and peripheral neuropathy. DNS typically occurs from 2 to 40 days after poisoning, and the incidence is from 25% to 50% after severe poisoning.

^†References 33–39.

Administration of supplemental oxygen is the cornerstone of treatment for CO poisoning. Oxygen inhalation will hasten dissociation of CO from hemoglobin as well as provide enhanced tissue oxygenation. HBO₂ causes carboxyhemoglobin dissociation to occur at a rate greater than that achievable by breathing pure oxygen at sea level. Additionally, HBO₂, but not ambient pressure oxygen treatment, has several actions that 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,⁴⁰ inhibition of lipid peroxidation,⁴¹ and impairment of leukocyte adhesion to injured microvasculature.²² Animals poisoned with CO and treated with HBO₂ have been found to have more rapid improvement in cardiovascular status,⁴² lower mortality,⁴³ and lower incidence of neurologic sequelae.⁴⁴

Despite online criticisms of their analysis, a meta-analysis by the Cochrane Library concluded that it is unclear whether HBO₂ reduces the incidence of adverse CO-mediated neurologic outcomes.⁴⁵ There are five prospective, randomized trials that have assessed clinical efficacy of HBO₂ for acute CO poisoning.^{30,31,32,46,47} Several failed to find benefit,^30,47 but methodological weaknesses discussed by several authors^39,48 diminish their clinical impact. Only one clinical trial satisfies all items deemed to be necessary for the highest quality of randomized controlled trials.⁴⁹ HBO₂ treatment also appears to diminish acute mortality, based on a retrospective analysis.⁴⁸

Blood Loss Anemia

In rare instances when transfusion is not possible due to cross-matching incompatibilities or religious beliefs, intermittent use of HBO₂ has been applied to temporarily relieve physiologic stress from severe acute anemia. Anecdotal reports describe using 2.5 to 3.0 ATA O₂ to raise PaO₂ in plasma to meet metabolic needs.^50–53 Treatments are often administered for only brief times when physiologic decompensation occurs, because O₂ toxicity can be a problem (see later discussion). Short-term treatments, applied many times over several days, have been used to support life until red cells become available or until adequate red cell mass is generated endogenously.

Clostridial Myonecrosis (Gas Gangrene)

Successful treatment of gas gangrene depends on prompt recognition and aggressive intervention. Mortality rates from 11% to 52% have been reported. There are five retrospective comparisons and 13 case series in the literature. These have been discussed in several reviews.^1,54,55 Because of difficulties with comparison among patient groups, impartial assessment of HBO₂ efficacy based on mortality or “tissue salvage” rates is difficult. Most authors comment on clinical benefits associated with treatment. Temporal improvement of vital signs in patients with gangrene can be among the most dramatic observations in day-to-day practice.

Crush Injury

There is limited experience with HBO₂ for acute traumatic peripheral ischemia and suturing of severed limbs. A single randomized controlled trial (involving 36 patients) on this type of injury has been performed, which found HBO₂ to improve healing and reduce infection and wound dehiscence.⁵⁶ In a case series of 23 patients, HBO₂ was deemed to improve limb preservation, and it was also observed that the change in transcutaneous tissue oxygen level from ambient to hyperbaric conditions may predict outcome.⁵⁷ The rationale for considering HBO₂ is to temporarily improve oxygenation to hypoperfused tissues and because arterial hyperoxia will cause vasoconstriction that can diminish edema formation.^58,59 This latter mechanism has been demonstrated most convincingly in the context of experimental compartment syndrome.⁶⁰ Broad comparative evaluation of HBO₂ treatment for traumatic injuries is described as showing considerable benefit.⁶¹

Progressive Necrotizing Infections

The use of HBO₂ for treatment of necrotizing fasciitis and Fournier’s gangrene, which are mixed aerobic-anaerobic infections, has been reported in six nonrandomized comparisons and four case series.* As with gas gangrene, variations in time of diagnosis and clinical status on admission compromise assessment of the existing literature. Most studies have reported that when HBO₂ is added to surgery and antibiotic therapy, mortality is reduced versus surgery and antibiotics alone. Animal trials have been difficult to assess because synergistic bacterial processes are difficult to establish. One report has found HBO₂ to potentiate antibiotics in streptococcal myositis),⁷² and several animal models of polymicrobial bacteremia and sepsis have reported increased survival with HBO₂.^73–75 Mechanisms of action may include suppressed growth of anaerobic microorganisms and improved bactericidal action of leukocytes (that function poorly in hypoxic conditions).^11,76–78