Hyperbaric Oxygen Therapy
by Grim, Pamela S.; Gottlieb, Lawrence J.; Boddie, Allyn; Batson, Er
Abstract
Hyperbaric oxygen (HBO) therapy involves intermittent inhalation
of pure oxygen under a pressure greater than one atmosphere.
During the 1960s, HBO was proposed as a treatment for cancer,
heart attack, senility, and other conditions, but research
studies did not obtain reproducible results. The skepticism
engendered among medical personnel by these failures extended to
HBO's use for treating clinical conditions that it had been shown
to help. A review of these conditions is provided. HBO acts both
mechanically, due to its pressure component, and physiologically,
due to its oxygen component.
HBO therapy has been effective in treating decompression sickness
(the illness resulting from too-rapid changes in pressure by
divers or aviators), and air embolism (introduction of air into
the circulatory system, often unintentionally by medical
personnel) by mechanically reducing the size of gas bubbles, and
increasing oxygen levels in the blood.
Oxygen is essential for proper function of certain cells of the
immune system and, in certain injuries, such as burns and crush
injuries, HBO treatment can increase the supply of oxygen to
tissues otherwise deprived of it. Complications of HBO treatment
include trauma to or rupture of cavities, neurotoxicity resulting
from exposure to 100 percent oxygen for long periods, and other
sequelae.
HBO therapy is indicated for decompression sickness, air
embolism, carbon monoxide poisoning, acute traumatic ischemia
(crush injuries that deprive tissues of oxygen), and bacterial
invasion of a necrotic wound (in which tissue has died). HBO may
also stimulate regrowth of blood vessels in damaged tissue
adjacent to areas treated by radiation therapy and may promote
bone formation in cases of osteomyelitis (bone infection) that
have not responded to other treatments. This therapy also shows
promise for treating a variety of 'problem wounds', but
randomized, prospective studies are lacking.
Overall, HBO therapy is safe and effective for certain
conditions, and well-formulated clinica l trials could help
extend its use to others. (Consumer Summary produced by Reliance
Medical Information, Inc.)
hyperbaric oxygen and briefly evaluates animal and clinical data
substantiating these indications. Areas in which the mechanism of
action of hyperbaric oxygen is still not well understood, as well
as possible new areas of applications, are discussed.
HYPERBARIC oxygen (HBO) therapy involves intermittent inhalation
of 100% oxygen under a pressure greater than 1 atm. [1]
Both therapeutic and toxic effects result from two features of
treatment: mechanical effects of increased pressure and
physiologic effects of hyperoxia.
Hyperbaric oxygen therapy has long been accepted as a primary
treatment for decompression sickness [2]; however, other proposed
indications have been controversial. During the 1960s there was
widespread enthusiasm for hyperbaric treatment of myocardial
infarction, stroke, senility, and cancer. Enthusiasm waned after
results of clinical trials (and direct experience) showed little
benefit for these diseases. The overzealous claims about the
effectiveness of HBO therapy have left a legacy of skepticism
among physicians. [3] However, animal studies, clinical trials,
and greater clinical experience over the last two decades have
produced a set of indications for which HBO therapy appears
beneficial. These clinical conditions are substantially different
from those in the 1960s. However, there has been no recent
interdisciplinary review of HBO therapy delineating these current
indications, despite their broad applications.
Thus, while substantial evidence supports use of HBO therapy in
certain carefully de fined settings, many patients who might
benefit go untreated because of their physician's unfamilarity
with recent research and overall uncertainty about the legitimacy
of HBO as therapy. We discuss the mechanism of action of HBO
therapy and the commonly accepted clinical indications (Table 1)
as delineated by the Undersea and Hyperbaric Medical Society, [1]
the professional association of physicians administering HBO
therapy, and we briefly review the data supporting current
indications.
MECHANISMS OF ACTION
Pressure
In disease such as air embolism and decompression sickness, the
therapeutic effect of HBO therapy is achieved through the
mechanical reduction in bubble size brought on by an increase in
ambient pressure. A 5 atm a bubble is reduced to 20% of its
original volume and 60% of its original diameter.
Increasing pressure in HBO therapy is often expressed in
multiples of atmospheric pressure absolute (ATA); 1 ATA equals 1
kg/c[m.sup.2] or 735.5 mm Hg. Most HBO treatments are performed
at 2 to 3 ATA. In air embolism and decompression sickness, where
pressure is crucial to therapeutic effect, treatments frequently
start at 6 ATA.
This additional pressure, when associated with inspiration of
high levels of oxygen, substantially increases the level of
oxygen dissolved into blood plasma. This state of serum hyperoxia
is the second beneficial effect of hyperbaric oxygen therapy.
Hyperoxia: Life Without Blood
At sea level in room air, hemoglobin is approximately 97%
saturated with oxygen (19.5 vol% oxygen, of which approximately
5.8 vol% is extracted by tissue). The amount of oxygen dissolved
into plasma is 0.32 vol%. An increase in P[O.sub.2] has a
negligible impact on total hemoglobin oxygen content; however, it
does result in an increase in the amount of oxygen dissolve
directly into plasma. With 100% inspired oxygen the amount of
plasma oxygen increases to 2.09 vol%. At 3 ATA plasma contains
6.8 vol% oxygen, a level equivalent to the average tissue
requirements for oxygen. Thus, HBO treatment could and has
sustained life without hemoglobin. [4]
The immune system, wound healing, and vascular tone are all
affected by oxygen supply. Oxygen alone has little direct
antimicrobial effect, even for most anaerobes [5]; it is,
however, a crucial factor in immune function.
Neutrophils require molecular oxygen as a substrate for microbial
killing. The oxidative burst seen in neutrophils after
phagocytosis of bacteria involves a 10-to 15-fold increase in
oxygen consumption. [6] Here oxygen serves as a substrate in the
formation of free radicals, which directly or indirectly initiate
phagocytic killing. [7] This endogenous antimicrobial system
virtually ceases functioning under conditions of hypoxia. A
tissue [PO.sub.2] of at least 30 mm Hg of oxygen is considered
necessary for normal oxidative function to occur. [8] Oxygen
partial pressures below this are often seen in damaged and
infected tissues. Increasing the oxygen level in this tissue can
allow restoration of white blood cell function and return of
adequate antimicrobial action. [9] The cardiovascular effects of
hyperbaric oxygen include a generalized vasoconstriction and a
small reduction in cardiac output. [10] This ultimately may
decrease the overall blood supply to a region, but the increase
in serum oxygen content results in an overall gain in delivered
oxygen. In conditions such as burns, cerebral edema, and crush
injuries, this vasoconstriction may be beneficial, reducing edema
and tissue swelling while main taining tissue oxygenation. [11]
COMPLICATIONS
Usual complications of HBO therapy are listed in Table 2. They
are a result of either barometric pressure changes or oxygen
toxicity. The most common complications involve cavity trauma due
to change in pressure. [12] Any air-filled cavity that cannot
equilibrate with ambient pressure, such as the middle ear when
the eustachian tube is blocked, is subject to deformity and
barotrauma during pressure changes in HBO therapy.
Pneumothorax is a rare complication of HBO treatment,
usually occurring only in patients with severe lung disease.
Air embolism, presumably resulting from a small tear in
the pulmonary vasculature, is another rare complication. [13] One
hundred percent oxygen under high pressure is neurotoxic and can
lower the seizure threshold and affect central nervous system
control of respiration. However, neurotoxicity is rare with the
low-pressure, short-duration treatments used clinically in HBO
therapy. In one series the incidence was reported as 1.3 seizures
per 10 000 treatments. [14]
Pulmonary oxygen toxic reactions can occur with 100% inspired
oxygen at less than 1 ATA with prolonged exposure. Almost all
patients will show pulmonary toxicity after 6 continuous hours of
inspired oxygen at 2 ATA. [15] No clinical HBO protocol requires
this length of continuous exposure to 100% oxygen. However, HBO
treatments may contribute to the pulmonary oxygen toxicity seen
in critically ill patients who receive high concentrations of
inspired oxygen between hyperbaric treatments.
Although a concern in premature newborns, retrolental fibroplasia
has not been noted in infants, children, or adults undergoing HBO
therapy. [16] Development of cataracts has been reported in
patients receiving more than 150 HBO treatments. [17]
HBO ADMINISTRATION
Hyperbaric oxygen can be administered in either a multiplace or a
monoplace chamber.
Multiplace Chamber
Multiplace chambers are large tanks accommodating 2 to 14 people
(Fig 1). They are usually built to achieve pressures up to 6 atm
and have a chamber lock-entry system that allows personnel to
pass through without altering the pressure of the inner chamber.
Patients can be directly cared for by medical staff within the
chamber. The chamber is filled with compressed air; patients
breathe 100% oxygen through a face mask, head hood, or
endotracheal tube. Although fire hazards restrict the use of
certain electronic equipment, some monitors and ventilators with
solid-state circuitry can be used within the chamber, allowing
intensive care of critically ill patients. [18] The multiplace
chamber's ability to maintain pressures of 6 atm or more, makes
it the chamber of choice for decompression sickness and air
embolism.
Monoplace Chamber
Monoplace chambers (Fig 2) are far less costly than their larger
counterparts and have allowed hospitals to institute HBO programs
without prohibitive capital outlays. Most chambers are sized to
allow a single patient to lie supine under a transparent acrylic
dome or viewing port. The internal environment of a monoplace
chamber is maintained at 100% oxygen; thus, the patient does not
wear a mask. This high concentration of oxygen precludes the use
of any electronic equipment in the chamber. However, specially
adapted ventilators and monitoring systems do allow treatment of
critically ill patients.
CLINICAL INDICATIONS
Acute Conditions
Decompression Sickness:
Although occasionally seen in aviators, decompression sickness is
generally a disease of divers. During a dive, the diver is
exposed to pressures greater than 1 atm, and tissue uptake of
nitrogen increases according to the principles of Henry's law.
With ascent, a pressure gradient develops, and nitrogen leaves
the tissue, dissolving into the blood and passing to the lungs,
where it is exhaled. With rapid ascent a steep pressure gradient
develops and intravascular nitrogen gas bubbles form. [19] These
can be detected in asymptomatic divers. [20] With greater
pressure gradients, the nitrogen bubbles become large enough and
prevalent enough to mechanically deform tissue and obstruct blood
vessels. The gas-fluid interface also interacts with blood cells,
platelets, and proteins, causing disruption of the intravascular
coagulation system. [21] Decompression sickness results.
Divers can experience decompression sickness as pain only,
usually as a "deep and dull ache" in the extremities. More
serious cases can present as paraplegia or cardiovascular
collapse due to embolization of bubbles into the cardiac or
central nervous system.
Hyperbaric oxygen therapy mechanically decreases the size of the
bubbles, oxygenates ischemic tissue, and reduces the nitrogen
gradient. Any patient with decompression sickness should be
transferred immediately to the nearest HBO facility with the
capacity to decompress to 3 to 6 ATA, as this has been shown in
numerous series to be the most reliable and effective treatment.
[22,23] The Duke University Divers Alert Network maintains a
24-hour emergency consultation telephone number, (919) 684-8111,
and can identify the closest available HBO facility.
Air Embolism.
Air embolism can be a complication of uncontrolled ascent in
diving but more frequently is seen medically in iatrogenic
misadventures. Bubbles can embolize to the cerebral or cardiac
circulation, producing either severe neurologic symptoms or
sudden death. Hyperbaric oxygen therapy has been part of
successful treatment of air embolism due to cardiovascular
procedures, [24,25] lung biopsies, [26] hemodialysis, [27] and
central line placement. [28] Presumably, HBO therapy decreases
the volume of the embolism and oxygenates local tissues.
Treatment involves immediate descent to 6 ATA for 15 to 30
minutes on air, followed by decompression to 2.8 ATA, where the
patient receives prolonged oxygen treatment. Carbon Monoxide
Poisoning.—Carbon monoxide poisoning accounts for half of all
fatal poisonings in the United States. Multiple series have shown
that patients with carbon monoxide poisoning improve markedly
following treatment with HBO. [29-31] However, both the mechanism
of carbon monoxide toxicity and the therapeutic effect of HBO are
poorly understood. Carbon monoxide toxicity was long thought to
be due to anoxia alone; [32] however, there is evidence that the
pathophysiologic effects occur with carbon monoxide binding to
the cytochrome-oxidase system, causing anoxia at the
mitochondrial level. [33] In either case, HBO therapy is the most
rapid way of displacing carbon monoxide bound to hemoglobin and
cytochromes. The serum half-life of carboxyhemoglobin is
decreased from 5 hours 20 minutes with room air to 80 minutes
with 100% oxygen and 23 minutes with 100% oxygen at 3 ATA. [34]
In treating patients with carbon monoxide poisoning, it is
important to remember that serum carboxyhemoglobin levels do no t
reflect tissue levels of carboxyhemoglobin and, therefore, may
not correlate with the degree of toxicity. Accompanying signs and
symptoms are as important to guiding therapy as the serum
carboxyhemoglobin level. [35] Although HBO therapy remains the
preferred treatment for significant exposure (Table 3), only a
few controlled human studies with inconclusive results have
compared HBO with 100% oxygen at 1 atm. [36,37]
Clostridial Myonecrosis.
Clostridial myonecrosis occurs when a hypoxic environment within
a necrotic wound allows clostridial spores to convert to
vegetative organisms. These organisms produce exotoxins that
destroy red blood cells, cause tissue necrosis, and abolish local
host defenses. The most important exotoxin is alpha toxin. A
tissue [PO.sub.2] of 250 mm Hg inhibits the production of alpha
toxin by Clostridium. [38]
Hyperbaric oxygen is commonly used as an adjunct therapy in
clostridial infections. In vivo studies have demonstrated
decreased mortality rates and diminished tissue loss in infected
mice. [39,40] In a study by DeMello et al, [41] using a dog model
of clinical Clostridium infection, 100% of infected control dogs
and dogs randomized to either HBO therapy or surgery died. Fifty
percent of the dogs that received antibiotics survived, 70% of
the dogs that received antibiotics and underwent surgery
survived, and 95% of the dogs that received antibiotics and HBO
therapy and underwent surgery survived.
Multiple series have evaluated the effect of HBO therapy on
clostridial infections in humans. [42,43] Surgeons experienced
with its use emphasize that early HBO treatment reduces systemic
toxic reactions so that patients in shock seem more stable and
better able to tolerate surgery, and there is clearer demarcation
of viable and nonviable tissue. There have, however, been no
randomized, controlled studies.
Hyperbaric oxygen therapy has been recommended for treatment of
necrotizing fasciitis, since anaerobic bacteria play a role in
the disease. [44,45] The diversity of clinical states in
retrospective studies and the paucity of experimental data make
it difficult to demonstrate the effect of HBO therapy on
nonclostridial soft-tissue infection. Although necrotizing
fasciitis is an accepted indication for HBO, the benefit HBO
therapy may provide is still poorly understood, and surgery
remains the cornerstone of therapy. [46]
Acute Traumatic Ischemia.
Acute crush injury to an extremity may cause severe edema and
ischemia in tissue and capillary beds not relieved by restoration
of arterial perfusion. Hyperbaric oxygen therapy may aid salvage
during the acute stages of revascularization by reducing edema
via vasoconstriction and increasing oxygen delivery via plasma
flow. [47] Investigators have used HBO therapy successfully as an
adjunct to surgery in crush injuries. [48,49] Additional evidence
has demonstrate d that HBO therapy may also serve as an adjunct
therapy in the compartment syndrome. [50]
CHRONIC CONDITIONS
Irradiated Tissue.
Radiation therapy, in addition to its therapeutic effects, can
damage normal adjacent tissue. The initial pathologic process is
a progressive obliterative endarteritis, resulting in areas of
tissue hypoxia and eventual cell death. [51] Large areas of
hypocellular, hypovascular, and hypoxic tissue are created that
are devoid of functioning fibroblasts and osteoblasts. [52]
Hyperbaric oxygen therapy appears to assist in salvaging such
tissue by stimulating angioneogenesis in marginally viable
tissue. [53] Marx and Johnson [54] emphasize that, in
reconstructive surgery involving recently irradiated tissue,
presurgical HBO treatment can help promote a well-vascularized
wound bed that will enhance reconstruction and graft take. Using
a specific HBO protocol of presurgical and postsurgical
treatments, they demonstrated a satisfactory surgical outcome in
92% of their patients and a complication rate of 9%.
In osteoradionecrosis, tissue destruction progresses to breakdown
of overlying tissues and symptomatic destruction of bone. Prior
to the introduction of HBO therapy, only 5% to 30% of patients
who developed osteoradionecrosis could expect remission with
conservative therapy. [55] In a protocol developed by Marx, [56]
a series of 58 patients received an initial series of HBO
treatments, followed by debridement and further HBO treatment, as
dictated by their clinical course. All 58 patients studied had
resolution of symptoms of osteoradionecrosis, with good results
on long-term follow up. These impressive results have been
corroborated by others. [57,58] Successful results have also been
demonstrated for radiation-induced cystitis [59] and other
radiation-damaged soft tissue. [60] Hyperbaric oxygen therapy is
beneficial for patients at risk for the development of
osteoradionecrosis, such as irradiated patients requiring tooth
extraction. In a randomized trial comparing HBO and penicillin
therapy in 74 pr eviously irradiated patients, 30% of the
patients who received penicillin developed osteoradionecrosis,
while 5.4% of the patients who received HBO developed
osteoradionecrosis. [61] Similar results have been reported
elsewhere. [62]
Refractory Osteomyelitis.
Hyperbaric oxygen is currently being used as an adjunctive
therapy with debridement and antibiotics in osteomyelitis that