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Hyperbaric Oxygen Applications in Infection Disease
Hyperbaric Oxygen Applications in Infection Disease
26 (2008) 571–595
* Corresponding author.
E-mail address: colin.kaide@osumc.edu (C.G. Kaide).
0733-8627/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.emc.2008.01.005 emed.theclinics.com
572 KAIDE & KHANDELWAL
13 indications for HBO for which there is in vitro and in vivo evidence to sup-
port its use (Box 1) [1]. Some of these conditions involve infectious processes.
In this article we discuss the use of HBO as an adjunct to aggressive med-
ical and surgical management of infectious processes.
Hyperbaric physiology
HBO therapy is the application of pressures greater than 1 atmosphere
absolute (ATA) to an environment of 100% oxygen, which results in the in-
crease in the partial pressure of oxygen, proportional to the increase in pres-
sure. When a patient is placed into a hyperbaric chamber, the oxygen is
delivered by the lungs to the entire body. This systemic delivery of oxygen
should not be confused with topical oxygen therapy, in which a specific
body part is subjected to oxygen under pressure with the oxygen delivered
locally to an open wound.
Under normobaric conditions, we live at 1 ATA of pressure measured at
sea level. That is to say that a person at sea level has downward pressure
exerted on his body equal to the weight of the atmosphere above him. In me-
dial applications, it is customary to measure atmospheric pressure in milli-
meters of mercury (mm Hg). A pressure of 760 mm Hg is equal to 1
ATA, 14.7 psi, 760 torr, or 33 ft of seawater.
At the depth of 33 ft of seawater, a diver is exposed to 2 ATA: 1 ATA
from the atmosphere above the water and 1 ATA from the pressure exerted
by the 33 ft (10 m) of seawater. Henry’s law specifies that the partial pressure
Data from Feldmeier JJ, editor. Hyperbaric oxygen 2003: indications and
results: the Hyperbaric Oxygen Therapy Committee Report. Kensington (MD): Un-
dersea and Hyperbaric Medical Society; 2003.
HYPERBARIC OXYGEN 573
experience and multiple small clinical reports suggest that HBO can play
a valuable role in the overall management plan for many patients suffering
from this devastating disease [21].
Of the clinical series supporting the use of HBO in NF, the most compel-
ling were published by Mader (1988), Riseman (1990), and Escobar (2005)
[23–25]. Mader [24] reported on 22 patients who had NF involving the scro-
tum and perineum (Fournier gangrene). He noted a reduction in mortality
from 67% to 25% when HBO was added to standard treatment.
Riseman and colleagues [25] reported on 17 patients who had NF who
received HBO plus standard therapy compared with 12 patients who re-
ceived standard therapy alone. The HBO group was described as more seri-
ously ill on admission. The reduction in mortality from 66% to 23% in the
HBO group, along with a decrease in the number of necessary débridements,
prompted the authors to strongly advocate that HBO be added to standard
therapy in institutions where it is available. The authors went as far as to say
that withholding HBO will cause unnecessary deaths and is therefore
unethical.
The most recent study by Escobar and colleagues (2005) [23] retrospec-
tively evaluated 42 patients who had NF in various body locations. These
patients had significant comorbidities, including diabetes mellitus, chronic
renal failure, intravenous drug abuse, peripheral vascular disease, and ma-
lignancy. They used a standard regimen for HBO, which was added to ag-
gressive surgical débridement, antibiotic therapy, and critical care. Their
patient population incurred a mortality of 11.9%, compared with the na-
tional average mortality rate of 34%. There were no amputations in the
HBO-treated group compared with the reported rate of 50% nationally.
Their study further refuted two common criticisms of HBO: delaying surgi-
cal intervention and creation of HBO-induced complications. They demon-
strated no delays to operative intervention or interference in standard care.
There were no clinically relevant complications related to the HBO.
To date there has only been one study that suggested a potential harm
associated with HBO in NF. In 1977, Tehrani and Ledingham [26] re-
ported an 88% mortality in 14 patients who received HBO along with
conservative surgical treatment. In this study, however, the first 8 patients
received HBO plus only incision and drainage as the primary surgical in-
tervention as opposed to aggressive surgical debridement. Seven of the pa-
tients died. In the final 6 patients, a more aggressive surgical débridement
along with HBO lead to a 33% mortality. This outcome argues more
against the dangers of conservative surgical intervention than it does re-
garding the adjunctive HBO. See Table 1 for a summary of studies of
HBO in NF.
Table 1
Summary of studies on hyperbaric oxygen treatment in necrotizing fasciitis
Author Year Study conclusions
Tehrani et al [26] 1977 Conservative surgery combined with HBO therapy
was associated with high mortality (88%)
Eltorai et al [98] 1986 100% survival
Gozal et al [99] 1986 Mortality rate of 12.5%
Riseman et al [25] 1990 Significant decrease in mortality and the number of
débridements in the HBO-treated group
Brown et al [100] 1994 A nonsignificant decrease in mortality with HBO
therapy; no difference in length of hospitalization
or number of débridements
Shupak et al [101] 1995 No significant difference in mortality or number of
débridements
Korhonen et al [102] 1998 Mortality rate of 9% in patients who had Fournier
gangrene
Escobar et al [23] 2005 11.9% mortality in HBO group with no
amputations; 34% mortality in historical controls
with 50% amputation rate
Data from Feldmeier JJ, editor. Hyperbaric oxygen 2003: indications and
results: the Hyperbaric Oxygen Therapy Committee Report. Kensington (MD):
Undersea and Hyperbaric Medical Society; 2003.
578 KAIDE & KHANDELWAL
may be initiated before surgery only if the treatment does not further delay
débridement. When patients are at hospitals that do not have HBO avail-
able, surgical management should take precedence and transfer to an
HBO center can be done postoperatively after the patient is stabilized if it
is clinically indicated.
Gas gangrene
Gas gangrene is a rapidly progressive, invasive clostridial infection of pre-
viously healthy muscle tissue. It is also known as clostridial myonecrosis. It
produces massive local tissue destruction along with severe systemic symp-
toms. It is a relatively rare disease with 1000 to 3000 cases per year in the
United States [27].
Gas gangrene is caused by various species of Clostridium. These are
Gram-positive, spore-forming, anaerobic rods normally found in soil and
the human and animal gastrointestinal tract. The most common species im-
plicated in gas gangrene is Clostridium perfringens (80%–90%) [28]. This or-
ganism is the causative agent in traumatic and postsurgical cases. Direct
inoculation of a traumatic wound with C perfringens in a hypoxic wound en-
vironment with a compromised blood supply is the perfect milieu for
growth. Many traumatic wounds are contaminated with Clostridium spores,
but only a small percentage actually develop gas gangrene. It seems that
both inoculation with the organism and a relatively hypoxic tissue environ-
ment are necessary for the clinical disease process to develop. Although it is
an anaerobe, C perfringens can grow in a restricted fashion in oxygen ten-
sions up to 70 mm Hg.
Clostridium septicum, which is more aerotolerant, is most commonly im-
plicated in cases of spontaneous gas gangrene [28]. This infection usually oc-
curs when bacteria enter from the gut by way of breaks in the gastric mucosa
in patients who have colon cancer. Hematogenous spread causes infection in
muscle tissue. Other Clostridia species make up a minority of cases and in-
clude bifermentans, fallax, histolyticum, and a few others.
The clinical syndrome of infection with C perfringens begins with pain at
the infection site that seems out of proportion to the size of the wounded
area. Local tissue destruction results in bleb and bullae formation. Rapid ex-
tension of the wound almost seems to happen in real time, at rates up to 15
cm/h [29]. When present, gas can sometimes be seen on radiographs and felt
in the tissue as crepitus [28]. In at least 50% of cases, however, gas is not
demonstrable, either on radiographs or clinically. Owing to variability,
the detection of gas should not be used to make or break the diagnosis of
clostridial infection. A ‘‘sickly sweet’’ odor can be detected from the wound
drainage. Systemic symptoms include a low-grade fever, disproportionate
tachycardia (140–160), and cognitive symptoms ranging from a flat affect
to severe anxiety. Hypotension is a late finding and heralds impending cir-
culatory collapse and death.
HYPERBARIC OXYGEN 579
Data from Feldmeier JJ, editor. Hyperbaric oxygen 2003: indications and
results: the Hyperbaric Oxygen Therapy Committee Report. Kensington (MD):
Undersea and Hyperbaric Medical Society; 2003.
HYPERBARIC OXYGEN 581
Anatomic Type
Physiologic Class
Data from Feldmeier JJ, editor. Hyperbaric oxygen 2003: indications and
results: the Hyperbaric Oxygen Therapy Committee Report. Kensington (MD):
Undersea and Hyperbaric Medical Society; 2003.
Intracranial abscess
Intracranial abscess (ICA) encompasses cerebral abscess, subdural empy-
ema, and epidural empyema. Although many factors, such as early and
Data from Feldmeier JJ, editor. Hyperbaric oxygen 2003: indications and
results: the Hyperbaric Oxygen Therapy Committee Report. Kensington (MD):
Undersea and Hyperbaric Medical Society; 2003.
588 KAIDE & KHANDELWAL
Table 2
Wagner grading system for diabetic foot ulcers
Grade Clinical description
0 Intact skin
1 Superficial without penetration into deeper layers
2 Deeper, reaching tendon, bone, or joint capsule
3 Deeper, with abscess, osteomyelitis, or tendonitis extending to those
structures
4 Gangrene of some portion of the toe or forefoot
5 Gangrene involving the entire foot or enough of the foot that local
procedures are not an option
Data from Feldmeier JJ, editor. Hyperbaric oxygen 2003: indications and results: the Hyper-
baric Oxygen Therapy Committee Report. Kensington (MD): Undersea and Hyperbaric Med-
ical Society; 2003; with permission.
more accurate diagnosis, better surgical techniques, and more accurate an-
tibiotic coverage, have led to decreases in mortality over time, ICA con-
tinues to show mortality rates of around 20% [89].
that warrant a more aggressive strategy (Box 8). Adjunctive HBO therapy
should be considered if any of the following are present [89]:
Multiple abscesses
Abscesses in a deep or dominant location
A compromised host
Situations in which surgery is contraindicated
Inadequate or no response to standard surgical and antibiotic treatment
Data from Feldmeier JJ, editor. Hyperbaric oxygen 2003: indications and
results: the Hyperbaric Oxygen Therapy Committee Report. Kensington (MD):
Undersea and Hyperbaric Medical Society; 2003.
590 KAIDE & KHANDELWAL
Summary
HBO is clearly not a panacea. It has some specific, generally accepted ap-
plications in infectious diseases that are often additive or adjunctive to reg-
ular medical therapy. Admittedly, there is a paucity of RCTs for HBO. With
the low incidence of the diseases discussed above, however, the randomiza-
tion of patients would be difficult. In our opinion, withholding HBO be-
cause of the lack of randomized trials in the face of a huge body of
clinical experience and in vitro studies, especially in these devastating disease
processes, would be bordering on unethical.
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