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The role of hyperbaric oxygen therapy in the treatment of clostridial gas gangrene and necrotizing fasciitis
(Portuguese PDF version)

Edgard de Barros Lima¹, Carlos Henrique A. Bernardes², Antônio Carlos Giometti Martins³, Carla M. Marcondes⁴

1. Professor, School of Medicine, Universidade Metropolitana de Santos, Santos, Brazil. Hyperbaric Medicine Service, Santa Casa de Misericórdia de Santos, Santos, Brazil.
2. Professor, School of Medicine, Universidade Metropolitana de Santos, Santos, Brazil. Head of the Vascular Surgery Service, Santa Casa de Misericórdia de Santos, Santos, Brazil.
3. Head of the Hyperbaric Medicine Service, Santa Casa de Misericórdia de Santos, Santos, Brazil.
4. Angiologist, Santa Casa de Misericórdia do Rio de Janeiro, Rio de Janeiro, Brazil.

Correspondence:
Dr. Edgard de Barros Lima
Av Conselheiro Nébias, 730/54
CEP 11045-002 - Santos - SP
Phone: +55 13 3234.4999
Fax: +55 13 3222.1266
E-mail: cir.vascular@globo.com

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ABSTRACT

Objective: The objective of this article is to describe the use of hyperbaric oxygen therapy in the treatment of clostridial gas gangrene and necrotizing fasciitis, with special emphasis on physiological features, types of injury, and results found in the literature. The authors conclude that the use of hyperbaric oxygen, not as an isolated treatment, but always as an adjunctive therapy to the necessary surgical debridement and adequate antibiotic therapy, helps to reduce the high mortality rate of these diseases.

Key-words: hyperbaric oxygenation, gas gangrene, necrotizing fasciitis.
Palavras-chave: oxigenoterapia, gangrena gasosa, fasciite necrosante.

J Vasc Br 2003;2(3):219-22

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Clostridial gas gangrene and necrotizing fasciitis are not very common diseases, but their morbidity and mortality rates are high.¹ Clostridial myonecrosis, also called clostridial gas gangrene, is an infection of the underlying muscle caused by clostridia. Most non-clostridial necrotizing infections and some of the clostridial infections develop in the subcutaneous fascia between the skin and the deep fascia, and are usually called necrotizing fasciitis.²

Clostridium perfringens is the most common pathogen of gas gangrene, and is found in 80 to 90% of all cases. The other five causative agents that affect humans are C. novyi, C. septicum, C. hystoliticum, C. bifermentans, and C. fallax.³ Necrotizing fasciitis is caused by aerobic and anaerobic agents, such as beta-hemolytic streptococci, hemolytic staphylococci, coliforms, enterococci, pseudomonas and bacterioids.⁴ Bacterial flora, however, changes during the course of the disease, which complicates treatment.

The first mention to necrotizing fasciitis in literature was made by Hippocrates in the fifth century BC,⁵ but the term "necrotizing fasciitis" was first used by Wilson in 1952.⁶ In 1883, the Frenchman Jean Alfred Fournier described five cases of an "inexplicable penis and scrotum gangrene" characterized by three typical findings: sudden onset in healthy young men, rapid progression, and absence of a specific causative agent. Later, other authors expanded Fournier's description to include fasciitis that affects women as well as men.⁷

In necrotizing fasciitis, the lesion appears 24 to 48 hours after surgery or trauma that wound the skin, such as an insect bite.⁸ The lesion may also appear spontaneously in children.⁹ Onset is characterized by sudden pain, which is out of proportion to initial findings.¹⁰ The lesion has no distinct borders, the skin rapidly develops a dark discoloration, and blisters and bullae appear, initially filled with serous exudate that later becomes hemorrhagic. At this stage, the infection is in located in the subcutaneous tissues, and progresses into the superficial fascia and fat. A watery foul-smelling fluid is produced; the skin still looks normal, and the adjacent muscle is intact.¹¹

Clostridial gas gangrene can be divided in four types:^12-14

Type 1 - diffusely spreading clostridial myonecrosis (true gas gangrene): incubation time is usually short; skin develops a bronzed discoloration, and underlying muscle becomes necrotic; patient presents with toxemia; there is still little gas production, which only increases later in the course of the disease.

Type 2 - localized clostridial myonecrosis: patient does not have signs of systemic toxicity although the muscle in the affected area becomes necrotic.

Type 3 - clostridial cellulitis with toxicity: may be accompanied by toxemia similarly to diffuse clostridial myonecrosis, and may have an equally poor prognosis. All the underlying tissue, including the fascia, becomes necrotic, but underlying muscle is not affected. Gas production is abundant in the initial stages of infection.

Type 4 - clostridial cellulitis without toxicity: symptoms and findings are similar to those of toxic cellulitis, but it is a localized process and there is no toxicity.

DEFINITION OF HYPERBARIC OXYGEN THERAPY

Hyperbaric hyperoxia treatment is defined as the intermittent inhalation of 100% oxygen at a pressure higher than one atmosphere absolute (ATA). It is administered in a hyperbaric chamber for one single patient or for several patients (multiplace chamber).¹⁵ The immediate effect of hyperbaric hyperoxia is hyperoxygenation, resulting in an increase in oxygen dissolved in plasma, which is directly proportional to the partial pressure of inhaled oxygen.¹⁶ Hyperoxygenation causes several physiological and basic metabolic effects, which are summarized on Table 1.

Table 1- Basic physiological and metabolic effects of hyperbaric oxygen therapy*

Antimicrobial activity

Microbicidal and microbiostatic (bacteria and fungi)

Direct (strict anaerobes and microaerophillic aerobes)

Indirect (facultative/obligate aerobes)

Compensatory effects in cell hypoxia

PCO2 functional compensation (cell activity - healing processes)

PO2 critical compensation (cell survival – normalization of metabolism)

Physiological and biophysical effects

Peripheral and visceral vasoconstriction

Antiedemic activity

Reduction in cardiac deficit

Decrease in pulmonary AP*

Increase in inert gas diffusion (for example, nitrogen)

Mechanical effects of pressure

Decrease in size of gas bubbles

Effects of synergistic pharmacodynamic interaction

Specific antibiotics (sulfonamides, aminoglycosides, among others)

Specific chemotherapy drugs (bleomycin, adriamycin)

Radiotherapy

Other specific drugs: antiarrythmic, diuretic, narcotic, hypotensive

PCO2 - partial carbon dioxide pressure; PO2 - partial oxygen pressure; PA - arterial pressure.
*Adapted from Iazzeti¹⁷

INDICATIONS FOR HYPERBARIC OXYGEN THERAPY

The classical treatment of clostridial gas gangrene and necrotizing fasciitis consists of extensive surgical debridement and adequate antibiotic therapy. Another treatment option, which has improved morbidity and mortality rates, is hyperbaric oxygen therapy (HBO). It is extremely important to stress that HBO is not an isolated treatment, but rather an adjunctive therapy to the classical treatment with surgical debridement and antibiotic therapy. Several reports can be found in literature about the use of HBO in the treatment of these pathologies in many countries, such as France,¹⁸ Italy,¹⁹ USA,^20,21 Finland,²² and China.²³ In Brazil, the Conselho Federal de Medicina (Federal Medicine Council) has published a resolution in the Diário Oficial da União (the Union's Official Gazette) which regulates the use of HBO in this country. Among the indications included in the resolution are clostridial gas gangrene and necrotizing fasciitis.

HBO acts by increasing partial oxygen pressure in hypoxic or septic tissues and, at the same time, maintaining tissue oxygenation in the absence of hemoglobin.²⁴ By eliminating local hypoxia, HBO stimulates the bactericidal activity of leukocytes, enhances fibroblast replication, increases collagen formation, and promotes neovascularization.²⁵ HBO has antibacterial activity against C. perfringens, C. novyi, C. hystoliticum, and C. tetani.²⁶ Oxygen tensions of 300 to 400 mmHg have been measured during HBO at 2 ATA. These tensions are similar to the levels necessary for the interruption of toxin production by Clostridium in culture media. As toxin production is interrupted, the cycle of the disease is also broken, and residual toxins are rapidly attached to tissues.²⁷ Hyperoxya also promotes the bactericidal activity of polymorphonuclear neutrophils against pathogens such as S. epidermidis, P. aeruginosa, E. coli and S. aureus in ischemic areas.²⁸ Moreover, neutrophils need oxygen for their bactericidal activity against E. coli, Serratia marcescen, Klebsiela pneumoniae and Proteus vulgaris.²⁹

The indication of HBO in the treatment of gas gangrene should be based on the type of clostridial infection:^14,27

Type 1 - The patient had severe toxemia in true gas gangrene. Clostridial infection is usually controlled in patients that survive the first three sessions administered in the first 24 hours.

Type 2 - The excision of affected muscle and adequate antibiotic therapy are usually enough in localized clostridial myonecrosis. However, local myonecrosis may progress into Type 1 disease, and HBO may be indicated as prophylaxis.

Type 3 - The treatment for clostridial cellulitis with toxicity is the same as the one for true gas gangrene.

Type 4 - Incisions, drainage, and antibiotic therapy are adequate and sufficient therapeutic measures for clostridial cellulitis without toxicity.

OTHER STUDIES ABOUT HYPERBARIC OXYGEN THERAPY

Many other studies in literature report on the favorable results of the combination of debridement, antibiotic therapy, and HBO. Riseman et al.³⁰ described 29 patients with necrotizing fasciitis: 12 underwent surgical debridement, and 17 underwent HBO combined with antibiotic therapy and debridement. Twenty-nine percent of the patients treated with HBO and 8% of the patients in the other group were in shock at admission. Mortality rate was 23% in the group treated with HBO and 66% in the other group. Fewer additional surgical debridement procedures were necessary in the HBO group (1.2 v. 3.3).

Hollabaugh et al.³¹ studied 26 patients with Fournier's gangrene; all patients were treated with broad-spectrum antibiotics and surgical debridement. Fourteen of their patients received HBO as an adjunctive treatment - there was no hyperbaric chamber in the hospital where the other patients were treated. They found a 7% mortality rate in the group treated with HBO and 42% in the group that did not receive HBO.

Niinikoski and Aho³² reported on a 10-year study with 133 patients divided in two groups. Forty-four patients were treated with debridement and antibiotic therapy, and 89 received adjunctive HBO therapy. They found a 22% mortality rate in the group treated with HBO and 45% in the group that did not receive HBO.

In Finland, Korhonen³³ investigated the effect of HBO on O₂ and CO₂ tensions in patients with necrotizing fasciitis. They found that, during exposure to HBO at 2.5 ATA, arterial PO₂ increased about seven times, while arterial PCO₂ increased at a lesser degree. During HBO, however, PO₂ in the underlying tissue increased four to five times from basal values both in infected and healthy tissues; PCO₂ also increased, though at a lesser degree. In patients with necrotizing fasciitis, PO₂ was higher around the affected area than in the healthy area, but the difference was not statistically significant. The author concluded that this fact might be explained either by the vasodilation and the increase of microcirculation induced by the inflammatory process that accompanies infection, or by the decrease in the use of oxygen by the tissue in the site, or by both. Tissue PCO₂ values tend to increase during HBO probably due to hypoventilation, or to the reduction in tissue CO₂ withdrawal caused by the fact that hemoglobin in venous blood is completely saturated with oxygen.

CONCLUSION

HBO is a valuable therapy in the treatment of clostridial gas gangrene and necrotizing fasciitis, not as an isolated measure, but in combination with surgical debridement and adequate antibiotic therapy. Treatment indication should be adequate, and the therapy should be initiated as early as possible to decrease the high mortality rate usually found for this type of pathology.

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