03. Clostridial Myositis And Myonecrosis (Gas Gangrene)


Clostridial myositis and myonecrosis or gas gangrene is an acute, rapidly progressive, non-pyogenic, invasive clostridial infection of the muscles, characterized by profound toxemia, extensive edema, massive death of tissue, and a variable degree of gas production.(1) 

The infection is caused by anaerobic, spore‑forming, Gram‑ positive encapsulated bacilli of the genus clostridium, discovered by William H. Welch in 1891.(2) More than 150 species of clostridium have been recognized but the most commonly isolated is C. perfringens type A (95%) either alone or in combination with other pathogenic clostridia, C. novyi (8%), C. septicum (4%), and C. histolyticum, C. fallax, and C. sordelli (1% or less of the infections).(3,4) 

A further subdivision can be made in clostridia that are toxo-genic, i.e., C. perfringens, C. septicum, C. novyi, and clostridia that are believed to be only proteolytic, i.e., C. histolyticum, C. bifermentans, C. sporogenes, and C. fallax, which augment an infection by their proteolytic capabilities but do not cause the classical gas gangrene syndrome. C. tertium, C. sphenoides, and C. sordelli can be considered as contaminants. It is not known if and what these microorganisms add to the disease process. The essential role of alpha-toxin in the pathogenesis of gas gangrene was recently confirmed by Williamson and Titball,(5) who developed a genetically engineered vaccine against alpha-toxin. Immunization with the C-Domain of α-toxin proved to be of value in animal experiments.(6) 


The complete genome sequence of C.Perfringens has been published recently by Shimizu et al.(8) 



The most prevalent is the O2‑stable lecithinase‑C, alpha‑ toxin, which is hemolytic and tissue‑necrotizing. It destroys platelets and polymorphnuclear leukocytes and causes widespread capillary damage and is often lethal.(12) 

The other toxins are ancillary to the alpha‑toxin, which gives rise to hemoglobinuria, hemolysis, jaundice, anemia, tissue necrosis, renal failure, and serious systemic effects such as cardiotoxicity and brain dysfunction. The other exotoxins are synergistic and enhance the rapid spread of infection by destroying, liquefying, and dissecting healthy tissue. The clostridial organisms surround themselves with toxins. Local host defense mechanisms are abolished when the toxin production is sufficiently high. This results in fulminating tissue destruction and further clostridial growth. Alpha‑toxin can be fixed to susceptible skin cells in 20-30 min, is detoxified within 2 hours after its elaboration, and causes active immunity with production of a specific antitoxin.(10,13) The infection, however, is so progressive with continuous production of alpha‑toxin that the patient dies before any immunity can develop. 


In earlier papers, Stevens et al(15,1) already described the lethal effects and cardiovascular effects of purified alpha- and theta-toxins from C.perfringens. 

An extensive and updated review about the role of clostridial toxins in the pathogenesis of gas gangrene was given by Stevens and Bryant.(16) 

Awad et al,(17) showed genetic evidence for the essential role of alpha-toxin in gas gangrene. 


The action of HBO2 on clostridia (and other anaerobes) is based on the formation of O2 free radicals in the relative absence of free radical degrading enzymes, such as superoxide dismutases, catalases, and peroxidases. Van Unnik(20) showed that an O2 tension of 250 mmHg is necessary to stop alpha‑ toxin production. Although it does not kill all clostridia, it is bacteriostatic both in vivo and in vitro.(20-24) Tissue O2 measurements made by Schoemaker,(25) Kivisaari and Niinikoski,(26) and Sheffield(27) have shown that treatment with HBO2 at 3.0 atm abs is required to achieve tissue partial pressures above 300 mmHg. Free-circulating toxins and/or tissue‑ bound toxins are not affected by high O2 levels but they are rapidly detoxified by normal host factors.(9,21,28,29) 



Roggentin et al.(30) developed an immunoassay for rapid and specific detection of C. perfingens, C. septicum, and C. sordelli by determining their sialidase activity (neuraminidase) in serum and tissue homogenates. Sialidases produced by these three clostridia were bound to polyclonal antibodies raised against the respective enzymes and immobilized onto microtiter plates. Applied to nine samples from patients, there was a high correlation between the results of the immunoassay and the bacteriological analysis of the infection.(30) 

Scheven(31) described identification of C.perfringens in mixed-infected clinical materials by means of a modified reversed CAMP-test. 

The onset of gas gangrene may occur between 1 and 6 hours after injury or an operation and begins with severe and sudden pain in the infected area before the clinical signs appear. This seemingly disproportionate pain in a clinically still normal area must make the clinician highly suspicious for a developing gas gangrene, especially after trauma or an operation. The body temperature is initially normal but than rises very quickly. The skin overlying the wound in the early phases appears shiny and tense and then becomes dusky and progresses to a bronze discoloration. The infection can advance at a rate of 6 inches per hour. Any delay in recognition or treatment may be fatal. Hemorrhagic bullae or vesicles may also be noted. A thin, sero-sanguinolent exudate with a sickly, sweet odor is present. Swelling and edema of the infected area is pronounced. The muscles appear dark red to black or greenish. They are noncontractile, and do not bleed when cut. 

The tissue gas seen on radiographs appears as feather‑like figures between muscle fibers and is an early and highly characteristic sign of clostridial myonecrosis. Crepitus is usually present as well. 


A minimum of three to four HBO2 treatments is necessary for this response. Treatment starts on the basis of the clinical picture and the positive Gram‑stained smear of the wound fluid (without leukocytes). HBO2 treatment stops alpha‑toxin production and inhibits bacterial growth thus enabling the body to utilize its own host defense mechanisms.(20-24) 

The first clinical results in gas gangrene were remarkable, but were difficult to reproduce in the animal model.(22,23,46) 

Despite wide variations in O2 tolerance between small and large laboratory animals and human beings, HBO2 therapy has been used to treat experimental clostridial infections in animals. The greatest reduction in mortality in dogs was achieved by a combination of HBO2, surgery, and antibiotics.(24) In general, studies of several investigators(22,23,32,33,34,46) have shown that HBO2 substantially reduced mortality and morbidity in animals following clostridial infections, when used in combination with surgery and antibiotics. 


The work by Brummelkamp et al.(39,40) updated by Bakker(41,1) totaling 409 cases of clostridial gas gangrene showed a mortality directly related to the clostridial infection of 11.7%. All 48 patients who died did so within 26 h after the start of HBO2 therapy. HBO2 therapy also greatly reduced the amputation rate: only 18% required amputation post-hyperbaric therapy vs. 50-55% following primary surgery.(4,35,36) 

Hart et al.(42) reported a 17% amputation rate with combined therapeutic management. Reduced mortality rates were also demonstrated by Hart et al.,(42) Hitchcock et al.,(10) Holland et al.,(43) Van Zijl,(44) and Heimbach.(45) Heimbach(11) showed a 5.1% mortality rate among 58 patients whose HBO2 therapy began within the first 24 hours; these results reinforce earlier clinical trials. 

Mortality in the series of Hirn(46) was 28%. He concluded that mortality and morbidity could be reduced if the disease is recognized early and appropriate therapy applied promptly. He recommends adequate and operative debridement, antibiotics, HBO2, and surgical intensive care. 


In the multimicrobial gas gangrene model, the additon of HBO2 to surgery tended to reduce mortality, but the difference between the groups was not statistically significant. However, the combined therapy with surgery and HBO2 was highly effective in reducing morbidity and mortality and improving wound healing compared with surgical debridement alone.(46) 

The advantages of early HBO2 treatment are that: 
In 1984 Peirce already concluded that the modern treatment of gas gangrene involves the simultaneous use of antibiotics, surgical debridement and hyperbaric oxygen.(47) He also believed, that even at that time, it would be unethical to carry out a randomized clinical study to compare these three modalities. This opinion was based on the results published until 1984.(41,47) 

