Hyperbaric, Clostridial Myositis And Myonecrosis

Article Author:
Jacob Sison-Martinez
Article Editor:
Jeffrey Cooper
Updated:
4/26/2018 9:46:35 AM
PubMed Link:
Hyperbaric, Clostridial Myositis And Myonecrosis

Introduction

Clostridial myositis and myonecrosis (gas gangrene) are both life-threatening infections caused by the anaerobic, spore-forming, exotoxin-producing bacteria species Clostridium perfringens. If not quickly recognized, gas gangrene can quickly lead to death. Thus, fast recognition and treatment are required whenever gas gangrene is suspected.

Etiology

Gas gangrene is caused by Clostridia species, most commonly Clostridium perfringens. These gram-positive encapsulated anaerobic bacilli are ubiquitous and are found everywhere including the environment and within the body. However, Clostridia infections have a particular association of wound contamination with soil particles.

Epidemiology

In the United States, there are about 3000 cases per year. Infections can be categorized as post-traumatic, post-surgical, or spontaneous. Post-traumatic gas gangrene accounts for about 60% of cases overall, usually involving automobile collisions. The infection has no sexual bias, although there are rare reports of gynecological infection and clostridial endometritis after amniocentesis, cordocentesis, molar pregnancy, vaginal delivery, cesarean section, medical/spontaneous abortion, ablation, and cervical procedures.

Pathophysiology

Clostridial myonecrosis or gas gangrene is an acute, rapidly progressive disease complicated by toxemia, edema, massive tissue death with gas production. 

Trauma most commonly introduces clostridial organisms into deep tissue. Additionally, the tissue damage can disrupt blood supply, helping form an anaerobic environment with low oxidation-reduction potential and acidic pH. This setting is ideal for clostridial organisms with necrosis progressing within 24 to 36 hours of the injury.

C. perfringens produces more than 20 extracellular toxins. However, 2 toxins heavily mediate the disease process: alpha and theta.

Alpha toxin is essential to the development of gas gangrene. A hemolytic toxin, it has both phospholipase C and sphingomyelinase activity. Alpha toxin also stimulates platelet aggregation and upregulates adherence molecules on neutrophils and endothelial cells. This leads to the formation of occlusive intravascular aggregates composed of activated platelets, leukocytes, and fibrin which causes rapid, irreversible decline in muscle blood flow and ischemic necrosis of tissue. Decreased perfusion promotes the development of the anaerobic environment and contributes to the rapidly advancing margins of tissue destruction characteristic of clostridial gas gangrene. Alpha toxin is also responsible for the characteristic absence of tissue inflammatory response. As previously mentioned, large aggregates of activated platelets and neutrophils reduce the ability of neutrophils to cross the endothelial cell barrier into infected tissues. This is accomplished by alpha toxin-induced activation of the platelet fibrinogen receptor, glycoprotein IIb/IIIa. Alpha and theta toxin also are cytotoxic to neutrophils; the toxins most likely destroy the small number of leukocytes that do successfully migrate into tissue.

Theta toxin, also known as perfringolysin O, is a member of the cholesterol-dependent cytolysin family of which members are characterized as pore-forming toxins. Theta toxin appears to contribute to pathogenesis by its effects on vascular and immune cells. One proposed mechanism is by neutrophil-dependent adherence molecules such as integrin CD11/CD18, promoting distal vascular injury with the activation of neutrophils and endothelial cells.

Shock associated with gas gangrene may be attributable to both direct and indirect effects of alpha and theta toxins. Alpha toxin directly suppresses myocardial contractility and may contribute to profound hypotension via a sudden reduction in cardiac output.

Histopathology

Infected regions may initially appear normal and often present with only severe pain that seems out of proportion to the exam. Later, the skin will start to appear shiny and taut, eventually becoming dusky and then to a bronze discoloration. Hemorrhagic bullae are later noted, and massive swelling and edema follow. Muscles can start to appear dark red, black, or greenish. Thin, serosanguinous exudate with a sweet odor can also form along the infected area. Tissue gas can be found in subcutaneous tissue and between muscle fibers.

History and Physical

Suspicion for gas gangrene should arise with traumatic wounds causing vascular compromise, especially with soil involvement. Common settings and conditions associated with gas gangrene include bowel and biliary tract surgery, gunshot wounds, knife wounds, compound fractures, abortion, retained placenta, prolonged rupture of the membranes, intrauterine fetal demise, and intramuscular injection.

Traumatic gas gangrene usually presents with sudden onset of severe pain. The mean incubation period is less than 24 hours, depending on a variety of factors, including the amount of bacterial introduction and the extent of the vascular compromise. The skin over the infected area initially appears pale. The area then becomes a bronze color, eventually transitioning to purple, red, or black discoloration. Eventually, dark hemorrhagic bullae develop along with massive edema. Crepitus may be felt due to gas production, although this is dependent on the amount of edema. Sometimes odor may accompany the wound and is often described as a sweet smell. Fever and tachycardia may also be present.

Evaluation

Diagnosis of clostridial myonecrosis is clinical. A patient with excruciating pain at a site of traumatic injury, systemic symptoms such as fever and tachycardia, and gas within the soft tissue is supportive. Definitive diagnosis requires microscopic identification of large gram-variable rods (gram-positive rods when seen in culture) obtained from the wound. Exudate is not purulent, and neutrophils are absent as well.

Treatment / Management

Early treatment with hyperbaric oxygen is essential for reducing morbidity and mortality as well as maximizing salvageable tissue. Some studies have demonstrated a 50% relative mortality reduction with the addition of hyperbaric oxygen to surgery and antibiotic therapy.  Clostridium perfringens growth is restricted at O2 tensions up to 70 mm Hg, and alpha-toxin production is halted at tensions of 250 mm Hg. High O2 tensions also achieve bacteriostasis, encourage free radical formation, and facilitate neutrophilic oxidative burst function.

Because alpha-toxin production is rapid and tissue infection can spread up to 6 inches an hour, adequate HBO treatment not only halts disease process but also allows for optimal debridement since a clearer delineation of dead versus viable tissue can be seen. Recommended treatment is O2 at 3 ATA for 90 minutes three times in the first 24 hours and twice a day for the next 2 to 5 days. Treatment length should be tailored to the patient’s therapeutic response. Surgical debridement should be performed in between HBO treatments. Proper antibiotic therapy is also essential; animal models favor the combination of intravenous penicillin plus clindamycin. An example regimen would be ticarcillin-clavulanate 3.1 g every 8 hours and clindamycin 900 mg every 8 hours. Carbapenems are an alternative therapy.

Differential Diagnosis

Gas gangrene is important to distinguish from other clinical entities. Differential diagnoses should include the following:

  • Group A Streptococcus infection
  • Vibrio vulnificus infection
  • Pyomyositis, most commonly secondary to Staphylococcus aureus
  • Viral myositis
  • Rhabdomyolysis

Prognosis

Typically viewed as a grim prognosis. Varies widely, with mortality rates 25% in recent studies although can approach 100% with delayed treatment.

Complications

Signs of systemic toxicity emerge rapidly including tachycardia and fever, followed by shock and multiorgan failure. Bacteremia occurs in about 15% of cases and may be associated with brisk intravascular hemolysis. Additional complications of clostridial myonecrosis include jaundice, renal failure, hypotension, and liver necrosis. Renal failure is largely due to the combined effects of hypotension, hemoglobinuria, and myoglobinuria. Bacterial toxins may also exert a direct effect on renal tubular cells.