Gas gangrene: causes, symptoms, diagnosis, treatment, prognosis, and treatment

Gas gangrene, also known as clostridial myonecrosis, is a serious infection caused by Clostridium exotoxins and is characterized by muscle necrosis, systemic toxicity, sudden onset, and rapid progression. The main pathogen is Clostridium perfringens. Other pathogens include Clostridium septicum, Clostridium novy, Clostridium histolyticu, Clostridium bifermentan, Clostridium falla, Clostridium oedematien, and Clostridium chaovoe. Patients can be infected with more than one serovar of Clostridium or with other bacteria. Most bacteria are in soil, and endogenous bacteria are mostly from the intestines or biliary tract. Clostridium produces at least 12 exotoxins.


Causes

Clostridium is a Gram-positive, spore-forming anaerobic bacterium, with flagella, widely distributed in the natural world. The bacteria can be often found in soil and intestines of human and animals. Most bacteria are saprophytic, and few are pathogenic. There are at least 103 Clostridia in a gram of soil and 109 - 1010 Clostridia in a gram of feces. However, there are few Clostridia on the normal skin and in the mouth. The most common isolate is Clostridium perfringens (Cp), often with various serovars of Clostridium. The production of exotoxins needs special circumstances to promote the growth and reproduction of Clostridium in the human body, and simple wounds or bacteria on the skin do not cause diseases. Clostridium infections are caused by mostly Clostridium perfringens, occasionally Clostridium septicum, Clostridium novy, Clostridium histolyticu, Clostridium bifermentan, Clostridium falla, Clostridium oedematien, and Clostridium chaovoe. Clostridium infections vary in severity, and Clostridium can cause different diseases including sepsis, focal infections at different anatomical sites, and tissue toxicity. The most common pathogen is Clostridium perfringens, and the pathogenicity results from its exotoxin. According to the vitality of four major lethal toxins α, β, ε, and ι (iota), Clostridium perfringens is divided into type A, B, C, D, and E. Five types can cause disease in animals, and type A and type C can cause disease in humans. α toxin is the most important causative agent of Clostridium perfringens.

Pathogenesis

The main cause of Clostridium invading muscles and producing toxins is hypoxia and a decrease in tissue oxidation-reduction potential (Eh). The disease often occurs in areas with thick muscles, such as the buttocks, thighs, and shoulder blades. Due to aortic injury, necrosis occurs in large pieces of muscle due to ischemia and hypoxia, Eh of tissue drops to below 50mV, and Clostridium in local wounds grows and reproduces. Clostridium perfringens can decompose sugar and generate a large amount of gas. A large amount of muscle glycogen in the muscle produces lactic acid by anaerobic glycolysis, and the decreased pH is more favorable for the growth of anaerobic bacteria. Ischemia and acid production in the muscle promote the decomposition of muscle proteins into amino acids and polypeptides, providing a material base for the production of toxins. There is no neutrophil accumulation at the junction of the diseased tissue and the normal tissue. Neutrophil attachment can be seen in the capillaries, arterioles, and postcapillary venules. Subsequently, leukostasis can occur in large vessels. Studies have shown that θ toxin and α toxin concentrated in the infected site destroy local tissues and inflammatory cells. Toxins infiltrating into the peripheral tissue or entering the systemic circulatory system can cause abnormal regulation of adhesion between neutrophils and endothelial cells and up-regulate respiratory burst of leukocytes, leading to intravascular leukostasis, endothelial cell damage, and local tissue hypoxia. Hypoperfusion of the tissue is conducive to the growth of anaerobic bacteria, and the range of lesions of gas gangrene is rapidly expanded. In addition, α toxin can cause severe hemolysis and tissue necrosis. The occurrence of shock is partly related to the direct and indirect effects of toxins. In vitro tests indicate that α toxin can directly inhibit myocardial contractility and can cause hypotension due to a sharp decrease in cardiac output. Under the action of θ toxin, the production of endogenous mediators such as nitrous oxide, lipid secretion, prostacyclin, and platelet activating factor (PAF) increases, which reduces the tension of the blood vessel wall and promotes the occurrence and development of shock. Toxins promote endothelial cell to produce platelet activating factor and promote monocytes to produce tumor necrosis factor (TNF). Experiments have shown that PAF and TNF cause a rapid decrease in vascular tone. In Gram-negative bacterial sepsis, compensatory increase of cardiac output follows a sharp drop in mean arterial pressure. However, these reaction are absent in shock caused by Clostridium perfringens, which may be associated with α toxin in the inhibition of myocardial contractility. Decreased systemic vascular tone and cardiac output can lead to refractory shock.


Signs and Symptoms

The incubation period is 1 - 5 days. Sudden onset is present. Patients have systemic symptoms such as high fever, rapid pulse, tachypnea, anemia, and irritation. Infected areas are predominantly the contaminated wound in the deep muscles. Obvious swelling and distending pain in the wound are present. When pressed, bloody and purulent fluids can be discharged, with gas bubbles. Severe septicemia is present. The necrotizing muscle in the wound is purplish red or dusty grey, and the skin around the wound is grayish white, with or without bullae. Because the pathogen of this disease can produce a lot of gas and toxins, crepitation in the skin lesions is present in palpation, and special odors are present in the wound.


Diagnosis

The diagnosis of this disease mainly depends on clinical manifestations, such as severe pain in traumatic or surgical wounds, systemic toxicity, fever, and gas accumulation in tissues. The bacterial detection in the wound has little significance, as Clostridium is present in more than 80% of traumatic wounds without infection.

Regular X-ray examinations help to detect early gas gangrene. The increased amount of gas, linear gas, or gas expanding along the muscles and fascia suggests the disease.


Treatment

When suspicious symptoms of Clostridium infection are found, immediate and rapid intervention is required. In addition to antibiotic treatment, rapid drainage and debridement are required.

The treatment regimen is penicillin G 30,000 - 40,000U intravenously once every 4 - 6 hours or clindamycin 600 - 900mg intravenously once every 6 - 8 hours. If Gram-negative bacteria are suspected, broad-spectrum antibiotics such as ticarcillin-clavulanate potassium, ampicillin-sulbactam, or piperacillin-tazobactam can be selected. Patients allergic to penicillin can be treated with clindamycin alone or in combination with metronidazole.

Hyperbaric oxygen therapy is effective in the treatment, especially for limb infections, and can be an adjunct treatment other than antibiotics and surgical interventions. Hyperbaric oxygen therapy is also effective against necrosis and can reduce morbidity, but cannot take the place of debridement.


Prognosis

Poor prognosis may be present if without prompt treatment, and severe septicemia can cause death.


Prevention

Wounds down to deep muscles such as the buttocks, thighs, calves, and shoulders, complex fractures, severe crush injuries, and high velocity missile injuries are most susceptible to infections. The most important preventive measure is rapid and thorough debridement and removal of all foreign bodies and necrotizing tissues, and fine hemostasis is also important. Deep irregular wounds must remain open and the wound site should not be wrapped too tightly. Adequate attention should be paid to the blood supply, and inappropriate use of tourniquets or bandages may have adverse consequences and should be avoided. Antitoxins and hyperbaric oxygen therapy have no preventive value. On the contrary, antibacterial drugs have a positive effect in the prevention. Penicillin is the first choice, should be an adjuvant treatment for surgical treatment, and should be used as soon as possible after injury. Chloramphenicol is the second choice.