AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Gas gangrene, a subset of necrotizing myositis, is an infectious disease emergency. Organisms in the spore-forming clostridial species including Clostridium perfringens, Clostridium septicum, and Clostridium novyi cause most of the cases. A nonclostridial form is caused by a mixed infection of aerobic and anaerobic organisms. The hallmarks of this disease are rapid onset of myonecrosis with muscle swelling, severe pain, gas production, and sepsis.

Pathophysiology

Clostridium species are gram-positive, spore-forming, anaerobic rods normally found in soil and the gastrointestinal tract of humans and animals. They most often cause disease in the setting of trauma or surgery but can also occur spontaneously in the absence of definite risk factors or exposures. Not all wounds contaminated with clostridia develop gas gangrene; the myonecrosis seems to only develop when sufficient devitalized tissue is present to support anaerobic metabolism.

Traumatic gas gangrene and surgical gas gangrene occur through direct inoculation of a wound. With a compromised blood supply, the wound has an anaerobic environment that is ideal for C perfringens, the cause of 80-95% of cases of gas gangrene.

Spontaneous gas gangrene is most often caused by hematogenous spread of C septicum from the gastrointestinal tract in patients with colon cancer. The organism enters the blood via a small break in the gastrointestinal mucosa and subsequently seeds muscle tissue. Unlike C perfringens, C septicum is aerotolerant and can infect normal tissues.

With C perfringens the local and systemic manifestations are due to the production of potent extracellular protein toxins by the bacteria. These are most notably alpha-toxin (a phospholipase C) and theta-toxin (a thiol-activated cytolysin). These toxins hydrolyze cell membranes, cause abnormal coagulation leading to microvascular thrombosis, and have direct cardiodepressive effects. Furthermore, the products of tissue breakdown, including creatine phosphokinase, myoglobin, and potassium, cause secondary toxicity.

Frequency

United States

Estimates of incidence of gas gangrene vary; however, cases are relatively rare. Data from 1975 estimate 900-1000 cases per year, or 0.03-5.2% of open wounds, depending on type of wound and treatment.

International

No data are published, but incidence is probably higher internationally than in the United States. Incidence is highest in areas with poor access to proper wound care.

Mortality/Morbidity

• Mortality from traumatic gas gangrene is greater than 25%.
• Mortality from nontraumatic gas gangrene caused by C septicum ranges from 67-100%.

Age

• Occurrence is not age specific.
• Diabetic peripheral vascular disease and other chronic immunocompromised states that can predispose individuals to gas gangrene are more prevalent in older populations.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

• The incubation period is usually less than 24 hours but has been described to be anywhere from 7 hours to 6 weeks, though when symptoms start, clinical deterioration can occur within hours.
• Muscle swelling and severe pain are prominent features. The pain is often out of proportion to physical findings, reflective of the hypoxic state of the muscle tissue, and is a key to distinguishing gas gangrene from simple cellulitis.
• Systemic toxicity may cause altered mental status, and the progression to toxemia and shock can be rapid.

Physical

• Vital signs: Unusually, fever is not a prominent feature of infection and may only be low grade throughout the clinical course. The degree of systemic involvement may produce a spectrum of changes from tachycardia through outright septic shock including hypotension and diaphoresis.
• Overlying skin: Initially, it may be normal and then progress through a yellowing or bronzing of the skin to bulla formation to patches of green/blue/grey/black necrosis. Serosanguineous drainage may be present, described classically as having a “mousy” or slightly sweet odor.
• Extremity examination: Most notable is extreme pain of the affected area with or without movement and with palpation, which may be out of proportion to the extent of the overlying skin changes. Tense edema with crepitance due to subcutaneous air may be noted and is proportional to the extent of underlying necrosis.
• Vascular examination: Distal pulses may be normal or diminished depending on the extent of local damage.
• Neurologic examination: Decreased pain or anesthesia at the site of infection can indicate that cutaneous nerve endings are being destroyed and that the disease is advanced.

Causes

• Risk factors for gas gangrene
• • Atherosclerosis
  • Burns
  • Chronic alcoholism
  • Corticosteroid use
  • Diabetes
  • Gastrointestinal malignancy
  • Hypoalbuminemia
  • Intravenous drug abuse
  • Malnutrition
  • Obesity
  • Peripheral vascular disease
  • Surgery
  • Trauma

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Other causes of necrotizing myositis (group A streptococci, polymicrobial aerobic-anaerobic flora, and nonclostridial anaerobes)
Cutaneous anthrax
Vaccinia vaccination
Acute gout
Septic arthritis
Familial Mediterranean fever
Fixed drug reaction
Pyoderma gangrenosa
Sweet syndrome
Wells syndrome
Carcinoma erysipeloides
Pyomyositis
Water-borne skin infections (Vibrio vulnificus, Aeromonas hydrophila, Mycobacterium marinum)
Other causes of soft tissue gas (eg, pneumomediastinum, pneumothorax, fractured larynx, fractured trachea)

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• Gram stain and culture of bullae fluid: The presence of gram-positive rods with few white blood cells is indicative of clostridial etiology, while the presence of many white cells is more suggestive of a mixed bacterial infection. While this information can be helpful, simple superficial wound swabs should not be obtained. Microorganisms that colonize the skin surface often do not contribute to the underlying infection.
• Complete blood count: CBC may reveal anemia, thrombocytopenia, and evidence of intravascular hemolysis on smear from destruction by the toxins.
• Electrolyte level: Hyperkalemia can result from cell breakdown. Hypocalcemia may result from subcutaneous fat necrosis.
• Renal panel: Kidney dysfunction may occur secondary to hypotension, hemoglobinuria, and myoglobinuria.
• Coagulation panel: Coagulopathy and thrombocytopenia can result.
• Liver function tests: Hyperbilirubinemia and liver dysfunction may result from release of toxins.
• Arterial blood gas determination: Gas gangrene can cause metabolic acidosis.
• Myoglobin level: Myoglobinemia and myoglobinuria can result from cellular breakdown.
• Blood cultures: This may help narrow antibiotic coverage.

Imaging Studies

• Gas in the soft tissues is neither sensitive nor specific for gas gangrene. Many different bacteria, trauma, and visceral perforation can cause soft tissue gas. Plain radiographs or ultrasonography can be used to look for the presence of gas.
• Computed tomography or magnetic resonance imaging can help to evaluate the depth of soft tissue inflammation.

Procedures

• Tissue biopsy is the criterion standard in helping make the diagnosis of gas gangrene.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Prehospital Care

• Oxygenation
• Intravenous (IV) fluids

Emergency Department Care

Gas gangrene is a true emergency, and concurrent evaluation, treatment, and coordination of care should be carried out.

Generally speaking, the treatment is a combination of antibiotics, surgery, and hyperbaric oxygen.

• Airway and breathing: Oxygen and airway management as necessitated by the clinical picture.
• Circulation: Good vascular access and liberal use of intravenous fluids is indicated. Frequent reassessment of the circulatory status is necessary. If pressors are necessitated, vasoconstrictors should only be used if absolutely necessary; they can decrease perfusion to already ischemic tissue.
• Administer tetanus toxoid if indicated.
• Administer antibiotics.
• Correct electrolyte abnormalities.
• Check compartment pressures if severe pain and evidence of compartment syndrome are present with minimal cutaneous evidence of infection.

Consultations

• Surgery
• • Obtain immediate surgical consultation.
  • Definitive treatment of gas gangrene is wide debridement of necrotic muscle. This is identifiable because it does not bleed or contract when debrided.
  • While laboratory studies and imaging studies may help make the diagnosis of gas gangrene, the criterion standard is tissue biopsy.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Antibiotics may not penetrate the ischemic muscle but are important adjuncts to surgery.

Drug Category: Antibiotics

Clostridial species are exquisitely sensitive to a combination of penicillin G and clindamycin. However, because it is difficult initially to distinguish gas gangrene from other soft tissue infections, such as necrotizing fasciitis, which is caused by a broad spectrum of pathogens, empiric first-line antibiotic therapy should be broad.

Antibiotic treatment should include gram-positive (penicillin or cephalosporin), gram-negative (aminoglycoside, third-generation cephalosporin, or ciprofloxacin), and anaerobic coverage (clindamycin or metronidazole). In addition, vancomycin or linezolid should be considered in those at risk for methicillin-resistant Staphylococcus aureus (MRSA). In some communities, MRSA infections are now being isolated even in those without risk factors (8-25%); the risk factors traditionally associated with MRSA are a history of hospitalization, surgery, dialysis, residence in a long-term care facility, presence of a permanent indwelling catheter or percutaneous medical device (eg, tracheostomy tube, gastrostomy tube, Foley catheter), or previous isolation of MRSA.

Antibiotics should be administered IV since absorption by other routes is inconsistent given the hypotension and suboptimally performing gastrointestinal tract of seriously ill patients.

Drug Category: Medicinal gas

Hyperbaric oxygen (HBO) produces a tissue level of 300 mm Hg of oxygen. This is approximately 50 mm Hg greater than the partial pressure necessary to induce bacteriostasis and halt toxin production. This then decreases the extent of debridement and possible amputation needed to control infection.

Drug Category: Toxoids

Toxoids are used to induce active immunity.

Drug Category: Immunoglobulins

Immunoglobulins are used to induce passive immunity.

Drug Category: Analgesics

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who have sustained trauma or have sustained injuries.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• Urgent surgical debridement may be indicated.
• Admit the patient to an ICU with invasive monitoring as necessary.

In/Out Patient Meds

• Inpatient medications include intravenous antibiotics and analgesics.

Transfer

• Transfer the patient if appropriate surgical specialist and ICU setting are unavailable.

Deterrence/Prevention

• Appropriate wound care at time of injury (eg, debridement of crushed or dead tissue, copious irrigation) may deter infection.
• Prophylactic antibiotics may prevent subsequent infection in selected circumstances.

Complications

• Disease may progress rapidly; patients often become septic.

Prognosis

• Early diagnosis and aggressive treatment are the keys to decreasing mortality.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Gas gangrene and necrotizing myositis in general can present with very subtle signs early in its course. A high index of suspicion is necessary to avoid catastrophes. Once the diagnosis is established, timely intervention with aggressive resuscitation, appropriate antibiotics, and surgical intervention is indicated.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Wende R Reenstra-Buras, MD, PhD, and N Ewen Wang, MD, for the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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• Miller LG, Perdreau-Remington F, Rieg G, Mehdi S, Perlroth J, Bayer AS, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med. Apr 7 2005;352(14):1445-53. [Medline].
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• Smith-Slatas CL, Bourque M, Salazar JC. Clostridium septicum infections in children: a case report and review of the literature. Pediatrics. Apr 2006;117(4):e796-805. [Medline].
• Stevens DL. The pathogenesis of clostridial myonecrosis. Int J Med Microbiol. Oct 2000;290(4-5):497-502. [Medline].
• Swartz MN. Clinical practice. Cellulitis. N Engl J Med. Feb 26 2004;350(9):904-12. [Medline].
• Temple AM, Thomas NJ. Gas gangrene secondary to Clostridium perfringens in pediatric oncology patients. Pediatr Emerg Care. Jul 2004;20(7):457-9. [Medline].
• Trott AT. Skin and Soft-tissue Infections. In: Wolfson AB, et al, eds. Harwood-Nuss' Clinical Practice of Emergency Medicine. 4th. Lippincott Williams & Wilkins; 2005:715-717.
• Wang C, Schwaitzberg S, Berliner E, Zarin DA, Lau J. Hyperbaric oxygen for treating wounds: a systematic review of the literature. Arch Surg. Mar 2003;138(3):272-9; discussion 280. [Medline].

Article Last Updated: Dec 4, 2007