Gas Gangrene or Clostridial Myonecrosis

Last Updated on October 28, 2023

Gas gangrene is a necrotizing soft tissue infection that affects skeletal muscle. It is also called clostridial myonecrosis and is  is typically caused by Clostridum baceteria, most commonly Clostridium perfringens, Clostridium septicum, and Clostridium novyi.

It is an opportunistic infection that is spreads extremely fast and is lethal.

Clostridium is a genus of anaerobic, gram positive bacteria. Clostridium use anaerobic fermentation to produce hydrogen gas and carbon dioxide, creating the gas in the blisters that are symptomatic of gas gangrene.

80-90% of gas gangrene cases are caused by Clostridium perfringens.

Other bacteria are also capable of producing gas, and nonclostridial organisms  causing gas gangrene are aerobic gram-negative bacteria like Escherichia coli,Proteus species, Pseudomonas aeruginosa, and Klebsiella pneumoniae.

Untreated clostridial myonecrosis almost always results in death.

Advanced age and comorbid conditions are associated with a higher likelihood of mortality.

Pathophysiology of Gas Gangrene

C perfringens is the most common agent that causes gas gangrene. Other common clostridial species that cause gas gangrene include Clostridium bifermentans, Clostridium septicum, Clostridium sporogenes, Clostridium novyi, Clostridium fallax, Clostridium histolyticum, and Clostridium tertium.

Clostridium species can be found in environments ranging from the human gastrointestinal tract to soil.

The infection occurs when open or traumatic wounds are exposed to these bacteria and subsequently become contaminated with spores or vegetative cells.

After infection, incubation of Clostridium can range from one hour to many weeks.

Local wound conditions are more important than the degree of clostridial contamination in the development of gas gangrene.

Disrupted or necrotic tissue provides the necessary enzymes and a low oxidation/reduction potential, allowing for spore germination.

Spread of infection occur by rapid multiplication of bacteriae and secretion of  exotoxins such as lecithinase, collagenase, hyaluronidase, hemagglutinin and hemolysins into the surrounding tissue.

Necrosis of muscle and subcutaneous fat and thrombosis of blood vessels occurs. Marked edema may further compromise blood supply to the region.

Fermentation of glucose leads to gas production in gas gangrene. The exact composition of gas varies in different species.

These local effects further  create an environment that facilitates rapid spread of the infection. ^[13]

Systemically, exotoxins may cause severe hemolysis. Hemoglobin levels may drop to very low levels and, when occurring with hypotension, may cause acute tubular necrosis and renal failure. A rapidly progressive infection can quickly result in shock. The mechanism of shock is poorly understood. Unconcentrated filtrate from C perfringens, purified alpha-toxin, and purified phi-toxins cause hypotension, bradycardia, and decreased cardiac output when injected into laboratory animals. Because alpha-toxins and phi-toxins are lipophilic and may remain locally bound to tissue plasma membranes, the toxins may stimulate synthesis of secondary mediators that cause cardiovascular abnormalities.

Infections are typically characterized with very little host response to Clostridium. Immune response is in reaction to exotoxins produced by Clostridium rather than actual bacterium.

There is usually no pus created during infection.

The exact reason as to why there is poor immune response is not exactly known.

It is worth noting that about 90% of contaminated traumatic wounds exhibit Clostridium culture but less than 2% develop myonecrosis, probably related necessity of anerobic enviroment for the bacteria.

Myonecrosis can also occur without an open wound if blood flow to tissues is reduced. This can occur in people who have vascular disease affecting blood flow to extremities (such as diabetes mellitus or atherosclerosis).

Bacterial Toxins and Cell Damage

Clostridium perfringens produces more than twelve disease-causing toxins, out of which at least eight of the are thought to be lethal.

The major toxins of Clostridium perfringens are alpha, beta, epsilon, and iota.

Alpha-toxin has three important roles

• Eevade leukocytes
• Daamge to the vascular system [causes reduction in blood supply]
• Changes host cell metabolism by activating protein kinase C and arachidonic acid cascade

Alpha-toxin and  beta-toxin releases arachidonic acid and produce transmembrane pores in cells and have hemolytic activity.

Delta-toxin is also a hemolytic toxin that bind to the GM2 ganglioside on erythrocytes.

Kappa-toxin digests collagen in connective tissues, breaking down skeletal muscle.

Epsilon-toxin is a toxin that forms pore leading to leakage of red blood cells and serum proteins.

Iota-toxin is a binary toxin that performs ADP-ribosylation of actin.

Theta toxin is also known as perfringolysin O t is a pore-forming chlosterol-dependent cytolysin and acts synergistically with the alpha-toxin. 

Causes of Gas Gangrene

Gas gangrene can be classified as posttraumatic, postoperative, or spontaneous.

Posttraumatic gas gangrene

Posttraumatic gas gangrene accounts for 60% of all gas gangrene cases. [Historically warfare was the main cause]

Most of these cases involve automobile collisions.

Crush injuries, compound fractures, gunshot wounds, thermal or electrical burns, and frostbite are other main cause.

Farm or industrial injuries contaminated with soil are very prone to developing gas gangrene.

Intramuscular or subcutaneous injections with insulin, epinephrine, quinine, heroin or cocaine are rare antecedent events leading to gas gangrene.

Postoperative clostridial infections

Postoperative clostridial infections  have been mostly reported in cases of colon resection, ruptured appendix, bowel perforation,  biliary or other gastrointestinal surgery, including laparoscopic cholecystectomy and colonoscopy. It has also been reported following liposuction procedures. 

Septic back-street abortions are the main cause of uterine gas gangrene.

Spontaneous gas gangrene

It occurs without any external wound or injury

It generally occurs in patients who have serious underlying conditions.

Major risk factors are

• Colorectal adenocarcinoma
• Hematologic malignancy
• Neutropenia in children
• Diabetes
• Neutropenic colitis

In many cases, no predisposing condition can be found.

Patients with C septicum infections have overt or occult malignancies approximately 5 times more often than patients with other clostridial infections.

Clinical Presentation

Gas gangrene is a very aggressive infection and requires immediate recognition and aggressive treatment.

Extremities are most commonly affected and symptoms  develop six to forty-eight hours after initial infection of Clostridium, sudden and severe pain at the site of infection being the first.

Except for patients with occult malignancy, there would be an associated wound, either from trauma or surgery.

Pain disproptionate to wound is the usual first complaint.  The pain gradually worsens and spreads as the underlying infection spreads.

Body temperature is initially within normal range but quickly rises soon after. Skin surrounding the infection site is initially tight and bronze shiny but then quickly becomes greyish and then dark. Muscles are dark red, black, or green and do not contract or bleed. A sickly sweet odor is often present. Necrosis can spread as quickly as 6 inches per hour. Shock and death can occur within 12 hours.

Other than fever, vomiting, tachycardia and increased sweating may be present.

Within hours, the entire region may become markedly edematous and crepitus may be present on examination.

Dispropotionate tenderness would be present.

Late signs of gas gangrene include hypotension, renal failure, and a paradoxical heightening of mental acuity.

Differential Diagnoses

• Emphysematous Cholecystitis
• Group A Streptococcal (GAS) Infections
• Septic Shock
• Toxic Shock Syndrome
• Vibrio Infections

Diagnostic Work Up

Lab Studies

Studies show

• Rapidly developing hemolytic anemia
• Increased lactate dehydrogenase (LDH)
• Leucocytosis is not generally present [ C sordellii or C septicum may cause toxic shock syndrome causing hemoconcentration  and extreme leukocytosis.]
• Gram stain of the exudate or infected tissues
  • Shows box-car, large gram-positive bacilli without neutrophils.
• Metabolic abnormalities like metabolic acidosis and renal failure.
• ELISA
  • Rapid detection of alpha-toxin or sialidases (ie, neuraminidases) as early as 2 hours
  • Not widely available
  • Potential diagnostic tool
• PCR
  • Not yet used in clinical practice
  • Has been used to isolate clostridial species.

Imaging

Typical feathering pattern of gas in soft tissue  may be visible in x-rays but is not always present.

CT scanning is helpful in abdominal cases of gas gangrene.

MRI is less sensitive, time-consuming and hence not preferred.

Surgical Exploration

Surgical exploration confirms the diagnosis of myonecrosis. Affected muscle appears pale and shows no contractile function when incised or electrically stimulated.

The threshold for operative exploration should be very low if the diagnosis is under consideration as disease is very morbid and fatal.

Laboratory Risk Indicator for Necrotizing Fasciitis Scoring System (LRINEC)

This score is based on routine lab parameters and can be used as a screening tool to distinguish necrotizing fasciitis from other soft tissue infections rapidly and accurately.

A score

• > 6 – Consider diagnosis of necrotizing fasciitis
• >8 –  Highly suggestive of necrotizing fasciitis

But it must be kept in mind that none of the parameters in LRINEC is specific for necrotizing fasciitis and all can be abnormal in any inflammatory condition or infection.

Laboratory Risk Indicators for Necrotizing Fasciitis or the LRINEC score
Variable	Score
C-reactive protein level
<150 mg/L	0
≥150 mg/L	4
Total WBC count
<15 cells/µL	0
15-25 cells/µL	1
>25 cells/µL	2
Sodium level
≥135 mmol/L	0
<135 mmol/L	2
Hemoglobin level
>13.5 g/dL	0
11-13.5 g/dL	1
<13.5 g/dL	2
Creatinine level
≤ 141 mmol/L	0
>141 mmol/L	2
Glucose level
≤10 mmol/L	0
>10 mmol/L	1

Treatment of Gas Gangrene

Antibiotics and aggressive surgical debridement  are mainstay of the therapy.

A combination of penicillin and clindamycin is used. Clindamycin and other protein synthesis inhibitors like chloramphenicol, rifampin, tetracycline inhibit the synthesis of clostridial exotoxins

In case the patient is allergic to penicillin, a combination of clindamycin and metronidazole is a good choice.

However a combination of penicillin and metronidazole is antagonistic and is not recommended.

Additional antibiotic coverage is indicated for nonclostridial bacteriae frequently found in gas gangrene tissue cultures

Patients frequently require intensive supportive care due to end-organ failure and other concomitant serious medical conditions.

Serum calcium monitoring should be done when large areas of necrotic fat may lead to its deposition.

Worsening Signs

Suggestive of toxic shock syndrome and/or tissue necrosis despite medical treatment.

• WBC counts > 25,000/µL or <4,000/µL
• Band cells [immature WBCs] >10% independent of the total WBC count
• Hb<11 mg/dL
• Massive hemoconcentration (hematocrit >45%)
• Thrombocytopenia due to disseminated intravascular coagulopathy (DIC)
• Serum sodium > 135 mEq/L
• Creatinine> 1.6 mg/dL
• Glucose level> 180 mg/dL
• Anion gap metabolic acidosis
• Bicarbonate level less than 15 mg/dL
• Lactic acid level more than 2.2 mmol/L

Systemic signs of severe sepsis include the following:

• Septic shock
• Adult respiratory distress syndrome
• Disseminated intravascular coagulation
• Hemolysis

Surgery

Debridement of all wounds should be performed as soon as possible.

Debridement removes damaged, contaminated, and necrotic tissue. Sutured wounds should be reopened and cleaned.

Debridements may be required to be done daily.

Amputation of the extremity may be necessary and life saving. Abdominal involvement requires excision of the body wall musculature.

Uterine gas gangrene following septic abortion usually requires hysterectomy. But it could be a difficult decision in nulliparous woman and should be considered for

• Failure to respond to antibiotics within first 24 hours
• Rapid deterioration of clinical status despite medical therapy
• Evidence of necrotizing soft tissue infection
• Intraabdominal or pelvic fluid collection [suggestive of suggestive of abscess collection]
• Evidence of gas within the uterine myometrial tissue

Complications

• Massive hemolysis leading to severe anemia
• Disseminated intravascular coagulation
• Surgical debridement
• Acute renal failure
• Acute respiratory distress syndrome
• Shock
• Sepsis

Prognosis

Following factors are associated with better prognosis

• Incubation period < 30 hours
• Limb involvement
• Absence of serious medical conditions
• Disease without complications

Spontaneous gas gangrene frequently carries a much worse prognosis than other forms of gas gangrene.

A clinical algorithm was designed to categorize necrotizing soft tissue infections (NSTI) to predict the risk of unfavorable outcomes. The clinical score is based on six admission parameters.

Clinical Score Predictive of Death for Patients with Necrotizing Soft Tissue Infections

Variable on Admission	Points
Heart rate >110 bpm	1
Temperature <36°C	1
Serum creatinine level >1.5 mg/dL	1
Age >50 years	3
WBC count >40,000/µL	3
Hematocrit >50%	3

Risk of death is calculated as

Group category	Number of points	Mortality risk (%)
1	0-2	6
2	3-5	24
3	≥6	88

 

Untreated clostridial myonecrosis carries a 100% fatality rate. Treated myonecrosis has a mortality rate of 20-30%.

Spontaneous cases have a mortality rate between 67-100%.

Infections in the trunk of the body have a higher mortality rate than extremities such as arms or legs.

 

References

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