Gangrene and Necrotising Soft Tissue Infection

Introduction and classification

Gangrene is death of macroscopic tissue, and the clinically useful classification is by whether infection is present, because that single question determines whether the patient can be planned for an elective operation next week or needs to be in theatre within the hour.

Fournier gangrene is necrotising fasciitis of the perineum, scrotum and perianal region, and deserves separate mention because it is frequently the presentation of an unrecognised anorectal or urological source in a diabetic patient.

Aetiology and risk factors

Causes of ischaemic necrosis

• Peripheral arterial disease with chronic limb-threatening ischaemia - the commonest cause of dry gangrene in UK practice
• Acute limb ischaemia from embolus or thrombosis
• Diabetes mellitus, through the combination of distal arterial disease, neuropathy that hides injury, and impaired immunity
• Vasculitis, scleroderma and Raynaud phenomenon with critical digital ischaemia
• Frostbite and burns
• Ergotism, and vasopressor-induced peripheral ischaemia in the critically ill
• Compartment syndrome and crush injury
• Meningococcal septicaemia with purpura fulminans, particularly in children

Factors predisposing to infective necrosis

• Diabetes mellitus - the single most consistent association across necrotising infections and Fournier gangrene
• Immunosuppression - corticosteroids, chemotherapy, HIV, malignancy, neutropenia
• Intravenous drug use, particularly with skin popping or contaminated injection
• Trauma and surgery, especially with contaminated or devitalised tissue
• Obesity, alcohol excess, malnutrition and chronic kidney disease
• Peripheral vascular disease and chronic venous ulceration
• Recent varicella infection or NSAID use in children - a recognised association with group A streptococcal necrotising fasciitis

Clinical features

Dry gangrene

• Progression from pallor to dusky blue to black, over days or weeks
• Dry, shrivelled, mummified tissue which is cold and hard
• A sharp line of demarcation between dead and living tissue, which becomes clearer over time
• Preceding rest pain, which often diminishes once the nerves have died
• Absent pulses and other signs of chronic ischaemia - hair loss, shiny skin, thickened nails
• No swelling, no crepitus, no discharge and no systemic upset

Wet gangrene

• Swelling, blistering and a boggy texture, with skin that is discoloured rather than uniformly black
• Foul, putrid discharge and a distinctive smell
• Poorly demarcated, spreading erythema with surrounding cellulitis and lymphangitis
• Systemic sepsis - fever, tachycardia, hypotension and confusion
• Rapid progression over hours, in contrast to the indolent course of dry gangrene

Necrotising fasciitis and gas gangrene

In gas gangrene specifically, the incubation period after a contaminated wound is short - often less than 24 hours. The affected muscle is initially pale and non-contractile, later becoming brick red and then black, and does not bleed when cut. The classic thin, brown, sweet-smelling watery discharge, sometimes described as dishwater fluid, is distinct from the frank pus of an abscess.

Investigations

In suspected necrotising infection, investigations run alongside resuscitation and must never delay surgical exploration.

• FBC - marked leucocytosis, or leucopenia in overwhelming sepsis; anaemia and thrombocytopenia
• U&Es, creatinine, glucose and HbA1c - acute kidney injury is common, and undiagnosed diabetes is frequently found
• CRP - usually very high in necrotising infection
• Creatine kinase - raised in myonecrosis and a useful marker of muscle involvement
• Venous or arterial gas with lactate, and a clotting screen
• Blood cultures and deep tissue cultures taken at operation. Superficial swabs are unhelpful and may mislead.
• Plain radiograph - may show soft tissue gas, but is normal in most cases of necrotising fasciitis
• CT or MRI - shows fascial thickening, fluid tracking along fascial planes and gas. Useful only in the patient who is stable and where the diagnosis is genuinely uncertain; never as a reason to delay theatre.
• ABPI, duplex ultrasound and CT angiography where the underlying problem is arterial, to assess whether revascularisation is possible before deciding an amputation level

Management

Dry gangrene

The tissue is already dead, so the questions are whether the perfusion of the remaining limb can be improved and where to draw the line.

1. Assess and treat the arterial supply. Urgent vascular referral with duplex and angiography, and revascularisation by angioplasty or bypass wherever feasible, since a better inflow may allow a more distal amputation or none at all.
2. Analgesia, which is often substantial and may need neuropathic agents
3. Meticulous wound care and offloading, keeping the tissue dry and protected, with specialist podiatry and tissue viability involvement
4. Antibiotics are not indicated for uninfected dry gangrene, and reflex prescribing simply selects resistant organisms. Treat promptly if it becomes wet.
5. Amputation at a viable level once demarcation is established and perfusion is optimised. Auto-amputation, in which a mummified digit separates spontaneously, is an acceptable strategy for a single toe in a patient unfit for surgery.
6. Secondary prevention - smoking cessation, statin, antiplatelet, glycaemic control - and referral to the multidisciplinary diabetic foot service with a documented foot protection plan³
7. Rehabilitation planning from the outset where a major amputation is likely, involving physiotherapy, occupational therapy and the prosthetics service

Wet gangrene, gas gangrene and necrotising fasciitis

These are managed identically in principle, because the principle is source control. Antibiotics cannot penetrate tissue whose blood supply has thrombosed, which is precisely what has happened in the affected fascia and muscle, so surgery is the treatment and antibiotics are the adjunct.²

1. A to E assessment with aggressive fluid resuscitation, and immediate critical care involvement. These patients need substantial volumes and often vasopressor support.
2. Blood cultures, then broad-spectrum intravenous antibiotics within the hour - typically a carbapenem or piperacillin-tazobactam plus clindamycin, following local microbiology policy and with early microbiology advice
3. Clindamycin is given specifically for its antitoxin effect, suppressing streptococcal and clostridial exotoxin production by inhibiting protein synthesis. It works even against organisms in stationary phase, when beta-lactams are least effective.
4. Immediate radical surgical debridement, removing all necrotic tissue back to healthy bleeding tissue. This is the intervention that determines survival, and delay of even a few hours measurably increases mortality.
5. Mark the extent of erythema with a pen and record the time, so that progression can be judged objectively
6. Planned relook and repeat debridement at 24 to 48 hours, and often several times. The initial operation is rarely the last.
7. Amputation where a limb cannot be salvaged or sepsis cannot otherwise be controlled
8. Supportive care - organ support, glycaemic control, nutrition, and later reconstruction with skin grafting or flaps
9. Intravenous immunoglobulin is used in some centres for streptococcal toxic shock syndrome, and hyperbaric oxygen for clostridial myonecrosis. Both are adjuncts with limited evidence and neither should ever delay debridement.

Complications

• Septic shock and multi-organ failure, the commonest cause of death in wet and necrotising disease
• Streptococcal toxic shock syndrome, with a diffuse erythroderma, hypotension and rapid multi-organ failure
• Extensive tissue loss requiring repeated debridement, grafting and reconstruction
• Limb loss, with the associated mortality, mobility and psychological consequences
• Acute kidney injury from sepsis, hypoperfusion, rhabdomyolysis and nephrotoxic antibiotics
• Osteomyelitis underlying a chronic diabetic foot ulcer, which requires prolonged treatment or resection
• Phantom limb pain and stump complications - neuroma, infection, breakdown and poor prosthetic fit
• Contralateral limb loss - having lost one limb to arterial disease, the risk to the other is substantial, and around half of major amputees have a further amputation within five years

Red flags

Prognosis

Dry gangrene in an otherwise stable patient has a good short-term prognosis, and where revascularisation is successful a limited digital amputation may be all that is required. The longer-term outlook is dominated by the underlying arterial disease and the associated cardiovascular mortality.

Necrotising soft tissue infection is a different matter. Mortality remains around 20 to 30% overall, higher in Fournier gangrene and in patients with septic shock at presentation, and the two strongest determinants are time to first debridement and the adequacy of that debridement. Delay beyond 12 to 24 hours roughly doubles mortality in most series.

The lesson is uncomfortable but simple. There is no investigation that reliably excludes necrotising infection, and a patient with severe pain, systemic toxicity and unimpressive skin is exactly the patient in whom the diagnosis is missed. The correct response to genuine clinical suspicion is a surgical exploration that may turn out to be negative, and a negative exploration in this setting is a good outcome rather than an error.