What are the management strategies for late-stage frostbite (also known as frostbite with gangrene or deep tissue injury)?

From the Guidelines

Late-stage frostbite management requires immediate medical attention in a hospital setting, with treatment beginning with rapid rewarming of the affected tissue in circulating water at 37-40°C (98.6-104.0°F) for 20-30 minutes until the skin becomes soft and pliable, as recommended by the 2024 American Heart Association and American Red Cross guidelines for first aid 1. The rewarming process should be done with caution to avoid refreezing, and pain control is essential during this process, typically with opioid medications like morphine or hydromorphone. After rewarming, treatment includes:

• Tetanus prophylaxis
• Ibuprofen (400mg every 12 hours) to inhibit harmful prostaglandins, as recommended by many experts and included in many treatment guidelines, although direct clinical evidence is lacking 2
• Antibiotics such as cefazolin (1g IV every 8 hours) if infection is suspected
• Topical aloe vera may be applied to affected areas
• The limb should be elevated with loose, dry bandages between digits to prevent maceration
• Blisters should be left intact, particularly blood-filled ones which indicate deeper tissue damage For severe cases, thrombolytic therapy with tissue plasminogen activator (tPA) may be considered within 24 hours of injury to improve tissue perfusion. Daily hydrotherapy and physical therapy help maintain function. Surgical debridement or amputation is delayed for 1-3 months until clear demarcation between viable and non-viable tissue occurs, as tissue that initially appears dead may recover, and this conservative approach to surgical intervention is crucial because premature amputation can result in unnecessary loss of viable tissue. It is also important to remove constricting items such as jewelry and tight clothing to prevent further tissue damage, as recommended by the 2024 American Heart Association and American Red Cross guidelines for first aid 3.

From the FDA Drug Label

The efficacy of intravenous (IV) iloprost for the treatment of severe frostbite to reduce the risk of digit amputations is derived from a published open-label, randomized controlled trial that enrolled patients with severe frostbite (Cauchy et al, 2011; Cheguillaume, 2011) The trial randomized 47 patients at a single site between 1996 and 2008 At enrollment, all eligible patients (n=47) were treated with rapid rewarming of areas with frostbite, aspirin 250 mg IV, and buflomedil 400 mg IV and then randomized to Groups A, B or C. All patients continued to receive aspirin 250 mg IV daily up to 8 days In addition, Group A (n=15) received buflomedil 400 mg IV for up to 8 days, Group B (n=16) received iloprost IV for 6 hours daily for up to 8 days, and Group C (n=16) received recombinant tissue plasminogen activator IV on Day 1 and iloprost IV for 6 hours daily for up to 8 days

The management strategies for late-stage frostbite (also known as frostbite with gangrene or deep tissue injury) include:

• Rapid rewarming of areas with frostbite
• Aspirin 250 mg IV daily up to 8 days
• Iloprost IV for 6 hours daily for up to 8 days
• Recombinant tissue plasminogen activator IV on Day 1 (in combination with iloprost) 4

From the Research

Management Strategies for Late-Stage Frostbite

The management of late-stage frostbite, also known as frostbite with gangrene or deep tissue injury, involves several strategies to reduce morbidity and mortality.

• Initial care includes protection of the extremity from trauma or partial thawing 5.
• Rapid rewarming in a warm water bath at 104 degrees to 107.6 degrees F (40 degrees to 42 degrees C) for 15 to 30 minutes is recommended 6, 7.
• Débridement of necrotic tissues is generally delayed until there is a clear demarcation from viable tissues, a process that usually takes from 1 to 3 months from the time of initial exposure 6.
• Immediate escharotomy and/or fasciotomy is necessary when circulation is compromised 6.
• Thrombolytic therapy (tPA) and prostacyclin are most effective if used within the first day after tissue rewarming 8, 9.
• With deep frostbite and late medical care, surgical treatment is fundamental, including amputation and debridement after the formation of the demarcation line 9.
• To replace soft tissue defects that extend beyond the fingers, it is preferable to use fasciocutaneous flaps 9.
• Timely diagnosis and complex treatment are the defining moments in the treatment of deep frostbite 9.

Medical Interventions

Several medical interventions have been proposed for the treatment of frostbite injuries, including:

• Hyperbaric oxygen therapy 8
• Sympathectomy (nerve block) 8
• Thrombolytic (blood-thinning) therapy 8
• Vasodilating agents such as iloprost, reserpine, pentoxifylline, and buflomedil 8
• Iloprost and iloprost plus rtPA may reduce the rate of amputations in people with severe frostbite compared to buflomedil alone 8