Frostbite

Etiology

Direct tissue exposure to freezing conditions causes frostbite. Longer exposure and lower subfreezing temperatures increase the likelihood and severity of injury. Certain preexisting conditions may worsen tissue injury, including peripheral vascular disease, malnutrition, Raynaud phenomenon, diabetes mellitus, and tobacco use.[1][2] Freezing occurs when inadequate tissue perfusion cannot compensate for heat loss.[1] 

Risk factors for frostbite include: 

• Winter season
• Lack of shelter or inadequate protection from the cold
• High wind chill factor
• High-altitude exposure
• Prolonged duration of exposure
• Prolonged exposure to wet conditions
• Altered mental status
• Mental health disorders
• Alcohol or substance use disorder
• Current tobacco use
• Malnutrition
• Immobilization
• Extremes of age
• Homelessness
• Comorbid conditions such as diabetes mellitus, hypothyroidism, peripheral vascular disease, stroke, or arthritis [3][4]

Epidemiology

Historically, frostbite injuries were common among military personnel and individuals exposed to high altitudes; however, contemporary cases occur among recreational athletes, outdoor workers, and vulnerable populations. Unhoused individuals, children, and older adults are especially vulnerable to frostbite. Risk factors include behavioral factors (alcohol or substance use and inadequate clothing or access to shelter), physiological factors (dehydration, high altitude, and hypoxia), and comorbid conditions that predispose tissues to hypoxia, including diabetes, peripheral vascular disease, and Raynaud phenomenon.[5] Populations in regions not typically associated with freezing temperatures are also at risk due to infrastructure challenges, delayed recognition, and social vulnerability.[6]

Pathophysiology

Normal skin blood flow is approximately 250 mL/min, but during frostbite, cutaneous vasoconstriction reduces it to approximately 20 to 50 mL/min. When the temperature falls below 0 °C (<32 °F), blood flow can cease, leading to necrosis and gangrene.[7][8] Distal extremities, digits, and exposed areas with reduced perfusion and insulation, including the nose, ears, cheeks, and chin, are at the highest risk of frostbite.

Decreasing temperatures in exposed skin can cause endothelial cell damage and localized edema in the affected extremity. Initial tissue cooling causes vasoconstriction and a progressive reduction in blood flow. Extracellular ice crystal formation increases osmotic gradients, promotes cellular dehydration, and disrupts membrane function. Continued exposure leads to endothelial injury, edema, hemoconcentration, microvascular stasis, thrombosis, and tissue ischemia.[2][9][10][11][12] If cooling is halted during the early prefreeze phase (before ice crystal formation), permanent damage may be avoided; once the freeze-thaw injury cascade begins, deeper injury is often irreversible.[2]

Frostbite causes injury in the following ways:

• Direct freezing damage to the tissues
• Indirect damage caused by dehydration
• Formation of ice crystals leading to alterations in electrolyte concentrations and lipid layers
• Microvascular stasis leading to thrombosis and ischemia
• Reperfusion injury

Histopathology

Initially, extracellular ice crystals form in exposed tissue. Continued cold exposure can cause intracellular ice crystals to form. The resulting cell membrane damage causes electrolyte imbalances. As the transmembrane osmolarity gradient increases, cell membranes can rupture, resulting in cell death. During tissue thawing, a reperfusion-associated inflammatory response mediated by proinflammatory cytokines may cause additional tissue damage. Moreover, repeated thaw-refreeze cycles can progressively worsen tissue ischemia and promote subsequent thrombosis.[1]

History and Physical

A patient history should include external temperatures, duration of exposure, exposure to moisture and wind, and any attempts at thawing. The events surrounding the injury should also be clearly documented, including the medical and socioeconomic risk factors listed above. Physical examination can reveal a range of presentations from erythema and edema to gangrene. See the Staging section below for findings associated with each staging system.

Patients may report heaviness in an exposed extremity as numbness progresses. In the later stages of frostbite, exposed areas may become dark or purplish due to poor vascular tone and blood pooling. Superficial frostbite, involving the epidermis and superficial dermis, typically produces clear or milky cloudy blisters upon rewarming.

Deep, full-thickness frostbite causes hemorrhagic blistering with rewarming and may progress to gangrene.[9] The demarcation between viable and injured skin becomes well-defined over the following days to months, depending on the depth of the injury. Notably, the initial examination does not accurately reflect the extent of injury.

During rewarming, frostbite injuries evolve over hours to weeks. Edema typically develops after thawing and may persist for several days. Blisters typically form within the first 24 to 48 hours. In severe frostbite, progressive ischemia and necrosis lead to eschar formation over the following days to weeks, and mummification with a visible line of demarcation can develop over 1 to 3 months.

Evaluation

Frostbite is a clinical diagnosis based primarily on the patient history and physical examination. Imaging with technetium-99m triple-phase bone scanning, magnetic resonance angiography, single-photon emission CT combined with CT, and angiography may help determine the extent of injury without waiting months for development of the line of demarcation, thereby supporting earlier decisions regarding amputation.[10][13] Technetium-99m bone imaging may also assist in determining candidacy for thrombolytic therapy.[14]

Treatment / Management

Patients should be protected from further injury by covering exposed areas. Treatment of frostbite begins with rewarming in the field if refreezing is not anticipated because repeated thawing and refreezing can worsen the injury.[9] Patients should be removed from the wind, and wet clothing should be removed and replaced with dry clothing. Vigorous rubbing should be avoided because it can cause additional tissue damage.[11](B3)

In-hospital treatment of frostbite should first address hypothermia, major trauma, or other life-threatening conditions. Patients with hypothermia should be treated to raise core temperature to more than 35 °C using warm intravenous fluids and other modalities as clinically indicated.[11] Rewarming of affected tissue can occur concurrently with mild hypothermia, but it should proceed after moderate and severe hypothermia have been corrected.

A warm water bath at approximately 37 °C to 39 °C (98.6 °F–102.2 °F) should be used until the tissue is soft and pliable. The 2024 American Heart Association and American Red Cross First Aid Guidelines recommend a slightly broader temperature range of 37 °C to 40 °C (99 °F–104 °F) for 20 to 30 minutes. Frequent reexamination of sensation should accompany rewarming. Once rewarming is complete, the tissue should be dried without rubbing, covered with a dry dressing, and elevated.

Ibuprofen, a nonsteroidal anti-inflammatory drug, should be started as soon as possible to inhibit prostaglandin- and thromboxane-mediated vasoconstriction; the 2024 Wilderness Medical Society guidelines suggest ibuprofen at 12 mg/kg/d divided twice daily (the minimum dose required for an antiprostaglandin effect) up to a maximum of 2400 mg/d divided into 4 daily doses.[2] Nonsteroidal anti-inflammatory drugs additionally provide pain control, but stronger analgesics, including opioids, may be necessary. Tetanus immunization status should be obtained and updated for all patients with frostbite. Antibiotic prophylaxis is not necessary. However, therapeutic antibiotics should be used if signs or symptoms of infection are present.(A1)

Current practice supports selectively draining clear, cloudy, or tense blisters (eg, through needle aspiration) while leaving hemorrhagic blisters intact, although comparative data are insufficient to make an absolute recommendation.[2] The Wilderness Medical Society recommends topical aloe vera application every 6 hours with dressing changes because of its antiprostaglandin effect.[2] Overly aggressive surgical debridement or amputation may remove otherwise viable skin; therefore, complete rewarming and tissue demarcation (1 to 3 months or longer after injury) should occur before surgical debridement. However, sepsis caused by wet gangrene warrants earlier surgical debridement. Signs of compartment syndrome (pain disproportionate to physical examination findings, pallor, paresthesia, paralysis, and pulselessness) should also prompt urgent fasciotomy; however, the classic signs may be unreliable because affected extremities may be insensate with reduced movement at baseline.[15][16](A1)

Patients with full-thickness injuries, evidence of ischemia, and no restoration of tissue perfusion after rewarming may be candidates for intravenous or intra-arterial tissue plasminogen activator (tPA) therapy. The 2024 Wilderness Medical Society guidelines suggest tPA for deep injury extending to the proximal interphalangeal joint or a more proximal location (Cauchy grades 3 to 4) within 24 hours of thawing. This strong recommendation is supported by low-quality evidence, and tPA may reduce the need for digit amputation.[2][17] Tissue plasminogen activator should be initiated only if the bleeding risk is acceptable, ideally as early as possible, because each hour of delay reduces the digit salvage rate. Intravenous heparin used as an adjunct to tPA may also reduce the need for digit amputation, but heparin should not be used as monotherapy.[14](A1)

Iloprost, a prostacyclin analog with potent vasodilator and antiplatelet effects, is also used to prevent ischemia in frostbite.[9] The 2024 Wilderness Medical Society guidelines give iloprost a strong recommendation (supported by low-quality evidence) for deep frostbite extending to the distal interphalangeal joint or a more proximal location (grades 2 to 4) up to 72 hours after rewarming, although treatment should begin as soon as possible. Evidence is strongest for grades 3 to 4, whereas the benefit for grade 2 injury remains uncertain. Iloprost has been approved by the United States Food and Drug Administration for adults to reduce the risk of digit amputation since February 2024.[2] (A1)

Recovery from frostbite depends on the depth and extent of the injury. Superficial frostbite may resolve over days to weeks. Deeper injury requires 1 to 3 months or longer for demarcation.[2](A1)

Differential Diagnosis

Frostnip, chilblains, trench foot, thermal burns, trauma, Raynaud phenomenon, cellulitis, peripheral arterial disease, acute extremity ischemia, vasculitis, and pressure injuries may present similarly to frostbite.

Staging

Several staging systems are used for frostbite because they were developed to answer different clinical questions. No single system is ideal for all purposes. Some systems are mainly descriptive, whereas others support early triage, predict eventual tissue loss, or identify patients who may benefit from time-sensitive extremity salvage therapy.[2][18][19]

Traditionally, frostbite has been classified using a system similar to burn classification to provide an anatomic description of injury depth:

• First degree: Numbness or dysesthesia, central pallor, surrounding erythema, edema, desquamation without gross tissue loss
• Second degree: Clear or milky skin blistering with surrounding erythema and edema
• Third degree: Full-thickness loss and hemorrhagic blisters due to involvement of the dermal vasculature
• Fourth degree: Tissue loss extending into deeper structures, resulting in loss of the affected part

The Wilderness Medical Society endorses a 2-tier classification system that divides frostbite into superficial and deep. This approach facilitates earlier bedside triage and immediate treatment. After thawing, superficial frostbite generally corresponds to injuries with little to no anticipated tissue loss. Conversely, deep frostbite indicates anticipated tissue loss and a higher risk of ischemia, necrosis, and amputation.[2]

The Cauchy classification grades severity according to the extent of the initial lesion (the area of discoloration) on day 0 after rapid rewarming. The classification is refined using day 2 bone scan radiotracer uptake and blister type to provide an earlier prediction of the eventual amputation level.[18] The original 4-tier scheme includes the following grades:

• Grade 1: No initial lesion; no amputation or sequelae predicted
• Grade 2: Initial lesion on the distal phalanx; soft-tissue amputation and nailbed sequelae predicted
• Grade 3: Initial lesion on the intermediate or proximal phalanx; bone amputation of the digit and functional sequelae predicted
• Grade 4: Initial lesion at the carpal or tarsal level; extremity amputation, with possible systemic involvement or sepsis, and functional sequelae predicted

The 2024 Wilderness Medical Society update also presents an expanded 6-tier anatomical classification comprising grades 0 to 5, which adds finer proximal gradations of discoloration.[2] Collectively, these classification systems are complementary rather than competing.

Prognosis

Prognosis depends on the depth of injury, the duration of freezing, and the presence of thawing and refreezing.[18] Findings after rewarming that predict a poor outcome, including deeper injury and greater eventual tissue loss, include hemorrhagic blistering, nonblanching or persistent cyanosis, absence of edema, persistent mottling, firm or frozen-feeling skin, and frank gangrene.[9] Final tissue demarcation may take 1 to 3 months, which has led to the classic adage: "Freeze in January, amputate in July."[20] Patients should avoid cold exposure for up to 1 year after the initial injury because cold sensitivity may persist. Overall, outcomes after frostbite injury are guarded and depend on the extent of the injury. Most patients have residual sensory or functional deficits.

Complications

Long-term and residual complications of frostbite include:

• Paresthesias
• Loss of nails
• Anhidrosis or hyperhidrosis
• Cracked skin
• Muscle atrophy
• Chronic pain
• Joint stiffness
• Phantom pain
• Tremor

Patients with a history of frostbite may have cold intolerance in previously affected areas, which may result from vasospasm and abnormal autonomic tone following cold injury. Complex regional pain syndrome is a common complication.[12] Furthermore, autoamputation of an affected digit may precede surgical amputation. Gangrenous tissue can progress from dry gangrene to wet gangrene, increasing the risk of sepsis.