Frostbite

Etiology

Skin exposure to freezing conditions causes frostbite. Prolonged duration and lower temperatures increase the likelihood and the extent of the injury. Certain pre-existing conditions may worsen tissue injury because of frostbite, including peripheral vascular disease, malnutrition, Raynaud's disease, diabetes mellitus, tobacco use, etc. A unifying pattern among these conditions is poor impaired internal organ insulation or dysfunctional vasculature.

Risk factors for frostbite include:

• Winter season
• No or inadequate shelter from the cold
• High wind chill factor
• Exposure at a high altitude
• Prolonged duration of exposure
• Prolonged exposure to a wet condition
• Altered mental status
• Alcohol or drug abuse
• Malnutrition
• Immobilization
• Extremes of age
• Homeless
• Presence of medical disorders like diabetes, hypothyroidism, peripheral vascular disease, stroke or arthritis
• Smoker

Epidemiology

Classically, frostbite injuries were common in military personnel. However, with the increase in technology and accessibility, recreational sports have become a significant repository for frostbite cases. Homeless populations, children, and the elderly are especially vulnerable to frostbite. Risk factors include behavioral (lack of clothing, alcohol/drug consumption, access to shelter), physiological (dehydration, high altitudes, hypoxia), and other comorbidities with a predilection for tissue hypoxia (diabetes, peripheral vascular disease, Raynaud phenomenon).[1]

Pathophysiology

Frostbite has a prejudice for distal extremities, digits, and those portions of exposed skin with decreased perfusion (nose, ears) and less insulation. As the temperature of exposed skin drops, endothelial cell damage can cause localized edema in the extremity. Hyperviscous intravascular flow and vasodilation causes slowing forces, resulting in microthrombi. The constellation of microvascular injury, venous stasis, and microthrombi all contribute to the development of ischemia attributed to frostbite. Depending on the extent of the exposure and subsequent cellular damage, injuries may be reversible or irreversible.

Normal skin blood flow is about 250 ml/min but during frostbite, the flow drops to less than 20-50 ml/min. As the temperature drops to below 0 degrees Centigrade, blood flow ceases. The slower venous system freezes before the arterial system.

Frostbite causes injury in the following ways:

• Direct damage of the cold to the tissues
• Indirect damage caused by dehydration
• Formation of ice crystals that leads to alteration in electrolytes and lipid layers
• Stasis of the microvessels leading to thrombus formation and ischemia
• Reperfusion injury

Recovery

Frostbite injury is classified into three zones which include:

1. Zone of coagulation which is the most distal and often the most severely injured. Here the injury is irreversible
2. Zone of stasis is the middle zone where the injury can be moderate to severe. but it reversible.
3. Zone of hyperemia is the proximal zone, which is the least injured.

In most cases, recovery from frostbite can take 5-30 days, depending on the severity of injury.

Histopathology

Initially, extracellular ice crystals form in exposed tissue. Continued cold exposure can cause intracellular ice crystals to form. Cell membrane damage results in electrolyte imbalances. As the transmembrane osmolarity gradient increases, cell membranes can rupture, resulting in cell death. Should tissue thawing occur, a reperfusion-associated inflammatory response through proinflammatory cytokines may cause additional tissue damage. Even more dangerous, additional cycles of thaw-refreeze can cause progressively worsening tissue ischemia and subsequent thrombosis.[2]

History and Physical

History of the patient should include duration and external temperatures during exposures.

Physical examination may reveal blanched, white skin. Patients may complain of heaviness in an exposed extremity as numbness progresses. In later stages of frostbite, exposed areas may become dark or purplish in hue due to poor vascular tone and pooling of blood. Superficial frostbite affecting the epidermis and subcutaneous fat will have pale, white blisters upon rewarming. Deep, full-thickness frostbite will become hemorrhagic with rewarming and may become gangrenous.[3] Injured skin may be well-demarcated with surrounding viable skin.

It is important to know that the initial exam will not accurately reveal the final depth and extent of the injury.

Rewarming injury

During rewarming, edema may start to appear within 3-5 hours and may last 7 days. Blisters tend to appear within 4-24 hours.

Presence of eschar will be obvious at 10-15 days and mummification with a line of demarcation may develop in 3-8 weeks.

Evaluation

Frostbite is a clinical diagnosis. Using additional laboratory testing may be helpful in determining the extent to which comorbid conditions may be contributing to tissue ischemia. Technetium-99 (Tc-99) triple phase scanning and magnetic resonance angiography (MRA) may help to determine extent of amputation in the first few days after injury.[4][5] Tc-99 bone imaging may also assist in determining candidacy for tPA.[6]

Treatment / Management

Patients should have protection from further injury by covering exposed areas. The care of patients with frostbite begins with rewarming in the field if there is no anticipation of refreezing, as thaw-refreezing may worsen injuries.[3] Remove patients from the wind. Remove wet clothing and replace with dry clothing. Avoid vigorous rubbing as this can cause further damage.[7](B3)

In-hospital management includes warm water baths, approximately 40-42 degrees C. Patients with systemic hypothermia should be managed by raising core temperature above 35 degrees C using warm IV fluids, and this should precede warming of the affected extremity.[7] This rewarming protocol also includes patients with other comorbidities or significant trauma. NSAIDS (ibuprofen) are indicated for controlling pain and preventing further inflammation, but stronger analgesics including narcotics may be necessary to achieve pain control. Frequent re-examination for sensation should accompany rewarming.

Although controversial, some sources recommend drainage or excision on white, cloudy-appearing blisters, while hemorrhagic blisters should be left intact. As with burn patients, particular care to prevent infections and dehydration should be a priority. Overly aggressive surgical debridement may remove skin that is otherwise viable, so complete rewarming should be achieved before surgical debridement. Signs of compartment syndrome (edema, pulselessness, extreme pain) should prompt urgent surgery. Delayed amputation (up to 6 weeks following injury) until the determination of tissue viability may prevent surgical morbidity from unnecessary procedures.[8][9](B2)

Patients with full-thickness injuries and evidence of ischemia and no restoration of tissue perfusion after rewarming may be candidates for thrombolytic (tPA) therapy.[10] tPA may reduce the need for digital amputation.[11] Combination therapy with tPA and IV heparin may also reduce the need for digital amputation.[6] Iloprost, a potent vasodilator, has been used as a potential treatment to prevent ischemia in frostbite.[3] IV Iloprost is unavailable in the United States.(A1)

Differential Diagnosis

Careful assessment for systemic hypothermia and full-thickness tissue injury are essential in patients with apparent frostbite. Failure to correct for underlying comorbidities associated with frostbite (i.e., intoxication, cardiovascular compromise, significant environmental exposure, trauma) may cause systemic collapse and death. 

Staging

Traditionally, frostbite has a staging system similar to burns: 

• First degree - numbness, central pallor, surrounding erythema/edema, desquamation, dysesthesia
• Second degree - skin blistering with surrounding erythema/edema
• Third degree - tissue loss involving entire thickness of skin, hemorrhagic blisters
• Fourth degree - tissue loss involving deeper structures, resulting in loss of the affected part

Another classification based on frostbite on hands/feet has been proposed, which incorporate early imaging studies and may better predict outcomes.[12]

• Grade 1 - no cyanosis on the extremity; no risk of amputation or sequelae predicted
• Grade 2 - cyanosis on distal phalanx only; amputation to soft tissue and sequelae of fingernail/toenail sequelae predicted
• Grade 3 - cyanosis on intermediate and proximal phalanges; amputation to the bone of the digit and functional sequelae predicted 
• Grade 4 - cyanosis over carpal/tarsal bones; amputation to limb and functional sequelae predicted.

With this classification system, as grade increases, so does the likelihood of limb amputation.

Prognosis

Functional sequelae of frostbitten areas depend on the extent of tissue injury.[12] Unfavorable factors in frostbite include hemorrhagic blistering, non-blanching cyanosis, and firm skin after rewarming.[3] Patients should avoid cold exposure for up to a year after the initial injury.

Frostbite injury is associated with morbidity which is worse in the presence of the following:

• Presence of hemorrhagic blisters
• No edema
• Ongoing mottling
• Frank presence of frozen tissue

Complications of frostbite include:

• Paresthesias
• Loss of nails
• Anhidrosis of hyperhidrosis
• Cracked skin
• Atrophy of muscles
• Chronic pain
• Joint stiffness
• Phantom pain
• Tremor

Complications

Frostbite survivors may have an intolerance to cold in previously frostbitten areas, which may be a consequence of vasospasm and abnormal autonomic tone following cold injury. Complex regional pain syndrome is a common complication.[10] Autoamputation of an affected digit may precede surgical amputation.