Frostbite

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Background

Frostbite, the most common type of freezing injury, is defined as the freezing and crystalizing of fluids in the interstitial and cellular spaces as a consequence of prolonged exposure to freezing temperatures. This article deals with the clinical presentation and treatment of frostbite as a distinct entity. (See also Cold Injuries, Fingertip Injuries, and Frostbite.) Associated conditions, such as hypothermia, pernio (chilblains), and trench foot, are discussed elsewhere and will not be addressed in detail here.

Frostbite may occur when skin is exposed to extreme cold, at times combined with high winds, resulting in vasoconstriction. The associated decrease in blood flow does not deliver sufficient heat to the tissue to prevent the formation of ice crystals. The anatomic sites most susceptible to frostbite include hands, feet, and exposed tissues (eg, ears, nose, and lips).

Because frostbite tends to occur in the same setting as hypothermia, most cases are observed in the winter. Homeless individuals, those who work outdoors, winter sport enthusiasts, and mountaineers are examples of those at risk.[1, 2, 3] More novel activities that can predispose to frostbite include paragliding at extreme heights[4] and kite skiing.[5] The prevalent use of alcohol in colder climates is a factor as well. High-altitude mountaineering frostbite, a variant of frostbite that combines tissue freezing with hypoxia and general body dehydration, has a worse prognosis.

Until the late 1950s, frostbite was a disease entity primarily reported by the world’s military, which had the most experience in its diagnosis and treatment. Most of the data in the current literature originated from military studies or from Scandinavian countries.[6] However, civilian physicians are becoming more cognizant of the diagnosis and treatment of this condition in urban and rural civilian populations. A scientifically based treatment protocol for frostbite was developed by McCauley et al in 1983.[7]

In addition, as with the appearance of high-altitude frostbite in World War II bomber crews, reports of novel causes of frostbite continue to appear in the literature. These include ice pack burns,[8, 9] recreational use of nitrous oxide and other volatile agents,[10, 11] liquid nitrogen handling,[12] liquid oxygen handling,[13] fluorinated hydrocarbon propellant abuse,[14] and work with pressurized liquid ammonia.[15]

The goal of frostbite treatment is to salvage as much tissue as possible, to achieve maximal return of function, and to prevent complications. This may involve both medical and surgical measures as appropriate.

Pathophysiology

Cutaneous circulation and thermal homeostasis

The cutaneous circulation plays a major role in maintaining thermal homeostasis. The skin loses heat more easily than it gains heat. Thus, humans acclimatize better to heat than to cold. Cutaneous vasodilation is controlled by direct local effects and decrease of sympathetic vascular tone. Maximum reflex vasodilation occurs when the sympathetic system is blocked.

The fingers, toes, ears, and nose—the skin structures most at risk for frostbite—contain multiple arteriovenous anastomoses that allow shunting of blood in order to preserve core temperature at the expense of peripheral tissue circulation.

The effect of skin temperature on cutaneous blood flow involves the following:

Mechanisms of frostbite injury

Mechanisms of frostbite injury include the following:

Heat conduction and radiation from deeper tissue circulation prevents freezing and ice crystallization until the skin temperature drops below 0°C. Once tissue temperature drops below 0°C, cutaneous sensation is lost and the frostbite injury cascade is initiated. This cascade comprises the following four phases, which may overlap:

  1. Prefreeze phase - This phase consists of superficial tissue cooling, which results in the increased blood viscosity, microvascular constriction, ischemia, and endothelial plasma leakage that precede the formation of ice crystals
  2. Freeze-thaw phase - This phase consists of ice crystal formation, more in the extracellular space than in the intracellular space.  Thawing may induce reperfusion injury with an inflammatory response.
  3. Vascular stasis phase - This phase consists of arteriovenous shunting at the margin between injured and noninjured tissue. Vasoconstriction may alternate with vasodilation. This may result in a combination of both progressive microvasculature erythrocyte sludging, stasis, coagulation, and thrombus formation, and leakage of blood from the vessels.
  4. Late progressive ischemia phase - This phase consists of thrombus-induced inflammation, hypoxia, and anaerobic metabolism leading to tissue necrosis

Initial injury is mediated by extracellular-tissue ice crystal formation. These crystals damage the cellular membranes, initiating the cascade of events that cause cellular death. As freezing continues, a shift in intracellular water to the extracellular space leads to dehydration, increased intracellular osmolarity, and eventually, intracellular ice crystal formation. As these ice crystals form and expand, the cell undergoes mechanical damage, which is irreversible.

Damage also is caused by a cycle of vascular changes referred to as the hunting reaction, which involves alternating cycles of vasoconstriction and vasodilation. Vasoconstriction with associated conservation of heat is maximal at approximately 15°C. As exposure to lower temperatures continues below 10°C, the hunting reaction causes alternating vasoconstriction and vasodilation, which warms the exposed affected tissues and slows the rate at which extracellular and intracellular ice formation occurs.

Frostbite of peripheral tissues is delayed by the extraction of heat from the body’s core. This process is helpful in relatively warm and insulated situations but is potentially deadly if it accelerates core heat loss.[18] The hunting reaction has been examined extensively by studies comparing Caucasians with Japanese patients[19] and healthy individuals with those who have Raynaud disease.[20] In addition, it has been evaluated with regard to sex, season, and environmental temperature.[21]

When the hunting reaction stops at colder temperatures, vasoconstriction persists uninterrupted. This invariably leads to hypoxia, acidosis, arteriolar and venular thrombosis, and ischemic necrosis. Prostaglandin F2 and thromboxane A2,which are released during the course of freezing and thawing, potentiate vasoconstriction, platelet aggregation, and thrombosis.

Various authors have compared the effects of quick freezing and slow freezing at the microscopic level. Rapid freezing is thought to increase intracellular ice formation superficially, whereas slow freezing causes deeper and more extensive cellular injury by causing freezing of water in the intracellular and extracellular spaces. Because extracellular freezing progresses more rapidly than intracellular freezing, osmotic shifts occur. These shifts cause intracellular dehydration, which decreases the viability and survival of individual cells.

Reperfusion and ischemia

As tissue is rewarmed, reperfusion injury becomes prominent. Progressive edema of the frostbitten area develops over the first 48-72 hours, followed by bleb formation and necrosis of devitalized tissue. Demarcation of necrotic tissue occurs in the next 60-90 days.

Microscopically, reperfusion results in intracellular swelling, tissue edema with increased compartment pressure, platelet aggregation and thrombosis, and inflammatory leukocyte infiltration with release of free oxygen radicals, prostaglandins, and thromboxane. To date, however, agents that block these mediators have had only marginal clinical success.

Zook et al, in a study of a live gracilis muscle preparation, found that time to reperfusion of muscle after freezing varied but that almost all circulation was restored 10 minutes after rewarming.[22] Blood flow in the microcirculation resumed at near-normal levels after rewarming, suggesting that the vascular structures were not damaged by freezing. The most significant damage was created by white clots and fibrin formation with associated microvascular thrombosis, beginning at 5 minutes after rewarming and continuing for as long as 1 hour after rewarming).

Zook et al noted that platelet abnormalities and fibrin formation resulted in the greatest early and late tissue damage and that classic reperfusion injury did not seem to be as important a factor as was previously believed.[22] This may explain the varied results noted in the literature after attempts to modify mediators of ischemia-reperfusion injury, which do not affect platelets or fibrin formation.

The true effect of chemical mediators remains controversial. However, ischemia-reperfusion injury may still occur because of delayed microvascular thrombosis, compounding the mechanical effects of ice formation and the chemical effects of platelet abnormalities and fibrin microvascular clot formation.

Recovery from injury

Frostbite injury can be divided into the following 3 zones. The zone of coagulation is the most severe and distal region of injury and consists of irreversible tissue damage. The zone of stasis is the middle region and is characterized by severe tissue damage that may be reversible. The zone of hyperemia is the most proximal and least damaged region. Generally, recovery is expected and occurs in about 10 days.

When external warmth is applied, ischemic insult may occur because perfusion from deep blood vessels tends to return slowly relative to the accelerated tissue oxygen demand. Rapid rewarming is favored over slow rewarming because it minimizes this discrepancy.[23] Prolonged exposure to cold, refreezing of partially thawed tissue, and slow rewarming predispose the tissue to greater ischemic insult, resulting in greater tissue loss.

Etiology

Risk factors for frostbite include the following[24] :

Underlying conditions that may predispose to frostbite include the following:

Frostbite severity and resultant tissue injury are a function of 2 factors: (1) absolute temperature and (2) duration of cold exposure. With regard to these 2 factors, data suggest that the duration of exposure has the greater impact on the level of injury and the amount of tissue damage; however, short-term exposure to extreme cold may produce the same overall injury pattern as excessively prolonged exposure to lesser degrees of cold.

The wind chill factor will greatly affect the severity of frostbite. Although the actual ambient temperature does not change as a result of wind chill, the increased rate of cooling creates a much lower effective temperature on exposed skin and accelerates the rate of cooling and the process of freezing in the tissues.

Epidemiology

United States statistics

Because no standardized reporting system or database for frostbite is available, its prevalence is unknown. Frostbite is uncommon in most of North America, except for northern states, Alaska, and Canada. US Army data noted an incidence of all cold weather injuries of 38.2 cases per 100,000 persons in 1985, decreasing to 0.2 case per 100,000 persons in 1999. Woman and African American men were 2.2-4.0 times more likely to exhibit cold injuries.[25]

International statistics

In the civilian population, the largest published series reviewed a 12-year experience in Saskatchewan, which noted alcohol intoxication and psychiatric illness as the leading risk factors for frostbite incidence and severity.[26] In Finland, authors calculated an annual occurrence of frostbite of 2.2% and a lifetime risk of 44% in military recruits aged 17-30 years.[27]

Among the civilian population in Finland, the annual incidence of frostbite was 2.5 per 100,000 inhabitants.[28] In Montreal, the incidence was 3.2 per 100,000 persons.[29] Among 637 mountaineers queried in Iran, the incidence of frostbite injury was 366 per 1000 persons per year. This appeared to be related mostly to the use of inappropriate clothing or to the incorrect use of equipment.[30]

When compared with the incidence of frostbite in the general population, such data clearly show that an increased risk of frostbite exists for individuals participating in military activities and extreme sports activities.

Age-related demographics

The most commonly affected group includes adult males aged 30-49 years, although all age groups are at risk. In one case series, the mean patient age was 41 years.[26] Younger children have less adaptive behavioral reaction to cold stress; therefore, they have a greater risk of frostbite. Recent US military data indicate a decreasing rate of cold-related injuries in general with increasing age. However, this data set did not specifically address an association of age with frostbite.[6]

Sex-related demographics

Most frostbite victims are male.[31] This disparity may result from increased outdoor activity among males as opposed to genetic predisposition. However, it has also been noted that women are at greater risk of developing hypothermia than are men. Thus, there may be gender variations in susceptibility to cold-related injuries that have not yet been fully elucidated.

Race-related demographics

Unacclimatized individuals from tropical climates are at increased risk of frostbite. Individuals from cold climates, such as Eskimos and Tibetans, are acclimated and consequently are less prone to frostbite. However, no definitive studies on the role of racial predisposition to frostbite have been completed.

During the Korean War, frostbite was more common among black soldiers than whites. Similarly, a US Army study of all cases of cold weather injuries, including frostbite, from 1980-1999 demonstrated that African American men and women were 4 times and 2.2 times, respectively, as likely to sustain cold weather injuries as their white counterparts.[25] An increased risk among those of African descent was noted by British investigators during the Falklands Islands War in 1982,[32] and a subsequent British Army study showed that soldiers of African descent had a 30 times greater chance of developing a peripheral cold injury than did white soldiers.[33] A small study suggests a potential explanation for the observed increased susceptibility of African Americans to frostbite. When their arms were immersed in water cooled to 10°C, vasoconstriction was noted to continue longer and the rate of rewarming when removed from the water was slower in African Americans compared with whites.[34] This raises a possible racial variation in vascular response to cold.

Arabs appear to be similarly predisposed to cold weather injuries, as are individuals from warmer climates, such as Pacific Islanders.

Prognosis

Frostbite is primarily a disease of morbidity. Mortality may occur if injured tissue becomes infected or if concurrent hypothermia occurs. Children have a larger body surface area–to–weight (volume) ratio and, therefore, are at greater risk for hypothermia than are adults.

Favorable prognostic indicators include the following:

Poor prognostic indicators include the following:

Healing can take 6-12 months. Long-term sequelae include the following:

Patient Education

The primary defense against frostbite is to get out of the cold. If this is not possible, preplanning and use of appropriate clothing are mandatory. Follow weather forecasts, with special attention to both predicted temperature as well as wind-chill temperature index. Patients should be advised to do the following:

Patients should be informed that the frostbitten area may be more sensitive to cold, with associated burning and tingling. Individuals who have sustained a cold-related injury are at a 2- to 4-fold greater risk of developing a subsequent cold-related injury. Therefore, patients with frostbite should be counseled about their increased susceptibility to frostbite injury and about appropriate strategies to avoid it. They should also be given general advice on preparing for cold weather exposure.

For patient education resources, see the Environmental Exposures and Injuries Center and the Infections Center, as well as Frostbite and Tetanus.

History

Frostbite is a completely preventable injury that can occur with or without hypothermia. Below –10°C, any tissue that feels numb for more than a few minutes may become frostbitten. Progressive symptoms of frostbitten areas are as follows:

Numbness over the affected area is the initial symptom of frostbite. After rewarming, severe throbbing and hyperemia begin and may last for weeks. Many patients complain of paresthesias. Long-term symptoms include cold sensitivity, sensory loss, and hyperhidrosis.

Physical Examination

The initial appearance of frostbite does not accurately predict the eventual extent and depth of tissue damage. Signs and symptoms vary according to severity of the frostbite injury. The hands, feet, ears, and nose are the most commonly affected (see images below).



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Frostbite of the hand.



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Frostbite of the foot. Photo courtesy of Kevin P. Kilgore, MD, Department of Emergency Medicine, Regions Hospital.



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Frostbite of the ear. Photo courtesy of Kevin P. Kilgore, MD, Department of Emergency Medicine, Regions Hospital.

Physical examination in patients with superficial frostbite reveals the presence of soft, palpable skin. If a thumbprint can be left in the skin, the patient usually has more viable underlying tissue. Individuals with deeper frostbite effects present with skin that is hard to the touch.

Other signs may include the following:

Degrees of frostbite injury

Four classic stages of frostbite injury have been defined: first degree, second degree, third degree, and fourth degree. This staging system has limited clinical usefulness, however, because it has not been shown to have a direct correlation with survival or tissue loss.

First-degree frostbite has the following characteristics:

Sequelae over the next few weeks include desquamation, transient swelling and erythema, and cold sensitivity.

Second-degree frostbite has the following characteristics:

Blisters contain high amounts of thromboxane and prostaglandins. They contract and dry within 2-3 weeks, forming a dark eschar that sloughs off in 4 weeks, leaving poorly keratinized skin that is easily traumatized. Sequelae include paresthesias, hyperhidrosis, and persistent or transient cold sensitivity.

Third-degree frostbite has the following characteristics:

Sequelae include tropic ulceration, severe cold sensitivity, and growth plate injury.

Fourth-degree frostbite has the following characteristics:

Demarcation between living and nonviable tissue takes 1 month. Spontaneous amputation takes another month after demarcation.

Superficial versus deep frostbite injury

Some experts have moved to a simpler classification of the severity of frostbite injury, in which frostbite is described as either superficial (ie, first- and second-degree injury) or deep (ie, third- and fourth-degree injury). This approach yields a better correlation between severity of injury and final outcome.

Superficial injury is characterized as follows:

Deep injury is characterized as follows:

Postrewarming injury

Rewarming edema appears within 3 hours and lasts 1 week. Large clear blebs appear within 6-24 hours with superficial injuries. Small hemorrhagic blebs appear after 24 hours with deep injuries.

Eschar forms in 9-15 days and is described as a shrunken black carapace shell covering the wound. If the frostbite is superficial, new skin appears beneath the carapace. With deep injury, the area self-amputates. Mummification results in an apparent line of demarcation in 3-6 weeks.

Complications

The degree of long-term disability is related to the severity of frostbite injury. An increased risk of frostbite with lesser exposures and poor cold tolerance in the previously injured extremity are commonplace. Permanent sensory loss is also common.

Wound infection, which is observed in 30% of patients, may be caused by Staphylococcus aureus, beta-hemolytic streptococci, gram-negative bacilli, or anaerobes and may present with the following:

Other complications may include the following:

Approach Considerations

Laboratory studies of tissue samples, blister fluid, or blood ordinarily do not provide any useful, clinically relevant information in isolated frostbite. Concurrent hypothermia, prolonged exposure with systemic physiologic changes, and previous medical illnesses may exist, however, and laboratory studies in these cases may be helpful.

Imaging studies early in the diagnosis and treatment of frostbite may help determine the extent of the frostbite injury and any associated trauma, such as fractures. They may also assist in predicting prognosis. Because transitory vascular instability lasts 2-3 weeks after the frostbite injury, no imaging technique (eg, thermography, angiography, plethysmography, radioisotope bone scanning) reliably predicts tissue demarcation during the initial frostbite presentation.

Laboratory Studies

Frostbite is a clinical diagnosis. Although laboratory studies are not important in the initial diagnosis and management of frostbite, they may be helpful in identifying delayed systemic complications, such as wound infection with sepsis or complications of underlying hypothermia.

Baseline laboratory studies to consider include complete blood count (CBC), electrolytes, blood urea nitrogen (BUN), creatine, glucose level, and liver function tests. Urinalysis may be used to detect evidence of myoglobinuria. Obtain Gram stains and cultures from suspected frostbite wound infections.

Radiography and Angiography

Radiography often demonstrates soft-tissue edema but does not distinguish viable from nonviable tissue. Plain radiographs are not useful except to screen for trauma-related fractures or dislocations. They may assist in the diagnosis of long-term complications, such as osteomyelitis.

Angiography often shows slowing of blood flow to the distal vasculature, but this too does not correlate well with eventual tissue loss. When a vasodilator is added, this technique can more accurately predict the final pattern of ischemia that will be observed after 2-3 weeks of observation. In centers using thrombolytics to manage frostbite injuries, angiography is used to identify appropriate patients. Unlike technetium-99m scintigraphy, angiography does not visualize the microcirculation soon after injury.

Scintigraphy and Bone Scans

Technetium-99m (99mTc) scintigraphy is sensitive and specific for tissue injury. Some authors recommend using it early in the management of frostbite (48 hours after injury) to aid in directing earlier debridement of nonviable soft tissue. This allows nonviable tissue to be visualized earlier than by clinical examination and thus presumably shortens patient hospitalization.[37, 38] In addition, scintigraphy is useful in assessing the response of damaged tissue to therapy. In some centers, 99mTc scanning is used to identify appropriate patients for treatment with thrombolytics.

Similarly, bone scans, particularly triple-phase bone scans, may help to delineate nonviable bone but should be reserved until microscopic tissue damage has had time to present itself clinically, generally 2-3 weeks post injury.[17]

Histologic Findings

The presence of a greater number of intracellular ice crystals compared to extracellular ice crystals suggests a rapid cooling of the skin.

The time frame of frostbite injury is as follows:

Imaging Studies

Magnetic resonance imaging (MRI), when combined with physical findings, may also be helpful in the early determination of margins of tissue viability. However, experience with this application of MRI is limited.

Approach Considerations

The goal of frostbite treatment is to salvage as much tissue as possible, to achieve maximal return of function, and to prevent complications.[39] If treating personnel are unfamiliar with the management of frostbite and its sequelae, transfer of the patient to another facility should be considered. In some settings, burn units have particular expertise in managing severe frostbite injuries. In one report, 29% of homeless patients admitted to a burn unit were admitted for frostbite.[40] Therefore, transfer to a facility with a burn unit may be an option.

Prehospital care starts with taking the patient to a warm environment. If needed, pad or splint the affected area to minimize injury en route. Remove wet clothing. Avoid walking on frostbitten tissue. Do not rewarm frostbitten tissue if there is a possibility of refreezing before reaching definitive care. Lastly, do not rub or use a stove/fire to rewarm frostbitten tissues.

Be sure to correct the ABCs (A irway, B reathing, and C irculation) and life-threatening conditions before treating frostbite. Make sure that the frostbitten area does not refreeze. Rewarm the frostbitten area as quickly as possible to salvage as much tissue and function as possible. Rewarming is most effectively accomplished by immersing the affected area in water heated to 37-39 °C (98.6-102.6 F). Do not allow the water to get too hot or too cold. Avoid premature termination of the rewarming process. Remember to treat pain associated with rewarming.

Avoid early amputation until after the nonviable tissue is clearly demarcated. Inform patients that the injury site is more prone to recurrent damage when exposed to even moderate changes in environmental temperature.

Consider obtaining a photographic record on admission, 24 hours after admission, and serially every 2-3 days until discharge.

The management of frostbite itself may be divided into 3 phases: field management, rewarming, and postrewarming management.[24]

Field Management

The first step in the management of frostbite is prevention. The US Army decreased the incidence of cold injury of all types in soldiers from 1985-1999. This was accomplished through training, education, and improved clothing.[25] When suspected frostbite does occur, transport to a trauma or burn center becomes a priority. Field rewarming should be started only if the time to arrival at a definitive care center exceeds 2 hours.

As a general principle, always address the ABCs and treat any life-threatening conditions (eg, hypothermia) first. Correct any systemic hypothermia to a core temperature of 34°C before treating the frostbite.

Remove the patient from cold. Replace wet and constrictive clothing with dry loose clothing. Remove jewelry from the affected area.  Dress the extremity in a manner that minimizes mechanical trauma.

Rewarm the frostbitten area if no danger of refreezing is present. However, rewarming should be avoided if it cannot be maintained (freeze-thaw-freeze cycle). Walking on frozen frostbitten areas and risking tissue chipping and fracture is considered better than thawing and refreezing. Reports from Canada show that forced-air rewarming with portable units can be used effectively to warm victims of hypothermia and frostbite in the field and during transport to a regional medical center.[41]

Rewarming

Rapid rewarming is the single most effective therapy for frostbite.[42] Variations on the original work of McCauley et al are used at most centers experienced in the management of the frostbite patient.[28] This includes admission of all frostbite patients to a specialty unit, if possible. Consider obtaining photographic records on admission, at 24 hours, and serially every 2-3 days until discharge.

On admission, rapidly rewarm the affected area in circulating water (ie, a whirlpool bath) at 37-39°C. The circulation of water allows a constant temperature to be applied to the affected area. Warming is continued for 15-30 minutes or until thawing is, by clinical assessment, complete (ie, when the distal area of the extremity is flushed, soft, and pliable). The addition of an antiseptic solution such as povidone-iodine or chlorhexidine to the bath may be beneficial.

Avoid inadvertent slow rewarming or overheating. Encourage active gentle motion of the frostbitten area during the rewarming. Constantly monitor water temperature. Thawing takes about 20-40 minutes for superficial injuries and as long as 1 hour for deep injuries.

The most common error in this stage of treatment is premature termination of the rewarming process because of reperfusion pain. Mechanical trauma (massaging or rubbing with ice or by hand) and rewarming at higher temperatures and for longer periods of time are detrimental to preserving viable tissue and should be avoided. Direct dry heating using fire or a heater can lead to burns secondary to loss of temperature sensation and so should be avoided.

Partial thawing and refreezing generate more damage than does prolonged freezing alone, through the release of multiple inflammatory mediators. In patients who experience a refreezing injury of thawed areas, rewarming should be delayed until it can be maintained.

Postrewarming Management

Once the skin is thawed, protect the area from further injury and reexposure to cold. Elevate the area and splint the extremity. Sterile, nonadherent dressings should be applied.  They should be changed  2-4 times a day and local wound care performed. The injured area should be closely monitored for signs of infection.

Management of blisters is somewhat controversial. Aspiration or debridement of clear blisters to prevent thromboxane- and prostaglandin-mediated tissue damage may make theoretical sense, especially if overlying a joint. In order to avoid desiccation and infection of underlying deep layers, hemorrhagic blisters should not be debrided. However, if they interfere with movement, hemorrhagic blisters may be aspirated. Fractures and dislocations should be managed conservatively until thawing is complete.

Pharmacologic Therapy

Analgesics (eg, ibuprofen and morphine) for pain relief are indicated during and after rewarming.

Apply topical aloe vera cream to all frostbitten areas every 6 hours to inhibit the arachidonic cascade, especially thromboxane synthesis.

Administer tetanus prophylaxis (tetanus toxoid or immune globulin).

Antibacterial prophylaxis is generally not recommended. Frostbite infections tend to involve staphylococci, streptococci, enterococci, and Pseudomonas pathogens. If infection develops, oral or parenteral antibiotics should be administered based on local sensitivities.

While supporting evidence is limited, infusion of low-molecular-weight dextran may be beneficial by preventing erythrocyte clumping in cold-injured blood vessels, with an associated decrease in tissue necrosis.[43]

Growing evidence supports the use of intravenous or intra-arterial thrombolysis with tissue plasminogen activator (tPA) in the management of frostbite. When administered within 24 hours of thawing, it has been shown to decrease amputation rates. It is generally administered as a bolus followed by an infusion, along with heparin or enoxaparin.[44, 45] Thrombolysis should only be performed after a careful risk-benefit analysis and in a setting in which the patient can be closely monitored for complications. Thus, the current recommendation is intra-arterial tPA plus intravenous heparin in patients with high-risk amputations (eg, multiple digits, proximal amputation) without contraindications who present within 24 hours of injury. Some protocols include the addition of the vasodilator iloprost, a prostacyclin analog, which has been shown to reduce amputation rates.[16, 46, 47, 48, 49]

Other ancillary modalities that may be helpful but have not been tested in well-controlled human trials include the following:

Surgical Removal of Nonviable Tissue

It may take weeks to months for frostbitten tissue to be declared viable. The affected area generally heals or mummifies without surgery. Lower-extremity involvement, infection, and delay in seeking medical attention are associated with an increased likelihood that operative therapy will be necessary.

Early surgery usually is contraindicated in frostbite, because of the time the nonviable tissue takes to demarcate. Older series show that performing debridement earlier than 2-3 weeks after warming significantly increases the amount of viable tissue removed and is harmful to the patient, resulting in increased amputation rate, mortality, and morbidity. The only indication for early surgical intervention is postthaw compartment syndrome warranting fasciotomy.

Whereas some advocate an aggressive approach, with bone and tissue scanning employed to identify nonviable tissue at 10 days, this is not considered routine or standard of care. Caregivers are cautioned to wait for demarcation of clearly necrotic tissue before surgical intervention. This usually takes about 3-4 weeks but may take longer. Commonly accepted indications for surgical debridement at 3-4 weeks include gangrene and clearly necrotic or nonfunctional tissue.

Wet gangrene is treated by urgent surgical excision of the affected area.

Standard surgical techniques are used for excision and debridement after tissue demarcation. Amputation skin grafting and bone and tissue coverage, potentially with muscle flaps, may be considered.[54]

Skin grafting may be required. Escharotomy may be appropriate if the eschar is preventing circulation or limb motion. Fasciotomy may be appropriate if elevated compartment pressure occurs. Escharotomy and fasciotomy have no proven prophylactic role in the management of frostbite. Ischemic injury in frostbite is most often caused by vascular compromise from thrombosis and not by compression from edematous tissue, making decompression unnecessary. Only when proven compartment syndrome is present is decompression needed.

Because of the extreme difficulty in differentiating viable tissue from nonviable tissue in the first few weeks after frostbite injury, amputation surgery is best avoided until complete demarcation and separation of gangrenous tissue occurs. This process normally takes 6-8 weeks. Consider early amputation if liquefaction, moist gangrene, or infection develops in the frostbitten area.

Early surgical sympathectomy was been proposed in the past to reduce vasoconstriction-associated tissue loss.  However, evidence to support this practice is limited or lacking.  It is therefore not recommended. 

Pressure dressings, occlusive dressings, and elastic wraps will decrease tissue perfusion and increase the risk of tissue loss. The presence of a concomitant injury with active bleeding requires direct pressure over the bleeding site, but caregivers should be aware that such actions are performed as life-saving measures and can result in increased morbidity.

In a report of a single patient treated with vacuum-assisted closure (VAC) therapy, Poulakidas et al described improved tissue salvage and early reepithelialization, suggesting that VAC may be of some benefit in the management of frostbite-induced tissue damage.[52]

Further Inpatient Care

Because the initial insult is not predictive of the final outcome, most patients with frostbite must be hospitalized for 24-48 hours to assess the extent of injury. The mean length of hospital stay for all levels of frostbite ranges from 8.5-33.2 days.

Daily wound care includes bivalving of any constricting eschars. Most skin grafting and amputations occur during weeks 3 or 4 after the injury.

Use hydrotherapy (ie, whirlpool bath filled with lukewarm water [40°C] and surgical soap) for 30-45 minutes twice daily until the eschar sloughs off. This measure reduces infection, facilitates debridement, and softens the eschar.

Avoid smoking, because nicotine causes vasoconstriction.[27] No restriction on diet is required, but a high-protein, high-calorie diet is suggested to promote healing.

Rest the injured area initially. Elevation helps to reduce swelling. Place cotton pledgets between frostbitten digits to decrease tissue maceration. Perform physical therapy to increase flexibility and dexterity once the injury begins to heal. Encourage active motion of the affected part as soon as possible.

Prevention

Prevention is the key to decreasing the number and overall morbidity of frostbite injuries. Frostbite prevention involves having a working knowledge of the environmental risks and hazards of outdoor activities in colder climates, using adequately protective clothing against cold and wind, and having a basic field knowledge of treatment options for frostbite. In conditions conducive to frostbite, patients should be advised to do the following:

When frostbite injuries do occur, expeditious treatment at a specialty center results in the least amount of permanent disability and tissue loss.

Consultations

Frostbite treatment is a multidisciplinary process and may involve the following specialists:

Early surgical consultation for amputation is rarely needed. Surgical consultation is appropriate for guiding long-term management, including debridement for infections that do not respond to conservative management or for skin grafting.

Long-Term Monitoring

Long-term surgical management includes the following options:

Counsel patients that the frostbitten area is more vulnerable to future heat and cold injury. Encourage patients to undergo active physical therapy.

Further outpatient care includes wound management, analgesia, and avoiding re-exposure to the cold. The choice of outpatient medications is dictated by the patient’s hospital course and may include antibiotics, analgesics, and ibuprofen.

There are rare reports of nonmelanoma skin cancer following frostbite.[55]

Guidelines Summary

Guidelines on the prevention and treatment of frostbite were released in July 2019 by the Wilderness Medical Society.[56]

Prevention

Preventive measures include maintaining peripheral perfusion, exercise, and protection from cold.

The following measures can be used to ensure local tissue perfusion:

Exercise can be used to maintain peripheral perfusion by elevating core and peripheral temperatures and enhancing cold-induced peripheral vasodilation. An important caveat is that it can induce exhaustion, which may lead to profound systemic heat loss.

The following measures can be used to ensure protection from the cold:

Field and initial hospital treatment

The following is a summary of field treatment (>2 hours from definitive care):

The following is a summary of initial hospital management:

Medication Summary

The goal of medical management is to rewarm the injury as quickly as possible, provide pain control during rewarming, reduce reperfusion injury, prevent frostbite complications, and decrease long-term sequelae.

Ibuprofen (Ibuprin, Advil, Motrin, Caldolor)

Clinical Context:  Ibuprofen inhibits inflammatory reactions and pain by blocking synthesis of thromboxane and prostaglandins to reduce reperfusion injury. It prevents platelet aggregation. Ibuprofen is preferable to aspirin, which irreversibly blocks synthesis of the prostaglandins needed for normal cell function and integrity, because it is not associated with Reye syndrome.

Naproxen (Aleve, Anaprox, Naprosyn, Naprelan)

Clinical Context:  Naproxen is a member of the propionic acid group of NSAIDs. It is available in low-dose form as an over-the-counter (OTC) medication. It is highly protein-bound, is metabolized in the liver, and is eliminated primarily in the urine. Naproxen may reversibly inhibit platelet function.

Sulindac (Clinoril)

Clinical Context:  Sulindac decreases COX activity and, in turn, inhibits prostaglandin synthesis. This results in decreased formation of inflammatory mediators.

Celecoxib (Celebrex)

Clinical Context:  Celecoxib primarily inhibits COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID gastrointestinal (GI) toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek the lowest dose of celecoxib for each patient.

Meloxicam (Mobic)

Clinical Context:  Meloxicam decreases COX activity, and this, in turn, inhibits prostaglandin synthesis. These effects decrease the formation of inflammatory mediators.

Flurbiprofen

Clinical Context:  Flurbiprofen may inhibit COX, thereby, in turn, inhibiting prostaglandin biosynthesis. These effects may result in analgesic, antipyretic, and anti-inflammatory activities.

Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort and may have sedating properties, which are beneficial for patients who have sustained trauma or injuries.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic and antipyretic activities. Their mechanism of action is not known, but these agents may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil and platelet aggregation, and various cell-membrane functions.

Morphine (Duramorph, MS Contin, Oramorph, Avinza)

Clinical Context:  Morphine is the drug of choice for strong analgesia because of its reliable and predictable effects, good safety profile, and ease of reversibility with naloxone. Morphine sulfate administered intravenously (IV) may be dosed in a number of ways and is commonly titrated until the desired effect is obtained.

Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort and may have sedating properties, which are beneficial for patients who have sustained trauma or injuries. These agents are used for pain control during rewarming

Aloe vera

Clinical Context:  Aloe vera inhibits the arachidonic cascade, especially thromboxane synthesis.

Class Summary

Topical agents are applied to debrided clear blisters and intact hemorrhagic blisters to minimize thromboxane synthesis.

Penicillin G (Pfizerpen)

Clinical Context:  Penicillin G interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Class Summary

Antibiotics are used for wound infection prophylaxis. Their use is controversial and not recommended by some experts unless signs of infection develop. If antibiotic prophylaxis is employed, it should be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Tetanus immune globulin (TIG) (Hyper Tet, HyperTET S/D, TIG)

Clinical Context:  Tetanus immune globulin is used for passive immunization of any person not been previously vaccinated for tetanus who has a wound that may be contaminated with tetanus spores

Class Summary

Immunizing agents are used to treat any person with a wound that might be contaminated with tetanus spores. Patients who may not have been immunized against Clostridium tetani products should receive tetanus immune globulin.

Diphtheria and tetanus toxoids (Decavac)

Clinical Context:  Tetanus and diphtheria toxoids are used to induce active immunity against tetanus in selected patients. They are the immunizing agents of choice for most adults and children older than 7 years. Booster doses must be administered to maintain tetanus immunity throughout life. Pregnant patients should receive only tetanus toxoid, not a diphtheria antigen-containing product.

In children and adults, tetanus and diphtheria toxoids may be administered into the deltoid or the midlateral thigh muscles. In infants, the preferred site of administration is the mid thigh laterally.

Class Summary

Toxoids are used for tetanus immunization in patients at risk of frostbite-associated tetanus. Booster injection in previously immunized individuals is recommended to prevent this potentially lethal syndrome. In a patient who was never fully immunized, these should be supplemented with tetanus immune globulin 250 U intramuscularly (IM).

What is frostbite?What is the pathophysiology of frostbite?What are the pathophysiologic mechanisms of frostbite injury?What are the phases of a frostbite injury cascade?What is the role of reperfusion and ischemia in the pathogenesis of frostbite?What are the zones of frostbite injury?What are the risk factors for frostbite?What causes frostbite?What is the prevalence of frostbite in the US?What is the global prevalence of frostbite?How does the prevalence of frostbite vary by age?What are the sexual predilections of frostbite?What are the racial predilections of frostbite?What is the prognosis of frostbite?What are favorable prognostic indicators in patients with frostbite?What are the poor prognostic indicators in patients with frostbite?What are the long-term sequelae of frostbite?What should be included in patient education about frostbite?What are the signs and symptoms of frostbite?Which physical findings are characteristic of frostbite?What are the characteristics of first-degree frostbite?What are the characteristics of second-degree frostbite?What are the characteristics of third-degree frostbite?What are the characteristics of fourth-degree frostbite?What are the characteristics of a superficial frostbite injury?What are the characteristics of a deep frostbite injury?Which physical findings are characteristic of a postrewarming frostbite injury?What are the possible complications of frostbite?Which conditions should be included in the differential diagnoses of frostbite?What are the differential diagnoses for Frostbite?Which studies are performed in the workup of frostbite?What is the role of lab testing in the diagnosis of frostbite?What is the role of radiography and angiography in the diagnosis of frostbite?What is the role of scintigraphy and bone scans in the diagnosis of frostbite?Which histologic findings are characteristic of frostbite?What is the role of MRI in the diagnosis of frostbite?How is frostbite treated?What is included in the field management of frostbite?What is the role of rewarming in the treatment of frostbite?What is included in the postrewarming treatment of frostbite?What is the role of pharmacologic therapy in the treatment of frostbite?What other ancillary modalities may be helpful but have not been tested in well-controlled human trials relative to frostbite?What is the role of surgery in the treatment of frostbite?What is the role of skin grafting in the treatment of frostbite?What is the role of amputation in the treatment of frostbite?What is the role of surgical sympathectomy in the treatment of frostbite?What is the role of pressure or occlusive dressings in the treatment of frostbite?What is included in inpatient care for frostbite?How is frostbite prevented?Which specialist consultations are beneficial to patients with frostbite?What are the long-term surgical options for frostbite?What is included in the long-term monitoring of patients with frostbite?What is the goal of medical treatment for frostbite?Which medications in the drug class Vaccines, Inactivated, Bacterial are used in the treatment of Frostbite?Which medications in the drug class Immune Globulins are used in the treatment of Frostbite?Which medications in the drug class Antibiotics are used in the treatment of Frostbite?Which medications in the drug class Topical Skin Products are used in the treatment of Frostbite?Which medications in the drug class Opioid Analgesics are used in the treatment of Frostbite?Which medications in the drug class Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are used in the treatment of Frostbite?

Author

Bobak Zonnoor , MD, Resident Physician, Department of Emergency Medicine, SUNY Downstate Medical Center, Kings County Hospital

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

C Crawford Mechem, MD, MS, FACEP, Professor, Department of Emergency Medicine, University of Pennsylvania School of Medicine; Emergency Medical Services Medical Director, Philadelphia Fire Department

Disclosure: Nothing to disclose.

David Cheng, MD, Associate Professor of Emergency Medicine, Education Director, Associate Emergency Medicine Residency Director, Case Medical Center

Disclosure: Nothing to disclose.

Ramy Yakobi, MD, MBA, Medical Director, Department of Emergency Medicine, Beth Israel Medical Center

Disclosure: Nothing to disclose.

Tonya M Thompson, MD, MA, Assistant Professor, Departments of Pediatrics and Emergency Medicine, Associate Fellowship Director, Pediatric Emergency Medicine Fellowship, Associate Medical Director, The PULSE Simulation Center, Arkansas Children's Hospital, University of Arkansas for Medical Sciences College of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

H Scott Bjerke, MD, FACS Clinical Associate Professor, Department of Surgery, University of Missouri-Kansas City School of Medicine; Medical Director of Trauma Services, Research Medical Center; Clinical Associate Professor, Department of Surgery, Indiana University School of Medicine

H Scott Bjerke, MD, FACS is a member of the following medical societies: American Association for the History of Medicine, American Association for the Surgery of Trauma, American College of Surgeons, Association for Academic Surgery, Eastern Association for the Surgery of Trauma, Midwest Surgical Association, National Association of EMS Physicians, Pan-Pacific Surgical Association, Royal Society of Medicine, Southwestern Surgical Congress, andWilderness Medical Society

Disclosure: Nothing to disclose.

Burt Cagir, MD, FACS Assistant Professor of Surgery, State University of New York, Upstate Medical Center; Consulting Staff, Director of Surgical Research, Robert Packer Hospital; Associate Program Director, Department of Surgery, Guthrie Clinic

Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, and Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

John Geibel, MD, DSc, MA Vice Chairman, Professor, Department of Surgery, Section of Gastrointestinal Medicine and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital

John Geibel, MD, DSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, and Society for Surgery of the Alimentary Tract

Disclosure: AMGEN Royalty Other

Dawn Hackshaw, MD Consulting Staff, Northwest Pediatrics, Inc

Disclosure: Nothing to disclose.

David L Morris, MD, PhD Professor, Department of Surgery, St George Hospital, University of New South Wales, Australia

Disclosure: RFA Medical None Director; MRC Biotec None Director

Harold K Simon, MD, MBA Professor of Pediatrics and Emergency Medicine, Associate Division Director of Pediatric Emergency Medicine, Director of Research, Division of Pediatric Emergency Medicine, Emory University School of Medicine, Children's Healthcare of Atlanta at Egleston

Harold K Simon, MD, MBA is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, American Pediatric Society, and Sigma Xi

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Amit Tevar, MD Staff Physician, Department of Surgery, Methodist Hospital of Indianapolis and University of Indiana

Amit Tevar, MD is a member of the following medical societies: Indiana State Medical Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Wayne Wolfram, MD, MPH Associate Professor, Department of Emergency Medicine, Mercy St Vincent Medical Center

Wayne Wolfram, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Pediatrics, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose

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Frostbite of the hand.

Frostbite of the foot. Photo courtesy of Kevin P. Kilgore, MD, Department of Emergency Medicine, Regions Hospital.

Frostbite of the ear. Photo courtesy of Kevin P. Kilgore, MD, Department of Emergency Medicine, Regions Hospital.

Frostbite of the foot. Photo courtesy of Kevin P. Kilgore, MD, Department of Emergency Medicine, Regions Hospital.

Frostbite of the ear. Photo courtesy of Kevin P. Kilgore, MD, Department of Emergency Medicine, Regions Hospital.

Frostbite of the hand.