You find yourself working the overnight shift on sub-zero night in February. You stop outside of a room to listen to the ambulance report about a homeless patient who has been brought in for foot pain. He is intoxicated and was found asleep in a snow bank.
You find yourself working the overnight shift on sub-zero night in February. You stop outside of a room to listen to the ambulance report about a homeless patient who has been brought in for foot pain. He is intoxicated and was found asleep in a snow bank. After confirming that your patient is not hypothermic you begin undressing him and are surprised to find toes with multiple areas of eschar and tissue loss.
Frostbite is a freezing injury of peripheral tissues. It is characterized by extracellular crystal formation and micro-vascular thrombi that lead to localized cell death and inflammation, placing the digits or limbs involved at risk for amputation.
When peripheral tissues are exposed to temperatures below 10°C, microvascular vasoconstriction promotes interstitial plasma leakage. As temperatures drop below 0°C, extracellular ice crystals begin to form, resulting in localized cell death related both to structural damage from ice crystals and efflux of free water from intracellular spaces.
Additional injury occurs with tissue thawing and is characterized by localized micro-vascular thrombi and inflammation. Micro-vascular thrombi are related to sludging of highly viscous blood, persistent microvascular vasospasm and localized endothelial damage. These microvascular thrombi lead to distal ischemia and necrosis. The combination of tissue necrosis from both cellular collapse and ischemia related to microvascular thrombosis causes activation of an inflammatory cascade, resulting in tissue edema and bullous formation.
Classifying the degree of tissue injury
Irreversible tissue damage can ultimately lead to tissue gangrene, which requires surgical debridement and amputation. The process of tissue demarcation can take several weeks to months. As such, many attempts have been made to predict the extent of cell injury and death in the more acute phase so that early treatment can be initiated.
Historically frostbite has been classified in much the same fashion as burns:
- First degree: Superficial injury. Characterized by localized pallor with waxy texture and anesthesia with surrounding erythema and tissue edema.
- Second degree: Superficial partial-thickness injury. Characterized by clear fluid filled blisters that form within the first 24 hours and are located at the distal aspects of the affected tissue.
- Third degree: Deep partial-thickness injury. Characterized by smaller, more proximal hemorrhagic vesicles.
- Fourth degree: Full thickness injury. Characterized by tissue injury that extends into underlying muscle, tendon and bone. On exam, tissue is firm and non-mobile with inability to move tissue over the underlying bone. Results in tissue mummification.
While this historical classification system provides a convenient method for describing the acute injury pattern it is not effective in predicting the degree of tissue loss or need for amputation. A more practical classification of frostbite simply describes tissue injury pattern as superficial (corresponding to first and second degree injury) or deep (corresponding to third and fourth degree injury).
Additional adjuncts to assessing degree of tissue injury include plain radiographs and dual phase scintigraphy. Plain radiographs can evaluate for bony injury or subcutaneous gas, the latter of which is an ominous sign and predictive of need for emergent debridement or amputation. In more chronic injuries, findings include degenerative changes and, in pediatric populations, dwarfing of phalyngeal bones, collapse of growth plates and abnormal articular surfaces. Generally these findings take weeks to months to develop and are not particularly useful in emergent evaluation.
There is evidence that Technitium-99 scintigraphy can be useful in the acute to subacute phase for predicting the need for amputation. In retrospective studies of patients with severe frostbite, high bony uptake during dual phase scintigraphy is highly predictive of tissue healing, with a negative predictive value for amputation of 99%. Conversely, low to no uptake in the bony phase has a sensitivity, specificity and positive predictive value for amputation of 96%, 99% and 92%, respectively [1,2]. However, most studies performed imaging 2-8 days after rewarming, thus the role of scinitigraphy in the emergency department is limited.
While extremity frostbite can be limb threatening, providers should first exclude more life threatening conditions such as systemic hypothermia, concomitant trauma, or dehydration and electrolyte abnormalities associated with prolonged exposure to extreme environmental conditions.
The mainstay of treatment for frostbite involves rapid and definitive rewarming of the tissues. This should occur in a stable environment where there is no risk of re-freeze, as continued freeze/thaw cycles can lead to increasing tissue damage and necrosis. The ideal method for rewarming is a water bath set at a temperature between 37C-42C.
Rewarming often takes 10-30 minutes and should continue until the injured tissue becomes pliable and distal erythema is noted. It is important to completely rewarm tissues, as incomplete rewarming can result in worsening tissue damage. Of note, the rewarming process can be quite painful and patients often require parenteral pain control during this period.
Given the high degree of morbidity associated with frostbite, particularly the frequent need for amputation, a number of adjunctive medical therapies have been proposed to further salvage tissues that have previously been considered non-viable. These include thromboxane inhibitors, pentoxifylline, thrombolysis, and hyperbaric oxygen.
The use of thromboxane inhibitors has long been considered an adjunct in the treatment of frostbite injury. In an animal model of induced frostbite and various thromboxane inhibitors, methimazole use resulted in a 34% increase in viable tissue, topical aloe vera resulted in a 28% increase, and aspirin resulted in a 22% increase in viable tissue .
Pentoxifylline has long been used in the treatment of peripheral vascular disease, specifically vascular claudication, due to its anti-inflammatory properties and ability to improve red cell deformities and reduce blood viscosity. As increased blood viscosity lead to microvascular thrombi, prevention of these thrombi should theoretically improve outcomes in moderate to severe frostbite. This improvement in outcome has been demonstrated in multiple animal studies; however, to date there have been no human studies confirming these effects [4,5].
Given the significant role microvascular thrombosis plays in the pathophysiology of frostbite, the use of thrombolysis has been proposed to improve tissue survival. While heparin has not been shown to improve outcomes in frostbite, several studies have demonstrated that intravenous or intra-arterial tissue plasminogen activator (tPA) results in improved tissue survival and reduced amputation rate. Generally, tPA is restricted to patients who have failed treatment with rapid rewarming (as noted by lack of distal pulses on exam and/or with no uptake noted on technitium bone scan) who have had less than 24-48 hours of cold exposure, have not had multiple freeze-thaw cycles and have less than 6 hours of warm ischemic time. In this specific patient population, studies have shown up to an 81% digit salvage rate [6,7].
Finally, there are multiple case reports of hyperbaric oxygen therapy improving function and pain with severe frostbite, as well as preventing amputations. However, there are no large studies that have fully evaluated the risks, benefits and specific populations for which hyperbaric therapy is safe and effective.
Generally patients with severe frostbite require admission for rewarming and pain control. When possible, severe frostbite should be treated in centers that specialize in the treatment of similar wounds, such as burn centers. In cases where tPA is indicated transfer to a center with experience in managing these severe cases may be warranted.
Other cold weather injuries
Pernio, or chilblains, is a non-freezing injury that results in edematous red lesions to the fingertips or toes, usually occurring in young females. Patients typically complain of intense pain, itching, or burning. This exaggerated inflammatory response is due to local vasoconstriction, resulting in hypoxemia and vascular inflammation. Standard treatment is re-warming and patients should be advised lesions typically last 1-2 weeks . Some patients develop recurrent episodes of pernio, and may benefit from a calcium channel blocker such as nifedipine, which has been shown in randomized trials to reduce pain, facilitate healing, and prevent new lesions .
Trench foot, or immersion foot, is a non-freezing injury initially described in soldiers during World War I, but is now more commonly seen in homeless individuals due to prolonged exposure to cold and damp conditions. On exam, trench foot appears swollen, red, and edematous with numbness and burning. Later in the clinical course, this progresses to pallor with increased skin sensitivity, blistering, and tissue maceration. Treatment for trench foot consists of removing any wet shoes or socks, cleaning and drying the feet, then applying warm packs to the affected area with placement of new dry footwear .
Jesse Loar, MD and Howard Kim, MD are PGY-4 residents at the Denver Health Residency in Emergency Medicine.
Michael Breyer, MD is an Associate Program Director at Denver Health.
Photos courtesy of Peter Pryor, MD
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2. Cauchy et al. “The role of bone scanning in severe frostbite of the extremities: a retrospective study of 88 cases.” Eur J Nucl Med. 2000 May; 27 (5): 497-502
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