1079-6061/00/4801-0171 The Journal of Trauma: Injury, Infection, and Critical Care Copyright 2000 by Lippincott Williams & Wilkins,

, Inc.

Vol. 48, No. 1 Printed in the U.S.A.

REVIEW ARTICLES

Frostbite: Pathogenesis and Treatment

James V. Murphy, MB, ChB, FRCS, Paul E. Banwell, MB, BS, BSc, FRCS, Anthony H. N. Roberts, BSc, MA, FRCS, and D. Angus McGrouther, MSc, MD, FRCS
Frostbite, once almost exclusively a military problem, is becoming more prevalent among the general population and should now be considered to be within the scope of the civilian physicians practice. Studies into the epidemiology of civilian frostbite have identified several risk factors that may aid the clinician in the diagnosis and management of cold injuries. Research into the pathophysiology has revealed marked similarities in inflammatory processes to those seen in thermal burns and ischemia/reperfusion injury. Evidence of the role of thromboxanes and prostaglandins has resulted in more active approaches to the medical treatment of frostbite wounds. Although the surgical management of frostbite involves delayed debridement 1 to 3 months after demarcation, recent improvements in radiologic assessment of tissue viability have led to the possibility of earlier surgical intervention. In addition, several adjunctive therapies, including vasodilators, thrombolysis, hyperbaric oxygen, and sympathectomy, are discussed.

rostbite may be defined as the acute freezing of tissues when exposed to temperatures below the freezing point of intact skin. The severity of injury is related to the temperature gradient at the skin surface and the duration of exposure. Once seen as a military phenomenon, the frequency in the civilian population has risen over the past two decades. Effective treatment of this condition has therefore become an issue, not only for the rural physician in polar climates, but also for many urban hospitals in the United Kingdom. HISTORICAL PERSPECTIVE The earliest documented evidence of frostbite dates back 5,000 years to a pre-Columbian mummy found in the Chilean mountains.1 More recent descriptions of cold injury have centered around military campaigns, from Xenophons writings of 210 BC2 to Dr. James Thatchers reports during the American Revolution3 and cases from the Korean and Falklands wars. Baron Dominique Larrey, Napoleons military surgeon, gave the first description of the pathophysiology of frostbite during the infamous 1812 retreat from Moscow.4 He wrote: The natural heat is absorbed and a discharge of calorick takes place, the pores close and the capillary vessels fall into a state of contraction; the fluids are condensed and flow more slowly. Larrey introduced the concept of friction massage with ice or snow and was the first to describe the similarities to burns. He recognized that warming was beneficial, but
Submitted for publication September 11, 1998. Accepted for publication January 4, 1999. From the Burns and Reconstructive Surgery Research Trust, Stoke Mandeville Hospital, United Kingdom (J.M., P.B., A.R.), and the Phoenix Tissue Repair Unit, Department of Plastic Surgery, University College, London, United Kingdom (P.B., D.M.). Address for reprints: James Murphy, MB, CHB, Stoke Mandeville Hospital, Dept of Plastic/Recon Surg, Mandeville Rd., Aylesbury, Bucks, HP21 8AL, England; Fax: 44 1296 315182.

noted the deleterious effects of the freeze-thaw-freeze cycle with the men refreezing their feet while marching on successive days. The extreme effects of cold on ground troops were again seen during the world wars of the 20th century. Many of these injuries were sustained at nonfreezing temperatures and, although similar to frostbite, were caused by prolonged immersion in cold water (1.6C 4.4C). This led to the term trench foot2,5 or immersion foot.6 Cold injury, however, was not limited to ground troops. High-altitude frostbite, first described in 1943, was recognized from the treatment of aviators during World War II. In fact, heavy bomber crews sustained more injuries from frostbite than from all other causes combined.6 Exposed to temperate days and cold nights, troops in the Korean War did not go untouched. Tropical immersion foot was noted in soldiers exposed to constant wetness at comparatively warm water temperatures7,8 and bore many similarities to the cold injuries previously described. As recently as the Falklands campaign of 1982, both British and Argentinean troops reported injuries similar to those described by Larrey after exposure to both freezing and nonfreezing water temperatures.9,10 Methods of treatment of frostbite injuries remained essentially unchanged from the time of Larreys descriptions until 1956, when Hamill first attempted rapid rewarming at 37.8C on a patient with frostbite and hypothermia.11 This landmark work has become the cornerstone of frostbite treatment today. EPIDEMIOLOGY As described, military personnel have had the greatest risk of cold weather injury until recently.12 During the past 20 years, the increasing numbers of homeless people, along with a growing participation in outdoor pursuits such as climbing and skiing, have been the factors responsible for an increased frequency of cold exposure in the civilian population.12 Although many of the larger epidemiologic studies have been
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undertaken in military populations,1317 these recent changes in demography have prompted investigators to examine the risk factors for frostbite injury in the civilian population.18 22 In a 12-year retrospective review of inpatient frostbite injuries in the northern prairies of Saskatchewan,19 alcohol consumption (46%), psychiatric illness (17%), vehicular trauma (19%), vehicular failure (15%), and drug misuse (4%) were all identified as risk factors. The high frequency of alcohol consumption in this series is of particular significance and may be explained by the observation that the severity of frostbite injury appears to correlate with duration of exposure rather than with ambient temperature. Although tissue freezes more quickly at lower temperatures, the degree of irreversible damage is related to the length of time the tissue remains frozen; therefore, either a delay in presentation or extended exposure to cold will greatly worsen the prognosis. For this reason, alcohol consumption has been identified as a particular risk factor because of its effects on an individuals judgement as well as its vasodilatory effects.19,20,23 Similarly, psychiatric illness may lead to inappropriate behavior or clothing. In the Saskatchewan study, 17% of the frostbite patients whose cases were reviewed displayed overt psychiatric illness. This occurred in a predominantly rural population; studies of urban frostbite populations have suggested the overall rate of occurrence may be higher. In one series of 20 patients, all had overt or covert psychiatric disease.18 This prompted a retrospective review that placed the rate of occurrence between 61% and 65%. Some centers now advocate psychiatric screening in all cases of urban frostbite injury. Medical conditions with associated circulatory impairment, such as atherosclerosis, have also been implicated, as has the vasoconstrictive effect of smoking.21,22 The role of diabetes mellitus in frostbite is unclear, but it may be related to underlying peripheral vascular disease as well as to peripheral neuropathy clouding patient awareness of pain. Other studies have identified homelessness, fatigue, improper clothing, previous history of cold weather injury, and high altitude (above 17,000 feet)22 as important factors.21,24 26 Contrary to some studies,27,28 the elderly and the young do not appear to be high-risk groups. Adults aged between 30 and 49 years are most commonly affected,19,26,29 31 with men generally outnumbering women by 10 to 126 or more.22 The extremities are the most susceptible anatomic sites; hands and feet account for 90% of all recorded injuries. Other common sites include ears, nose, cheeks, and penis.14,19,26,29 33 Frostbite injury usually results in a prolonged reduction in tolerance to cold in the injured part.26 Conversely, the concept of physiologic adaptation to cold is controversial. It has been suggested that Eskimos feel the cold less than inhabitants of temperate climates do. Many authors, however, allege that this resistance is no more than a result of experience in Arctic survival and day-to-day living.13,34 Furthermore, although they may not feel the cold as fast, Eskimos freeze just as quickly as others do given the same contact situation.35 There is, as yet, no convincing evidence that true tolerance to cold exists.
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PATHOPHYSIOLOGY Frostbite represents a spectrum of injury severities ranging from irreversible cellular destruction to the reversible changes seen after rewarming. The exact mechanism of injury has been the subject of increasing investigation in recent years. Two distinct mechanisms are apparently responsible for tissue injury: (1) cellular death occurring at the time of exposure to the cold, and (2) deterioration and necrosis attributable to progressive dermal ischemia.36 38 Direct Cellular Damage The freezing of tissue leads initially to the formation of extracellular ice crystals. These crystals directly damage the cell membrane and change the osmotic gradient across it, resulting in intracellular dehydration.24 The intracellular electrolyte concentration increases dramatically, initiating cell death. As the temperature of the tissue continues to fall, intracellular ice forms. These ice crystals expand, causing the mechanical destruction of cells.39 Initially, the body responds to tissue cooling by alternating cycles of vasoconstriction and vasodilatation; this is known as the hunting reaction.40 With vasodilatation comes the reestablishment of blood flow and, thus, thawing; it is this partial thawing and refreezing, as first described by Larrey,4 that causes the most damage.27,39 After repeated freeze/thaw cycles, a progressive thrombotic phase is seen to take place.41,42 Attempts to prevent this thrombosis with agents like heparin, low molecular weight dextran, vasodilating agents, or sympathectomy have yielded mixed results.37,43,44 This suggests that systems other than the coagulation cascade mediate this delayed process of progressive dermal ischemia. Progressive Dermal Ischemia The process of progressive ischemic damage seen in cases of frostbite shows marked similarities to that seen in thermal burn injury cases44,45 (Fig. 1). Numerous studies in burn models have produced considerable evidence regarding the role of inflammatory mediators such as prostaglandins and thromboxanes,46 49 bradykinin,50 and histamine51 in edema formation, endothelial injury, and subsequent arrest of dermal blood flow52,53 (Jacksons zone of stasis54). This evidence has prompted investigators to examine the role of the same inflammatory mediators in frostbite. Robson and Heggers, using the classic frostbite rabbit ear model, found markedly elevated levels of prostaglandin F2 and thromboxane B2 (a stable metabolite of thromboxane A2) in frostbite blister fluid;44 these results closely mirrored their findings in burn injury studies.55,56 Manipulation of these mediators has had similar effects in both conditions. Inhibitors of eicosanoid production have been shown to have significant effects on dermal perfusion and tissue survival in both burn and frostbite animal models. Several studies demonstrated preservation of the dermal microcirculation by the use of various thromboxane and prostaglandin inhibitors in burns.57 61 Similarly, Raine et al.62 found significantly improved tissue survival in rabbit ear frostbite with prostaglandin and thromboxane inhibitors.

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FIG 1. The pathophysiology of progressive ischemia in frostbite injury. TXA2, thromboxane A2; PGF2 , protaglandin F2 ; CAMs, cellular adhesion molecules; MMPs, matrix metalloproteinases; ROS, reactive oxygen species.

The metabolites of arachidonic acid have thus been heavily implicated as mediators of progressive dermal ischemia in burn, frostbite, or ischemia/reperfusion injuries. Studies in burns have suggested that edema formation and endothelial injury, widely held to be responsible for the arrest of blood flow, are caused by a number of interrelated mechanisms and that other components of the inflammatory response may also play a role. The obstruction of postcapillary venules28 by what are believed to be either leukocytes63 or platelet microthrombi, 64,65 as well as eicosanoid-mediated changes in vascular permeability, have been observed in burn wounds. Adherent neutrophils have also been cited as important components of ischemia/reperfusion injury66 68 and are increasingly thought to be important in burns.69,70 The shedding of white clots within small arterioles, followed by obstruction of the lumen, has been observed in both burn64,65 and frostbite injury,71 although the exact nature of the vascular injury and the composition of these microemboli are, as yet, undetermined. CLINICAL MANIFESTATIONS At the time of initial evaluation, most true frostbite injuries appear similar. For this reason, classification of frostbite is applied after rewarming. Historically, frostbite has been categorized into four degrees. In first-degree frostbite, there is a numb central white plaque with surrounding erythema. Second degree injury causes blister formation surrounded by erythema and edema. These blisters fill with clear or milky fluid in the first 24 hours. Third degree injury is characterized by hemorrhagic blisters that result in a hard black eschar 2 weeks later. Fourth degree injury produces complete necrosis and tissue loss. Although these are accurate descriptions of wound conditions after rewarming, they have not proven useful in predicting the extent of progressive damage that then occurs; therefore, they do not correlate well with clinical outcome. They also do
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little to aid the clinician in initial management because the treatment for all classes of frostbite is the same until demarcation has occurred 3 to 4 weeks after injury. Some authors, therefore, prefer to describe just two classes of injury, superficial (1 and 2) and deep (3 and 4), which, being broader groups, appear to predict outcome more accurately. Physical examination of the injured part can reveal favorable prognostic indicators such as sensation to pinprick, normal skin color, and large blisters that fill with clear, rather than milky, fluid. In addition, the ability of the skin to deform under direct pressure is taken as a sign of dermal viability and thus good prognosis. Conversely, dark fluid-filled blisters, nonblanching cyanosis, and hard, nondeforming skin herald a poor prognosis. Symptoms follow a predictable pathway and their severity can provide indications as to the potential severity of the injury. Initially, the patient may describe a feeling of numbness in the affected part. In the case of the hands, this is often accompanied by clumsiness and a lack of fine control. This numbness often gives way to a throbbing sensation on rewarming that may last for days or even weeks. A residual tingling sensation may then develop, with occasional electric shock-type sensations. In the long term, cold sensitivity, sensory loss, and hyperhidrosis may persist in the affected part for years.12 Less commonly, growth plate disturbances,40,72 osteoarthritis,73 chronic pain,40 and heterotopic calcification74 have also been reported. Chilblains, or pernio, represent a mild form cold injury that may be considered separately from true frostbite. They consist of red, itchy lesions, usually on the dorsum of the foot, caused by prolonged exposure to above-freezing temperatures in the presence of high humidity. The condition is self-limiting and treatment is conservative, with elevation and application of moisturizing lotions. Mere numbness followed by tingling after rewarming does not constitute bona fide frostbite. Even in its mildest forms, true frostbite damages the affected tissues. RADIOLOGY The difficulties associated with an early and accurate diagnosis of the level of tissue destruction prevent the routine use of early surgical debridement in the cold-injured patient. In addition, there is often a discrepancy between the limit of the skin lesions and the extent of damage to deeper structures. Several radiologic techniques have been applied to this problem in an attempt to provide an accurate early assessment of tissue viability. These include plain radiographs, venous radioisotope scanning (131I, 133Xe, and 99Tc), angiography, and digital plethysmography for assessment of tissue perfusion. Plain radiographs may be helpful in the assessment of frostbitten extremities. Early radiographic manifestations include soft tissue swelling and loss of tissue, especially at the tips of the digits; osteoporosis and periosteitis may occur at a slightly later stage.75 Late skeletal manifestations are variable. In children, epiphyseal injuries involve primarily the distal phalanges,

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although other phalangeal epiphyses and, rarely, metacarpal or metatarsal epiphyses can be affected.75 Fragmentation, destruction, and disappearance of epiphyseal centers are seen. Premature epiphyseal fusion may be noted, resulting in brachydactyly, and secondary infection of bone or joint may also be apparent on plain radiographs. Interphalangeal joint abnormalities that relate to injury to the articular cartilage may eventually simulate osteoarthritis. Tuftal resorption of terminal phalanges, a common late manifestation, can usually be traced to loss of overlying soft tissue structures.76 In the early stages, arteriography demonstrates marked slowing of blood flow in sizeable branches. As rewarming occurs, arterial flow improves but residual occlusions are often noted.77 Angiography has been used in the diagnosis and treatment of cold injury, although arteriograms obtained soon after injury do not sufficiently clarify levels of viability.5 The addition of a vasodilator during early arteriography has been useful in predicting the final pattern, seen 3 weeks or more after injury.78 Laser Doppler flowmetry appears to offer accurate assessment of vasomotor status,79 although no series have been published in this context. Technetium scintigraphy has become the standard imaging study used within the first few days after injury.80 82 Use of this technique has been suggested to assess tissue viability in an effort to allow earlier debridement of soft tissue and coverage of ischemic bony structures.83,84 Bone scans, however, fail to show either the condition of the surrounding tissue or a clear-cut soft tissue demarcation, and some authors85 are now advocating magnetic resonance imaging and magnetic resonance angiography as superior techniques. These techniques, by allowing direct visualization of occluded vessels and imaging of the surrounding tissues and by showing a more clear-cut line of demarcation of ischemic soft tissue, may make earlier surgical intervention possible. The fact that the fingers and toes contain little or no striated muscle may, however, limit this potentially useful technique to more proximal injuries.79 Overall, no prognostic technique has been conclusively shown to be satisfactorily accurate in the immediate postthaw period. A delay of two to three weeks is still necessary to exceed the period of transitory vascular instability before any radiologic technique can reliably distinguish the line of demarcation and the required level of debridement or amputation. Magnetic resonance techniques may alter this situation; as yet, no significant series have been published. MANAGEMENT OF FROSTBITE The treatment of cold injury is surrounded by controversy and only a few principles appear to be universally accepted. Broadly speaking, treatment can be divided into three phases: (1) prethaw field care phase, (2) immediate hospital (rewarming) phase, and (3) postthaw care phase, which continues for several weeks or months. 1. Prethaw Field Care. Before evaluation by a specialist center, care of the patient with a potential frostbite injury is focused on protection of the involved part from mechanical trauma and avoidance of thawing until definitive rewarming
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TABLE 1. Treatment protocol for frostbitea

1. 2.

Admit frostbite patient to a specialist unit, if possible. On admission, rapidly rewarm the affected areas in warm water at 4042C (104108F) for 15 to 30 minutes or until thawing is complete. 3. On completion of rewarming, treat the affected parts as follows: a. Debride white blisters and institute topical treatment with aloe vera (Dermaide aloe) every 6 hours. b. Leave hemorrhagic blisters intact and institute topical aloe vera (Dermaide aloe) every 6 hours. c. Elevate the affected part(s) with splinting as indicated. d. Administer antitetanus prophylaxis (toxoid or Ig). e. Analgesia: opiate, intramuscularly or intravenously as indicated. f. Administer ibuprofen 400 mg orally every 12 hours. g. Administer benzyl penicillin 600 mg every 6 hours for 48 to 72 hours. h. Perform daily hydrotherapy for 30 to 45 minutes at 40C. 4. For documentation obtain photographic records on admission, at 24 hours and serially every 2 to 3 days until discharge. 5. Prohibit smoking.
a

Adapted from McCauley et al.45

can be performed. Rubbing of the affected tissue with a warm hand or snow, once the mainstay of treatment, does not augment local blood flow and may cause undesirable mechanical trauma.3,40 As previously stated, repeated bouts of thawing and refreezing result in worsening injury.27,39 During transport to hospital facilities, therefore, the extremity should not be intentionally rewarmed and should be protected against slow partial rewarming by avoiding patient contact with fires or heaters. The extremity should be padded and splinted for protection, but no other treatment should be initiated. 2. Rewarming. It has only been since the Second World War that the importance of rapid rewarming has been appreciated. Prior to that time, it was postulated that application of external heat to a cold-injured part would increase the metabolic demands of the tissue to an extent that would cause a greater degree of necrosis than the cold injury alone.37 Studies by Fuhrman and Crimson,86,87 and later by Finneran and Schumacker,88 have shown this not to be the case. Entin and Baxter seemed to settle the issue in a controlled series of experiments, concluding that the ideal temperature at which the part should be rewarmed was 40C.89 The current thinking in hospital frostbite care is largely based around the work of McCauley and Heggers, and many units protocols5,23,29 follow their example (Table 1). Rewarming should be carried out in a waterbath with a mild antibacterial agent (hexachlorophene or povidone-iodine) at the generally accepted temperature of 40C to 42C.5,35,40,62 Adherence to this narrow temperature range is important; rewarming at lower temperatures is less beneficial to tissue survival and rewarming at higher temperatures may compound the injury by producing a burn wound.11 Rewarming should be continued for 15 to 30 minutes until thawing is complete. A red/purple appearance and pliable texture of the involved part signal the end of vasoconstriction and are signs that warming should cease.40,90 Active motion during re-

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warming is helpful, but massage should be avoided. Intravenous fluid resuscitation is not normally required for frostbite injury itself, although there are cases reported of rhabdomyolysis and subsequent renal failure.91 In addition, the hypothermic patient may exhibit a cold diuresis because of suppression of antidiuretic hormone secretion at low temperatures.113 This often requires compensation with intravenous fluid. 3. Postthaw Care. Rapid rewarming does reverse the direct effects of ice crystal formation within the tissue, but it does nothing to prevent the progressive dermal ischemia seen in the postthaw phase; actually, it appears to contribute to it (Fig. 1). Work by McCauley et al.45,92 into the pathophysiology of progressive dermal ischemia has resulted in a protocol for the acute management of frostbite injuries in the rewarming and postthaw phases that attempts to combat the inflammatory processes previously described (Table 1). This protocol represents the only published attempt to base a therapeutic strategy on current knowledge of the pathophysiology of this condition, and that aims to suppress local and systemic production of thromboxane by the injured tissue as well as rewarm, provide adequate analgesia, and prevent potentially catastrophic infection. There are, however, several points that warrant discussion. White or clear blisters represent superficial injury and require debriding to prevent further contact with the high levels of protaglandin F2 and thromboxane A2 in the exudate.44 Hemorrhagic blisters, however, represent structural damage to the superficial dermal plexus and, although it may be beneficial to aspirate the exudate from these blisters, the risk of desiccation has led most,23,29,39 although not all,40 authors to advocate that they be left intact. This controversy is undoubtedly a result of the distinct absence of practical clinical data supporting either practice. In the past, aspirin has been given as a systemic antithromboxane agent.27,45,62 However, the correct dose of aspirin for thromboxane inhibition has not been established.35 Aspirin inhibits the synthesis of prostaglandins, including some prostaglandins that are beneficial to wound healing.45 For these reasons, aspirin has been superseded by ibuprofen12,24,40 for this application. Aloe vera is used as a topical inhibitor of thromboxane62 and, when used in conjunction with ibuprofen and prophylactic penicillin, has been shown to result in less tissue loss.39 Similarly, when used in conjunction with the vasodilator oxpentifylline, topical aloe vera led to a 30% improvement in tissue survival.93 Elevation, and the subsequent minimization of edema, has two effects. Edema formation has been implicated in the pathogenesis of progressive dermal ischemia.52,64,65 In addition, edema has been found to inhibit the skins own streptococcicidal properties. For this reason, penicillin is the prophylactic antibiotic of choice for many centers,19,24,29 although some authors reserve antibiotics for specific infectious complications.12 The cold-injured part should be considered a tetanus-prone wound; therefore, prophylaxis is indicated, depending on the patients immunization record3,24,40
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The regime of daily hydrotherapy aids debridement of devitalized tissue,40,45 but is also aimed at maintaining active and passive ranges of movement and is essential for the preservation of function.94 ADJUNCTIVE THERAPIES A number of therapeutic modalities have been examined in attempts to prevent or diminish the progressive dermal ischemia seen in frostbite. Low-molecular weight Dextran. The phenomenon of erythrocyte clumping seen in the microcirculation does not represent true thrombosis and may be a result of increased blood viscosity.35 It has, therefore, been suggested that the use of low-molecular weight dextran may be of benefit in the early treatment of frostbite. This has yet to be confirmed in any clinical trial, but animal experiments have demonstrated protection against tissue loss.36 Anticoagulation. In the first few days after thawing, thrombosis is seen to occur in the superficial dermal plexus. Anticoagulation, particularly with heparin, has been suggested as a possible treatment for frostbite but, despite investigation,95 there is no evidence that heparin or any other anticoagulant alters the natural history of frostbite.35 Vasodilators. Intra-arterial injection of reserpine has been angiographically successful in reducing vasospasm.96 However, this has not translated into significant reductions in tissue loss. Snider et al97 compared slow rewarming with various combinations of dextran and vasodilators in animal models. All drug combinations were better than slow rewarming alone but rapid rewarming was as effective as any of the drugs. Reserpine may have a role in patients presenting late and in those who have not been rapidly rewarmed, but there is no controlled clinical data to back this up. Thrombolysis. Thrombolytic agents have been investigated in animal models with striking improvements in the degree of tissue survival.98 In addition, it has been noted that streptokinase, used in this study, was effective when begun 12 to 24 hours after insult. These results have yet to be repeated in a clinical environment. In a pilot study of 14 patients with third-degree frostbite, 10 received supportive treatment only, whereas the other 4 received infusions of tissue plasminogen activator.99 All 10 patients in the control group had amputations at or near the level of vascular cutoff (assessed by Tc-99 bone scans). The tissue plasminogen activator group showed significant reperfusion distal to the vascular cutoff level, and three of the four patients avoided surgery altogether. Both of these studies present promising, but inconclusive, results. However, a multicenter trial is now planned. Sympathectomy. The role of regional sympathectomy has received considerable attention. The current literature contains work both supporting and discrediting its use.100 102 Experimental evidence indicates that sympathectomy performed within the first few hours of injury increases edema formation and accelerates tissue destruction.36,103 However, if sympathectomy is delayed until 24 to 48 hours after thawing, there appears to be more rapid resolution of edema and decreased tissue loss.103 Until a prospective randomized se-

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ries is published in this regard, the indications and optimum timing of sympathectomy will remain unclear. Of interest, Flatt104 has described the use of digital surgical sympathectomy in the management of chronic vasospasm in the hand. His results in relieving vasospastic pain were significant and this form of therapy appears encouraging. Hyperbaric oxygen. The potential benefits of hyperbaric oxygen (HBO) therapy are based on outdated concepts of the pathophysiology of frostbite. That said, there are numerous case reports available, although control data are few. In human volunteers, HBO has caused vasoconstriction and reduction in blood flow. Hyperbaric treatment begun between days 5 and 10 after injury resulted in pinking of the affected areas and an immediate increase in warmth and limb movement;105 it also appeared worthwhile in another series of three patients.106 Experiments in rabbits, however, showed that tissue loss and variation in injury were no different with or without HBO.107,108 Other studies have contradicted these results by finding that, when administered immediately after rewarming, the mean tissue loss was decreased in the rabbit if HBO was given for 2 hours daily; however, 1 hour treatments, or a delay in treatment beyond 24 hours, was considerably less effective.109,110 Surgical treatment. Frostbite in January, amputate in July.40 Surgical debridement is normally reserved for the late treatment of frostbite.35 Escharotomy or fasciotomy may be indicated in the early phase if circulation is impaired or compartment syndrome develops,40,45 though this is rare. Limited or early debridement should only be undertaken in the presence of subeschar infection that cannot be controlled by topical antimicrobials.111 Normally, aggressive therapeutic and medical measures, as described above, can prevent the development of progressive injury and gas gangrene. In the absence of gas gangrene, mummification of the extremity occurs over 1 to 3 months. At this stage the decision can be made whether to debride (with or without reconstruction) or to allow autoamputation. Historically, aggressive early surgical intervention and attempted salvage have been thought to insult potentially viable, recovering tissue and thus increase tissue loss. The absence of accurate radiologic assessment of viability has meant that the appropriate level of amputation is not clear until the tissue declares itself. Some authors are now advocating a more aggressive approach with the advent of technetium scintigraphy80,81,83,84 and advancing role of magnetic resonance imaging.85 Preliminary results suggest that improved imaging may lead to reduction in length of hospital stay and still allow maximum stump length preservation.112 In this setting, the viability of injured bone, tendon or nerve is felt by some to be improved by coverage with vascularized tissue and free tissue transfer, rather than autograft, is often required.114,115 CONCLUSION Increased participation in outdoor activities and the epidemic of homelessness have caused the incidence of frostbite injury in the civilian population to rise significantly over the past 2 decades. Knowledge of the treatment of frostbite is, therefore, crucial for
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physicians in both rural and urban areas. Research over the past 15 years has led to a greater understanding of the pathophysiology of cold injury and a realization of the significance of the inflammatory mediators, prostaglandin F2 and thromboxane A2, involved in this process. This has resulted in the development of new active regimes for the treatment for frostbite, such as use of the antiprostaglandin agents ibuprofen and aloe vera, as well as the widespread acceptance of the importance of rapid rewarming. Parallel work performed in burn and reperfusion injury research will continue to provide new avenues of investigation for other adjuvant therapies. Together with improved radiologic assessment of tissue viability, research should allow a more aggressive and proactive approach to the management of this condition.
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