J Am Board Fam Pract: first published as 10.3122/15572625-11-1-34 on 1 January 1998. Downloaded from

CLINICAL REVIEW : Review and Current Concepts

Brian V. Reamy, MD, Maj, USAF

Background: A literature review was conducted to analyze developments in the epidemiology, pathogenesis, treatment, and prevention of frostbite . Increased participation in outdoor activities, as well as the epi­ demic of homelessness, makes knowledge of the treatment of frostbite crucial for physicians in both rural and urban areas. Methods: A literature search, using the key words "frostbite" and "cold," was done using MEDUNE and In­ dex Medicos. This search focused on the epidemiology, pathogenesis, treatment, and prevention of frostbite. Results: Research done during the past 15 years has clarified the pathogenesis of frostbite injury and led to a better understanding of how to limit tissue loss. The etiology of frostbite is commonly related to alcohol use, psychiatric illness, or motor vehicle problems. The pathogenesis is linked to tissue freezing, hypoxia, and the release of inflammatory mediators. The initial clinical manifestations of frostbite injury are similar for superficial and deep tissue damage, so early treatment is identical for all . Optimum therapy is based on the rapid reversal of tissue freezing by rewarming in 104-108°F water and the institution of oral and topical antiprostaglandin therapy to limit the release of inflammatory mediators. Conclusion: Rapid triage and treatment of frostbite can lead to dramatic improvements in outcome and prognosis. Increased awareness of antiprostaglandin therapy and preventive measures is crucial for physi­ cians in diverse practice environments. U Am Board Fam Pract 1998;11:34-40.)

Research during the past 15 years has clarified the of homelessness in the United States has made pathogenesis of frostbite injury and led to a frostbite injury and its effective treatment an issue clearer understanding of what ideal therapy com­ not only for the rural physician practicing in the prises. New treatments now can limit the extent heart of Alaska, but also for many urban hospitals of tissue loss and increase the speed of rehabilita­ across the country.2,3 In addition, increased partic­ tion. At the same time, the usefulness of many ipation in outdoor activities and sports in in-.

pharmacologic agents, the debridement of blis­ clement environments has contributed to an in­ http://www.jabfm.org/ ters, and the use of prophylactic has creased population at risk for frostbite injury and been refined. its oftentimes crippling sequelae.4 In the past frostbite was primarily a concern of Knowledge of new research findings permits the military. It has been a leading cause of devas­ physicians to use rapid triage and proper therapy tating casualties in wars from the time of Hanni­ for frostbite injury, which are key in improving the

bal, who lost one half of his army crossing the AIps prognosis and future functional level of their cold­ on 1 October 2021 by guest. Protected copyright. in 218 Be, to World War II and the Korean War, injured patients. This literature review summa­ where more than 10 percent of total American ca­ rizes current insights into the epidemiology,· sualties were due to cold injuries. The German pathogenesis, and prevention of frostbite. In addi­ Anny alone performed more than 15,000 amputa­ tion, a suggested approach to the treatment of the tions for cold-related injuries on the Russian front frostbite-injured patient is outlined. in the winter of 1942.1 Recently concern about frostbite injury has Methods become more widespread. The growing epidemic A search was done of the literature from 1966 to 1996 in MEDLINE and from 1960 to 1965 in In­ dex Medicus, using the key words "frostbite," and Submitted 29 April 1997. From the Department of Family Practice, David Grant "cold." These principal key words were cross­ Medical Center, Travis Air Force Base, Calif. Address reprint referenced with epidemiology, pathogenesis, requests to Maj Brian V. Reamy, MD, Department of Family Practice, David Grant Medical Center, 101 Bodin Circle, signs and symptoms, diagnosis, treatment, and Travis Air Force Base, CA 94535. prevention.

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Epidemiology Pathogenesis There are several risk factors for frostbite injury The pathophysiologic mechanism that underlies that have been described in many large epidemio­ frostbite injury has been studied in humans, rab­ logic studies done around the world.5-7 A 12-year bit , hamster cheeks, and other models for study tracking injuries to 650,000 people living in years. Currently there is a general consensus Saskatchewan found the following predisposing among investigators as to the events that cause in­ factors: alcohol consumption (46 percent), motor jury and ultimately cell death if frostbite is not re­ vehicle problems (19 percent), and psychiatric ill­ versed early.4,9,13,15-l7 Three pathways trigger the ness (17 percent).8 Alcohol consumption is par­ pathologic changes of frostbite: tissue freezing, ticularly devastating because it has deleterious ef­ hypoxia, and the release of inflammatory media­ fects on judgment and promotes peripheral tors. These pathways occur almost simultane­ vasodilatation, so it can result in subsequently ously and intensify the damage caused by each more severe local injury. Other studies from Nor­ other (Figure 1).4,9,13,15-17 way, Finland, and the United States have linked The freezing of tissue leads to the formation of frostbite to homelessness, improper clothing, a ice crystals, first extracellularly and then intracel­ history of previous cold injury, fatigue, in­ lularly, which damage cell membranes. Subse­ fection, atherosclerosis, , and smoking.9- quently, water is osmotically drawn out of cells, 12 The vasoconstrictive effects of smoking can leading to intracellular dehydration and cell death. both trigger and compound cold injury to the Additionally, freezing irreversibly denatures mem­ . In contrast, acclimatization, physical train­ brane lipid-protein complexes, triggering further ing, general good health, normovolemia, exercise, cellular damage.9 and adequate protective clothing can help pre­ The second pathway leading to damage is cold­ vent frostbite even under extremely difficult cir­ induced local vasoconstriction, which leads to tis­ cumstances.13 sue hypoxia. Initially the body responds to tissue Earlier studies have classified the elderly and cooling by alternating cycles of vasoconstriction young children as groups at high risk for frost­ and vasodilatation, "the hunting reaction."IS bite injury. 14 Although this grouping seems intu­ When the maintenance of overall body core tem­ itively correct, the published epidemiologic stud­ perature is threatened by continued exposure to ies do not show a high incidence of frostbite in cold, the hunting reaction ceases and local vaso­ these age groups. Instead, frostbite injury is most constriction persists, triggering hypoxia, acidosis, common in adults aged 30 to 49 years.2,3,6,8,1l and increased local viscosity. Eventually http://www.jabfm.org/ Studies also reveal clear evidence of the anatomic capillary blood flow ceases, arterioles and venules sites most at risk for frostbite. The feet, the most become thrombosed, and irreversible tissue hy­ commonly affected site, and the hand account for poxia occurs. 90 percent of injuries reported. The next most Endothelial injury, hypoxia, and local throm­ frequently injured sites are the ears, nose, cheeks, bosis promote the third pathway of damage-the and the penis.2,3,5-8,1l release of inflammatory mediators. The release of The need to amputate injured parts in most the potent prostaglandins PGF2 and thromboxane on 1 October 2021 by guest. Protected copyright. studies was closely correlated with the duration of A2 trigger further vasoconstriction, platelet aggre­ cold exposure rather than temperature.S,8,ll Al­ gation, and blood vessel thrombosis, which though the skin freezes more quickly at colder worsen endothelial damage and set off a further temperatures, the amount of permanent damage is cascade of hypoxia and cell death.9,13,15-17 These linked to the total time the tissue is frozen. The mediators have been found in cold-injured tissues detrimental effects of ice crystal formation, intra­ and the fluid of damaged skin. Further­ cellular dehydration, vasoconstriction, and the more, they have been shown to be the prime me­ formation of inflammatory mediators that lead to diators of progressive tissue in both cold­ cell death are time-dependent phenomena. For and heat-injured skin. I6,17 The release ofthese these reasons psychiatric disturbance and alcohol mediators peaks during rewarming, and cycles of abuse are important risk factors for frostbite in­ recurrent freezing and warming increase their tis­ jury, because they can impair judgment and result sue levels. 16 Consequently, rewarming should not in extended exposure to cold. be attempted until the thawed body part can be

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Tissue freezing

1. Ice crystals I 2. Intracellular dehydration I 3. Cell death t Frostbite injury ~ ~ 4. iVasoconstriction 4. Endothelial injury /' ""'- 3. Vessel thrombosis 3. Vessel thrombosis /' ""'- 2. Platelet aggregation 2. ielood viscosity ./ 1. PGF2• TA2• O2 radicals 1. Local acidosis" Release of Local inflammatory hypoxia mediators

Figure 1. Pathogenesis of frostbite injury. PGF2 - prostaglandin F2, TA2 - thromboxane A2, O2 - molecular oxygen. kept thawed and refreezing can be prevented. acterized by complete necrosis and loss of tissue. Rapid rewarming to stop freezing, increasing These classifications, which are useful for de­ blood flow to limit local hypoxia, and administer­ scribing what is seen clinically, have not been http://www.jabfm.org/ ing to block the release of inflamma­ found to help predict the extent of future tissue tory mediators would clearly reverse the three damage. Other investigators prefer to describe pathways of tissue damage. These tools are the only two classes of injury, superficial (first- and foundation of effective treatment of frostbite. second-degree) and deep (third- and fourth-de­ gree), since the treatment for all classes of frost­

Clinical Manifestations bite is the same until tissue demarcation between on 1 October 2021 by guest. Protected copyright. Classically, frostbite has been categorized accord­ viable and nonviable tissue occurs at 22 to 45 days ing to four degrees of injury. This description is after injury. IS applied after rewarming, because most injuries The symptoms of frostbite injury are fairly uni­ appear to be similar at the time of initial evalua­ form and can help predict the severity of injury. At tion. With first-degree injury there is numbness, first most patients describe a cold numbness that a central white plaque, and surrounding ery­ progresses to a feeling of clumsiness in the in­ thema. Second-degree injury causes filled volved pan. After rewarming, this numbness will with a clear or milky fluid that develop during the give way to a severe throbbing pain that can per­ first 24 hours. These blisters are surrounded by sist for days to weeks. This throbbing sensation erythema and edema. Third-degree injury trig­ then results in a mild tingling sensation in the in­ gers hemorrhagic blisters, which are a sign of volved part; an electric shock is also described by deeper tissue injury, that result in a hard black es­ some patients. Sensory loss, increased cold sensi­ char 2 weeks later. Fourth-degree injury is char- tivity, and hyperhidrosis can also develop and per-

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Table 1. Treatment of Frostbite.

1. Evaluate for hypothennia, concomitant injury, or complicating problems 2. Rapidly rewarm the affected areas in precisely controlled water at 104-108°F (40-42°C) until thawing is complete (15 to 30 min, or skin returns to a red-purple color and regains a pliable texture) 3. Debride clear or white blisters and apply aloe vera (at least 70% concentration without alcohol or perfume). Cover with loose, bulky, protective . Repeat aloe vera application every 6 h. Hemorrhagic blisters should be left intact but with aloe vera applied 4. Splint and elevate the extremity 5. Administer ibuprofen orally at 12 mglkg/d in divided doses 2 to 4 times a day 6. Administer tetanus toxoid and tetanus immune globulin if> 10 Y since last tetanus booster 7. Administer intravenous penicillin, 500,000 U every 6 h for 72 hj add further antibiotics only if evidence of 8. Control pain with parenteral narcotics (morphine or meperidine) as needed 9. Administer daily hydrotherapy in 40°C water with hexachlorophene for 30 to 60 min 10. Prohibit smoking sist for years after the initial injury. 1 Arthritis, lack of any diagnostic tests that definitively guide growth plate damage, and chronic pain are less therapy in the first days after injury require that a common long-term sequelae.15 comprehensive treatment regimen be applied for Favorable findings at the time of initial physical all cases of frostbite injury. examination include sensation to pinprick, skin that will indent when pressure is applied (indicat­ Treatment ing elasticity of viable deeper skin), normal color, The treatment of frostbite is directed at reversing and large blisters filled with clear fluid. Small vesi­ the pathologic effects of ice crystal formation, cles filled with dark, blood-tinged fluid, non­ vasoconstriction, and the release of inflammatory blanching cyanosis, and skin that feels wooden to mediators. It can be divided into three phases: the touch and does not indent with pressure her­ prethaw field care phase, immediate hospital care ald a poor prognosis.19 phase, and postthaw care phase, which continues for several weeks. The field care phase begins Diagnosis once frostbite is suspected. Transport to emer­ In addition to physical examination findings, there gency services should not be delayed. Field warm­ are several diagnostic tests that have been used to ing should be undertaken only if refreezing can be help predict the severity and prognosis of the prevented and the estimated time until arrival at a http://www.jabfm.org/ frostbite injury. Techniques have included con­ hospital is expected to exceed 2 hours.9 The in­ ventional , angiography, digital jured part should be protected with a splint and plethysmography, Doppler flow studies, laser­ bulky loose padding. The patient should have wet Doppler flow studies, thermography, NMR 31 P clothing removed to prevent hypothermia. Rub­ spectroscopy, bone scintigraphy (technetium 99), bing the fragile frostbitten extremity with snow, and other forms of intravenous radioisotope cloth, or the rescuer's hand is harmful. Alcohol scintigraphy to assess blood flow. 4,13 No tests are and smoking are prohibited during transport. All on 1 October 2021 by guest. Protected copyright. definitive in the first 3 to 5 days immediately after prehospital treatments should focus on preventing rewarming because of the effects of persistent vas­ partial thawing and refreezing, which causes much cular spasm and instability.4,9,2o more devastating damage from the increased re­ During the initial period after thawing, some lease of inflammatory mediators than does a sim­ tests can be used to assess the boundaries of tissue ple prolonged freezing. 14,16 viability and thus help plan surgical removal of de­ The immediate care phase begins upon arrival vitalized tissue. From 1 to 3 weeks after injury, at the hospital. The current state of the art in frost­ Doppler studies and angiography can help assess bite care is based in large part on the work of Heg­ vascular status,4 and by 2 to 3 weeks after injury, gers and McCauley (fable 1).13,16,17,22 The injured bone scintigraphy can help demarcate areas of se­ part should be rapidly warmed in water maintained vere frostbite that will need .20,21 Nev­ within a precise temperature range of 104°F to ertheless, the difficulty of using initial physical ex­ 108°F (40°C to 42°C) for 15 to 30 minutes to stop amination findings to predict prognosis and the quickly any further ice crystal formation and to re-

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Table 2. Possible Adjuvant Therapies for Frostbite. enteral narcotic analgesia is usually required dur­ Agent or Procedure Usefulness ingrewarming because the patient will experience intense pain as sensation returns to the cold-in­ Low molecular weight dextran Doubtful jured part. Heparin None Mter this initial treatment further modalities Coumadin None can optimize healing and minimize tissue loss dur­ Steroids None ing the post-thaw phase of care. Almost all pa­ Vitamin C Doubtful tients, except those with the most minimal dam­ Streptokinase or urokinase Doubtful Surgical sympathectomy None early, possibly age, should be admitted to the hospital. Given that useful late alcohol overindulgence, psychiatric disease, and Hyperbaric oxygen Possible homelessness are common features of the frostbit­ Intra-arterial reserpine Possible (as a late ten patient, immediate discharge is rarely prudent. intervention) Subsequent wound care, which can be intense, is Tissue plasminogen activator Possible also most easily accomplished in the hospital. Prostaglandin E) analogs Possible Nifedipine Possible Daily hydrotherapy in water with hexa­ PentoxifyIline Possible chlorophene at 40°C aids debridement of devital­ 15 17 Superoxide dismutase Possible ized tissue. - Physical therapy to enhance flexi­ bility and strength is begun as soon as the edema resolves. 15 Escharotomy or fasciotomy is per­ verse vasoconstriction. IS Water outside this range formed if circulation is impaired or a compart­ can exacerbate tissue damage, and dry heat can ment syndrome develops in the involved extrem­ trigger uneven warming and cause bum injury to ity.15-17 Limited tissue debridement is undertaken the numb, damaged tissue. 16.23 A red-purple ap­ only when infection cannot be controlled.27 De­ pearance and pliable texture of the involved part finitive amputation of tissue should be delayed un­ signal the end of vasoconstriction and are signs to til 22 to 45 days after injury, when the demarca­ cease warming.15.23 Blisters containing clear or tion between viable and nonviable tissue is clear.18 milky fluid, which is rich in inflammatory media­ Amputation done before this interval will be based tors, should be debrided and covered with aloe on an incorrect estimate of the need for tissue re­ vera, a potent anti prostaglandin agent, every 6 moval, because the early clinical signs are similar hours.15-17.24 Splinting, elevating, and wrapping for most degrees of injury.

the affected part in a loose, protective dressing Numerous adjuvant therapies for frostbite have http://www.jabfm.org/ should follow the application of aloe vera cream. undergone trials with varying degrees of success. Hemorrhagic blisters should be left intact. A list and summary of the current usefulness of An immediate oral administration of ibupro­ these therapeutic alternatives is shown in Table fen at a dose of 12 mglkg/d provides systemic an­ 2.4.13.15.28-41 Many have been tested only in animal tiprostaglandin activity that limits the cascade of models, and further randomized trials in humans inflammatory damage.16.17 Ibuprofen is also a are needed before their helpfulness can be defini­ on 1 October 2021 by guest. Protected copyright. more potent inhibitor of thromboxane than are tively established. At present, agents that inhibit other anti-inflammatory drugs. 16.17 Aspirin is not formation of free radicals, such as superoxide dis­ recommended because it prolongs blockade of all mutase, and agents that have platelet antiaggre­ prostaglandin synthesis, including some prosta­ gant activity, such as pentoxifylline, hold some glandins that are beneficial for tissue healing. 17 promise as adjunctive agents with negligible asso­ Tetanus toxoid is given; tetanus immune glob­ ciated risks.29.36 ulin is reserved for patients for whom more than 10 years have passed since their last booster.25 Prevention Penicillin, 500,000 U every 6 hours, is adminis­ The world's highest mountain peaks have been tered during the first 72 hours when the skin is climbed without cold injury, and the military en­ edematous, because the edema makes the skin gages in maneuvers in cold environments with a more susceptible to infection by gram-positive or­ minimum of cold injuries.1 Protective clothing ganisms. 15.26 Further use is indicated and footwear have improved dramatically with the only if there is evidence of infection. 16.17 Par- introduction of synthetic fabrics that are lighter,

38 JABFP Jan.-Feb. 1998 Vol. 11 No.1 J Am Board Fam Pract: first published as 10.3122/15572625-11-1-34 on 1 January 1998. Downloaded from more insulating, and faster-drying than wool. The injury. A new understanding of the importance of military in particular has come up with many pre­ inflammatory mediators in worsening frostbite in­ ventative measures to limit cold injuries.l jury has led to powerful new treatments, and ap­ The foundation of these measures comprises plying these treatment precepts, with special at­ adequate knowledge of the behaviors that lead to tention to rapid rewarming at 104°F to 108°F, cold injury, experienced leadership, good physical debriding blisters filled with milky fluid, and ad­ condition, adequate nutritional status, normal hy­ ministering the antiprostaglandin agents ibupro­ dration, elimination of smoking and alcohol use, fen and aloe vera, will optimize the outcome for and investment in appropriate clothing.1,5,23,42 All the cold-injured patient. Future research should clothing should be fitted to prevent constriction of be directed toward outlining the benefits of other the extremities. Clothing should be worn in layers adjuvant therapies, such as free radical inhibitors with air spaces between the layers and covered by and platelet antiaggregants. an outer wind- and water-resistant garment. Lay­ ering conserves body heat, is flexible, and permits References the removal of layers during strenuous exertion. It 1. Bowen TE, Bellamy RE Cold injury. In: Emergency also prevents the clothing from becoming perspi­ War . Washington, DC: Department of De­ ration soaked or otherwise wet, which can dramat­ fense, US Government Printing Office, 1988. ically increase the risks of cold injury. 2. Pulla RJ, Pickard LJ, Carnett TS. Frostbite: an Footwear should also be layered within an overview with case presentations. J Foot Ankle Surg outer waterproof barrier. Military vapor barrier 1994;33:53-63. 3. Antti-Poika I, Pohjolainen T, Alaranta H. Severe boots and Native Alaskan-inspired mukluk boots frostbite of the upper extremities-a psychosocial are models of these principles. Hand coverings problem mostly associated with alcohol abuse. ScandJ should also be layered, with a protective water-re­ SocMed 1990;18:59-61. pellent outer mitten over fingered and layered in­ 4. Foray J. Mountain frostbite. Current trends in prog­ ner gloves. The mitten can be removed to permit nosis and treatment (from results concerning 1261 work requiring dexterity. Habituation to cold cases). IntJ Sports Med 1992;13(Suppll):S193-6. 5. Rosen L, Eltvik L, Arvesen A, Strand en E. Local cold weather can also limit the risk of cold injury.42 injuries sustained during military service in the Nor­ The reasons for this protective effect remain con­ wegian Anny. ArcticMed Res 1991;50:159-65. troversial, however, because it is difficult to sort 6. Hermann G, Schecter DC, Owens JC, et a1. The out the behavioral benefits of increased knowl­ problem of frostbite in civilian medical practice. Surg Clin North Am 1963;43:519-36.

edge gained from living in a cold environment http://www.jabfm.org/ 7. Ervasti E. of the extremities and their se­ from any possible physiologic effects that occur quelae. Acta Chir Scand SuppI1962;299: 1-69. 13 after time in a cold climate. ,23,42 8. Valnicek SM, Chasmar LR, ClapsonJB. Frostbite in Finally, it is critical to reduce the population at the prairies: a 12-year review. Plast Reconstr Surg risk for frostbite. Education in frostbite preven­ 1993;92:633-41. tion for participants in outdoor sports can be in­ 9. Bracker MD. Environmental and thermal injury. Clin corporated into the preparticipation physicals. SportsMed 1992;11:419-36.

10. Christenson C, Stewart C. Frostbite. Am Fam Physi­ on 1 October 2021 by guest. Protected copyright. Further education at the time of frostbite treat­ cian 1984;30:111-22. ment would also help to reduce subsequent rein­ 11. Boswick JA Jr, Thompson JD, Jonas RA. The epi­ jury. Nevertheless, a substantial reduction in risk demiology of cold injuries. Surg Gynecol Obstet will occur only when there is a decrease in two of 1979;149:326-32. our nation's most vexing social problems, alco­ 12. Kyosola K. Clinical experiences in the management holism and homelessness. of cold injuries: a study of 110 cases. J Trauma 1974; 14:32-6. 13. McCauley RL, Smith DJ, Robson MC, HeggarsJP. Conclusion Frostbite and other cold-induced injuries. In: Auer­ The rise in homelessness and increase in outdoor bach PS, editor. Wilderness medicine. 3rd ed. St cold weather activities have made frostbite a com­ Louis: Mosby, 1995. mon occurrence in urban as well as remote rural 14. Washburn B. Frostbite. N EnglJ Med 1962;266:974- 89. areas. Within the past 15 years medical research 15. Britt LD, Dascombe WH, Rodriguez A. New hori­ has been able to clarify the best approach to the zons in management of hypothermia and frostbite in­ diagnosis, treatment, and prevention of frostbite jury. SurgClin NorthAm 1991;71:345-70.

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16. Heggers JP, Robson MC, Manavalen K, Weingarten 31. Okuboye JA, Ferguson Ce. The use of hyperbaric MD, CarethersJM, BoeronanJA, et aI. Experimental oxygen in the treatment of experimental frostbite. Can and clinical observations on frostbite. Ann Emerg J Surg 1968;11:78-84. Med 1987;16:1056-62. 32. Snider RL, Porter JM. The treatment of experimental 17. McCauley RL, Hing DN, Robson MC, HeggersJP. frostbite with intra-arterial sympathetic blocking Frostbite injuries: a rational approach based on the drugs. Surgery 1975;77:557-61. pathophysiology.] Trauma 1983;23:143-7. 33. Purkayastha SS, Chhabra PC, Verma SS, Selvamurthy 18. Orr KD, Fainer DC. Cold injuries in Korea during W. Experimental studies on the treatment of frostbite winter of 1950-1951. Fort Knox, Ky: Army Medical in rats. IndianJ Med Res 1993;98: 178-84. Research Laboratory, 1951. 34. Salimi Z, Wolverson MK, Herbold DR, Vas W, Salimi 19. Mills WJ Jr. Summary of treatment of the cold-in­ A. Treatment of frostbite with Lv. streptokinase. AJR jured patient. Alaska Med 1973;15(2):56-62. Am] RoentgenoI1987;149:773-6. 20. Miller BJ, Chasmar LR Frostbite in Saskatoon: a re­ 35. Skolnick AA. Early data suggest clot-dissolving drug view of 10 winters. CanJ Surg 1980;23:423-6. may help save frostbitten limbs from amputation. 21. Mehta RC, Wilson MA. Frostbite injury: prediction JAMA 1992;267:2008-10. of tissue viability with triple-phase bone scanning. Ra­ 36. Miller MB, Koltai PJ. Treatment of experimental diology 1989; 170:511-4. frostbite with pentoxifylline and aloe vera cream. Arch 22. McCauley RL, Heggers JP, Robson Me. Frostbite. Otolaryngol Head Neck Surg 1995; 121:678-80. Methods to minimize tissue loss. Postgrad Med 37. Saito S, Shimada H. Effect of prostaglandin El ana­ 1990;88(8):67-8,73-7. logue administration on peripheral skin temperature 23. Fritz RL, Perrin DH. Cold exposure injuries: preven­ at high altitude. Angiology 1994;45 :45 5 -60. tion and treatment. Clin SportsMed 1989; 8:111-28. 38. Groechenig E. Treatment of frostbite with iloprost. 24. Page RE, Robertson GA. Management of the frostbit­ Lancet 1994;344:1152-3. ten hand. Hand 1983;15:185-91. 39. Rustin MH, NewtonJA, Smith NP, Dowd PM. The 25. Didlake RH, KukoraJS. Tetanus following frostbite treatment of with nifedipine: the results of a injury. Contemp Orthop 1985;10:69-74. pilot study, a double-blind placebo-controlled ran­ 26. Cold hypersensitivity. Br MedJ 1975;1:643-4. domized study and a long-term open trial. Br J Der­ 27. Holm PC, Vanggaard L. Frostbite. Plast Reconstr matoI1989;120:267-75. Surg 1974;54:544-51. 40. Golding MR Protection from early and late sequelae 28. Schiavone FM, Osborn HH. Frostbite. Hosp Physi­ of frostbite by regional sympathectomy. Surgery 1963; cian 1988Jan:16-31. 53:303-306. 29. Mills WJ Jr. Comments on this issue of Alaska medi­ 41. Bouwman DL, Morrison S, Lucas CE, Ledgerwood cine-from then (1960) until now (1993). Alaska Med AM. Early sympathetic blockade for frostbite-is it of 1993;35:70-87. value? J Trauma 1980;20:744-9. 30. Schumaker HB. Studies in experimental frostbite: the 42. Kappes B, Mills W, O'Malley J. Psychological and effect of heparin in preventing gangrene. Surgery psychophysiological factors in prevention and treat­ 1947;22:900-5. ment of cold injuries. Alaska Med 1993;35:131-40. http://www.jabfm.org/ on 1 October 2021 by guest. Protected copyright.

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