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Frostbite is a condition caused by freezing of the skin and ultimately, if it progresses, freezing of deeper tissues. Frostbite injuries due to exposure are a result of an initial extracellular freezing injury followed by a reperfusion injury due to vasoconstriction and microthrombosis in affected tissues (11). Frostbite encompasses a range of injuries, from reversible changes upon rewarming to irreversible cell damage.
Two main mechanisms lead to tissue damage in the acute phase of frostbite injuries: immediate cellular death during cold exposure and progressive dermal ischemia leading to deterioration and necrosis (12-13). Upon rewarming of the affected tissue, reperfusion injury can lead to the generation of radical oxygen species and an inflammatory reaction (14), further damaging tissues. During freezing extra and intracellular ice crystal formation may lead to cell damage and circulatory stasis. A cascade of events occur at this point leading to further cell damage, thrombosis and vasoconstriction.
The degree of frostbite injury and outcomes are related to the degree of microvascular damage and thawing-refreezing cycles during the original tissue insult. Thrombosis and vasoconstriction are mediated by metabolites of the arachidonic acid pathway including thromboxane A2 (TxA2), prostaglandin F2α and thromboxane B2, and are a prominent feature of the reperfusion injury that occurs in rewarmed cyanotic tissue. This leads to intravascular coagulation, sustaining reperfusion injury and potentially causing microthrombi showers that damage the microvasculature, along with thrombus formation in larger vessels (15).
Tissue Freezing
Tissue Thawing
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Lorentzen AK, Penninga L. Frostbite-A Case Series From Arctic Greenland. Wilderness Environ Med. 2018 Sep;29(3):392–400.
Zhang Y, Song J, Huang G. Comprehensive Treatment of Single Finger Frostbite: A Case Study. J Burn Care Res Off Publ Am Burn Assoc. 2021 May 7;42(3):555–9.
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Davis A, Sinopoli B, Mann N, Stenbit AE. A Photographic Case of Frostbite Treated with Delayed Hyperbaric Oxygen Therapy. High Alt Med Biol. 2022 Jun;23(2):194–7.
Coward A, Endorf FW, Nygaard RM. Revision Surgery Following Severe Frostbite Injury Compared to Similar Hand and Foot Burns. J Burn Care Res Off Publ Am Burn Assoc. 2022 Sep 1;43(5):1015–8.
Endorf FW, Nygaard RM. Social Determinants of Poor Outcomes Following Frostbite Injury: A Study of the National Inpatient Sample. J Burn Care Res Off Publ Am Burn Assoc. 2021 Nov 24;42(6):1261–5.
Rossis CG, Yiacoumettis AM, Elemenoglou J. Squamous cell carcinoma of the heel developing at site of previous frostbite. J R Soc Med. 1982 Sep;75(9):715–8.
Mohr WJ, Jenabzadeh K, Ahrenholz DH. Cold injury. Hand Clin. 2009 Nov;25(4):481–96.
Weatherley-White RCA, Sjostrom B, Paton BC. Experimental studies in cold injury: II. The pathogenesis of frostbite. J Surg Res. 1964 Jan 1;4(1):17–22.
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Zhang Y, Song J, Huang G. Comprehensive Treatment of Single Finger Frostbite: A Case Study. J Burn Care Res Off Publ Am Burn Assoc. 2021 May 7;42(3):555–9.
Quintanilla R, Krusen FH, Essex HE. Studies on frost-bite with special reference to treatment and the effect on minute blood vessels. Am J Physiol. 1947 Apr;149(1):149–61.
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Manson PN, Jesudass R, Marzella L, Bulkley GB, Im MJ, Narayan KK. Evidence for an early free radical-mediated reperfusion injury in frostbite. Free Radic Biol Med. 1991;10(1):7–11.
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Heggers JP, Robson MC, Manavalen K, Weingarten MD, Carethers JM, Boertman JA, et al. Experimental and clinical observations on frostbite. Ann Emerg Med. 1987 Sep;16(9):1056–62.
McCauley RL, Hing DN, Robson MC, Heggers JP. Frostbite injuries: a rational approach based on the pathophysiology. J Trauma. 1983 Feb;23(2):143–7.
Heggers JP, Robson MC, Manavalen K, Weingarten MD, Carethers JM, Boertman JA, et al. Experimental and clinical observations on frostbite. Ann Emerg Med. 1987 Sep;16(9):1056–62.
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Ilomedin Package Insert. Bayer HealthCare
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