History of frostbite

Frostbite is a traumatic injury caused by the failure of normal protective mechanisms against the thermal environment, resulting in local tissue temperatures falling below freezing. The preponderance of documented experience with frostbite has come from military campaigns, where the success of many of these campaigns hinged on the incidence of cold injury. Cold-induced injury remains a relatively frequent injury in the United States owing to increasing interest in outdoor winter recreational activities as well as the common presence of homeless and socioeconomically disadvantaged individuals in large urban centers.^1,²

The incidence of and circumstances surrounding frostbite have been documented in numerous military histories.³ Hannibal lost nearly half of his army of 46 000 soldiers during a 2-week crossing of the Alps due to frostbite injury. During the Revolutionary War, Dr James Thatcher recorded that Washington lost 10% of his army to cold-related casualties during the winter of 1778. Baron Dominique Jean Larrey produced the first systematic medical observations of frostbite while serving as Surgeon General of Napoleon’s forces during the ill-fated invasion of Moscow in the Fall of 1812 and the subsequent retreat in a harsh Russian winter.⁴ Because of the epidemic nature of frostbite in this campaign, Larrey was able to create seminal descriptions of frostbite and to identify the debilitating effects of daily refreezing that occurred with bonfire thawing and subsequent marching in frigid conditions; in addition, many soldiers would burn their insensate frostbitten feet while attempting to rewarm them over bonfires. Larrey became convinced that the optimal therapeutic management consisted of friction massage with snow or ice, resulting in slow rewarming.⁴ These recommendations were maintained as the standard of care for frostbite in military medicine for more than 100 years.

In the winter of 1941–1942, German troops sustained an estimated 250 000 frostbite injuries in the attempt to take Moscow, constituting the largest reported number of related frostbite injuries in history.⁵ Although American troops persisted with the practice of slow rewarming, both German and Russian troops had moved to a philosophy of rapid rewarming; the Russian paradigm shift was based on work conducted at the Kirov Institute in the 1930s.^5,⁶ Following World War II existing Russian and German works were translated into English and became the basis for rapid rewarming as the predominant Western paradigm. In 1960, Mills published the first major clinical experience with rapid rewarming and included a philosophy of total care for frostbite with this report.⁷ Meryman subsequently edited a seminal text elucidating the scientific bases for frostbite injury.⁸ Both military and civilian cold-induced injury data continued to accrue over the subsequent three decades in the absence of any significant clinical advances in the care of frostbite.⁹^–¹⁶ Frostbite continues to present a tremendous clinical challenge, with the greatest clinical advance coming only in the last decade with the use of thrombolytic therapy in early management.¹⁷^–¹⁹

Pathophysiology and classification of frostbite

The injury associated with frostbite is attributed to two broad mechanistic categories: the first is that of direct cellular damage and death due to the cold insult, and the second is the delayed process mediated by progressive tissue ischemia.²⁰^–²³ The immediate effects of frostbite are evidenced by formation of extracellular ice crystals. These crystals cause direct injury to the cell membrane, resulting in cellular dehydration due to a change in the osmotic gradient.²⁴ The rate of cooling is reported to have an effect on the development of extracellular or intracellular ice crystals. Rapid cooling results in intracellular freezing, causing more severe cellular damage and cell death, while a slower rate of cooling produces extracellular ice crystals. This slower process results in a transmembrane osmotic shift that draws water from within the cell and produces intracellular dehydration. This dehydration causes changes in protein and lipid conformation as well as changes in biochemical processes that are deleterious to intracellular homeostasis.²⁵^–²⁹ As the temperature continues to fall, intracellular crystals develop regardless of cooling rate, with a loss of the linear relationship of temperature to metabolism, decreased DNA synthesis, and histamine response with skin flushing and development of a fluid-filled wheal (the triple response of Lewis).^13,³⁰^–³³

Microvascular pathophysiology may be even more important to outcome than the direct thermal injury to the cell. This was suggested by studies showing the survival of full-thickness skin subjected to freezing and thawing that progressed to necrosis when left in situ but survived when transplanted to a normal, uninjured recipient site.²³ Zacarian identified a number of processes that may play a role in the microcirculatory changes of frostbite. Transient vasoconstriction of both arterioles and venules with subsequent resumption of capillary blood flow appears to occur, and concomitant microemboli are present.³⁴ With thawing, the capillaries demonstrate restoration of blood flow that diminishes within minutes. Complete cessation of blood flow is often seen within 20 minutes of rewarming frozen tissue. Similar changes have been seen with random skin flap models after reperfusion, suggesting reactive oxygen species as mediators of injury.³⁵ Within 72 hours significant de-endothelialization and deposition of fibrin in the capillary bed occurs. Examination of the endothelial ultrastructure demonstrates swelling, fluid extravasation, endothelial cell dilation, and significant projection of the cell into the vascular lumen prior to cell lysis.³⁶ There is regional variation in the extent of injury, with venules being most profoundly affected, resulting in the hypothesis that, as evidenced by lower flow present in venules, stasis must play a role in this pathophysiologic process.³²

The pathobiochemistry of frostbite has been closely compared to the inflammatory response in the burn wound.³⁷ Inflammatory mediators such as eicosanoids in burn blister fluid as well as bradykinin and histamine release in the region of injury draw parallels with findings in cold-induced injury.³⁸^–⁴⁵ This has prompted investigators to hypothesize a frostbite model similar to that of Jackson’s for burns, including zones of necrosis and stasis.⁴⁶ Similar to their burn blister analysis, Robson and Heggers examined the fluid in frostbite blisters and found high levels of prostaglandin F₂ and thromboxane B₂.³⁷ These agents or their precursors have been implicated in vasoconstriction and leukocyte adherence. In addition, when refreezing follows thawing the cellular damage caused by ice crystals and the subsequent inflammatory response are exaggerated.^47,⁴⁸

Clinical findings and classification of frostbite injury

In many situations, the patient is unaware that frostbite is occurring. The presence of hypothermia and the frequent use of mind-altering substances by frostbite patients may contribute to this problem. Typical distribution of injury is acral, with injuries to ears, nose, cheeks and penis also being fairly common.^9,^14,⁴⁹ The patient may note insensitivity and clumsiness of the affected part. This complex of symptoms rapidly reverses upon rewarming. Severe pain occurs during and immediately after the rewarming process, is often described as throbbing in character, and typically requires parenteral opioids for relief.⁵⁰ This may evolve into severe neuropathic pain that can be aggravated by warm environments and dependent positioning of the injured body part.

Because of the nature of freezing injury, classification has traditionally been based on physical examination findings and adjunct imaging that occurs after rewarming. A condition often termed ‘frostnip’ may be present in which there is not true injury to the underlying dermis or soft tissues. The most common presentation of frostnip is numbness and pallor of exposed skin. Rewarming results in near-complete resolution of symptoms and physical findings, with the possible exception of minimal hyperemia, edema, and tingling in the region. True frostbite, on the other hand, always involves some degree of dermal and soft tissue injury. Clinical appearance evolves over a period of time after rewarming, although the initial appearance may be deceptive because of the hyperemia present in both frostbite and frostnip.^9,⁵¹ The development of skin blebs is time dependent and may require hours to days from the time of injury. After 12–24 hours the character of the blebs usually becomes apparent and an assessment of the degree of involvement can allow for planning of management of the injury.

Traditional classification of frostbite is similar to that of the burn injury. First-degree injury is superficial, without formation of vesicles or blebs. There may initially be an area of pallor with surrounding erythema that evolves into general edema and erythema without long-term sequelae. Second-degree injury has associated light-colored blisters and subsequent epidermal sloughing. This may correlate with partial dermal involvement but has a generally favorable prognosis. Third-degree frostbite typically has dark or hemorrhagic blisters that evolve into thick, black eschar over 1–2 weeks. Fourth-degree injury involves bone, tendon or muscle and uniformly results in tissue loss. Precision in depth of injury cannot be expected and some favor a more general classification of superficial (first- and second-degree injury) or deep (third- and fourth-degree) frostbite injury;^52,⁵³ clinically these can be delineated by clear vesicles, present with superficial injury, or hemorrhagic blisters, indicative of structural damage to the subdermal tissues.^53,⁵⁴ Cauchy most recently proposed an alternative classification system based on risk of amputation that includes the extent of the lesion immediately after rewarming, findings from bone scan on day 2, and the presence of blisters on day 2.⁵⁵ Although this system has not come into widespread use, the relationship of objective findings to prognosis may prove helpful for future therapeutic trials in the management of frostbite.

Initial management of freezing cold injury

Prevention is obviously the ideal means of treatment for frostbite. Frostbite continues to be a relatively frequent injury in the United States owing to increasing interest in wilderness activities, even during inclement weather. Further, the incidence of frostbite among homeless and mentally ill individuals persists, with these groups representing the most frequently seen local cold-injury patients; alcohol and drug intoxication heightens these risks.^1,^2,^49,^56,⁵⁷ Although the cases of frostbite that occur in intoxicated, mentally ill, and homeless individuals are truly preventable only through broader social interventions, simple techniques exist for those who sustain frostbite secondary to involvement in cold-weather wilderness activities. Frostbite prevention measures in cold-weather wilderness activity include, but are not limited to, wearing appropriate clothing, which may include layers, keeping that clothing dry (particularly clothing over acral areas, such as gloves and socks), responding appropriately to changing conditions, and performing ‘cold checks’ of at-risk or suspect areas.⁵⁸

If frostbite is identified in the field, the greatest management priority is to not incur further injury. Jewelry should be removed if present in the affected area; rubbing the area with ice or snow, although consistent with historical recommendations, is now known to incur further damage to fragile, injured tissue.^4,^50,^52,^59,⁶⁰ Injured areas should be mechanically protected from trauma because they are typically insensate and are at high risk for further injury.^50,^52,^59,⁶¹ The key decision that must be made in the field is whether thawing should be pursued prior to transfer to a facility that can provide definitive care for the frostbite injury. Based on the work of Mills at the Arctic Aeromedical Laboratory demonstrating the deleterious effects of thawing and refreezing on clinical outcomes from frostbite, rewarming in the field should not be pursued unless the ability to maintain the affected tissue in a thawed state is certain.^7,^59,^62,⁶³