WILDERNESS MEDICINE
Iloprost: A Hot New Solution for Frostbite Injury
SAEM PULSE | MAY-JUNE 2025
By Kailee Pollock and Kevin Watkins, MD, on behalf of the SAEM Wilderness Medicine Interest Group
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Frostbite, also known as freezing cold injury (FCI), occurs when skin and underlying tissues are exposed to freezing temperatures. It most commonly affects the distal extremities, such as fingers, toes, the nose, and ears, which are more vulnerable due to decreased insulation and reduced perfusion. The severity of frostbite is influenced by the ambient temperature, duration of exposure, and the extent of cellular damage. As tissue temperatures fall below freezing, intracellular and extracellular crystals form, leading to electrolyte disturbances, dehydration, and protein and lipid denaturation. This ultimately causes endothelial cell damage and tissue death. Upon thawing,
inflammatory mediators—including thromboxane A2, prostaglandins, bradykinin, and histamine—are released, initiating a cascade of events that results in inflammation, edema, hyperviscous intravascular flow, and vasoconstriction. These changes contribute to microthrombi formation, progressive ischemia, and eventual necrosis.
• Third-degree: Extends into subcutaneous tissue and possibly muscle • Fourth-degree: Penetrates all skin layers and involves muscles, tendons, or bones
• First-degree: Affects only the epidermis
The Cauchy classification system, more commonly used in Europe, categorizes frostbite based on pathological severity into four degrees. First-degree frostbite involves distal fingers and toes without cyanosis. Fourth-degree frostbite includes cyanotic injuries or hemorrhagic blisters that extend into the proximal phalangeal joints. The risk of amputation increases with the severity of the injury.
• Second-degree: Involves the epidermis and part of the dermis
Frostnip, a superficial, nonfreezing cold injury, often precedes frostbite
Frostbite progresses through four pathological phases: pre-freeze, freeze-thaw, vascular stasis, and late ischemia. In the United States, frostbite injuries are classified by depth of tissue involvement: