This treatment might be appropriate in grades 2–4 frostbite, when people get treatment within 48 hours. In addition to vasodilators, sympatholytic drugs can be used to counteract the detrimental peripheral vasoconstriction that occurs during frostbite.A systematic review and metaanalysis revealed that  iloprost alone or  iloprost plus recombinant tissue plasminogen activator (rtPA) may decrease amputation rate in case of severe frostbite in comparison to buflomedil alone with no major adverse events reported from iloprost or iloprost plus rtPA in the included studies. Surgery
Various types of surgery might be indicated in frostbite injury, depending on the type and extent of damage. Debridement or amputation of necrotic tissue is usually delayed unless there is gangrene or systemic infection (sepsis). This has led to the adage "Frozen in January, amputate in July". If symptoms of compartment syndrome develop, fasciotomy can be done to attempt to preserve blood flow. Prognosis
Tissue loss and autoamputation are potential consequences of frostbite. Permanent nerve damage including loss of feeling can occur. It can take several weeks to know what parts of the tissue will survive. Time of exposure to cold is more predictive of lasting injury than temperature the individual was exposed to. The classification system of grades, based on the tissue response to initial rewarming and other factors is designed to predict degree of longterm recovery.
Pathophysiology
The pathological mechanism by which frostbite causes body tissue injury can be characterized by four stages: Prefreeze, freeze-thaw, vascular stasis, and the late ischemic stage. Prefreeze phase: involves the cooling of tissues without ice crystal formation. Freeze-thaw phase: ice-crystals form, resulting in cellular damage and death. Vascular stasis phase: marked by blood coagulation or the leaking of blood out of the vessels. Late ischemic phase: characterized by inflammatory events, ischemia and tissue death. Diagnosis
Frostbite is diagnosed based on signs and symptoms as described above, and by patient history. Other conditions that can have a similar appearance or occur at the same time include:

Frostnip is similar to frostbite, but without ice crystal formation in the skin. Whitening of the skin and numbness reverse quickly after rewarming. Trench foot is damage to nerves and blood vessels that results exposure to wet, cold (non-freezing) conditions. This is reversible if treated early. Pernio or chilblains are inflammation of the skin from exposure to wet, cold (non-freezing) conditions. They can appear as various types of ulcers and blisters. Bullous pemphigoid is a condition that causes itchy blisters over the body that can mimic frostbite. It does not require exposure to cold to develop. Levamisole toxicity is a vasculitis that can appear similar to frostbite. It is caused by contamination of cocaine by levamisole. Skin lesions can look similar those of frostbite, but do not require cold exposure to occur.People who have hypothermia often have frostbite as well. Since hypothermia is life-threatening this should be treated first.