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Prostacyclin Useful in the Treatment of Severe Frostbite


Over the past decade, the use of thrombolytic therapy has been added to the treatment of frostbite in more emergency departments. Prostacyclin and rt-PA have been shown to be useful in the treatment of severe frostbite in a prospective trial published in the current New England Journal of Medicine.

Traditional therapy for frostbite has consisted of tissue rewarming, prolonged watchful waiting, and often delayed amputation. Hyperbaric oxygen, surgical and medical sympathectomy, and anticoagulation have been attempted, but have failed to result changes in the management of frostbite.

Emmanuel Cauchy, M.D and Benoit Cheguillaume, M.D, the University of Grenoble, have conducted a prospective randomized trial to evaluate three treatment regimens.

Between 1996 and 2008, the researchers randomly assigned 47 patients (44 men and 3 women) with severe frostbite were to one of three treatment regimens in an open-label study. One group (n = 15) received 250 mg of aspirin and buflomedil (400 mg for 1 hour per day), the second group (n = 16) received 250 mg of aspirin plus a prostacyclin (0.5 to 2 ng of iloprost per kilogram of body weight per minute for 6 hours per day), and the third group (n = 16) received 250 mg of aspirin, iloprost (2 ng per kilogram per minute for 6 hours per day), and fibrinolysis (100 mg of recombinant tissue plasminogen activator [rt-PA] for the first day only). The drug therapy lasted 8 days.

Each patient was assigned to a group only after meeting the study criteria: having no contraindications to use of the study drug, no severe trauma, and no hypothermia. In addition, each patient received care that involved rapid rewarming of the areas with frostbite plus 250 mg of aspirin and intravenous administration of 400 mg of buflomedil.

Severe frostbite was defined as having at least one digit (finger or toe) with frostbite stage 3 (lesion extending just past the proximal phalanx) or stage 4 (lesion extending proximal to the metacarpal or metatarsal joint).

Treatment efficacy was evaluated after 8 days in all 47 study patients by means of bone scans obtained with the use of technetium scintigraphy.

Frostbite occurred in the feet in 33 patients, in the hands in 29 patients, and in both hands and feet in 15 patients. The baseline characteristics of the patients and the localization of the frostbite were similar across treatment groups, except that stage 4 lesions were more common in the group receiving prostacyclin plus rt-PA.

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The risk of amputation was significantly lower in the prostacyclin groups: 0% (0 of 16 patients) in the group receiving prostacyclin alone and 19% (3 of 16 patients) in the group receiving prostacyclin plus rt-PA.

The risk of amputation in the buflomedil group was 60% (9 of 15 patients).

The authors write, “The efficacy of treatment with prostacyclin was confirmed when the number of digits amputated and the severity of the frostbite were considered. However, our results do not rule out a possible additive effect of rt-PA in selected patients.”

The only adverse reactions were minor (hot flushes in 55% of the patients, nausea in 25%, palpitation in 15%, and vomiting in 5%). None of these reactions led to discontinuation of the study medication.

The authors recommend that in the treatment of severe frostbite (stage 3 or above), after rapid rewarming, a combination of aspirin and prostacyclin should be used.

Basic first aid for frost bite:

  1. Shelter the person from the cold, moving him/her to a warmer place. Remove any constricting jewelry and wet clothing.
  2. If immediate medical help is available, wrap the affected areas in sterile dressings, separate affected fingers and toes, and transport the person to an emergency department for further care.
  3. If immediate care is not available, rewarming first aid may be given. Soak the affected areas in warm (never hot) water -- or repeatedly apply warm cloths to affected ears, nose, or cheeks -- for 20 to 30 minutes. Severe burning pain, swelling, and color changes may occur during warming. Warming is complete when the skin is soft and sensation returns to normal.
  4. Apply dry, sterile dressings to the frostbitten areas. Put dressings between frostbitten fingers or toes to keep them separated. Move thawed areas as little as possible.
  5. Do NOT thaw out a frostbitten area if it cannot be kept thawed. Refreezing may make tissue damage even worse.
  6. Do NOT use direct dry heat (such as a radiator, campfire, heating pad, or hair dryer) to thaw the frostbitten areas.
  7. Do NOT rub or massage the affected area.
  8. Do NOT disturb blisters on frostbitten skin.
  9. If the frostbite is extensive, give warm drinks to the person in order to replace lost fluids. Do NOT smoke or drink alcoholic beverages during recovery as both can interfere with blood circulation.
  10. Transport the individual to an emergency department as soon as possible


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A Controlled Trial of a Prostacyclin and rt-PA in the Treatment of Severe Frostbite; Emmanuel Cauchy, M.D, Benoit Cheguillaume, M.D.; N Engl J Med 2011; 364:189-190

Reduction of the Incidence of Amputation in Frostbite Injury With Thrombolytic Therapy; Kevin J. Bruen; James R. Ballard; Stephen E. Morris; Amalia Cochran; Linda S. Edelman; Jeffrey R. Saffle; Arch Surg, Jun 2007; 142: 546 - 553.