Management of severe frostbite with iloprost, alteplase and heparin: a Yukon case series

Abstract

F rostbite can occur in cold climates, affecting a range of patients from those who are homeless or unwell, to athletes in extreme sports events. The impact of severe frostbite can be debilitating. Frostbite injuries are a result of an initial extracellular freezing injury followed by a reperfusion injury due to vasoconstriction and microthrombosis in affected tissues. 1 The severity of injuries can range from mild to severe. A grading system developed by Cauchy and colleagues 2,3 describes grade 1 to grade 4 frostbite. The higher the grade, the more proximal the cyanotic changes in the digits, and the higher the amputation rate.The foundations of frostbite treatment have included rapid rewarming 4 and antithromboxane agents such as aloe vera for topical use and ibuprofen. 5 More recently, vasodilators and thrombolytics have been promoted to address the reperfusion injury caused by vasoconstriction and thrombosis. Beginning in the 1990s, a growing body of evidence has popularized the use of iloprost in frostbite, first in Europe and now in Canada. 6,11,15,16,21,24,27 Iloprost, a synthetic prostacyclin analogue, is a potent vasodilator that inhibits platelet aggregation and enhances fibrinolytic activity by releasing endogenous tissue plasminogen activator. 29 To our knowledge, there is a single randomized controlled trial published to date showing the benefit of iloprost combined to alteplase and heparin. 11 We developed and implemented a frostbite treatment protocol and preprinted orders at our institution based on the best available evidence in February 2015. The aim of the present study was to describe the demographic characteristics, treatment course and clinical outcomes of patients treated as per our protocol.

Effectiveness of intravenous prostaglandin to reduce digital amputations from frostbite: an observational study

“…Despite our results suggesting a benefit of iloprost for grade 3 and 4 injuries, the effect was not as dramatic as the Whitehorse or Chamonix experience, where no amputations were observed for grade 3 injuries [5,7]. This may be owing to the differences in medical and social comorbidities in our study population.…”

“…In our study, digits with the most severe grade 4 injuries treated with iloprost had a 46% amputation rate compared to standard care patients who had a 95% amputation rate. The iloprost group was similar to the Whitehorse iloprost experience who had an amputation rate of 50% in Grade 4 injuries [5]. Lower effectiveness for grade 4 injuries was not unexpected as these injuries are often so severe that the tissue is unsalvageable, but is still vastly improved from the historic prognosis for grade 4 injuries of nearly 100% amputation rate [8].…”

“…During the past 20 years, new treatment options have emerged for a condition that once had the grim prognosis of frequent digital amputations. One of the emerging therapies for advanced frostbite is the use of iloprost therapy [3][4][5][6][7]. Iloprost is a synthetic prostaglandin analogue historically used for the treatment of pulmonary hypertension and acts by dilating systemic and pulmonary arteries and impairing platelet aggregation.…”

“…To date, the literature examining iloprost for frostbite has focused predominantly on healthy mountaineers and outdoor adventurers from smaller communities in the French Alps and Northern Canada [4,5,7,8]. These patient populations contrast sharply from typical frostbite patients in large urban centres where addictions, homelessness and co-morbid medical issues may lead to more severe frostbite injuries and complicate prognosis and recovery.…”

“…The approval was based on a handful of small but important studies that showed positive results and a favourable safety profile for the drug [4,[6][7][8]. Since February 2019, most patients who presented to Calgary EDs within 72 h of grade 2 or greater frostbite injuries have been treated with 6-h daily iloprost infusions for a total of 5 days through a standardized treatment algorithm based on the Whitehorse Frostbite Protocol [4,5,9] (Fig. S1).…”