Prehospital Frostbite Management With Iloprost: Case Reports of Two Helicopter Evacuations in Northern Canada

Introduction

Cold weather injuries (CWIs) include both freezing and nonfreezing conditions resulting from prolonged exposure to cold environments. Freezing CWIs, such as frostbite, occur when tissue temperatures fall below freezing, leading to ice crystal formation, endothelial injury, vasoconstriction, and progressive microvascular thrombosis. This results in cellular necrosis and, if untreated, tissue loss and amputation. Nonfreezing CWIs, such as trench foot, result from sustained exposure to cold and wet environments above freezing, leading to sensory and autonomic dysfunction and potential long-term morbidity. ¹

Frostbite primarily affects the extremities. It is commonly encountered in remote or austere environments where prolonged exposure and delayed access to medical care can exacerbate injury severity. The pathophysiological process extends beyond the freezing event itself. Following rewarming, a warm ischemia phase characterized by ongoing microvascular dysfunction and thrombosis plays a critical role in determining the extent of tissue necrosis.^2,3

Historically, frostbite management involved expectant care after thawing and amputation if gangrene developed. In the 1980s, Mills demonstrated that rapid rewarming in water heated to approximately 38 °C was beneficial. ⁴ Following that, Heggers et al then showed that anti-thromboxane therapies such as ibuprofen and topical aloe vera were beneficial. ⁵ In recent years, the medical management of frostbite has evolved to include pharmacologic therapies aimed at restoring perfusion during the critical postrewarming period. Iloprost, a prostacyclin analogue, has emerged as a key treatment option for moderate to severe frostbite. It improves microcirculatory flow by inducing vasodilation, inhibiting platelet aggregation, and reducing leukocyte adhesion, and may have fibrinolytic properties.^6,7

Studies have demonstrated that iloprost significantly reduces amputation rates compared to standard care.^8,9 Thrombolysis can also be beneficial if administered within 24 h of rewarming. ¹⁰ Iloprost and alteplase have been included in frostbite treatment protocols in several jurisdictions, including the Yukon Frostbite Protocol since 2015. ¹¹

Despite growing evidence of their efficacy, iloprost and alteplase remain primarily hospital-based therapies, with the exception of 2 cases that describe the use of recombinant tissue plasminogen activators (rtPA) at K2 basecamp. Published studies to date have reported their use in hospital settings, typically after the patient has arrived at a hospital with an established frostbite protocol. This limitation is important given that expedited therapy may be beneficial. In a study by Nygaard et al, each hour of delay from rewarming to the initiation of thrombolytic therapy resulted in a nearly 30% decrease in tissue salvage (Nygaard RM. J Burn Care Res. 2017) ¹² Although this case series does not evaluate iloprost directly, it stands to reason that field administration of iloprost would lead to quicker treatment times, which could result in improved tissue salvage. Turner et al noted that most frostbite guidelines lack specific recommendations for prehospital care and emphasized the need for protocols tailored to the prolonged care phase common in austere environments. ¹³

In 2016, Cauchy et al proposed that thrombolytics and iloprost be considered for field treatment to maximize chances for recovery and reduce amputations; the authors reported the use of rtPA at K2 base camp in 2 mountain climbers with frostbite. ¹⁴ In a recent review, Lowe and Warner explored the theoretical potential for field-based iloprost administration in military contexts, highlighting its ease of use, better safety profile, and fewer contraindications compared to rtPA. ¹⁵ The 2024 Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite also advocates for field use of both iloprost and IV rtPA, highlighting that iloprost may be a safer alternative to rtPA. ¹⁶ However, to date, there is no published report involving field use of iloprost.

Recognizing this gap, the Yukon Emergency Medical Services (EMS) developed and implemented a prehospital iloprost protocol in 2021 (Appendix 1). The protocol was designed to enable trained paramedics to assess frostbite severity based on the Cauchy visual severity grading scale ¹⁷ and to initiate iloprost infusions during ambulance or helicopter evacuations when severe frostbite was suspected, particularly in cases with prolonged transport times. ¹⁸

This case report describes the use of iloprost administration initiated in the prehospital setting. These 2 cases were managed under a structured helicopter emergency medical services (HEMS) protocol during an extreme cold-weather endurance race in the Yukon Territory in northern Canada.

Cases Reports

Two endurance athletes participating in a 640 km race in February 2025 in the Yukon suffered from frostbite. They were participating in a self-supported race on foot, pulling sleds. Both had prolonged exposure to ambient temperatures ranging from −30 to −40° C.

Patient 1, a healthy 49-year-old male athlete, had been in the race for nearly 48 h and had traveled over 100 km at temperatures below −30° C. At a race checkpoint, a mandatory frostbite check by race medical volunteers showed potential frostbite to bilateral feet and to fingertips. Field rewarming started with immersion of feet in a warm water basin and passive rewarming of hands in the heated wall tent. Ibuprofen was administered. The athlete was pulled from the race, and a HEMS air ambulance was initiated. Using the Yukon EMS protocol, iloprost was collected by a team member at Whitehorse General Hospital. Upon paramedic arrival, a field assessment using the Cauchy visual scale identified at least grade 2 frostbite to the athlete's feet. They initiated iloprost intravenously and titrated up per protocol during helicopter transport. When the patient arrived at Whitehorse Generalmore than 2 hours of the infusion were completed. At the hospital, he was diagnosed with grade 2 frostbite involving 3 toes and 1 thumb. Given that he was ambulatory, he was treated as an outpatient for a total course of 5 days. He returned daily for iloprost infusion, hydrotherapy, and dressing changes. The patient had no adverse effects from the iloprost infusion during transport or over the next 4 days. At 6 weeks post-injury, he showed signs of complete recovery, avoiding amputation.

Patient 2, a healthy 47-year-old male athlete, had completed 150 km over 3 days when, after a 4-hour bivouac, he became concerned that he was suffering from frostbite to his fingers. He activated an SOS signal using a satellite GPS messenger. He was picked up by race volunteers and transported by snowmachine for 30 min to the nearest checkpoint. He was placed in a wall tent, and his extremities were rewarmed in warm water. After rewarming, he was noted to still have pale, waxy fingers. Ibuprofen was given, and HEMS air ambulance was arranged. Iloprost was retrieved from Whitehorse General Hospital and EMS arrived 4 hours after rewarming. The paramedics noted clear evidence of cyanosis to his distal phalanges consistent with grade 2 frostbite. Iloprost was started at a rate of 10 mL/hr using a 0.2 mcg/mL solution prior to transport. The infusion was well tolerated. Upon arrival at Whitehorse General, 1 hour of iloprost infusion was completed. The iloprost rate was increased in the emergency department (ED) per protocol, and the 50 mcg total dose completed. At the hospital, providers concurred with a diagnosis of grade 2 frostbite to 9 fingers. A full 5-day outpatient treatment of iloprost as per the Yukon frostbite protocol was completed with no adverse effects noted.

Discussion

We described 2 frostbite cases involving the prehospital administration of iloprost as part of HEMS retrievals in northern Canada. These cases demonstrate that intravenous iloprost delivery is operationally feasible in the prehospital setting. Administration was initiated during helicopter transport following field rewarming and was completed without complication.

In the 2 cases reported, the warm ischemia time was reduced by 1 and 2.5 h, respectively. It is increasingly recognized that early treatment post rewarming is better. Reducing the warm ischemia time can significantly decrease the risk of necrosis and tissue loss. In these 2 cases, the patient retrieval, helicopter, and ambulance transport were relatively short (less than 3 hours total). The accepted treatment window of iloprost is 72 h; prolonged evacuations to the hospital could use up that window in remote areas. Although not intended to evaluate clinical outcomes, these cases highlight the feasibility of prehospital iloprost use, which could have more significant benefits in longer or delayed evacuations.

These cases also raise clinical and operational considerations. In these cases, the race’s medical volunteers were familiar with recognizing signs of frostbite and evaluating severity. They initiated rewarming promptly and contacted EMS. As soon as the HEMS was activated, an EMS delegate presented to Whitehorse General Hospital to pick up iloprost prior to the flight. Given this was a race event in extreme cold conditions, frostbite cases were anticipated, and the hospital surgeon, hospital pharmacist, and EMS team had communicated prior to the event, clarifying the procedure beforehand.

Effective temperature management of both the patient and equipment, along with adequate analgesia, is an essential component of safe and effective field administration in extreme cold. The Yukon prehospital protocol addressed these elements through insulated equipment, portable syringe pumps, and dual intravenous lines when feasible. These adaptations may be applicable to other prehospital systems serving populations at risk of frostbite.

From a broader systems perspective, the ability to deliver iloprost in the field may represent a significant advancement in the management of frostbite. In geographically dispersed or resource-limited settings, prehospital pharmacologic intervention could help mitigate the negative outcomes associated with prolonged evacuation on tissue viability. This approach aligns with broader recommendations supporting early and coordinated frostbite care across the continuum of care.

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Supplemental Material