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Three Part Question

In [adult patients with frostbite], does Emergency Department treatment with [iloprost] lead to [improved clinical outcomes]?

Clinical Scenario

A 56 yo homeless man with a history of alcoholism and stroke is brought to the ED after he was seen sleeping on a park bench in the snow without shoes. He is rousable but 34 F [not sure about this - reads more like Celsius] and is clearly intoxicated with a blood EtOH of 0.22 mg/dL. After giving the patient initial re-warming treatment with warmed blankets, you notice his toes appear severely frostbitten. You know tPA therapy is absolutely contraindicated in this man, but wonder if something else will decrease the likelihood of this man’s toes being amputated.

Search Strategy

A short cut literature review was carried out to determine whether administration of Iloprost infusion improved the clinical outcomes of patients with frostbite presenting to the Emergency Department.
PubMed, Ovid, and BestBETs databases were searched using the terms [iloprost OR prostacycline OR epoprostenol OR treprostinil] AND [frostbite] LIMIT to human AND English Language

Search Outcome

PubMed identified 13 articles, 3 of which were clinical trials relevant to the question. OVID identified 8 articles, 3 of which were the same clinical trials relevant to the question. Browsing the articles’ references and BestBETs browsing did not yield any further articles relevant to this topic.

All relevant papers are summarized in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Cauchy et al. 2011 France	47 patients with severe frostbite presenting to ED directly after mountain rescue Follow-up in 3 months	Randomized controlled trial	Number of frostbitten digits amputated	aspirin + buflomedil: 106 digits with frostbite, 42 amputated aspirin + iloprost: 142 digits with frostbite, 0 amputated aspirin + iloprost + tPA: 159 digits with frostbite, 5 amputated	Only ~15 patients per study group No tPA given without iloprost Stage 4 frostbite more prevalent in tPA + iloprost group
Poole et al. 2016 Canada	2 patients with grade 3 frostbite presenting to the ED after an arctic race Follow-up in 6 months	Case report	Number of frostbitten digits amputated	Case 1 patient: 6 digits, right foot, and nose with frostbite, 0 amputations Case 2 patient: 2 digits with frostbite, 0 amputations	Case 2 patient missed one of the doses of iloprost infusion No controls, small study population
Groechenig 1994 Austria	5 patients with grade 2 and 3 frostbite presenting to the ED after exposure to cold Follow-up in at least 2 weeks	Case reports	Number of patients receiving amputation after frostbite diagnosis	None of the 5 patients required any amputation at follow-ups between 14 and 42 days	Uncertain localization of frostbite, unknown follow-up duration 1 patient treated with heparinization No controls, small and medically complex study population

Comment(s)

These promising findings necessitate follow-up with large randomized controlled trial to ensure broad reproducibility. Additionally, the long term effects of iloprostol therapy as well as its application in paediatric frostbite should be investigated.

Editor Comment

BAF using

Clinical Bottom Line

Although clinical outcomes associated with iloprostol therapy in frostbite have only been examined in 2 case study series and 1 small randomized controlled trial, this petite body of evidence demonstrates a uniformly favorable effect of iloprostol on patient outcomes. Iloprostol treatment for frostbite of any severity grade may significantly decrease the risk of requiring amputation for the frostbitten area.

References

1. Cauchy E, Cheguillaume B, Chetaille E A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite N Engl J Med 2011;364(2):189-90
2. Poole A, Gauthier J Treatment of severe frostbite with iloprost in northern Canada Emerg Med Clin North Am 2017;35(2):281-299
3. E Groechenig Treatment of Frostbite with Iloprost The Lancet Volume 344, No. 8930, p1152–1153, 22 October 1994