Working to investigate new treatments and
evaluating results; Comparison of Iloprost
therapy for frostbite in two Canadian cities
Domhnall O’Dochartaigh, Christopher Picard, Alex
Poole, Daniel Tiwana, Elaine Hyshka, Alexis Armour,
Alexis Mageau, Stacey Middleton, Lisa Allen, Sean Crooks,
Matthew Douma, Kathryn Dong, Brian Whiteside, Monty
Ghosh, Heather Briana Boucher, Jevon Brown, Lindsay
Burnett, Michael Zakhary, Jake Hayward, Yvonne Efegoma,
Kimberly Byrnes, Ted Harrigan, Lindsay Robinson, Yvonne
Efegoma, Lisa Watt, and Scott MacLean
Background: Edmonton and Calgary are cities with populations of more than one million. Both experience cold winter
temperatures, making frostbite a common emergency department (ED) presentation. Recently some EDs added iloprost
for frostbite care. Iloprost is available in Canada via the Special
Access Program. Its effectiveness for preventing amputations
requires further investigation. The primary study objective compares amputation rates in patients with severe frostbite who did
and did not receive Iloprost in two cities. Also assessed was iloprost adverse events.
Methods: This retrospective study assessed administrative data
of patients ≥18 years treated in Edmonton and Calgary with
grade 2–4 frostbite over a three-year period. Abstracted data
were categorized to include grade and amputation by digit, iloprost, and adverse medication events. Descriptive analysis and
multivariable linear regression controlling for potential confounders was performed to identify predictors of amputation,
for those receiving standard care (SC) or iloprost (IC).
Results: Two hundred and fifty-seven patients met inclusion
criteria (177/80 SC/IC). Mean age was 42.5 (13.7SD), male sex
n = 208 (80.9%), comorbidities: houseless 140 (54.5%), active
substance use/alcohol use disorder (175, 59.1%/69, 26.8%). 
Overall amputation rate for patients with Grade 2 injury was
similar between groups (SC 3/873.4%; IC 1/30 3.3%). For
Grade 3 injuries, there was a higher proportion of amputations
in SC (34/69, 69% vs IC 9/21, 42%; p = 0.042). For Grade 4
injuries, there was no difference between groups (SC 17/21,
81%; IC 16/19, 84%; p = 0.787). Logistic regression suggests
IC patients were less likely to have an amputation (p  = 0.038,
OR = 0.49, 95% CI = 0.25 - 0.96), and fewer digits amputated
(p < 0.001, βST = -0.6, 95% CI = -0.91 - -0.3). Adverse effects of
iloprost were reported in 49 (61.25%) patients, 44 (55%) having multiple adverse effects. Including (n): headache (25, 2.1%),
tachycardia >100 (14,13.1%), nausea (13,12.1%), hypotension
(13, 12.1%), flushing (10, 9.3%), vomiting (7, 6.5%), myalgias
(5, 4.7%), hypertension (4, 3.7%); dizziness/abdominal pain/
chills/palpitations (each n2, 1.9%); and chest pain, vein redness,
tiredness, restless (each n1, 0.9%).
Implications and lessons learned: Iloprost was associated with
a lower likelihood and number of amputations for Grades 2 and
3 frostbite injuries, but not in Grade 4 injuries when compared
to standard care.