Inhaled Epoprostenol Augments Cold-Induced Vasodilation: A Double-Blind Crossover Trial

IntroductionCold exposure initially induces peripheral vasoconstriction. After 5-10 min, distal blood vessels will transiently and cyclically vasodilate and vasoconstrict in a phenomenon known as cold-induced vasodilation (CIVD). Increased CIVD response is thought to improve dexterity and confer a reduced risk of frostbite injuries. Current guidelines recommend the use of an intravenous synthetic prostacyclin (PGI2) analog for the treatment of some cases of severe frostbite. This double-blind crossover study investigates the effects of the inhaled PGI2 analog epoprostenol on CIVD response through continuous finger temperature measurement during cold water immersion.ResultsFourteen healthy volunteers completed both sessions of the study and were included in the analysis. Compared to placebo, inhaled epoprostenol sessions showed higher mean finger temperature (9.16 vs 8.34° C; <i>p</i> = .027), mean maxima temperature (10.86 vs 9.88° C; <i>p</i> = .045), and mean minima temperature (7.45 vs 6.80° C; <i>p</i> = .024). No significant difference was detected in the number of cycles (10.0 vs 7.93; <i>p</i> = .104). No hypotension, hypothermia, or hypoxia was observed, and no subject requested discontinuation due to side effects.ConclusionIn this small study, inhaled epoprostenol induced a statistically significant increase in mean temperature, mean maxima temperature, and mean minima temperature in fingers immersed in a cold-water bath, consistent with an augmented CIVD response. The ability to deliver an inhaled PGI2 analog via nebulizer raises the possibility of early interventions to manage frostbite in austere environments, but further study is needed to draw any conclusions regarding the use of epoprostenol for frostbite care.