A systematic review of epinephrine degradation with exposure to excessive heat or cold

Epinephrine is a lifesaving drug in the treatment of anaphylaxis and cardiac resuscitation. Current US storage recommendations are for controlled room temperature (20°C-25°C), with excursions permitted from 15°C to 30°C. Maintaining epinephrine within this required range is challenging, particularly for patients carrying autoinjectors and during storage in emergency vehicles.

To study epinephrine degradation with extreme temperature exposure for epinephrine concentrations used in anaphylaxis and cardiac resuscitation.

We searched the literature for all studies of epinephrine in sealed syringes, vials, or ampules in concentrations between 1:1,000 and 1:10,000, that measured epinephrine in samples exposed to temperatures above and/or below the recommended storage temperature compared with control samples.

Nine studies were included. Heat exposure resulted in epinephrine degradation but only with prolonged exposure. Constant heat resulted in more degradation. None of the studies that evaluated epinephrine exposure to extreme cold found significant degradation. None of the studies evaluating the effects of real-world temperature fluctuations detected significant degradation. Only 2 small studies (1 evaluating heat and 1 freezing) involved autoinjectors, and all 40 devices tested fired correctly.

Temperature excursions in real-world conditions may be less detrimental than previously suggested. Freezing and limited heat excursions did not result in epinephrine degradation. Refrigeration of epinephrine appears to reduce degradation. However, the effect of extreme temperatures, particularly freezing, on autoinjectors is not sufficiently well established. More research in needed at clinically relevant high temperatures, with limited exposure to heat, and involving autoinjector devices.