Physical and pharmacostability of 15 essential medications in cold and ultracold environments.

Abstract

Background: Medications require storage and use at room temperature but are largely untested in extreme temperature environments. Deep freezing and frequent freeze-thaw cycling may be expected in Artic and Polar missions. We hypothesize that medications have variable tolerance to exposure of up to 90 days of deep freezing or freeze-thaw cycling.

Methods: With military stakeholder input, 15 essential medications were placed in programmed environmental chambers to maintain -60°F (-51°C, deep freeze) or cycle between 12 hours at -40°F (-40°C) and 68°F (20°C), mimicking possible operational scenarios. Controls were stored at room temperature. Six vials of each medication were placed in each environment for 30, 60, and 90 days of exposure. After exposure, each vial was examined for physical/visual abnormality and sent for concentration testing via high-performance liquid chromatography. Changes from labeled concentration >10% were considered significant, consistent with Food and Drug Administration guidance.

Results: Amiodarone, phenylephrine, norepinephrine, haloperidol, dexamethasone, rocuronium, and metoprolol show physical and pharmacostability through 90 days in both environments. Propofol shows disruption of the emulsion and significant degradation after 30 days in both environments. Sodium bicarbonate, tranexamic acid, calcium chloride, and succinylcholine vials frequently shattered by 30 days of exposure. One naloxone vial experienced degradation. At 30 days, all epinephrine vials had physical change with separation of protective caps from the vials, and two had breakage; unbroken vials showed no degradation in either environment. Atropine experienced limited breakage and no degradation.

Conclusion: Some critical medications experience physical failure and chemical degradation when exposed to up to 90 days of deep freeze or freeze-thaw cycles. Studied formulations of propofol, tranexamic acid, epinephrine, calcium chloride, succinylcholine, and sodium bicarbonate should not be deployed unless these temperature extremes can be avoided. Alternative formulations, packaging, and environmental mitigation solutions should be considered.