Ketamine Stability over Six Months of Exposure to Moderate and High Temperature Environments

Abstract

Background: All medications should be stored within temperature ranges defined by manufacturers, but logistical and operational challenges of prehospital and military settings complicate adherence to these recommendations. Lorazepam and succinylcholine experience clinically relevant heat-related degradation, whereas midazolam does not. Because ketamine's stability when stored outside manufacturer recommendations is unknown, we evaluated the heat-related degradation of ketamine exposed to several temperature ranges. Methods: One hundred twenty vials of ketamine (50 mg/mL labeled concentration) from the same manufacturer lot were equally distributed and stored for six months in five environments: an active EMS unit in southwest Ohio (May-October 2019); heat chamber at constant 120 °F (C1); heat chamber fluctuating over 24 hours from 86 °F-120 °F (C2); heat chamber fluctuating over 24 hours from 40 °F-120 °F (C3); heat chamber kept at constant 70 °F (manufacturer recommended room temperature, C4). Four ketamine vials were removed every 30 days from each environment and sent to an FDA-accredited commercial lab for high performance liquid chromatography testing. Data loggers and thermistors allowed temperature recording every minute for all environments. Cumulative heat exposure was quantified by mean kinetic temperature (MKT), which accounts for additional heat-stress over time caused by temperature fluctuations and is a superior measure than simple ambient temperature. MKT was calculated for each environment at the time of ketamine removal. Descriptive statistics were used to describe the concentration changes at each time point. Results: The MKT ranged from 73.6 °F-80.7 °F in the active EMS unit and stayed constant for each chamber (C1 MKT: 120 °F, C2 MKT: 107.3 °F, C3 MKT: 96.5 °F, C4 MKT: 70 °F). No significant absolute ketamine degradation, or trends in degradation, occurred in any environment at any time point. The lowest median concentration occurred in the EMS-stored samples removed after 6 months [48.2 mg/mL (47.75, 48.35)], or 96.4% relative strength to labeled concentration. Conclusion: Ketamine samples exhibited limited degradation after 6 months of exposure to real world and simulated extreme high temperature environments exceeding manufacturer recommendations. Future studies are necessary to evaluate ketamine stability beyond 6 months.

Keywords: degradation; heat; ketamine; stability; temperature.