The effect of cold-chain re-introduction on the molecular integrity of rocuronium bromide

Abstract

Introduction: This study aimed to examine the effect of breakages and re-introduction into cold chain on the rocuronium bromide compound. Rocuronium bromide is frequently used in routine theatre lists and plays a vital role in modified rapid sequence induction and intubation for emergency patients who have contraindications to the primarily used muscle relaxant, succinylcholine. With the current practice of removing the drug from, and then reintroducing it into the cold chain, unpredictable clinical effects, including delayed onset of action and shortened duration of action have been observed. This may pose significant risks to the patient.

Methods: Rocuronium bromide was subjected to different clinically applicable storage and temperature scenarios, after which the compound was analysed for integrity and quantities of the active compound, including detection of possible degradation products, by mass spectrometry, and compared to cold chain control samples.

Results: There were no significant differences between any of the temperature exposure groups (18 °C or 24 °C) or between single or double exposures at these temperatures. No statistically significant difference could be demonstrated between the two control groups (cold chain preserved and room temperature controlled) with testing done at weeks one and six. However, week twelve analysis revealed a statistically significant result which translates to a 26 μg/ml difference, which clinically would have no effect. Substantial results were obtained with a secondary exposure to air; which lead to a 20% decrease in rocuronium concentration (p = 0.02).

Conclusion: Practice should be adapted by keeping careful documentation as to when cold-chain was broken, and when the recommended 12 week period will lapse. Vial sharing as a standard is not recommended. If small quantities are repeatedly withdrawn from the vial during a prolonged case, the unused contents should be discarded after eight hours.