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"Our results show that this three-drug mixture is chemically stable for up to 24 hours after mixing, with a pharmacokinetic simulation illustrating safe, clinically useful predicted plasma concentrations when using the described admixture" Carpenter et al (2022).

Anaesthetic drug compatibility

Abstract:

The ability to combine and use drugs in a single infusion device may be useful in resource-limited settings. This study examined the chemical stability of an opioid-sparing mixture of ketamine, lidocaine and magnesium sulphate when combined in a single syringe. High-performance liquid chromatography and atomic absorption spectrophotometry were performed on six syringes containing the three-drug mixture. Since most opioid-sparing techniques typically rely on a 24-hour infusion regime, we tested stability at the initial admixing and 24 hours later. Stability was defined as a measured drug concentration within 10% of expected, with the absence of precipitation or pH alterations. Pharmacokinetic simulations were conducted to further show that the achieved plasma drug concentrations were well within an effective analgesic range. All mixed drug concentration measurements were within the required 10% reference limit. No obvious precipitation or interaction occurred, and pH remained stable. Drug stability was maintained for 24 hours. Pharmacokinetic simulations showed that ketamine and lidocaine were within their minimum analgesic effect concentrations. Our results show that this three-drug mixture is chemically stable for up to 24 hours after mixing, with a pharmacokinetic simulation illustrating safe, clinically useful predicted plasma concentrations when using the described admixture.


Reference:

Carpenter AM, Rodseth RN, Coetzee E, Roodt F, Bye S. Compatibility and stability of an admixture of multiple anaesthetic drugs for opioid-free anaesthesia. Anaesthesia. 2022 Aug 29. doi: 10.1111/anae.15846. Epub ahead of print. PMID: 36039022.