Compatibility and stability of an admixture of multiple anaesthetic drugs for opioid‐free anaesthesia

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.

Opioid-free Anesthesia Protocol on the Early Quality of Recovery after Major Surgery (SOFA Trial): A Randomized Clinical Trial

“…Recently, combining drugs in the same syringe has been proposed to facilitate these protocols. 30 Interestingly, we also allowed the use of these drugs in the standard group (almost 80% of the patients in the standard group received ketamine), as well as loco-regional anesthesia (used in almost 50% of the patients); the standard group was thus representative of current anesthesia protocol. One safety concern regarding OFA is the potential additive risk of adverse effects from the drugs used.…”

Can Opioid-Free Anaesthesia Be Personalised? A Narrative Review

“…This has been shown to reduce the risk of intraoperative awareness [ 41 ]. OFA covers different techniques and practices, including combining ketamine, lidocaine and magnesium sulphate infused through a single syringe infusion [ 42 ]. This combination, often in conjunction with an alpha-2 agonist and locoregional techniques, where indicated, has successfully produced OFA [ 43 ].…”

“…Combining the aforementioned medications into a single syringe is advantageous when multiple syringe drivers are unavailable—even if this is not approved in all countries. Additionally, the complexity of administering drugs is reduced when using a single infusion device, thereby reducing associated drug administration errors [ 42 ]. However, it may reduce the potential for a personalised approach.…”