BACKGROUND: In the context of the opioid epidemic, it is indispensable to reduce the use of opioids and develop new therapeutic alternatives. The combined use of ketamine, lidocaine and dexmedetomidine has been studied for opioid-free anaesthesia and the management of pain to reduce the use of opioids. An opioid-free anaesthesia mixture in one syringe for multimodal anaesthesia has been used in case series and is currently being studied in clinical trials. However, there are no data evaluating the compatibility of the admixture of these three drugs in syringes. The objective of this study was to evaluate the physicochemical stability of the combination of dexmedetomidine, ketamine and lidocaine. METHODS: The formulation combining the three active drugs was prepared at a final concentration of 1�����g/mL of dexmedetomidine, 1���mg/mL of ketamine and 10���mg/mL of lidocaine. The formulation was conditioned in syringes; three syringes were placed at 21��C and three others at 5��C. The concentration and the particle count were evaluated at predetermined time points up to 9���days. A validated stability-indicating HPLC method was developed. RESULTS: The study demonstrated the stability of ketamine (1���mg/mL) and lidocaine (10���mg/mL) in the injectable formulation when stored in polypropylene syringes at 5��C and 21��C for up to 9���days. However, dexmedetomidine (1�����g/mL) was stable for 9���days at 5��C, but only for 3���days when stored at 21��C. Therefore, the injectable formulation containing the three active compounds should be stored at 5��C in order to remain stable for 9���days. The particle count was below the threshold for injectable solution for 9���days at both temperatures. CONCLUSION: This study demonstrated the stability of dexmedetomidine (1�����g/mL), ketamine (1���mg/mL) and lidocaine (10���mg/mL) when stored in a polypropylene syringe at 5��C for up to 9���days.
