Physicochemical stability of an admixture of lidocaine and ketamine in polypropylene syringe used in opioid-free anaesthesia

Objectives Opioid-free anaesthesia is a treatment strategy of pain management based on the use of drugs such as lidocaine, ketamine and dexmedetomidine that do not interact significantly with opioid receptors. In particular, these drugs are used by anaesthesiologists to ensure adequate levels of analgesia during surgical procedures for burn patients such as daily wound dressings and graft surgeries. Furthermore, for hypothermia prevention and wound-healing purposes, ambient temperature must be kept high for these patients, usually between 27 degrees C and 30 degrees C. To facilitate the use of this technique, clinicians want to mix lidocaine and ketamine in the same syringe. No stability data is available to determine the feasibility of this admixture and at this temperature. The objective was to study the physicochemical stability of lidocaine 20mg/mL with ketamine 2.5mg/mL diluted with 0.9% sodium chloride (0.9% NaCl) stored at 28 degrees C in polypropylene syringe for 48hours. Methods Physical stability was evaluated by visual examination and by measuring turbidity with a spectrophotometer. Chemical stability was determined after preparation and after 6, 24 and 48hours of conservation with a high performance liquid chromatography and pH measurements. The method was validated according to International Conference on Harmonisation Q2(R1) guidelines. Results Both lidocaine (99.98%1.44%) and ketamine (100.70%+/- 0.95%) retained more than 95% of their initial concentration after 48hours storage. pH measurements remained stable over the course of the study (less than 0.21 point of variation). No signs of physical instability were observed after visual and subvisual inspections. Conclusions The physicochemical stability of lidocaine 20mg/mL and ketamine 2.5mg/mL diluted with 0.9% NaCl in a polypropylene syringe stored at 28 degrees C protected from light was demonstrated for 48hours. This infusion technique is therefore feasible from a pharmaceutical point of view in burn-unit settings.