St-Jean I, Hachemi D, Friciu M, Forest JM, Belliveau M , et al.
European journal of hospital pharmacy : science and practice •
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. The formulation combining the three active drugs was prepared at a final concentration of 1 µg/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. 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 µg/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. This study demonstrated the stability of dexmedetomidine (1 µg/mL), ketamine (1 mg/mL) and lidocaine (10 mg/mL) when stored in a polypropylene syringe at 5°C for up to 9 days.
Khan JS, Gilron I, Devereaux PJ, Clarke H, Ayach N , et al.
Trials •
Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).
