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

Abstract

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°C and 30°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 20 mg/mL with ketamine 2.5 mg/mL diluted with 0.9% sodium chloride (0.9% NaCl) stored at 28°C in polypropylene syringe for 48 hours. 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 48 hours 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 48 hours 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 20 mg/mL and ketamine 2.5 mg/mL diluted with 0.9% NaCl in a polypropylene syringe stored at 28°C protected from light was demonstrated for 48 hours. This infusion technique is therefore feasible from a pharmaceutical point of view in burn-unit settings.

Stability of dilutions of methadone alone, and in combination with lidocaine and ketamine

“…The extent of lidocaine degradation was also similar between those fluid bags stored at room temperature or in a refrigerator, suggesting that the reduction in concentration over time was not associated with temperature. The 0.9% NaCl and Hartmann's solution fluid bags used in this study were manufactured from polyvinylchloride, which has previously been shown to adsorb certain drugs when compared to a polypropylene delivery system (Noh et al 2009), and this is one possible explanation for the higher degree of apparent degradation of lidocaine in our study compared to that of Beiler et al (2020). Although the lidocaine appeared to decrease more rapidly and to a greater extent than either methadone or ketamine in the MLK solutions, there was no statistical difference between the rate of degradation of the three drugs, with all decreasing over time, with the exception of the methadone in MLK diluted in Hartmann's solution at 4°C.…”

“…2009), and this is one possible explanation for the higher degree of apparent degradation of lidocaine in our study compared to that of Beiler et al . (2020). Although the lidocaine appeared to decrease more rapidly and to a greater extent than either methadone or ketamine in the MLK solutions, there was no statistical difference between the rate of degradation of the three drugs, with all decreasing over time, with the exception of the methadone in MLK diluted in Hartmann's solution at 4°C.…”

“…A combination of lidocaine, 20 mg/ml, and ketamine, 2.5 mg/ml, diluted with 0.9% NaCl, stored in polypropylene syringes at 28°C and protected from light, was found to be stable, with retention rates of approximately 100% of the initial drug concentrations when assessed after 48 hours (Beiler et al . 2020). In contrast, in our study, lidocaine concentrations had declined by the first measurement point at 4 hours, and continued to decrease at each subsequent measurement, with all four groups having lidocaine degradation of greater than 10% by the final analysis at 240 hours from baseline.…”

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

“…Beiler et al studied the effect of combining lidocaine and ketamine with a sample size of three syringes (admixtures) [9]. A similar study by Schenkel et al investigated multiple different drug combinations but noted that they only performed investigations on five samples that were considered to be therapeutic [11].…”

Opioid-Free Anesthesia: Physico Chemical Stability Studies on Multi-Analyte Mixtures Intended for Use in Clinical Anesthesiology

“…Furthermore, some studies have demonstrated the stability and compatibility of dual combinations of the aforementioned drugs in polypropylene syringes. Recently, Beiler et al 17 showed the physico chemical stability of a 20 mg/ml Lid and 2.5 mg/ml Ket in polypropylene syringes at 28°C over a time period of 48 hours. Along these lines, Houlihan et al 18 proved the physical compatibility and chemical stability of Mg and Lid in prefilled polypropylene syringes at 25°C and 40°C over 6 months.…”