1. 2024;27;E89-E98Physicochemical Stability and Compatibility of Mixtures of Ropivacaine with Dexamethasone or Betamethasone for Epidural Steroid Injections: An In Vitro Study
   Observational Study
   Chung Hun Lee, MD, PhD, Sang Yoon Byun, MD, Tae Hoon Kang, MD, Sang Sik Choi, MD, PhD, and Heezoo Kim, MD, PhD.

BACKGROUND: Epidural steroid injections are widely used to treat spinal and radiating pain. However, crystal formation has recently been reported in mixtures of ropivacaine and nonparticulate steroids, commonly used in epidural steroid injections.

OBJECTIVES: Our study assessed the physicochemical stability of mixtures of different nonparticulate steroids and ropivacaine and aimed to propose a safe regimen for epidural steroid injections.

STUDY DESIGN: An in vitro protocol was used to examine the physicochemical stability of epidural steroid injection mixtures most commonly used at our institution.

SETTING: In vitro laboratory study.

METHODS: Twelve solutions were prepared by mixing 0.75% or 0.2% ropivacaine with dexamethasone or betamethasone at volume ratios of 1:1, 2:1, and 3:1 in propylene syringes at 24°C. The physical properties of the mixtures were observed with the naked eye and under a microscope, and their pH was measured. The concentration of each drug in the mixture was evaluated using high-performance liquid chromatography.

RESULTS: None of the ropivacaine and dexamethasone mixtures showed macroscopic or microscopic crystal formation after 2 hours, and there were no significant changes in pH. The concentrations of the 2 drugs remained stable for up to 2 hours. In contrast, at least 10 mu-m crystals were observed microscopically and macroscopically in all mixtures of ropivacaine and betamethasone; the ropivacaine concentration was reduced by > 10% after one hour.

LIMITATIONS: Confirming the stability of drugs in vitro does not ensure that their pharmacokinetics and pharmacodynamics remain unaltered in vivo.

CONCLUSION: The combination of ropivacaine and betamethasone should be avoided because of their physicochemical instability. Combinations of ropivacaine and dexamethasone should be administered cautiously because they are more physicochemically stable than combinations of ropivacaine and betamethasone.

KEY WORDS: Betamethasone, crystal formation, dexamethasone, drug stability, epidural injection, high-performance liquid chromatography, pH, physicochemical stability, spinal pain