title: Crystallization of Local Anesthetics When Mixed With Corticosteroid Solutions.
abstract: OBJECTIVE
  To evaluate at which pH level various local anesthetics precipitate, and to confirm which combination of corticosteroid and local anesthetic crystallizes.
  
  
  METHODS
  Each of ropivacaine-HCl, bupivacaine-HCl, and lidocaine-HCl was mixed with 4 different concentrations of NaOH solutions. Also, each of the three local anesthetics was mixed with the same volume of 3 corticosteroid solutions (triamcinolone acetonide, dexamethasone sodium phosphate, and betamethasone sodium phosphate). Precipitation of the local anesthetics (or not) was observed, by the naked eye and by microscope. The pH of each solution and the size of the precipitated crystal were measured.
  
  
  RESULTS
  Alkalinized with NaOH to a certain value of pH, local anesthetics precipitated (ropivacaine pH 6.9, bupivacaine pH 7.7, and lidocaine pH 12.9). Precipitation was observed as a cloudy appearance by the naked eye and as the aggregation of small particles (<10 µm) by microscope. The amount of particles and aggregation increased with increased pH. Mixed with betamethasone sodium phosphate, ropivacaine was precipitated in the form of numerous large crystals (>300 µm, pH 7.5). Ropivacaine with dexamethasone sodium phosphate also precipitated, but it was only observable by microscope (a few crystals of 10-100 µm, pH 7.0). Bupivacaine with betamethasone sodium phosphate formed precipitates of non-aggregated smaller particles (<10 µm, pH 7.7). Lidocaine mixed with corticosteroids did not precipitate.
  
  
  CONCLUSIONS
  Ropivacaine and bupivacaine can precipitate by alkalinization at a physiological pH, and therefore also produce crystals at a physiological pH when they are mixed with betamethasone sodium phosphate. Thus, the potential risk should be noted for their use in interventions, such as epidural steroid injections.
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyeoncheol
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jihong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Woo Hyung
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ja-Ho
authors.initials: JH
authors.lastname: Leigh
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sun G
authors.initials: SG
authors.lastname: Chung
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Chaiyoung
authors.initials: C
authors.lastname: Lim
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Keewon
authors.initials: K
authors.lastname: Kim
keywords: Alkalinization; Corticosteroid; Crystallization; Local anesthetics; Precipitation