Crystallization of local anesthetics when mixed with corticosteroid solutions

Hyeoncheol Hwang, Jihong Park, Won Kyung Lee, Woo Hyung Lee, Ja Ho Leigh, Jin Joo Lee, Sun Gun Chung, Chaiyoung Lim, Sang Jun Park, Kee Won Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

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. Conclusion 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.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalAnnals of Rehabilitation Medicine
Volume40
Issue number1
DOIs
StatePublished - 1 Jan 2016

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Crystallization
Local Anesthetics
Adrenal Cortex Hormones
dexamethasone 21-phosphate
Bupivacaine
Lidocaine
Epidural Injections
Triamcinolone Acetonide
Steroids
ropivacaine

Keywords

  • Alkalinization
  • Corticosteroid
  • Crystallization
  • Local anesthetics
  • Precipitation

Cite this

Hwang, Hyeoncheol ; Park, Jihong ; Lee, Won Kyung ; Lee, Woo Hyung ; Leigh, Ja Ho ; Lee, Jin Joo ; Chung, Sun Gun ; Lim, Chaiyoung ; Park, Sang Jun ; Kim, Kee Won. / Crystallization of local anesthetics when mixed with corticosteroid solutions. In: Annals of Rehabilitation Medicine. 2016 ; Vol. 40, No. 1. pp. 21-27.
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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. Conclusion 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.",
keywords = "Alkalinization, Corticosteroid, Crystallization, Local anesthetics, Precipitation",
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Crystallization of local anesthetics when mixed with corticosteroid solutions. / Hwang, Hyeoncheol; Park, Jihong; Lee, Won Kyung; Lee, Woo Hyung; Leigh, Ja Ho; Lee, Jin Joo; Chung, Sun Gun; Lim, Chaiyoung; Park, Sang Jun; Kim, Kee Won.

In: Annals of Rehabilitation Medicine, Vol. 40, No. 1, 01.01.2016, p. 21-27.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Crystallization of local anesthetics when mixed with corticosteroid solutions

AU - Hwang, Hyeoncheol

AU - Park, Jihong

AU - Lee, Won Kyung

AU - Lee, Woo Hyung

AU - Leigh, Ja Ho

AU - Lee, Jin Joo

AU - Chung, Sun Gun

AU - Lim, Chaiyoung

AU - Park, Sang Jun

AU - Kim, Kee Won

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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. Conclusion 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.

AB - 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. Conclusion 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.

KW - Alkalinization

KW - Corticosteroid

KW - Crystallization

KW - Local anesthetics

KW - Precipitation

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DO - 10.5535/arm.2016.40.1.21

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JO - Annals of Rehabilitation Medicine

JF - Annals of Rehabilitation Medicine

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