Crystallization of Local Anesthetics When Mixed With Corticosteroid Solutions

다국어 초록 (Multilingual 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 m) 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 m, pH 7.5). Ropivacaine with dexamethasone sodium phosphate also precipitated, but it was only observable by microscope (a few crystals of 10–100 m, pH 7.0). Bupivacaine with betamethasone sodium phosphate formed precipitates of non-aggregated smaller particles (<10 m, 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.

참고문헌 (Reference)

1 Peterfreund RA, "pH adjustment of local anesthetic solutions with sodium bicarbonate:laboratory evaluation of alkalinization and precipitation" 14 : 265-270, 1989

2 Schmidt AC, "The role of molecular structure in the crystal polymorphism of local anesthetic drugs: crystal polymorphism of local anesthetic drugs, part X" 22 : 2121-2133, 2005

3 Derby R, "Size and aggregation of corticosteroids used for epidural injections" 9 : 227-234, 2008

4 Hansen TG, "Ropivacaine: a pharmacological review" 4 : 781-791, 2004

5 McLure HA, "Review of local anaesthetic agents" 71 : 59-74, 2005

6 Koitabashi T, "Precipitation of pH-adjusted local anesthetics with sodium bicarbonate" 44 : 15-20, 1995

7 MacMahon PJ, "Injectable corticosteroid preparations: an embolic risk assessment by static and dynamic microscopic analysis" 32 : 1830-1835, 2011

8 Rodriguez RW, "How safe is epidural steroid injection? Examining drug-related factors" 14 : 31-35, 2014

9 Gharibo C, "Epidural steroid injections: an update on mechanisms of injury and safety" 13 : 266-271, 2009

10 Manchikanti L, "Epidural steroid injections safety recommendations by the Multi-Society Pain Workgroup (MPW): more regulations without evidence or clarification" 17 : E575-E588, 2014

11 Benzon HT, "Comparison of the particle sizes of different steroids and the effect of dilution: a review of the relative neurotoxicities of the steroids" 106 : 331-338, 2007

12 Chassard D, "Alkalinization of local anesthetics: theoretically justified but clinically useless" 43 : 384-393, 1996

13 Milner QJ, "Alkalinization of amide local anaesthetics by addition of 1% sodium bicarbonate solution" 17 : 38-42, 2000

14 Fulling PD, "Alkalinization and precipitation characteristics of 0.2% ropivacaine" 25 : 518-521, 2000

15 Brandis K, "Alkalinisation of local anaesthetic solutions" 34 : 173-175, 2011