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21KF-026
Non-particulate Steroids Combined with Local Anesthetics : A Potentially Unsafe Mixture
Eun-Joo Choi1 Dong-Hyun Kim1 Woong-Ki Han1 Ho-Jin Lee 2 Imhong Kang 3
Francis Sahngun Nahm 1,4 Pyung-Bok Lee 1,4
1Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 
2Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Korea;
3Department of Anesthesiology and Pain Medicine, Bundang Chuk Hospital, Seongnam, Korea; 
4Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
Background
Many pain physicians prefer non-particulate steroids to particulate steroids in epidural steroids injection. Because the former are generally considered more safe in epidural embolic adverse events than the latter. However, there has been no study about the safety of using a mixture of local anesthetics and non-particulate steroids yet. So we analyzed whether mixtures of commonly used non-particulate steroids and local anesthetics form crystals in solution.

Materials & Methods
We mixed commonly used non-particulate steroids with various local anesthetics at 1:1, 1:2 and 1:3 ratios on a prepared glass slide. Followed by we analyzed the solution with fluorescence microscopy to confirm the formation of crystals or not. And we also measured the pH of each local anesthetic, steroid and the mixture at different ratios.

Results
Microscopic analysis of mixtures
Mixture of levobupivacaine or ropivacaine with betamethasone sodium phosphate(BSP) produced large crystals above 50μm. The solution of levobupivacaine or ropivacaine and dexamethasone sodium phosphate(DSP) produced relatively small crystals below 10μm. Lidocaine and all non-particulate steroids produced no visible crystals. All local anesthetics and dexamethasone palmitate(DPA) did not form significant particulates.

Heating of particulates
All crystals, produced by levobupivacaine or ropivacaine mixed with BSP or DSP, were insoluble at 36-37°C of physiologic body temperature.

Measurement of pH
All local anesthetics showed acidic pH, but, BSP and DSP showed basic pH. The mixed solutions demonstrated a wide range of pH from acidic to basic.

Discussion
Non-particulate steroids have been thought to be more safe than particulate steroids. However, because some non-particulate steroids can form particulates when mixed with local anesthetics, these combinations should be avoided. There are some limitations in our study. Since the study was conducted as an in vivo assay it is unclear whether crystals may dissolve during actual procedures. And the concentration of the mixed solutions used for our experiment was higher than its concentration of commonly used for an epidural block. Nevertheless, for safety, mixtures of non-particulate steroids with local anesthetics that form less of crystals are recommended.

References
1. Hwang H, Park J, Lee WK, et al. Crystallization of local anesthetics when mixed with corticosteroid solutions. Ann Rehabil Med. 2016;40 (1):21
2. Makkar JK, Singh PM, Jain D, Goudra B. Particulate vs non-particulate steroids for transforaminal epidural steroid injections: systematic review and meta-analysis of the current literature. Pain Physician. 2016;19(6;7):327