Non-Particulate Steroids (Betamethasone Sodium Phosphate, Dexamethasone Sodium Phosphate, and Dexamethasone Palmitate) Combined with Local Anesthetics (Ropivacaine, Levobupivacaine, Bupivacaine, and Lidocaine): A Potentially Unsafe Mixture

Abstract

Purpose: Particulate steroids used in epidural steroid injections have been suspected as a cause of post-procedural embolic events. Some particulate steroids have been suspended only when the transforaminal approach is used for an epidural block of the spine. In contrast, non-particulate steroids are generally accepted for safety during epidural steroid injections. However, the safety of using a mixture of non-particulate steroids and local anesthetics is unknown. This study analyzed whether mixtures of commonly used non-particulate steroids and local anesthetics form crystals in solution.

Methods: We mixed non-particulate steroids (betamethasone sodium phosphate, dexamethasone sodium phosphate, and dexamethasone palmitate) and local anesthetics (ropivacaine, levobupivacaine, bupivacaine, and lidocaine) at different ratios. We used fluorescence microscopy to observe whether crystals formed in mixed solutions; we also measured the pH of each steroid, local anesthetic, and the mixtures.

Results: Ropivacaine or levobupivacaine and betamethasone sodium phosphate produced large crystals (>50 µm). Ropivacaine or levobupivacaine and dexamethasone sodium phosphate produced small crystals (<10 µm). Lidocaine and all non-particulate steroids produced no identifiable crystals; dexamethasone palmitate and all local anesthetics did not form significant particulates. Betamethasone sodium phosphate and dexamethasone sodium phosphate demonstrated basic pH, while all local anesthetics demonstrated acidic pH. Mixtures showed a wide pH range.

Conclusion: Non-particulate steroids can form crystals upon combination with local anesthetics. Crystal formation may be caused by alkalinization of steroids. The mixing of ropivacaine or levobupivacaine and betamethasone sodium phosphate may require caution during an epidural steroid injection. Lidocaine or bupivacaine is recommended as a local anesthetic. Dexamethasone palmitate is a candidate for a mixture, but additional studies on its safety and effectiveness are needed.

Keywords: epidural space; injections; lidocaine; local anesthetics; particle size; steroids.

Figure 1

Non-particulate steroids were pure liquid with no identifiable particle. (A) Microscopic findings of betamethasone sodium phosphate (BSP) (× 200), (B) dexamethasone sodium phosphate (DSP) (× 200), (C) dexamethasone palmitate (DPA) (× 200).

Figure 2

(A) Microscopic findings of betamethasone sodium phosphate (BSP) mixed with 0.75% ropivacaine HCl (ropivacaine) (× 100). (B) High density and extremely large particulates (>500 µm) in BSP mixed with ropivacaine (× 200). (C) BSP mixed with 0.75% levobupivacaine HCl (levobupivacaine) (× 100). (D) High density and large particulates (>100 µm) in BSP mixed with levobupivacaine (× 200). (E) BSP mixed with hyperbaric bupivacaine HCl (× 100). This shows dot-shaped particulates (<10 µm). (F) BSP mixed with 1% lidocaine HCl (× 100). No identifiable particulate is observed.

Figure 3

(A) Microscopic findings of dexamethasone sodium phosphate (DSP) mixed with 0.75% ropivacaine HCl (ropivacaine) (× 100). (B) Small and short rod-like shaped particulates (≤10 µm) in DSP mixed with ropivacaine (× 200). (C) DSP mixed with 0.75% levobupivacaine HCl (levobupivacaine) (× 100). (D) Small and short particulates in DSP mixed with levobupivacaine (× 200). (E) DSP mixed with hyperbaric bupivacaine HCl (× 100). (F) DSP mixed with 1% lidocaine HCl (× 100). No identifiable particulate is observed.

Figure 4

Microscopic findings of dexamethasone palmitate (DPA) mixed with 0.75% ropivacaine HCl (ropivacaine) (× 100).

Figure 5

Insoluble particulates after heating (36–37 °C) (× 400). These particulates were produced from betamethasone sodium phosphate (BSP) mixed with 0.75% ropivacaine HCl (ropivacaine).