Ropivacaine and dexamethasone: a potentially dangerous combination for therapeutic pain injections

Abstract

Introduction: Targeted spinal steroid injections are effective in reducing back pain in selected patient populations and carry a small risk of significant adverse neurological outcomes. Recent recommendations are for the use of non-particulate steroid agents for all spinal injections to reduce the risk of neurovascular embolic adverse events. Many injections have used a combination of local anaesthetic agent with the steroid. At our institutions, we have recently observed interactions between ropivacaine and dexamethasone combinations ascribed to the incompatibility of the former with alkaline solutions, resulting in rapid crystallisation. This study has further investigated the combinations of commonly used local anaesthetic and steroid combinations to determine if such precipitation effects are more widespread. Methods: The commonly used local anaesthetics (lignocaine, bupivacaine, ropivacaine) and the non-particulate steroid dexamethasone sodium phosphate combinations were evaluated macroscopically, microscopically, and pH values measured. Where crystallisation was observed the rate of precipitation and crystal size was measured. Contamination of ropivacaine with sodium bicarbonate solution was also evaluated. Particulate size of the particulate steroid agent betamethasone acetate was evaluated as a comparison. Results: All mixtures of ropivacaine and the non-particulate dexamethasone sodium phosphate assessed demonstrated a pH-dependent crystallisation of the solution. No precipitation was demonstrated with the combinations of dexamethasone and lignocaine or bupivacaine. Contamination of ropivacaine with residual sodium bicarbonate in a drawing up needle following air clearing had a precipitation effect. Conclusion: We describe the effect of crystallisation with the combination of ropivacaine and the non-particulate steroid, dexamethasone sodium phosphate, a mixture that has been used in the literature for targeted pain injections. As this may be considered a non-particulate steroid/anaesthetic injectate, this would potentially carry increased risk if inadvertent intravascular injection occurred during a targeted spinal injection, as has been described with particulate steroid agents. This is due to the elevated pH of dexamethasone and the incompatibility of ropivacaine with alkaline solutions.

Perineural versus intravenous dexamethasone as an adjuvant in regional anesthesia: a systematic review and meta-analysis

“…As such, the author advised that much attention be paid to the time- and concentration-dependent toxicity when dexamethasone is combined with ropivacaine 37. In agreement with previous results,38,39 in a preliminary animal experiment, we found that solutions of commonly used local anesthetics (bupivacaine, ropivacaine) in combination with nonparticulate dexamethasone sodium phosphate could crystallize, even in physiological pH (unpublished data). Therefore, the patient’s safety might be compromised when crystalliferous solution is unintentionally injected into the subarachnoid space or into the blood vessels.…”

Spine Injectables: What Is the Safest Cocktail?

“…The vasoconstricting activity of ropivacaine (in contrast to the vasodilating effects of lidocaine and bupivacaine) poses a similar hazard to neural tissue [72,73]. As stated previously, ropivacaine mixed with DSP may lead to crystallization and unexpected risk for intravascular embolization [28].…”

“…Celestone Soluspan (Merck Sharp Dohme) combines insoluble (betamethasone acetate) and soluble (betamethasone sodium phosphate) corticosteroids. The rod-shaped crystals in this formulation are overall small (10-30 μm), but the largest measure 50 μm, and aggregates reach 100 μm [24,28].…”

“…Although it is nonparticulate, DSP can rapidly crystallize when mixed with ropivacaine, an LA [28]. Crystallization does not occur when DSP is mixed with lidocaine or bupivacaine.…”

Three Epidural Steroid Techniques

“…Avoidance of particulate corticosteroids appears to be a safety measure that might eliminate the risk for embolization of an RMA, although the solubility of dexamethasone has recently been called into question when combined with ropivacaine but not with lignocaine or bupivacaine, leading to precipitation into non‐soluble particles [4‐6]. Importantly, avoidance of particulate corticosteroids does not preclude direct injury to the RMA.…”