Is It Time to Reassess Local Anesthetic and Adjuvant Mixtures? A Narrative Review of Practice, Evidence, and Risks

Mixtures of local anesthetics and adjuvants or mixtures of different local anesthetics are frequently used in regional anesthesia to accelerate the speed of onset and increase the effect and the length of action. Recent in vitro evidence revealed extensive crystallization in mixtures of local anesthetics or local anesthetic-adjuvant mixtures, including those previously deemed "safe"-like lidocaine plus sodium bicarbonate. Several guidelines recommend the use of local anesthetic-adjuvant or mixtures of local anesthetics. In this narrative review, the authors examine the chemical, pharmacologic, and clinical implications of local anesthetic mixture use, illustrate data on efficacy, and highlight critical limitations, including the risk of particle formation, lack of pharmacologic rationale, and unclear propensity for systemic toxicity. Moreover, the authors map out a practical risk versus benefit relationship with recommendations. In light of the unclear safety profile and equivocal clinical benefit of certain mixtures of local anesthetics and local anesthetic-adjuvant mixtures, the authors caution against the routine use of some mixtures at this point, especially for neuraxial techniques.