Time to rethink mixing local anaesthetics: A practical update for modern regional anaesthesia

Dear Editor, The long-standing practice of mixing short- and long-acting local anaesthetics (LAs) to combine rapid onset with prolonged duration has become a topic of renewed scrutiny.[1] Traditionally, it was believed that mixing agents such as lignocaine and bupivacaine offered the benefits of both fast onset and long duration. However, recent evidence suggests this practice may be less effective in modern clinical settings, particularly with advancements such as ultrasound-guided peripheral nerve blocks (US-PNB).[2] When LAs are mixed, the drug concentration is diluted for each agent, reducing the potency of both. Notably, this dilution diminishes the concentration gradient, critical for penetration into nerve tissues. Furthermore, the ionised versus unionised proportions of the drugs shift due to differences in pH, reducing their ability to cross lipid membranes and bind sodium channels.[1] For example, when lignocaine (a fast-acting agent) is mixed with bupivacaine (a long-acting agent), the resulting solution has a lower proportion of unionised lignocaine, potentially leading to delayed onset rather than the desired acceleration.[1] With the widespread use of US-PNB, the need for hastening block onset by mixing LAs has strikingly diminished.[2] Ultrasound allows for precise localisation and distribution of LAs around the nerves, improving the onset times of long-acting agents such as ropivacaine and bupivacaine. Combining short- and long-acting agents may no longer offer the clinical advantage it once did.[2] In addition, block duration may somewhat be shortened when mixing LAs, as seen in studies where the addition of lignocaine reduced the overall duration of sensory and motor blocks compared to using a long-acting agent alone.[3] Another important implication is that the mixing of LAs raises safety concerns. This is because systemic toxicity of two LAs is additive, which increases the risk of adverse effects such as cardiovascular or neurotoxic events.[4] Some combinations, such as lignocaine with ropivacaine, have been shown to increase neurotoxicity, which must be carefully considered in clinical practice.[1,5] In the context of US-PNB, where lower doses of LAs can be used effectively, the need to mix LAs becomes even less compelling because the potential risks outweigh the benefits.[5] We suggest that anaesthesiologists should prioritise the selection of LA for US-guided procedures based on the surgical procedure and patient profile without defaulting to the use of admixtures. Using single long-acting agents in conjunction with US-PNB techniques can offer both timely onset and prolonged analgesia.[2] Furthermore, avoiding admixtures simplifies dosing calculations and reduces the potential for toxicity.[1] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.