Adjuvants For Local Anesthetics: Efficacy, Safety, And Limitations (Narrative Review)

The duration to prolong the action of amide local anesthetics (LAs) is limited: increasing the dose and concentration is associated with increased neurotoxicity and systemic complications, while catheter techniques require resources and increase the risk of infection. No new LA molecules have emerged since the introduction of levobupivacaine. Therefore, the use of LA adjuvants is considered the most promising approach. A targeted search of Russian- and English-language publications was performed in PubMed (MEDLINE) and eLIBRARY.RU using combinations of the keywords «peripheral nerve block», «local anesthetics», «adjuvant», «neurotoxicity», «dexamethasone», «dexmedetomidine». A total of 66 full-text clinical and experimental studies on perineural or systemic use of adjuvants for peripheral and fascial plane blocks were selected for qualitative analysis. The main groups of adjuvants were identified: adrenergic receptor agonists, glucocorticoids, opioids, NMDA receptor antagonists, magnesium salts, and benzodiazepines. A statistically significant prolongation of sensory block and/or time to first request for analgesia was demonstrated. Adverse effects were described: hemodynamic instability with the use of α₂-agonists, hyperglycemia and possible delay in recovery of nerve function with dexamethasone, opioid-induced nausea and vomiting, hypermagnesemia, psychotomimetic effects of ketamine, and neurotoxicity of midazolam. Particular attention was paid to the phenomenon of "rebound pain." Perineural and/or systemic administration of dexamethasone and dexmetomidine, as well as their combination, appears to be the safest and most justified approach for extending the block duration. However, all adjuvants, with the exception of epinephrine, are used perineurally off-label, requiring an individual risk-benefit assessment and further randomized trials, including an assessment of long-term neurotoxicity.