Adjuvants to local anesthetics: efficacy, safety, and limitations

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Abstract

There are few options for prolonging the action of amide local anesthetics: an increase in dose and concentration is associated with a higher risk of neurotoxicity and systemic complications, whereas catheter-based techniques are resource-intensive and increase the risk of infection. No new local anesthetic molecules have been introduced since the development of levobupivacaine. Therefore, the use of adjuvants to local anesthetics is considered the most promising approach. A targeted search of publications in Russian and English was conducted in PubMed (MEDLINE) and eLibrary databases using the following keywords and their combinations: блокада периферического нерва / peripheral nerve block, местные анестетики / local anesthetics, адъювант / adjuvant, нейротоксичность / neurotoxicity, дексаметазон / dexamethasone, дексмедетомидин / dexmedetomidine. A total of 66 full-text clinical and experimental studies on perineural and/or systemic use of adjuvants in peripheral nerve and interfascial blocks were included in the analysis. The main groups of adjuvants identified were adrenergic receptor agonists, glucocorticoids, opioids, N-methyl-D-aspartate receptor antagonists magnesium salts, and benzodiazepines. A significant prolongation of sensory block and/or time to first analgesic request was demonstrated. Adverse effects were described, including hemodynamic instability associated with α2-agonists, hyperglycemia and possible delayed recovery of nerve function with dexamethasone, opioid-induced nausea and vomiting, hypermagnesemia, psychotomimetic effects of ketamine, and midazolam-related neurotoxicity. Particular attention is given to the phenomenon of rebound pain. Perineural and/or systemic administration of dexamethasone and dexmedetomidine, as well as their combination, appears to be the most justified and safe approach to prolonging block duration. However, all adjuvants except epinephrine are used perineurally off-label, which necessitates individualized risk–benefit assessment and further randomized studies, including evaluation of long-term neurotoxicity.

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About the authors

Anastasia G. Krestovnikova

YoshkarOla City Hospital; Mari State University

Author for correspondence.
Email: sereda993@yandex.ru
ORCID iD: 0009-0005-4118-3696
Russian Federation, Yoshkar-Ola; Yoshkar-Ola

Dmitry V. Zabolotskii

St. Petersburg State Pediatric Medical University; H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: zdv4330303@gmail.com
ORCID iD: 0000-0002-6127-0798
SPIN-code: 6726-2571

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg; Saint Petersburg

Victor A. Koriachkin

St. Petersburg State Pediatric Medical University; H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: vakoryachkin@mail.ru
ORCID iD: 0000-0002-3400-8989
SPIN-code: 6101-0578

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg; Saint Petersburg

Ionas S. Simutis

North-West District Scientific and Clinical Center named after L.G. Sokolov; Mechnikov North-Western State Medical University

Email: simutis@mail.ru
ORCID iD: 0000-0002-2537-0142
SPIN-code: 3619-2048

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg; Saint Petersburg

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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