Local anesthetic 'in-situ' toxicity during peripheral nerve blocks:  update on mechanisms and prevention.
OBJECTIVE
Peripheral nerve blocks induce undesired side-effects linked to the toxicity of local anesthetics on neuron and myocytes via different cell targets. The effects of local anesthetics on these targets are now well known and summarized in this review.


RESULTS
Local anesthetic-induced local cell toxicity involved different pathways leading to cell death, necrosis and different factors closely associated with the clinical practice modulated this toxicity. High concentration and prolonged duration of local anesthetic administration are closely associated with severe lesions.


CONCLUSIONS
Phenotypic analyses revealed that local anesthetics could induce histological damage with lesions ranging from local to extreme in skeletal muscle. Metabolic alterations were also described involving sarcoplasmic reticulum and calcium dysregulation, alteration of mitochondrial physiology and of oxidative phosphorylation with associated overproduction of harmful reactive oxygen species, typically leading to apoptosis or necrosis. Biochemical and cell biology investigations now indicate that local anesthetics interact with different molecular targets in mammalian cells as respiratory chain complex I or the prosurvival kinase Akt. Functional dysfunction in both muscle and neuron remains to be investigated with caution in patients, as local anesthetic toxicity remains under-evaluated. Likewise, the use of adapted local anesthetics in patients with particular diseases and neuromuscular disorder could further reduce the risk of undesired effect.We need to improve our practice, and the optimization of our clinical protocol could prevent from these side-effects. Lastly, experimental studies highlight the preventive effects of antioxidant drugs or of recombinant human erythropoietin but the pharmacokinetic feature of such strategies remain to be evaluated.
University Bordeaux, Maladies Rares, Génétique et Métabolique, Bordeaux, France. karine.nouette-gaulain@chu-bordeaux.fr
Karine
K
Nouette-Gaulain
Xavier
X
Capdevila
Rodrigue
R
Rossignol
D000779:Anesthetics, Local / Q000009:adverse effects* / Q000633:toxicity; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D007431:Intraoperative Complications / Q000517:prevention & control; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009407:Nerve Block / Q000009:adverse effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010525:Peripheral Nerves
D000779:Anesthetics, Local