The Myometrial Stimulatory Effect of Amide Anaesthetics – Fiction or Fact?

Introduction: Obstetric and/or dental anaesthesia is intended to provide optimal pain relief with reduced toxicity. Therefore an unanticipated effect on uterine contractility becomes of utmost importance. This study was therefore aimed at investigating the uterine stimulatory effects of local anaesthetics on uterine contractions.

Materials and Method: All animals used in this study were handled according to Institutional Guidelines for the care and use of animals and also according to the Guide for the Care and Use of Laboratory Animals, Eighth Edition.Lidocaine (0.05 -2.5 mM), bupivacaine (0.05 – 0.5 mM), procaine (0.1 – 1.0 mM), and benzocaine (0.05 – 500 µM) were tested on isolated non-pregnant uterine segments and compared to oxytocin (2.0 – 27 nM). Lidocaine was also tested on the isolated pregnant uterus. Lidocaine was investigated in the presence and absence of indomethacin (0.01 – 0.1 mM), tetraethylammonium (10 mM), L-Methionine (0.05 – 2 mM), and fluphenazine (0.2 mM). Metabolomic investigation was additionally performed to determine altered uterine metabolites. Data were analysed via one-way ANOVA p<0.05 considered significant. Chemometric and bioinformatics analysis were performed on metabolomic data.

Results: Lidocaine and bupivacaine significantly increased uterine contractions (EC50: 0.009 ±0.33 and 0.148 ± 0.20 mMrespectively) (p<0.001) while procaine and benzocaine produced no significant increase in uterine contractility. At concentrations above 0.1 mM, lidocaine and bupivacaine decreased the amplitude (52.6 ± 5.92% and 61.26 ± 4.49% respectively) but increased the tone of contractions (205.58 ± 21.06% and 146.87 ± 15.42% respectively). Indomethacin, fluphenazine and tetraethylammonium produced no significant effects on lidocaine-induced uterine contractions. Metabolomic analysis indicated an interaction of diacylglycerol signalling with the effect of amide anaesthetics.

Conclusion: In conclusion, this study has shown that amide anaesthetics stimulate myometrial contractility via a cascade of cellular mechanisms and possibly via calcium channels.