Clinical pharmacokinetics in pregnancy and perinatology. I. Placental transfer and fetal side effects of local anaesthetic agents.
Local anaesthetic agents, both of the amide type (e.g., lidocaine, bupivacaine, etidocaine) and of the ester type (e.g., 2-chloroprocaine) are widely used to relieve pain in obstetric and gynaecological practice. The pharmacokinetics of these compounds are discussed in this review, with particular emphasis on the fetal exposure and its relationship to adverse effects on the fetus. 2-Chloroprocaine is rapidly hydrolyzed by esterases, and only traces of this compound reach the fetus, even following multiple injections, suggesting safety for the fetus. The main disadvantage of this compound is the short duration of action (0.5-1 h). The amide-type agents are active for longer time periods (up to several hours). The fetal/maternal total concentration ratios were approximately 0.3 for bupivacaine and etidocaine, 0.5 for lidocaine, 0.7 for mepivacaine, and 1 for prilocaine. The low ratios of bupivacaine and etidocaine result from extensive binding (90%) of these drugs to maternal alpha1-acid glycoprotein which exceeds corresponding fetal protein binding (50%). These low fetal/maternal total concentration ratios cannot be equated with fetal safety, because fetal side effects are better related to the free drug levels. Since the amide-type anaesthetics are weak bases, fetal acidosis will increase the maternal/fetal pH gradient and will result in accumulation of free drug in the fetus and possible fetal side effects. Addition of epinephrine to the injection solution reduces the maternal blood levels of the amide-type compounds, but apparently not the fetal levels to the same extent. Because of possible unwanted effects of epinephrine (decreased uterine blood flow), the addition of this compound is not generally accepted to be of advantage. Paracervical blockade may result in elevated fetal blood levels (possibly by transarterial diffusion into uterine arteries) and possibly fetal bradycardia.
D000773:Anesthesia, Obstetrical; D000779:Anesthetics, Local / Q000009:adverse effects* / Q000378:metabolism; D002045:Bupivacaine / Q000009:adverse effects / Q000378:metabolism; D005041:Etidocaine / Q000009:adverse effects / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007743:Labor, Obstetric; D008012:Lidocaine / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008619:Mepivacaine / Q000009:adverse effects / Q000378:metabolism; D011247:Pregnancy
D000779:Anesthetics, Local; D008012:Lidocaine; D008619:Mepivacaine; D005041:Etidocaine; D002045:Bupivacaine