title: Adverse effects of maternally administered lidocaine on the asphyxiated preterm fetal lamb.
abstract: Lidocaine was infused at a constant rate of 0.1 mg.kg-1.min-1 for 180 min into 12 chronically prepared pregnant sheep while asphyxia, induced by partial umbilical cord occlusion, was maintained in the premature fetus (80% of gestation). In five similar preparations saline instead of lidocaine was infused into the mother for 180 min. Maternal and fetal arterial blood pressure, heart rate, pHa, PaCO2, and PaO2 were monitored, and fetal cardiac output and the distribution of blood flow to fetal organs were measured, using labeled microspheres, before and after asphyxia and again after maternal infusion of lidocaine or saline. Maternal and fetal arterial blood and maternal urine were obtained at intervals for determination of lidocaine concentrations and urinary drug clearance. At the end of infusion, these animals were killed and tissues dissected for determination of lidocaine concentrations and organ blood flow. Maternal and fetal lidocaine plasma concentrations at steady state were 2.32 +/- 0.12 and 1.23 +/- 0.17 microgram/ml, respectively, similar to those seen during human epidural anesthesia. Asphyxia resulted in a significant drop in fetal heart rate and increased blood flow to the brain, heart, and adrenals. Asphyxia and saline did not produce additional deterioration of the fetus, but asphyxia and lidocaine led to a significant increase in PaCO2 and decreases in pHa, mean arterial pressure, and blood flows to the brain, heart, and adrenals. It is concluded that the immature fetus loses its cardiovascular adaptation to asphyxia when exposed to clinically acceptable plasma concentrations of lidocaine obtained transplacentally from the mother.
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: H O
authors.initials: HO
authors.lastname: Morishima
authors.forename: H
authors.initials: H
authors.lastname: Pedersen
authors.forename: A C
authors.initials: AC
authors.lastname: Santos
authors.forename: H M
authors.initials: HM
authors.lastname: Schapiro
authors.forename: M
authors.initials: M
authors.lastname: Finster
authors.forename: G R
authors.initials: GR
authors.lastname: Arthur
authors.forename: B G
authors.initials: BG
authors.lastname: Covino
mesh_terms: D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D005260:Female; D005311:Fetal Hypoxia / Q000503:physiopathology*; D005333:Fetus / Q000187:drug effects*; D005865:Gestational Age; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000493:pharmacokinetics / Q000633:toxicity*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012756:Sheep; D014018:Tissue Distribution
chemical_list: D008012:Lidocaine