Toxicity and distribution of lidocaine in nonasphyxiated and asphyxiated baboon fetuses.
The dosage and blood concentration of lidocaine required to produce central nervous and cardiovascular system toxicity in both nonasphyxiated and asphyxiated fetuses were determined in ten pregnant baboons with fetuses of average gestation of 158 days (term, 185 days). Lidocaine was infused into the fetal jugular vein until cardiac arrest occurred, following which fetal brain, heart, lungs liver and kidneys were obtained. Mean dosage and blood concentration of lidocaine associated with seizures were 9.4 mg/kg and 15.2 micrograms/ml, respectively, in the nonasphyxiated fetuses, and 3.9 mg/kg and 5.6 micrograms/ml, respectively, in the asphyxiated ones. The dosage and blood concentration of the drug required to produce cardiac arrest were significantly higher in the nonasphyxiated group (35 mg/kg and 269 micrograms/ml, respectively) compared to the sphyxiated group (9 mg/kg and 40 micrograms/ml, respectively). Tissue-plasma ratios of lidocaine were significantly higher (P less than 0.05) in the brain, heart, and liver of the asphyxiated fetuses as compared with the nonasphyxiated ones. The relative proportion of the injected dose found in the organs was also higher (P less than 0.05) in the asphyxiated group. These results indicate that the increased sensitivity of the asphyxiated fetus to lidocaine may be related in part to a greater uptake of local anesthetics by the fetal organs.
D000818:Animals; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D008012:Lidocaine / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D010215:Papio; D011247:Pregnancy; D014018:Tissue Distribution
D008012:Lidocaine