Gestational differences in lidocaine toxicity in the fetal lamb

Effects of lidocaine on arterial pressure, heart rate and electrocortical activity were studied in nine fetal lambs at 0.77 to 0.92 gestation (116 to 138 days of gestation; term in sheep is 150 days). Lidocaine was administered into a fetal femoral vein either as a continuous infusion or as a bolus injection. Epileptiform activity was observed in all fetuses both after continuous infusion and after bolus injection of lidocaine. Fetal arterial concentrations of lidocaine at the time of the first epileptiform discharge during continuous infusion ranged from 6.9 to 40.0 mug/ml, and correlated negatively with gestational age (Y equals -1.727 x +242.7; r equals -0.94). The increases in fetal mean arterial pressure during epileptiform bursts correlated directly with the gestational age (Y equals 1.27 x -150.0; r equals 0.91). The convulsive doses of lidocaine injected as a bolus ranged from 8.0 to 34.1 mg/kg, and correlated negatively with gestational age (Y equals -0.991 x +144.9; r equals -0.88). The increased sensitivity to lidocaine of the fetal central nervous system with advancing gestation probably reflects differences in fetal brain development. The increase in cardiovascular responses to epileptiform activity with advancing gestation could be related to differences either in the strength of epileptiform discharges or in permeability of the blood-brain barrier to lidocaine, or to immaturity of the autonomic nervous supply to the cardiovascular system in young fetuses.