Lidocaine pharmacokinetics and toxicity in newborn pigs

Abstract

In newborn infants suffering from perinatal asphyxia seizures, lidocaine (LD) has proved to be an effective anticonvulsant. At high concentrations, however, LD can itself cause convulsions. The convulsive concentration of LD (LD(conv)) varies among species. The aim of this study was to describe LD pharmacokinetics and to define the LD(conv) in awake newborn pigs. Eighteen Land race newborn pigs aged 12-60 h, weight 1.0-2.5 kg, were enrolled. LD, 2 mg/kg intravenous (IV) bolus, (n = 11) was given to estimate pharmacokinetic variables. Continuous LD infusion 2 mg x kg(-1) x min(-1) IV (n = 5) and repeated bolus doses of 15 mg/kg (n = 4) were given until electroencephalogram-confirmed seizures appeared. After the bolus injection, the elimination half-life for LD was 0.87-5.44 h. Increasing plasma concentration (LD(pl)) during infusion resulted in sedation after 5-10 min and in shivering, nystagmus, neck extension, tonic-clonic seizures at LD(conv) of 40.6 +/- 12.7 mg/L (mean +/- SD). The unbound LD(pl) at seizures was 4.4 +/- 2.4 mg/L. Younger animals convulsed at higher LD(conv) (r2 = 0.85). LD pharmacokinetics in newborn pigs were found to be dose-dependent at high plasma concentrations. At lower plasma concentrations, LD pharmacokinetics appeared to be linear. The central nervous system is the primary target for the toxic effect of LD in awake newborn pigs. LD neurotoxicity is age-dependent, and younger pigs convulse at a higher LD(conv).