Paracetamol overdose in a preterm neonate

The first oral overdose of paracetamol in a neonate is reported. A 55 day old neonate, born 29 weeks premature, was accidentally given 135 mg/kg paracetamol. Treatment was with activated charcoal, supportive care, and N-acetylcysteine. There was no biochemical evidence of hepatotoxicity, and no long term sequelae. After modelling of the data, the following pharmacokinetic variables were calculated: absorption half life (t(abs)), 0.51 hours; volume of distribution (V/F-oral), 0.80 litres/kg; clearance (CL/F-oral), 0.22 litres/h; they were consistent with population pharmacokinetic studies. The increased plasma half life (T beta) of 5.69 hours thus reflected normal slower metabolism in infants, rather than toxicity. The toxicity of paracetamol in neonates is unclear, but appears to be low because of slow oxidative metabolism and rapid glutathione synthesis. In an overdose, estimates of toxicity can be made from dose and T beta in neonates, or from maternal toxicity in transplacental poisoning. Treatment includes N-acetylcysteine and supportive care, with activated charcoal for oral poisoning.