Paracetamol overdose in a preterm neonate

Abstract

The first oral overdose of paracetamol in a neonate is reported. A 55 day old neonate, born 29 weeks premature, was accidentally given 136 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 ) 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 in neonates, or from maternal toxicity in transplacental poisoning. Treatment includes N-acetylcysteine and supportive care, with activated charcoal for oral poisoning. (Arch Dis Child Fetal Neonatal Ed 2001;85:F70-F72)

Error de medicación en un prematuro de extremo bajo peso: sobredosis de paracetamol

“…12 Parecería que si se finaliza el embarazo dentro de las 24 horas de la exposición el riesgo es bajo, independientemente del cuadro materno y de los cuidados del recién nacido. 13 Una combinación entre una baja tasa de producción de metabolitos tóxicos y el rápido tratamiento podría explicar la no afectación de nuestra paciente, aun cuando tuvo una concentración de paracetamol 40 veces mayor que la terapéutica. En una comunicación similar a la nuestra, tampoco ocurrió mayor daño y se realizó también tratamiento temprano con N-acetilcisteína, aunque la concentración plasmática del fármaco estaba de- bajo de la "línea de tratamiento" propuesta.…”

Acetaminophen-induced hepatic failure with encephalopathy in a newborn

“…3 Anaphylactoid reactions (which can occur in up to 10% of patients) tend to be more significant with intravenous NAC compared to oral NAC. There are few toxicokinetic data of neonatal acetaminophen overdose available, 8 and the protocol used to treat acetaminophen toxicity in this case was based on adult studies. The adult 20 h intravenous NAC protocol 2 can be used to treat severe hepatic and oliguric renal failure in newborns effectively without significant adverse effects, as demonstrated in this case.…”

Medication error in an extremely low birth weight newborn: paracetamol overdose

“…12 It seems that if pregnancy ends within the first 24 hours of exposure the risk is low, regardless the maternal condition and the newborn infant care. 13 The combination between a low rate of toxic metabolite production and the fast treatment might account for the sparing of our patient, even though she experienced an paracetamol level 40 times greater than the therapeutic level. In a report similar to ours, a greater damage did not occur either and early treatment with N-acetylcysteine was also started even though the drug plasma concentration was below the proposed "treatment line".…”

“…Indications suggested for the treatment can be found on Ta- ble 1. A toxic dose would be greater than 150-200 mg/kg, 13,15 and our patient received a higher dose with blood drug levels well beyond the "treatment line" (Figure 1).…”

“…In a report similar to ours, a greater damage did not occur either and early treatment with N-acetylcysteine was also started even though the drug plasma concentration was below the proposed "treatment line". 13 Additionally, activated carbon was used in this patient to decrease the absorption of the toxic agent, which is slow according to pharmacokinetic data in children. 14 We did not prescribe it to our patient because the first dose had been administered over 12 hours before the error was discovered.…”