Acute liver failure in a term neonate after repeated paracetamol administration

Abstract

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL) after receiving oral paracetamol (10mg/kg/dose every 4 hours) for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

Acetaminophen and Acetylsalicylic Acid Exposure in a Preterm Infant after Maternal Overdose

“…There have been few case reports illustrating the use of NAC in neonates after accidental overdose. [10][11][12][13] There are even fewer that describe situations warranting NAC due to in utero exposure to APAP. 14,15 Steroid use has been reported as a cause of drug-induced liver injury in adult patients, but no reports of antenatal steroids contributing to hepatotoxicity in neonates have been reported.…”

Effect of prenatal and early life paracetamol exposure on the level of neurotransmitters in rats—Focus on the spinal cord

“…It is assumed, that for complete safety, paracetamol administration during the neonatal period should be an occasional and restricted to 48–72 h (Brandlistuen et al, 2013). Such limitation is dictated by the poorer metabolic clearance and reduced elimination capacity of paracetamol by the newborn (Allegaert et al, 2008; Allegaert et al, 2009; Allegaert et al, 2011; Allegaert and Naulaers, 2010; Bucaretchi et al, 2014; Porta et al, 2012). Clinical observations indicate that adequate, well‐tolerated dose in neonates is approximately of 10–30 mg/kg b.w.…”

A significant hepatotoxicity associated with paracetamol overdose in the absence of kidney injury in rabbits

“…In the present study, lack of nephrotoxicity, noted after 9 days of PCM treatment cannot definitely rule out late appearance of nephrotoxicity. PCM induced liver damage has been reported to occur within 24 hrs and reached maximum 3 days after ingestion, 21,22 which indicates that liver damage occurs before renal damage. These findings have some clinical importance since, by the time the liver is severely damaged, renal function is preserved and ready to play a role in elimination of the formed water soluble phase II glucuronide or sulfate conjugate or even the toxic metabolite (NAPQI) which may help minimize the burden on the liver.…”