Acute Liver Failure In A Term Neonate After Repeated Paracetamol Administration.

Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1 mEq/L), hypoglycemia (18 mg/dL), increased serum aminotransferase activity (AST=4,039 IU/L; ALT=1,087 IU/L) and hyperbilirubinemia (total: 9.57 mg/dL; direct: 6.18 mg/dL) after receiving oral paracetamol (10 mg/kg/dose every 4 hours) for three consecutive days (total dose around 180 mg/kg; serum concentration 36-48 hours after the last dose of 77 µg/ 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. 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.32144-

Falencia hepatica aguda en neonato a termino despues de la ingestion de dosis repetidas de paracetamol

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.Objetivo:A hepatoxicidade grave induzida pelo paracetamol é muito rara em neonatos. Relata-se o caso de um neonato de termo que desenvolveu falência hepática aguda após o uso de paracetamol.Descrição do caso:Menino, 26 dias, admitido com sangramento intestinal, sinais de choque, discreta hepatomegalia, coagulopatia, acidose metabólica (pH=7,21; bicarbonato: 7,1mEq/L), hipoglicemia (18mg/dL), aumento das aminotransferases séricas (AST=4.039UI/L; ALT=1.087UI/L) e hiperbilirrubinemia (total: 9,57mg/dL; direta: 6,18mg/dL), após uso de paracetamol via oral (10mg/kg/dose a cada quatro horas) por três dias consecutivos (dose total ao redor de 180mg/kg; nível sérico de 36-48 horas após a última dose de 77µg/mL). Além das medidas de suporte, o paciente foi tratado com N-acetilcisteína (infusão intravenosa contínua por 11 dias consecutivos), recebendo alta após 34 dias de internação. O seguimento mostrou recuperação clínica e dos parâmetros laboratoriais da função hepática.Comentários:A farmacocinética e a farmacodinâmica do paracetamol em neonatos e lactentes jovens (menores de um ano) diferem substancialmente de crianças maiores e adultos. Apesar de as taxas de metabolismo do sistema enzimático P-450 CYP2E1 estarem diminuídas e a capacidade de gerar glutationa, aumentadas - conferindo maior proteção após superdosagens -, existe a possibilidade de produção de metabólitos hepatotóxicos (N-acetil-p-benzoquinoneimina) que determinam lise celular, caso se esgotem as reservas de glutationa. A depuração é diminuída e a meia-vida de eliminação é prolongada, recomendando-se posologia distinta pelo risco de toxicidade de doses cumulativas. O presente relato destaca o risco de hepatotoxicidade grave em neonatos após o uso contínuo de paracetamol por mais de dois a três dias.Objetivo:La hepatotoxicidad grave inducida por el paracetamol es muy rara en neonatos. Se relata el caso de un neonato a término que desarrolló falencia hepática aguda después del uso de paracetamol.Descripción del caso:Niño, 26 días, admitido con sangrado intestinal, señales de choque, discreta hepatomegalia, coagulopatía, acidosis metabólica (pH=7,21; bicarbonato: 7,1mEq/L), hipoglucemia (18mg/dL), aumento de las aminotransferasas séricas (AST=4.039UI/L; ALT=1.087UI/L) e hiperbilirrubinemia (total: 9,75mg/dL; directa: 6,18mg/dL), después del uso de paracetamol por vía oral (10mg/kg/dosis a cada cuatro horas) durante tres días consecutivos (dosis alrededor de 180mg/kg; nivel sérico de 36-48 horas después de la última dosis de 77µg/mL). Además de las medidas de soporte, el paciente fue tratado con N-acetilcisteína (infusión intravenosa continua por 11 días consecutivos), recibiendo alta después de 34 días de internación. El seguimiento mostró recuperación clínica y de los parámetros laboratoriales de la función hepática.Comentarios : La farmacocinética y la farmacodinámica del paracetamol en neonatos y lactantes jóvenes (menores de un año) difieren substancialmente de niños más grandes y adultos. A pesar de que las tasas de metabolismo del sistema enzimático P-450 CYP2E1 están reducidas y la capacidad de generar glutatión, aumentada - confiriendo más protección después de superdosis -, existe la posibilidad de producción de metabólitos hepatotóxicos (N-acetil-pbenzoquinoneimina) que determinan lisis celular, caso se agoten las reservas de glutatión. La depuración es reducida y la media vida de la eliminación, alargada, recomendándose posología distinta por el riesgo de toxicidad de dosis cumulativas. El presente relato subraya el riesgo de hepatotoxicidad grave en neonatos después del uso continuo de paracetamol por más de dos a tres días.14414

T-piece versus self-inflating bag ventilation in preterm neonates at birth

Objective To verify whether the use of the T-piece resuscitator compared with the self-inflating bag in preterm infants ventilated at birth modifies survival to hospital discharge without major morbidities. Design Pragmatic prospective cohort study. Setting 20 Brazilian university hospitals of Brazilian Network on Neonatal Research. Patients were 1962 inborn infants in 2014-2015 ventilated at birth with 23-33' weeks gestation and birth weight 400-1499 g without malformations. Patients transferred until the 27th day after birth were excluded. Interventions Positive pressure ventilation at birth with T-piece resuscitator or self-inflating bag without positive end expiratory pressure valve. Intervention with ventilation followed the Brazilian Society of Pediatrics guidelines. The choice of the equipment was at the neonatologist's discretion in each delivery. The main outcome measures were survival to hospital discharge without bronchopulmonary dysplasia, severe peri-intraventricular haemorrhage and periventricular leucomalada. Logistic regression adjusted for confounding variables was applied for main outcome. Results 1456 (74%) were only ventilated with T-piece resuscitator and 506 (26%) with the self-inflating bag. The characteristics of those ventilated with T-Piece resuscitator versus self-inflating bag were birth weight 969 +/- 277 vs 941 +/- 279 g, gestational age 28.2 +/- 2.5 vs 27.8 +/- 2.7 weeks and survival to hospital discharge without major morbidities 47% vs 35%, Logistic regression adjusted for maternal characteristics, obstetric and neonatal morbidities showed that the T-piece resuscitator increased the chance of survival to hospital discharge without major morbidities (OR=1.38; 95% Cl 1.06 to 1.80; Hosmer-Lemeshow goodness of fit: 0.695). Conclusion This study is the first that highlights the effectiveness of T-piece resuscitator ventilation in improving relevant outcomes in preterm neonates.Univ Fed Sao Paulo, Div Neonatal Med, Sao Paulo, BrazilUniv Sao Paulo, Dept Pediat, Fac Med Ribeirao Preto, Ribeirao Preto, BrazilUniv Fed Maranhao, Dept Pediat, Sao Luis, BrazilUniv Estadual Campinas, Dept Pediat, Fac Ciencias Med, Campinas, SP, BrazilUniv Sao Paulo, Dept Pediat, Fac Med, Sao Paulo, BrazilUniv Estadual Paulista, Div Neonatol, Fac Med Botucatu, Botucatu, SP, BrazilFundacao Oswaldo Cruz, Div Neonatol, Rio De Janeiro, BrazilPontificia Univ Catolica Rio Grande do Sul, Dept Pediat, Hosp Sao Lucas, Fac Med, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Div Neonatol, Hosp Clin Porto Alegre, Porto Alegre, RS, BrazilUniv Estado Rio de Janeiro, Dept Pediat, Hosp Univ Pedro Ernesto, Rio De Janeiro, BrazilUniv Fed Minas Gerais, Div Neonatol, Belo Horizonte, MG, BrazilUniv Fed Uberlandia, Pediat, Uberlandia, MG, BrazilMaternidade Hilda Brandao, Dept Pediat, Fac Ciencias Med Minas Gerais, Belo Horizonte, MG, BrazilUniv Sao Paulo, Sch Med, Dept Pediat, Sao Paulo, SP, BrazilHosp Estadual Sumare, Neonatal Div, Sumare, BrazilHosp Geral Pirajussara, Neonatal Unit, Taboao Da Serra, BrazilHosp Estadual Diadema, Neonatal Unit, Diadema, BrazilUniv Estadual Londrina, Dept Pediat, Hosp Univ, Curitiba, Parana, BrazilUniv Fed Parana, Dept Pediat, Hosp Clin, Curitiba, Parana, BrazilInst Med Integral Prof Fernando Figueira, Dept Pediat, Recife, PE, BrazilInst Fernandes Figueira FIOCRUZ, Dept Pediat, Rio De Janeiro, BrazilUniv Fed Sao Paulo, Div Neonatal Med, Sao Paulo, BrazilWeb of Scienc