Acetaminophen Overdose in Pregnancy

Abstract

Acetaminophen (APAP) is the most common drug overdose in pregnancy. Available data regarding APAP overdose in pregnancy is limited to case reports and a small prospective case series. APAP has been demonstrated to cross the placenta and in toxic doses may harm the fetal and maternal hepatocytes. Fetal hepatocytes metabolize APAP into both active and toxic metabolites. These toxic metabolites may cause fetal hepatic necrosis. N-acetylcysteine (NAC) has also been demonstrated to cross the placenta and may bind toxic metabolites in both the mother and the fetus. Limited data suggest that the majority of morbidity and mortality from APAP overdose can be averted by initiation of NAC within the first 16 hours of ingestion and possibly even later. NAC may be safely administered during pregnancy and should be initiated early after APAP overdosage. The literature was reviewed through the use of OvidMEDLINE database, encompassing 1966 to the present. Searches were conducted using the key words acetaminophen, paracetamol, N-acetylcysteine, overdose, and hepatotoxicity. The search was further refined by selecting articles that contained these search words together with the key word pregnancy. Only English language papers were reviewed. Articles were selected on the basis of relevance to the topic. Pertinent citations found in the selected articles were also reviewed.

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

“…34 At near term, pregnant animals were anesthetized with ketamine (80 mg/kg) and xylazine (1 mg/kg) and administered a subcutaneous injection of lidocaine prior to receiving an abdominal incision. Age-matched fetuses (62 days, term ¼ 65 days) were excised via hysterotomy.…”

Medicamentos causantes de hepatotoxicidad en el embarazo: revisión estructurada

“…En una mujer de 22 años de edad se identificó toxicidad hepática a los 14 días, que requirió trasplante hepático y finalización de su embarazo con misoprostol (14). El problema de toxicidad se manifestó por dolor abdominal, ictericia, daño hepático y necrosis hepática en el feto (14,15). En general, se acepta que la toxicidad se debe al metabolito del acetaminofén, la N-acetil-pbenzoquinona imina.…”

“…En este contexto, en el caso del acetaminofén, la nitrofurantoína, la alfametildopa y la nevirapina, el aumento en los valores de la aspartato-aminotransferasa (AST) y alanino-aminotranferasa (ALT) fue mayor de 10 veces el límite superior normal (7,14,16,48). Además, otros síntomas inespecíficos, como la ictericia, los vómitos, el prurito y la anorexia, pueden aparecer en estas pacientes (15,16,34,40). Por su parte, en el feto, el acetaminofén puede causar necrosis hepática (15), mientras que el metimazol y carbimazol pueden causar defectos congénitos (11,47).…”

“…Además, otros síntomas inespecíficos, como la ictericia, los vómitos, el prurito y la anorexia, pueden aparecer en estas pacientes (15,16,34,40). Por su parte, en el feto, el acetaminofén puede causar necrosis hepática (15), mientras que el metimazol y carbimazol pueden causar defectos congénitos (11,47). El manejo que se dio en los casos de hepatotoxicidad en mujeres embarazadas fue la suspensión del medicamento sospechoso, con lo cual se logró, en algunos casos, mejorar la sintomatología.…”

Monster Phase of Acetaminophen Use in Pregnancy: Current Vision of an Old Drug

“…APAP toxicity in pregnancy is not rare and can result in significant morbidity and mortality in both the mother and the fetus. Over many years, use of acetaminophen, questions about its safety in pregnancy have been addressed by studies in different populations using different designs, but because of universal use of this medication and limitations of earlier studies, new studies continue to address the question [4]. APAP may influence the oxidative stress via disturbing inflammatory and immunological mechanisms.…”