Abstract
Acetaminophen overdose is one of the most common causes of acute hepatic failure in the developed world. There is strong evidence for N-acetylcysteine (NAC) as a safe and effective antidote for acetaminophen toxicity. However, there is less clarity in the management of massive overdoses (acute, single ingestions > 500 mg/kg with 4-hour equivalent concentrations ~6000 μmol/L) which are often associated with metabolic acidosis and multiorgan dysfunction. In such ingestions, the role of adjuvant treatments such as fomepizole and extracorporeal removal is unclear. We present a case of a 20-year-old female presenting with an acute ingestion of over 120 grams (1764.7 mg/kg) and an acetaminophen concentration of 5880 μmol/L who developed refractory shock, decreased level of consciousness, and metabolic acidosis requiring mechanical ventilation and vasopressor support. She was treated with gastric decontamination with activated charcoal, IV NAC, fomepizole, and hemodialysis. The patient had complete clearance of acetaminophen by 32 hours after presentation and normalization of her acid base and hemodynamic status without any organ failure. This case highlights the potential benefit of a triple strategy of NAC, fomepizole, and early hemodialysis in massive acetaminophen overdose, potentially sparing complications of prolonged intubation and ICU hospitalization.
Highlights
Acetaminophen (APAP) toxicity is among the most common medication-related overdoses and accounts for nearly half of all liver transplantations in the United States [1]
Up to 50% of absorbed APAP is metabolized by CYP2E1, leading to production of N-acetyl-p-benzoquinone imine (NAPQI), the hepatotoxic metabolite
Management consists of gastric decontamination and early administration of N-acetylcysteine (NAC) if the [APAP] is potentially toxic when plotted on the RumackMatthew acetaminophen treatment nomogram
Summary
Acetaminophen (APAP) toxicity is among the most common medication-related overdoses and accounts for nearly half of all liver transplantations in the United States [1]. In massive overdoses (above 500 mg/kg), clinical deterioration may occur rapidly (within 12 hours) with decreased level of consciousness and mitochondrial injury characterized by a high anion gap metabolic acidosis preceding severe liver injury [3]. In such cases, protective effects of NAC may be overwhelmed by the ingested dose. Massive overdose may require treatment with IV NAC beyond 21 hours and may expose the patient to prolonged intubation and ICU admission with potential complications of hospital-acquired infections and neuromuscular weakness. We report a case of massive acetaminophen overdose successfully treated with early administration of intravenous NAC, fomepizole, and prolonged intermittent hemodialysis
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