PITFALL 7

Using the same dosing protocol of NAC for all acetaminophen-toxic patients

In my opinion a toxicologist should be consulted for recommendations on NAC dosing as dosing adjustments should be made depending on a variety of complex factors including timing of ingestion, amount of acetaminophen, type of preparation, co-ingestions, and comorbidities.¹² Dose adjustments are also recommended for patients with massive overdose and those requiring dialysis.¹³

PITFALL 8

Failure to recognize massive acetaminophen overdose in patients with altered level of awareness who have normal transaminases

Massive acetaminophen overdose is defined as greater than 500 mg/kg.¹⁴ It typically presents with a very different toxidrome, characterized by early presentation, exceedingly high acetaminophen levels, coma and lactic acidosis, but with preservation of normal transaminases in this early stage. The reason that massive overdose is important to identify is because management of these patients requires consideration of fomepizole and dialysis in addition to a higher-than-usual dose of NAC. In addition, charcoal is indicated up to 4 hours in massive overdose (compared to 2 hours in  nonmassive overdose).¹⁵ Fomepizole 15 mg/kg given once can be considered as an adjunct to NAC.¹⁶ It is thought to halt the formation of N-acetyl-p-benzoquinone imine, and to inhibit cellular necrosis. The indications for fomepizole based on current evidence are unclear, as there have yet to be robust RCTs published. It is reasonable to consider fomepizole in the massive-overdose patient, those requiring hemodialysis, and those with evidence of significant hepatic injury. Typical indications for dialysis include altered mental status, metabolic acidosis, elevated lactate plus serum acetaminophen greater than 900 mg/L (5,960 mmol/L).¹⁶

Conclusions

Some patients with acetaminophen overdose are relatively straightforward to recognize and manage in the ED. But many present challenges, i.e., in recognition of the condition in unintentional ingestions or in the altered patient, in management due to factors that make the Rumack nomogram useless or misleading, or in dosing of NAC. Massive overdose patients require recognition of an entirely different toxidrome and specific management. Although common, acetaminophen toxicity is no simple matter.

A special thanks to Drs. Emily Austin and Margaret Thompson for their expertise on the EM Cases podcast that inspired this column.

Dr. Helman is an emergency physician at North York General Hospital in Toronto.

He is an assistant professor at the University of Toronto, Division of Emergency

Medicine, and the education innovation lead at the Schwartz/Reisman Emergency

Medicine Institute. He is the founder and host of Emergency Medicine Cases