Acetaminophen toxicity

Today we discussed acetaminophen toxicity. Some key points:

Stages of toxicity:
1) preclinical toxic effect with normal ALT (may see no elevation for first 24h)
2) hepatic injury (elevated ALT)
3) hepatic failure (injury with hepatic encephalopathy)- pts presenting here have 20-40% mortality

Glutathione is necessary for the pathway to a non-toxic metabolite. When it is depleted, NAPQI (the toxic metabolite) is formed.

Overdoses (acute or chronic) deplete glutathione and allow liver injury. N-acetylcysteine (NAC) restores glutathione.

If within 2h of ingestion, activated charcoal is used. Beyond 2h, benefit is limited. With a known time of ingestion, the Rumack-Matthew nomogram is used; if level is above line for time of ingestion, there is risk of hepatic injury and NAC should be given.

When no time is known, usual practice is to treat anyone who may have overdosed and has measurable level.

The nomogram is not useful with chronic ingestion, unknown time of ingestion, and with long-acting preparations

There is a PO NAC protocol (72h) and an IV NAC protocol (20h). There are no head to head trials comparing.

Most toxicologists recommend checking acetaminophen level and ALT prior to stopping NAC. Criteria for stopping NAC are falling ALT and undetectable acetaminophen level.

High risk features (i.e. predictive of fulminant failure): encephalopathy, INR over 6.5, Cr over 300, pH below 7.3, hypoglycemia, hyperbilirubinemia. Note that AST/ALT levels are not predictive of poor outcome; only indicate injury.

Link:

Click here for a NEJM review of acetaminophen toxicity