Acetaminophen Poisoning

• Max safe dose of acetaminophen per day is ~4 g in adults, but may be lower in predisposed patients such as chronic alcoholics and malnourished patients.  Most cases of poisoning occur with >10 g/day.
• Normal metabolism of acetaminophen – 90% via liver glucoronidation and sulfation --> excreted harmlessly in the urine.  2% excreted in urine unchanged.  Remaining 8% is metabolized via CYP2E1 into NAPQI , which is a reactive molecule which causes hepatotoxicity.  Normally, NAPQI is scavenged by glutathione in the liver (an antioxidant), but when this is depleted, hepatotoxicity ensues.

Risk factors for Acetaminophen Toxicity

• Chronic alcohol – due to depletion of glutathione and induction of CYP2E1 enzyme
• Malnutrition/fasting also does this.
• Note that acute alcohol ingestion with acetaminophen may actually be protective, due to the fact that EtOH competes with acetaminophen for CYP2E1 metabolism.

Management:
1. GI decontamination with activated charcoal – the sooner the better
2. N-acetylcysteine – antidote for acetaminophen: acts by restoring glutathione stores in the liver
Key is to start before you see rise in ALT – the earlier the better!
Methods:  20 hour IV protocol vs 72 hour PO protocol

• In general, both IV and PO are probably equally efficacious.  Main downside to IV NAC is risk of anaphylactoid reaction (in 10-20%) but usually this can be managed, especially in an ICU setting where the patients belong.
• Use IV if patients unable to take PO (obviously) or in all cases of fulminant hepatic failure.
• Despite the 20 and 72 hour protocols, many experts will continue IV NAC for longer, especially in hepatic failure --> typically continued until patient receives a liver transplant, OR until encephalopathy resolves and INR becomes <2.

(Chanu Rhee MD, 10/25/10)