Case #6

QUESTIONS and CONTROVERSIAL ISSUES

I) What is the interaction between ethanol and acetaminophen? (chronic vs acute)

A) Acute ethanol consumption 1) May be hepato-protective 2) Preoccupies the cytochrome P450 pathway responsible for creating toxic metabolite of APAP B) Chronic alcohol abuse 1) Results in chronic liver damage 2) Patient more susceptible to hepatotoxic effects of acetaminophen at lower toxic doses 3) In therapeutic doses, APAP still probably safer in the chronic alcoholic than ASA or NSIADs (GI bleed)

II) How is the the APAP level interpreted in a delayed or chronic presentation?

A) APAP nomogram is set-up to guide therapy for acute, single ingestions classically plotted at 4-24 hours postingestion. B) Nomogram not useful in multiple or chronic ingestions. C) In delayed or chronic presentations, the APAP level should still be obtained and half life (T1/2) calculated with a subsequent level D) If the T1/2 exceeds 3-4 hours, liver damage has occurred and antidotal therapy is recommended.

III) How does N-acetylcysteine protect against APAP toxicity?

A) Replenishes glutathione stores B) Directly reduces toxic metabolite NAPQI C) Supplies substrate for sulfination

IV) What if the patient is vomiting and can't tolerate oral NAC?

A) Repeat any dose that is vomited within 1 hour of ingestion B) Antiemetic 1) Metoclopramide (1mg/kg) 2) Ondansetron (0.15mg/kg)

V) Is late NAC administration beneficial?

A) NAC may work as an antioxidant in late APAP toxicity B) Microcirculation effects C) Increases oxygen delivery and oxygen extraction D) Current recommendations: 1) Start late NAC if any APAP detected > 24 hrs after ingestion or if LFTs are elevated. 2) If at 36 hrs there is no detectable APAP and LFTs not elevated, NAC therapy can be stopped. 3) If LFTs are elevated beyond 36 hrs, continue entire course of NAC. 4) In presence of hepatic failure, continue NAC until recovery, death, or liver transplant

VI) What are the indications for considering liver transplant?

A) Increasing PT on 4th day after ingestion B) pH >7.30 C) Peak PT> 100sec D) Creatinine > 3.5 (Hepatorenal syndrome) E) Hepaticencephalopathy

VII) Tylenol ER (Extended Relief)- Insufficient clinical experience

The pharmaceutical company recommends that levels be drawn at 4 and 8 hours after ingestion, and that if either level is in the toxic range (per the nomogram) that NAC treatment be initiated.

CLINICAL COURSE

The patient's second APAP level 4 hours after presentation is 23 mcg/ml. Oral NAC is instituted but is not tolerated by the patient due to severe nausea and vomiting. The patient's vomiting ceases after administration of ondansetron, and she tolerates the remaining doses. However, despite aggressive management, she goes into hepaticencephalopathy the second day of admission. The patient is placed on the liver transplant list, but expires before a suitable donor can be found.