Acetylcysteine for Acetaminophen Poisoning

Acetaminophen Poisoning

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Acetylcysteine for Acetaminophen Poisoning

N Engl J Med. July 17, 2008;359:285-92

4 Stages of Acetaminophen Poisoning 

1. Preclinical toxic effects (normal ALT) 
2. Hepatic injury (elevated ALT) 
3. Hepatic failure (hepatic injury with hepatic encephalopathy) 
4. Recovery

Clinical Use

It is prudent to administer acetylcysteine to any patient with an elevated ALT and a history of ingesting more than 4 g of acetaminophen per day.

The Rumack–Matthew Nomogram

Dosing of N-Acetylcysteine 

FDA-approved protocols for treatment of acute acetaminophen ingestion:

• Oral acetylcysteine is loading dose 140 mg/kg, with maintenance doses 70 mg/kg Q4H for 17 doses. 
• IV loading dose is 150 mg/kg over 15 to 60 minutes, followed by infusion 50 mg/kg over 4 hours, and finally infusion 100 mg/kg over 16 hours.

Many toxicologists would recommend repeating the measurements of ALT and acetaminophen concentrations as the patient approaches the end of the 16-hour infusion period and continuing treatment if the ALT is elevated or if the acetaminophen concentration is measurable.

OPD therapy may be considered for patients with a 

• confirmed accidental
• repeated supra-therapeutic ingestion
• supra-therapeutic acetaminophen concentration (threshold of <70 µg /ml)
• low-grade elevation of the ALT (<3 times the upper limit of the reference)

The patient can be discharged with 3 maintenance doses to be taken every 4 hours and be re-evaluated 12 hours after the loading dose. 

Treatment can be discontinued if the patient meets the criteria for stopping therapy (i.e., the ALT is decreasing, and acetaminophen concentration is undetectable).

Patients receiving intravenous acetylcysteine for liver failure should be hospitalized in ICU. Treatment is continued until the hepatic encephalopathy resolves and the ALT and creatinine and INR have substantially improved or until the patient receives a liver transplant.

Side Effects of N-acetylcysteine

• Vomiting is common with oral administration. 
• The most commonly reported adverse effects of intravenous N-acetylcysteine are anaphylactoid reactions (15%), including rash, pruritus, angioedema, bronchospasm, tachycardia, and hypotension.

United Kingdom National Health Service guideline recommends treating patients who have acute acetaminophen overdose and a acetaminophen concentration above the probable-toxicity line (the line that begins at 200 µg/ml at 4 hours after ingestion) and high-risk (alcoholic or malnourished) patients who have a concentration above high-risk line that begins at 100 µg/ml at 4 hours.

American College of Emergency Physicians recommends acetylcysteine therapy for any patient with acute acetaminophen ingestion and a timed serum concentration above the line that begins at 150 µg/ml at 4 hours, as well as for any patient with liver injury or liver failure.