Acetaminophen Overdose & Management

 Introduction

• Acetaminophen (Tylenol, Paracetamol, APAP) is a commonly used analgesic and antipyretic agent found in many over the counter and prescription medications.
• It is one of the most common toxic exposures responsible for an estimated 450 deaths annually in the United States, and it is the most common cause of acute liver failure in the United States.

Metabolism

• At therapeutic doses: Acetaminophen is primarily metabolized by the liver through glucuronidation and sulfation. A small percentage is metabolized by the cytochrome P-450 system to form the toxic metabolite NAPQI, which is detoxified by glutathione for renal excretion.
• At toxic doses:  Metabolism through glucuronidation and sulfation is saturated, sending more acetaminophen down the P-450 pathway, leading to a toxic buildup of NAPQI without enough glutathione to keep up with demand.
• Hepatotoxicity results once glutathione stores are depleted by 70%. NAPQI leads to liver injury.

Toxic Dose

• Acute single ingestion: >150 mg/ kg
• Chronic ingestion: > 4g/ day

Presentation

• During the first 24 hours after exposure, patients often have minimal or nonspecific symptoms of toxicity such as anorexia, nausea or vomiting.

Treatment Guidelines

• Presentation within 4 hours of ingestion:
• consider GI contamination with activated charcoal
• obtain a 4-hour acetaminophen level
• plot level on Rumack-Matthew Nomogram and treat with N-acetylcysteine (NAC) if level is above line

• Presentation between 4 and 24 hours after ingestion:
• GI contamination has limited role
• obtain acetaminophen level ASAP
•  if you can obtain lab within 8 hours, wait until acetaminophen level is available to determine if NAC therapy is necessary. Otherwise, empirically administer NAC within 8 hours

• Presentation after 24 hours or time of ingestion unknown:
•  obtain serum acetaminophen level, AST/ ALT, bilirubin, and prothrombin time
• treatment with NAC is indicated if acetaminophen concentration > 10 micrograms/mL or transaminases are elevated

 N- acetylcysteine (NAC)

• PO dose:  140 mg/kg loading dose; then 70 mg/ kg PO every 4 hours x 17 doses
• IV dose:  150 mg/kg loading dose; then 50 mg/kg over 4 hours; then 100 mg/kg over 16 hour.

• Anaphylactoid reactions possible. Infuse initial load over one hour.

Pearls

• NAC must be given within 8 hours of overdose to prevent hepatotoxicity.
• Contact Poison Control Center or your toxicologist for help.

References:

Hung OL, Nelson LS. Acetaminophen. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e New York, NY: McGraw-Hill; 2016.

Photo:

https://www.mdcalc.com/acetaminophen-overdose-nac-dosing