Acetaminophen overdose resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vidit Bhargava, M.B.B.S [2], Rim Halaby, M.D. [3]

Overview

Acetaminophen overdose is the intentional or accidental ingestion of a high dose of acetaminophen. Acute acetaminophen overdose occurs ≤8 hours before presentation, while chronic acetaminophen overdose occurs following the repeated supratherapeutic ingestion of acetaminophen.

Acetaminophen is available in the U.S. market under the following brand names:

• Tylenol
• Anacin-3
• Liquiprin
• Percocet
• Tempra
• Cold and flu medicines
• Aceta
• Actimin
• Apacet
• Aspirin Free Anacin
• Atasol
• Banesin
• Dapa
• Datril Extra-Strength
• Feverall
• Fibi
• Genapap
• Genebs
• Panadol

Acetaminophen Dosage

Shown below is a table summarizing the commonly used dosages of paracetamol.

Suppository	120 mg, 125 mg, 325 mg, 650 mg
Chewable tablets	80 mg
Regular strength	325 mg
Extra strength	500 mg
Liquid	160 mg/teaspoon
Drops	100 mg / mL, 120 mg / 2.5 mL

Shown below is a table summarizing the recommended maximum doses of paracetamol.

Patients	Maximum single dose	Minimum dosing intervals (hours)	Maximum dose in 24 hours
Adults	1 g	4	4 g
Children 6-12 years	500 mg	4	2 g
Children 1-5 years	240 mg	4	960 mg
Infants 3-12 months	120 mg	4	480 mg

Management

General Approach

Shown below is an algorithm depicting the approach to acetaminophen overdose.

Obtain a focused history: ❑ Time since last ingestion ❑ Number of tablets/other dosing form taken ❑ Frequency of dosage ❑ Other ingested substances

Characterize the symptoms & examine the patient: Stage I (first 24 hours): Preclinical toxic effects ❑ Asymptomatic ❑ Nausea & vomiting ❑ Diaphoresis ❑ Coma (with massive doses) Stage II (24 to 72 hours): Hepatic injury ❑ Right upper quadrant tenderness ❑ Oligouria ❑ Hematuria Stage III (72 to 96 hours): Hepatic failure ❑ Hepatic tenderness ❑ Jaundice ❑ Impaired consciousness ❑ Asterixis ❑ Foetur hepaticus ❑ Hemorrhage ❑ Death from multiorgan system failure

Order labs: ❑ Serum paracetamol concentration (4 hours after acetaminophen ingestion, but not later than 16 hours) ❑ Liver function tests ❑ Prothrombin time (PT) or International normalized ratio (INR) ❑ Renal function tests

Clear information on the timing of acetaminophen ingestion

No clear information on the timing of acetaminophen ingestion

❑ Order acetaminophen level ❑ Initiate N-acetylcysteine therapy without waiting for acetaminophen levels

< 2 hours

2-4 hours

4-8 hours

> 8 hours

Recurrent supratherapeutic ingestions

❑ Administer activated charcoal 1g/kg (max 50 kg) ❑ Wait until 4 hours has passed and measure acetaminophen level

❑ Wait until 4 hours has passed and measure acetaminophen level

❑ Measure acetaminophen level

❑ Order acetaminophen level ❑ Initiate N-acetylcysteine therapy without waiting for acetaminophen levels

Initiate N-acetlycysteine therapy if, one or more true: ❑ ALT is elevated, AND ❑ Ingestion of >4 g of acetaminophen per day OR ❑ Established hepatic failure

❑ Plot acetaminophen level on the Rumack-Matthew nomogram

Acetaminophen level below the nomogram line ❑ Discharge home

Acetaminophen level above the nomogram line ❑ Initiate N-acetylcysteine therapy

Acetylcysteine Therapy

Shown below is an algorithm depicting the oral and IV regimen of N-acetylcysteine.

N-Acetylcysteine treatment

Consider oral regimen in case of: ❑ Preclinical toxicity ❑ Hepatic injury

Consider IV regimen in case of: ❑ Malnourishment/eating disorders ❑ Failure to thrive in children ❑ AIDS ❑ Alcoholism ❑ Associated febrile illness ❑ Using drugs that induce CYP2E1 p450 system ♦ Carbamazepine, or phenytoin, or phenobarbital ♦ Rifampicin, or rifabutin ♦ Efavirenz, or nevirapine ❑ Hepatic failure ❑ Vomiting and intolerance to oral regimen ❑ Altered mental status

Outpatient

Critical care unit

Oral regimen: ❑ Administer a loading dose of 140 mg/kg ❑ Administer a maintenance dose of 70 mg/kg every 4 hours for 17 doses

IV regimen: ❑ Administer 150 mg/kg in 200 mL glucose 5% solution infused over 15 minutes ❑ Administer 50 mg/kg in 500 mL glucose 5% solution infused over the next 4 hours ❑ Administer 100 mg/kg in 1000 mL glucose 5% solution over the following 16 hours

❑ Monitor the patient for vomiting after the loading dose ❑ Discharge the patient with three maintenance doses to be taken at home

❑ Monitor ♦ Blood pressure ♦ Oxygen saturation ♦ Hypoglycemia ❑ Monitor the liver and renal function every 12 hours

Reevaluate the patient in 12 hours ❑ Measure ALT level ❑ Measure acetaminophen level

Continue the treatment until: ❑ Resolution of encephalopathy ❑ Improvement of ALT, creatinine and INR ❑ The patient receives a liver transplant (if applicable)

Rumack-Matthew Nomogram

Criteria for Liver Transplantation

• Arterial pH < 7.3
• Hepatic encephalopathy grade III/IV
• Serum creatinine concentration > 300 μmol/L
• Prothrombin time > 100 seconds
• Arterial lactate concentration > 3.5 mmol/L on admission or > 3.0 mmol/L 24 hours after paracetamol ingestion

Do's

• Measure serum acetaminophen concentrations between 4 and 16 hours post-ingestion. Values taken before 4 hours are not useful as it takes about 4 hours for maximal drug absorption. Likewise values taken after 16 hours are less useful as liver failure may have already occurred.

• Look for ketones on urinalysis and low blood urea concentration as a sign for malnourishment or starvation.

• In case of acetaminophen ingestion prior to 2 hours of the presentation, administer activated charcoal as it was found to be superior to gastric lavage and substance induced emesis, although both of them are potentially useful.

• N-acetylcysteine can be administered 8 hours following the ingestion of acetaminophen; however, it is most beneficial within the first 8 hours of ingestion.

• Provide a supportive treatment when needed: fluid replacement, symptomatic treatment for nausea and vomiting, intensive supportive treatment in case of acute liver failure.

• If a patient vomits following oral N-acetylcysteine, administer a trial of anti emetic; however, in such cases IV N-acetylcysteine is preferred.

• Stop the infusion if IV N-acetylcysteine precipitates an anaphylactoid reaction, treat with H1-antihistaminics and resume IV N-acetylcysteine at a slower infusion rate.

• If acetaminophen level can not be obtained, assume that that patient has overdose of acetaminophen and treat with N-acetylcysteine.

• Consider liver transplantation if the patient has liver failure and meets the criteria for transplantation.

Dont's

• Do not overlook acetaminophen in those who have signs suggestive of overdose with other agents.
• Do not use activated charcoal after 4 hours of acetaminophen ingestion.
• Do not delay treatment with antidote more than 8 hours following the ingestion of acetaminophen.
• Do not use the Rumack-Matthew nomogram to stratify patients who ingested acetaminophen more than 8 hours ago or whose history of ingestion is unclear.

References

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