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]

Definition

Acetaminophen overdose is the intentional or accidental ingestion of more than 7.5-10 g of acetaminophen in adolescents and adults. Acetaminophen overdose is acute if it occurs in ≤8 hours, while chronic acetaminophen overdose occurs following the repeated supratherapeutic ingestion of acetaminophen more than 8 hours ago.

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

Management

Shown below is an algorithm summarizing 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 the acetaminophen ingestion and 16 hours) ❑ Liver function tests (LFT's) ❑ Prothrombin time (PT) or International normalised ratio (INR) Renal function tests (RFT's)

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: ❑ AST is elevated ❑ Serum acetaminophen concentration > 10 mcg/mL

❑ Plot acetaminophen level on the Rumack-Matthew nomogram

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

Acetaminophen level above the nomogram line ❑ Discharge home

Acute overdose (Single ingestion within a 4 hour period)

Chronic overdose (Multiple ingestions over more than 4 hours)

❑ Begin therapy within 8 hours of ingestion ❑ Administer activated charcoal 1g/Kg max 50 Kg ❑ Supportive care Fluid resuscitation Symptomatic treatment of nausea & vomiting If liver failure established consider for liver transplant (see box below)

Initiate N-acetlycysteine therapy if, one or more true: ❑ Acetaminophen concentration above nomogram line ❑ AST is elevated ❑ Serum acetaminophen concentration > 10 mcg/mL

Initiate N-acetlycysteine therapy if, one or more true: ❑ AST is elevated ❑ Serum acetaminophen concentration > 10 mcg/mL

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/phenytoin/phenobarbital Rifampicin/rifabutin Efavirenz/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)

Criteria for possible liver transplantation: Arterial pH < 7.3 Hepatic encephalopathy grade III/IV Serum creatinine concentration > 300 μmol/L Prothrombin time > 100 secs Arterial lactate concentration > 3.5 mmol/L on admission or > 3.0 mmol/L 24 hours after paracetamol ingestion Discuss with transplant team when in doubt.

The following algorithm is based on guidelines from "Management of paracetamol poisoning" and "Acetaminophen toxicity and treatment" published by American college of emergency physicians.

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 by than and the values might not reflect a true picture.
• Ketones on urinalysis and low blood urea concentration point towards 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 as compared to gastric lavage and substance induced emesis, though both of them are also somewhat 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.
• 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 precipitated an anaphylactoid reaction, treat with H1-antihistaminics and resume IV N-acetylcysteine at a slower infusion rate.

Dont's

• Do not overlook acetaminophen in those who have signs suggestive of overdose with other agents.
• Do not rely on activated charcoal decontamination after 4 hours of ingestion, as it is found to be less reliable after that.
• Do not delay treatment with antidote, as the efficacy rapidly decreases after 8 hours.

References

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