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

Characterize the symptoms & examine the patient: Stage I: First 24 hours ❑ Asymptomatic ❑ Nausea & vomiting ❑ Diaphoresis ❑ Anion gap metabolic acidosis & coma (with massive doses) Stage II: 24 to 72 hours Clinical & lab features of hepatotoxicity ❑ Right upper quadrant tenderness ❑ Deranged LFT's, PT, Serum bilirubin Clinical & lab features of nephrotoxicity ❑ Oligouria, hematuria ❑ Deranged RFT's, proteinuria, hematuria, casts Stage III: 72 to 96 hours Signs of liver failure ❑ Hepatic tenderness ❑ Jaundice ❑ Impaired consciousness ❑ Asterixis ❑ Foetur hepaticus ❑ Hemorrhage Labs consistent with severe liver failure ❑ AST/ALT levels > 1000 mg/Dl ❑ Prolonged PT/INR ❑ Hypoglycemia ❑ Lactic acidosis ❑ Total bilirubin > 4.0 ❑ Renal failure ❑ Death from multiorgan system failure Stage IV: 4 days to 2 weeks ❑ Recovery

Order labs: ❑ Serum paracetamol concentration ( @4 hours and 16 hours) ❑ Liver function tests (LFT's) ❑ Prothrombin time (PT) or International normalised ratio (INR) Renal function tests (RFT's) ❑ Chart Rumack Matthew nomogram (not useful for chronic overdose)

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 ❑ Gastric decontamination 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.
• Activated charcoal was found to be superior as compared to gastric lavage and substance induced emesis, though both of them are also somewhat useful.
• N-acetylcysteine is most beneficial within first 8 hours of ingestion, however it can be still used after that if liver damage is suspected.
• If a patient is vomiting, a trial of anti emetic may be done, however in such cases IV N-acetylcysteine is preferred.
• IV N-acetylcysteine may sometimes precipitate an anaphylactoid reaction, in such cases stop the infusion, treat with H1-antihistaminics and resume 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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