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/toxicity occurs when there is intentional, accidental, acute and/or chronic ingestion of supratherapeutic doses of acetaminophen (paracetamol). It is the most widely used OTC (over the counter) analgesic in USA. It 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>br> Aspirin Free Anacin
Atasol
Banesin
Dapa
Datril Extra-Strength
Feverall
Fibi
Genapap
Genebs

Panadol

Common dosage forms and strengths

1. Suppository: 120 mg, 125 mg, 325 mg, 650 mg
2. Chewable tablets: 80 mg
3. Regular strength: 325 mg
4. Extra strength: 500 mg
5. Liquid: 160 mg/teaspoon
6. Drops: 100 mg / mL, 120 mg / 2.5 mL

Toxic Dose

The toxic dose of paracetamol is highly variable. In individuals over 6 years of age, single doses above 200 mg/kg consumed over a single 24-hour period have a reasonable likelihood of causing toxicity. If an individual has consumed large quantities of paracetamol over a 48 hour period, a dose of above 6 grams or 150 mg/kg in the subsequent 24 hour period may cause toxicity.

Management

Shown below is an algorithm summarizing the approach to Acetaminophen Overdose.

Take 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 ❑ Haemorrhage Labs consistent with severe liver failure ❑ AST/ALT levels > 1000 mg/Dl ❑ Prolonged PT/INR ❑ Hypogycemia ❑ Lactic ❑ 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 resusication Symptomatic treatment of nausea & vomiting If liver failure established consider for liver tansplant (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

N-acetylcysteine therapy: ❑ Oral: 140 mg/Kg loading dose followed by 70 mg/Kg 4 hourly for additional 17 doses OR ❑ IV: 150 mg/Kg in 200 cc D5W infused over 15 mins followed by 50 mg/Kg in 500 cc D5W infused over 4 hours then 100 mg/Kg in 1000 cc D5W over remaining 16 hours IV route is referred in following cases (High risk patients): ❑ Malnourished/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 ❑ Abnormal renal or hepatic function at presentation Pregnancy

At the completion of therapy check for: ❑ AST < 100 mg/dL ❑ Serum acetaminophen levels < 10 mcg/mL

Yes

No

Resolution

Continue therapy. Use following as end points of treatment: ❑ Normalization of INR ❑ Resolution of encephalopathy ❑ Decreasing ALT

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.

References

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