Causes

• Acetaminophen is primarily metabolized by the liver. Overdose acetaminophen can overwhelm the liver normally functions.
• Production of acetaminophen's toxic metabolite- NAPQI, causes liver damage, necrosis, and failure.
• If the liver is already damaged because of viral or bacterial infection, alcohol abuse, or other illness, there is increased susceptibility of damage from acetaminophen overdose.

Signs and symptoms

End-organ (liver and kidney) toxicity is often delayed 24-48 hours postingestion.

Patients with malnutrition, AIDS, chronic alcohol abuse, are at increased risk for morbidity because of deficient glutathione stores and inadequate detoxification of NAPQI.

Phase 1- (0 – 24 hrs)

• Asymptomatic
• Anorexia/ Malaise
• Nausea/Vomiting
• Pallor
• Diaphoresis/Increased sweating
• Subclinical rise in LFT (serum transaminases levels) begins at about 12 hours of ingestion

Phase 2- (24 – 72 hrs)

• Right upper quadrant abdominal pain
• Anorexia
• Nausea/vomiting
• Right upper quadrant abdominal tenderness
• Tachycardia
• Hypotension
• Continued rise in LFT (serum transaminases) levels

Phase 3 (72- 96 hrs)

• With centrilobular liver necrosis- the intensity and severity abdominal pain increases
• Jaundice
• Increased bleeding manifestation
• Hepatic encephalopathy
• Renal failure
• Fatality
• Tenderness in liver edge
• Gastrointestinal (GI) bleeding

Phase 4 (4 days – 3 wk)

Complete resolution of symptoms and organ failure

Tests and diagnosis

Serum acetaminophen concentration

Serum APAP concentration (N-acetyl-p-aminophenol)

Liver function test

• Transaminases levels- SGOT and SGPT, toxicity is defined as serum SGOT or SGPT levels greater than 1000 IU/L.
• Direct and indirect bilirubin levels
• Serum albumin and total proteins
• Prothrombin time, Bleeding time and Clotting time

Serum electrolytes

Renal function test- blood urea and creatinine

Human chorionic gonadotropin (HCG levels) in females of childbearing age

Urinalysis- proteinuria and hematuria in acute tubular necrosis

Arterial blood gas analysis

Treatment

Emergency care

• Supportive therapy with IV fluids, Oxygen and Cardiac monitoring

Gastric decontamination

• Activated charcoal is the drug of choice for patients presenting within 1-2 hrs of ingestion
• Activated charcoal avidly adsorbs acetaminophen and should be administered if the patient presents within 1 hour of ingestion
• 1 g/kg orally or 10 times the amount of drug ingested

Antidote- N-acetyl-cysteine

• Early administration of N-acetyl-cysteine, within 8 hours of ingestion, is nearly 100% hepato protective. 
• It’s the drug of choice for prevention and treatment of acetaminophen-induced hepatotoxicity.
• It can be administered orally after diluting with chilled juice or cola to a 5% solution.
• Can also be given by nasogastric tube, if nausea and vomiting is severe
• When administered IV, dilute in 5% dextrose solution.