What is the recommended evaluation and treatment for a 50‑year‑old adult with an acetaminophen (Tylenol) overdose?

Acetaminophen (Tylenol) Overdose in a 50-Year-Old Adult

For a 50-year-old with acetaminophen overdose, immediately administer N-acetylcysteine (NAC) if the ingestion exceeds 10 grams (or 200 mg/kg), if the serum level plots above the treatment line on the Rumack-Matthew nomogram (drawn 4–24 hours post-ingestion), or if there is any evidence of hepatotoxicity (elevated transaminases), regardless of timing—treatment within 8 hours prevents severe liver injury in 97% of cases. 1, 2, 3

Initial Assessment and Risk Stratification

When a patient presents with suspected acetaminophen overdose, obtain the following critical information immediately:

• Amount ingested: Ingestions ≥10 grams (or ≥200 mg/kg, whichever is lower) are potentially toxic and require emergency evaluation 1, 4
• Time of ingestion: Essential for using the Rumack-Matthew nomogram; if unknown, start NAC immediately 2, 3
• Pattern of ingestion: Single acute overdose versus repeated supratherapeutic ingestion (RSTI) 1, 4
• Risk factors: Chronic alcohol use, pre-existing liver disease, malnutrition, or fasting state—these patients develop toxicity at lower doses (as low as 4–5 g/day) 1

Draw serum acetaminophen level at least 4 hours post-ingestion (levels before 4 hours are unreliable and must be repeated). 2, 3 If the patient presents more than 8 hours after ingestion or timing is unknown, start NAC immediately without waiting for laboratory results. 2, 3

Treatment Algorithm Based on Presentation Timing

Presentation Within 8 Hours of Ingestion

• Administer activated charcoal (1 g/kg orally) if the patient presents within 4 hours and can protect their airway 2
• Obtain serum acetaminophen level at 4 hours post-ingestion 2, 3
• Use the Rumack-Matthew nomogram: If the level plots above the treatment line (≥200 mcg/mL at 4 hours or ≥50 mcg/mL at 12 hours), start NAC immediately 1, 2
• Treatment within 8 hours results in only 2.9% developing severe hepatotoxicity—this is the critical window for maximal protection 1, 2, 5

Presentation 8–24 Hours Post-Ingestion

• Start NAC immediately while awaiting laboratory results 2, 3
• Efficacy decreases significantly: 6.1% develop severe hepatotoxicity when treated within 10 hours, rising to 26.4% when treated 10–24 hours after ingestion 1, 2, 5
• Among high-risk patients treated 16–24 hours post-ingestion, 41% develop hepatotoxicity—still better than untreated controls (58%) 2

Presentation >24 Hours Post-Ingestion

• The Rumack-Matthew nomogram does NOT apply—treatment decisions must be based on acetaminophen levels, liver function tests (AST/ALT), and clinical presentation 2
• Start NAC immediately if acetaminophen is detectable or if transaminases are elevated (AST/ALT >50 IU/L), regardless of time since ingestion 2
• NAC still reduces mortality from 80% to 52% in established liver failure, even when started late 2

NAC Dosing Protocol (Intravenous)

The FDA-approved 21-hour IV protocol consists of three doses totaling 300 mg/kg: 3

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 2, 3
• Second dose: 50 mg/kg over 4 hours 2, 3
• Third dose: 100 mg/kg over 16 hours 2, 3

Dilute NAC before administration (it is hyperosmolar at 2600 mOsmol/L) in sterile water, 0.45% sodium chloride, or 5% dextrose. 3

When to Extend NAC Beyond 21 Hours

Continue NAC beyond the standard protocol if: 2

• Acetaminophen level remains detectable
• Transaminases are rising or remain elevated (AST/ALT >50 IU/L)
• INR is elevated or coagulopathy is present
• Delayed presentation (>24 hours), extended-release formulation, or repeated supratherapeutic ingestion
• Unknown time of ingestion with detectable levels

Special Scenarios Requiring Modified Management

Repeated Supratherapeutic Ingestion (RSTI)

The nomogram does not apply. Treat with NAC if: 1, 4

• ≥10 g or 200 mg/kg (whichever is less) in any single 24-hour period
• ≥6 g or 150 mg/kg (whichever is less) per 24-hour period for ≥48 hours
• For high-risk patients (chronic alcohol use, liver disease, malnutrition): >4 g or 100 mg/kg per day
• Serum acetaminophen ≥10 mg/mL or AST/ALT >50 IU/L

RSTI carries worse prognosis than acute overdose: patients with AST >1,000 IU/L have 14% mortality despite NAC treatment. 2

High-Risk Populations

Chronic alcohol users develop severe hepatotoxicity with doses as low as 4–5 g/day, with mortality rates of 20–33% in case series. 1 Treat these patients even if acetaminophen levels fall in the "non-toxic" range on the nomogram. 2

Patients with pre-existing liver disease or cirrhosis should receive NAC at lower thresholds and require maximum daily therapeutic doses limited to 2–3 grams. 1

Laboratory Monitoring and Hepatotoxicity Assessment

Obtain baseline and serial measurements: 2

• Serum acetaminophen level (at 4 hours post-ingestion, repeat if extended-release formulation)
• AST/ALT: Severe hepatotoxicity is defined as >1,000 IU/L; very high levels (>3,500 IU/L) are highly correlated with acetaminophen poisoning even without clear history 1
• INR/PT: Coagulopathy indicates severe liver injury
• Creatinine: Renal failure is more common in RSTI cases 6

Peak transaminases typically occur 48–96 hours after acute ingestion. 6 Patients can present in liver failure days later with undetectable acetaminophen levels. 6

Critical Red Flags Requiring ICU Care and Transplant Consultation

Immediately contact a liver transplant center if: 2

• AST/ALT >1,000 IU/L (severe hepatotoxicity)
• Any coagulopathy (elevated INR)
• Hepatic encephalopathy
• Renal failure
• Metabolic derangements

NAC reduces mortality in fulminant hepatic failure from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48%. 2 Transplant-free survival for acetaminophen-induced acute liver failure is 50%, significantly better than non-acetaminophen causes. 2

Common Pitfalls to Avoid

• Do not rely on patient history alone: Histories regarding timing and amount ingested are usually unreliable 6
• Low or absent acetaminophen levels do NOT rule out toxicity if ingestion was remote, occurred over several days, or timing is uncertain 1
• Do not miss combination products: Patients may unknowingly take acetaminophen from multiple sources (opioid combinations, cold remedies, sleep aids) 1
• Do not withhold NAC in late presentations: Even after 24 hours, NAC still provides mortality benefit 2
• Anaphylactoid reactions to IV NAC occur during loading doses in some patients—treat by stopping the infusion, giving antihistamines, then restarting at a slower rate 6