What is the treatment for acetaminophen (Tylenol) toxicity?

Treatment of Acetaminophen (Tylenol) Toxicity

Administer N-acetylcysteine (NAC) immediately for any suspected or confirmed acetaminophen overdose—ideally within 8 hours of ingestion to maximize efficacy, but NAC remains beneficial and should never be withheld even in late presentations beyond 24 hours. 1

Immediate Initial Management

First Steps (Within 4 Hours of Presentation)

• Give activated charcoal (1 g/kg orally) just prior to starting NAC if the patient presents within 4 hours of ingestion 1, 2
• Do not delay NAC while administering activated charcoal—give NAC immediately after charcoal 1
• Empty the stomach promptly by lavage or induce emesis with syrup of ipecac (15 mL for children, 30 mL for adults) if within the first hour 2

Laboratory Assessment

Draw blood immediately for: 1, 2

• Acetaminophen level (must be drawn 4-24 hours post-ingestion for nomogram use)
• AST, ALT, bilirubin
• Prothrombin time/INR
• Creatinine, BUN
• Blood glucose and electrolytes

NAC Administration Protocol

When to Start NAC Immediately (Do Not Wait for Labs)

Start NAC without delay in these scenarios: 1, 3

• Any acetaminophen level plotting above the "possible toxicity" line on the Rumack-Matthew nomogram
• Unknown or unreliable time of ingestion with detectable acetaminophen
• Any evidence of hepatotoxicity (elevated AST/ALT)
• Suspected or confirmed acute liver failure
• Extended-release formulation ingestion
• Repeated supratherapeutic ingestions (>4g per 24 hours for ≥48 hours)
• Presentation >24 hours post-ingestion (nomogram does not apply)

NAC Dosing Regimens

Intravenous Protocol (20-hour regimen): 1, 3

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

Oral Protocol (72-hour regimen): 1, 3, 2

• Loading dose: 140 mg/kg orally or via nasogastric tube
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses
• Dilute 20% solution to 5% concentration using diet cola or diet soft drinks 2
• If using gastric tube, water may be used as diluent 2

Both regimens are equally effective, though the 72-hour oral regimen may be superior when treatment is delayed 4

Time-Critical Treatment Windows

Optimal Window (0-8 Hours)

• NAC provides maximal hepatoprotection with only 2.9% developing severe hepatotoxicity when started within 8 hours 1
• No difference in outcome whether NAC starts 0-4 hours or 4-8 hours post-ingestion 4

Diminished but Still Effective (8-10 Hours)

• Severe hepatotoxicity develops in 6.1% when treatment begins within 10 hours 1, 4

Late but Still Beneficial (10-24 Hours)

• Severe hepatotoxicity develops in 26.4% when treatment begins 10-24 hours post-ingestion 1, 4
• Among high-risk patients treated 16-24 hours after ingestion, hepatotoxicity develops in 41%—still lower than untreated controls (58%) 1

Very Late Presentation (>24 Hours)

• NAC should still be administered as it reduces mortality from 80% to 52% in fulminant hepatic failure regardless of time since ingestion 1
• The Rumack-Matthew nomogram does NOT apply—base treatment decisions on acetaminophen levels and liver function tests 1

Special Clinical Scenarios

Established Acute Liver Failure

• Administer NAC immediately regardless of time since ingestion (Level B recommendation) 1, 3
• NAC reduces mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48% 1
• Early NAC treatment (<10 hours) results in 100% survival without progression 1
• Contact liver transplant center immediately 1
• Requires ICU-level care 1

Repeated Supratherapeutic Ingestions

Treat with NAC if: 1

• Serum acetaminophen ≥10 mg/mL, OR
• AST or ALT >50 IU/L, OR
• ≥10g or 200 mg/kg (whichever is less) during a single 24-hour period, OR
• ≥6g or 150 mg/kg (whichever is less) per 24-hour period for ≥48 hours

High-Risk Populations (Lower Treatment Threshold)

Treat even with levels in "non-toxic" range for: 1

• Chronic alcohol consumption (severe hepatotoxicity documented with doses as low as 4-5 g/day)
• Fasting patients
• Patients taking enzyme-inducing drugs

Extended-Release Formulations

• Standard NAC dosing applies 3
• Requires extended monitoring due to prolonged absorption 1
• May need longer NAC treatment course 1

Massive Overdoses

• Consider adjunctive therapies: fomepizole and hemodialysis/CVVH 5
• Increase NAC dosing beyond standard protocol 1
• For CVVH: IV NAC at 12.5 mg/kg/h plus oral NAC at 70 mg/kg every 4 hours 5

When to Stop NAC

Standard Criteria for Discontinuation

NAC can be stopped when ALL of the following are met: 1

• Acetaminophen level is undetectable
• AST and ALT remain normal (not just "stable"—must be normal)
• No coagulopathy
• Patient is clinically well

Scenarios Requiring Extended Treatment Beyond Standard Protocol

Continue NAC longer than standard protocol for: 1

• Delayed presentation (>24 hours post-ingestion)
• Extended-release acetaminophen
• Repeated supratherapeutic ingestions
• Unknown time of ingestion with detectable levels
• Chronic alcohol use
• Any elevation in AST or ALT above normal

Red Flags Mandating Continuation or Restart of NAC

Do NOT stop NAC or restart immediately if: 1

• Any elevation in AST or ALT above normal
• Rising transaminases
• Any coagulopathy (elevated INR)
• Detectable acetaminophen level
• Clinical signs of hepatotoxicity

If hepatotoxicity develops (AST/ALT >1000 IU/L), restart NAC immediately and continue until transaminases are declining and INR normalizes 1

Supportive Care

Monitoring

• Repeat AST, ALT, bilirubin, PT/INR, creatinine, BUN, glucose, and electrolytes daily if acetaminophen level is in toxic range 2
• Monitor for complications: encephalopathy, coagulopathy, renal failure, metabolic derangements 1

Specific Interventions

• Maintain fluid and electrolyte balance 2
• Treat hypoglycemia as necessary 2
• Administer vitamin K1 if PT ratio >1.5 2
• Give fresh frozen plasma if PT ratio >3.0 2
• Avoid diuretics and forced diuresis 2

ICU-Level Care Indications

• Severe hepatotoxicity (AST >1000 IU/L) 1
• Any coagulopathy 1
• Evidence of acute liver failure 1

Critical Pitfalls to Avoid

1. Never delay NAC while awaiting confirmatory acetaminophen levels if there is strong suspicion of overdose 1

2. Low or absent acetaminophen levels do NOT rule out acetaminophen poisoning if ingestion was remote or occurred over several days 1

3. The Rumack-Matthew nomogram is INVALID for: 1

   • Presentations >24 hours post-ingestion
   • Repeated supratherapeutic ingestions
   • Extended-release formulations
   • Unknown time of ingestion

4. Patients may present with elevated transaminases despite "no risk" stratification on nomogram due to inaccurate history or increased susceptibility 1

5. If patient vomits oral NAC within 1 hour of administration, repeat that dose 2

6. For persistent vomiting, administer NAC via duodenal intubation rather than withholding treatment 2

7. Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with acetaminophen poisoning—treat with NAC even without confirmatory history 1