Treatment of Acetaminophen (Tylenol) Overdose
Administer N-acetylcysteine (NAC) immediately to any patient with suspected acetaminophen overdose—do not wait for laboratory confirmation if the ingestion occurred within 24 hours, as treatment within 8 hours prevents severe hepatotoxicity in 97% of cases. 1
Immediate Actions (Do Not Delay)
Step 1: Stabilize and Decontaminate
- Give activated charcoal 1 g/kg orally within 4 hours of ingestion if the patient can protect their airway, administered just prior to starting NAC 1, 2
- Draw blood immediately for: acetaminophen level, AST, ALT, INR, creatinine, BUN, electrolytes, and glucose 3, 2
- Start NAC immediately without waiting for lab results if ingestion occurred within 24 hours 1, 2
Step 2: Initiate NAC Treatment
IV Protocol (Preferred): 1
- 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 (total 21-hour protocol)
Oral Protocol (Alternative): 1, 2
- Loading dose: 140 mg/kg diluted to 5% solution
- Maintenance: 70 mg/kg every 4 hours for 17 additional doses (total 72 hours)
- If vomiting occurs within 1 hour, repeat that dose 2
Risk Stratification Using the Rumack-Matthew Nomogram
The nomogram ONLY applies to: 4, 1
- Single acute ingestions
- Known time of ingestion
- Acetaminophen level drawn 4-24 hours post-ingestion
Critical timing thresholds: 1
- Levels drawn before 4 hours are unreliable—repeat at 4 hours
- Treatment within 8 hours: 2.9% develop severe hepatotoxicity
- Treatment within 10 hours: 6.1% develop severe hepatotoxicity
- Treatment after 10 hours: 26.4% develop severe hepatotoxicity
If the acetaminophen level plots above the "possible toxicity" line, continue full NAC course. 4, 1 If below the line and drawn 4+ hours post-ingestion with normal liver enzymes, NAC can be discontinued. 1
Special Scenarios Requiring Modified Management
Extended-Release Acetaminophen
- Obtain serial acetaminophen levels at 4 hours AND again 4-6 hours later (at 8-14 hours post-ingestion), as absorption continues beyond the typical 2-4 hour window 5, 1
- Initiate NAC if either level is above the nomogram line 5
- Three patients in one case series had initial levels below the treatment line but later rose above it 5
Repeated Supratherapeutic Ingestion (RSTI)
The nomogram does NOT apply—treat based on these criteria: 1, 6
- ≥10 g or 200 mg/kg (whichever is less) in any 24-hour period, OR
- ≥6 g or 150 mg/kg (whichever is less) per day for ≥48 hours, OR
- Any detectable acetaminophen level with AST or ALT >50 IU/L
Delayed Presentation (>24 Hours Post-Ingestion)
The nomogram does NOT apply—treat immediately if: 1
- Any detectable acetaminophen level, OR
- AST/ALT elevated (especially >1,000 IU/L), OR
- Clinical suspicion remains high
NAC still reduces mortality even when started late: from 80% to 52% in fulminant hepatic failure, regardless of time since ingestion 1
Chronic Alcoholics and High-Risk Patients
- Treat even with acetaminophen levels in the "non-toxic" range on the nomogram 1, 6
- Severe hepatotoxicity documented with doses as low as 4-5 g/day in chronic alcohol users 6
- Consider maximum daily therapeutic dose of 2-3 g in these patients 6
Unknown Time of Ingestion
- Treat with NAC if any detectable acetaminophen level 1
- Base decisions on acetaminophen level plus liver function tests, not the nomogram 1
When to Continue or Stop NAC
Continue NAC Beyond Standard Protocol If: 1
- Delayed presentation (>24 hours)
- Extended-release formulation
- Repeated supratherapeutic ingestion
- Unknown time of ingestion with detectable levels
- Any elevation in AST or ALT above normal
- Rising transaminases
- Any coagulopathy (elevated INR)
Safe to Discontinue NAC When: 1
- Acetaminophen level undetectable, AND
- AST and ALT completely normal, AND
- INR normal, AND
- Patient is not high-risk (no chronic alcohol use, known time of acute ingestion)
Monitor AST, ALT, and INR every 4 hours until aminotransferases peak and decline. 3
Critical Red Flags Requiring ICU and Transplant Consultation
Transfer to ICU and contact liver transplant center immediately if: 1
- AST or ALT >1,000 IU/L (severe hepatotoxicity) 6
- Any coagulopathy (elevated INR)
- Encephalopathy
- Acute renal failure 7
- Metabolic acidosis
Very high aminotransferases (>3,500 IU/L) are highly specific for acetaminophen poisoning and should raise suspicion even without clear overdose history. 3
Common Pitfalls to Avoid
Never wait for acetaminophen levels to start NAC if ingestion occurred within 24 hours 1, 2
Do not rely on a single 4-hour level for extended-release formulations—obtain a second level 4-6 hours later 5
Low or absent acetaminophen levels do NOT rule out toxicity if ingestion was remote, occurred over several days, or timing is uncertain 1
The nomogram is useless for: repeated supratherapeutic ingestions, unknown time of ingestion, delayed presentations >24 hours, and extended-release formulations 1
Do not stop NAC prematurely—if any doubt exists or transaminases are rising, continue treatment 1
Activated charcoal may reduce NAC absorption—if charcoal was given, consider lavage before NAC or accept potentially reduced effectiveness 2
Even therapeutic doses (4 g/day for 14 days) cause ALT elevations >3× normal in 31-41% of healthy adults—context matters when interpreting mildly elevated transaminases 6