Clinical Presentation of Acetaminophen Overdose
Acetaminophen overdose follows a predictable four-stage clinical course, with early symptoms often nonspecific and liver injury not apparent until 24–72 hours post-ingestion, making early recognition critical even when patients appear well. 1
Stage 1: Initial Phase (0–24 hours post-ingestion)
Early symptoms are nonspecific and easily missed:
- Nausea, vomiting, diaphoresis, malaise, and anorexia typically begin 7–14 hours after ingestion 2
- Right upper quadrant tenderness may be variably present 1
- Critical pitfall: The absence of symptoms during this first phase does not exclude serious poisoning—patients may feel relatively well despite having ingested a lethal dose 1
- Laboratory values (AST, ALT, bilirubin, INR) are typically normal during this stage 2
Stage 2: Latent Phase (24–48 hours post-ingestion)
Patients may paradoxically feel better while liver injury begins:
- Initial symptoms (nausea, vomiting) may diminish or resolve, creating false reassurance 2
- AST, ALT, bilirubin, and prothrombin time begin to rise 2
- Elevated liver enzymes (AST and ALT) start climbing toward levels potentially exceeding 1,000 U/L 1
- Jaundice may begin to appear 1
Stage 3: Hepatotoxic Phase (72–96 hours post-ingestion)
Maximum liver damage occurs with potentially catastrophic laboratory derangements:
- Peak hepatotoxicity with AST/ALT levels reaching thousands of units per liter—levels of 20,000 IU are not unusual 2
- Very high aminotransferase levels (AST/ALT >3,500 U/L) are highly correlated with acetaminophen poisoning and should raise suspicion even without clear overdose history 1
- Coagulopathy develops, indicated by elevated INR/prothrombin time 1
- Jaundice becomes prominent 1
Critical warning signs requiring immediate intensive intervention: 1
- Altered mental status or hepatic encephalopathy
- Severe coagulopathy
- Hypoglycemia
- Elevated arterial lactate
- Renal dysfunction (more common in repeated supratherapeutic ingestion patterns) 3
Stage 4: Recovery or Progression to Fulminant Hepatic Failure (4 days to 2 weeks)
Patients either recover completely or progress to multiorgan failure:
- Recovery: Gradual normalization of liver enzymes over 5–7 days in survivors 2
- Progression: Development of fulminant hepatic failure with cerebral edema, renal failure, metabolic derangements, and death 1
Special Clinical Scenarios
Massive overdose (>500 mg/kg or ~35 g in a 70 kg adult): 4
- Refractory shock requiring vasopressor support
- Decreased level of consciousness requiring mechanical ventilation
- Severe metabolic acidosis
- Multiorgan dysfunction syndrome
Repeated supratherapeutic ingestion (RSTI): 3
- Patients typically present with hepatotoxicity already established rather than early symptoms
- Renal failure is more common in this population compared to acute single ingestions 3
- May present days after last dose with undetectable serum acetaminophen concentrations but severe liver injury 3
Essential Initial Laboratory Assessment
When acetaminophen poisoning is suspected, obtain: 1
- Serum acetaminophen level (drawn at 4 hours post-ingestion or later for acute single ingestion)
- AST, ALT, alkaline phosphatase, total bilirubin
- Prothrombin time/INR
- Creatinine, blood urea nitrogen
- Arterial blood gas and arterial lactate
- Glucose
- Complete blood count
Critical timing consideration: Acetaminophen levels drawn before 4 hours are unreliable and must be repeated at 4 hours 5
Key Clinical Pitfalls
- Patients can present in liver failure days after ingestion with undetectable serum acetaminophen concentrations 3—do not rule out acetaminophen toxicity based solely on low or absent levels in delayed presentations 1
- The early clinical picture is not diagnostic 6—symptoms during the first 24 hours are nonspecific and easily attributed to other causes
- Histories concerning time of ingestion and amount ingested are usually unreliable 3—always obtain objective serum levels and treat based on laboratory evidence when history is uncertain