Laboratory Testing in Acetaminophen Overdose
In acetaminophen overdose, order baseline AST, ALT, INR, creatinine, BUN, electrolytes, and blood glucose immediately, then monitor AST/ALT and INR every 4 hours until aminotransferases peak and begin declining. 1, 2
Initial Laboratory Panel (Obtain Immediately)
The following tests should be ordered on presentation for all suspected acetaminophen overdoses:
- Hepatic function: AST (aspartate aminotransferase) and ALT (alanine aminotransferase) 1, 2
- Coagulation status: INR (international normalized ratio) or PT 1, 2
- Renal function: Creatinine and BUN 1, 2
- Metabolic status: Blood glucose and electrolytes 1, 2
- Bilirubin to assess hepatic synthetic function 2
These baseline labs are critical because they help predict outcome and guide treatment decisions. The FDA label explicitly requires monitoring of hepatic and renal function along with electrolyte and fluid balance 2.
Serial Monitoring Every 4 Hours
Monitor AST, ALT, and INR every 4 hours until you document that aminotransferases have peaked and are declining 1. This frequent monitoring is essential because:
- Aminotransferase levels rise progressively in hepatotoxicity and peak timing varies by patient 3
- AST falls with a half-life of approximately 15 hours, while ALT falls more slowly with a half-life of 40 hours 3
- The rate of decline helps determine when to discontinue N-acetylcysteine therapy 3
- INR monitoring every 4 hours identifies evolving coagulopathy, which predicts severe hepatotoxicity 1
Key Clinical Pearls
Very high aminotransferases (>3,500 IU/L) are highly correlated with acetaminophen poisoning and should prompt consideration of this diagnosis even without clear ingestion history 1. This threshold is critical because patients may present without knowing they took acetaminophen or may have unintentional overdose.
An AST:ALT ratio >2:1 at the time of N-acetylcysteine administration identifies the sickest patients with highest mortality risk 3. In one series, 4 of 6 patients with this ratio died 3.
Common Pitfalls to Avoid
Do not rely solely on initial normal aminotransferases to exclude toxicity. Case reports document moderate aminotransferase elevation occurring 29-36 hours after ingestion despite initial normal values and undetectable acetaminophen levels 4. Continue monitoring even if initial labs are reassuring.
Do not stop monitoring too early. Aminotransferases typically peak 3-5 days after ingestion in untreated severe cases 5. Serial monitoring should continue until clear downward trend is established.
Use AST rather than ALT to guide N-acetylcysteine discontinuation decisions, as AST declines approximately 24 hours faster than ALT 3. Waiting for ALT to decline prolongs treatment unnecessarily.
Additional Monitoring Considerations
If the patient develops signs of acute liver failure (coagulopathy, encephalopathy), expand monitoring to include 1:
- Arterial blood gas (for acidosis)
- Lactate (elevated lactate predicts poor prognosis)
- Phosphate (hypophosphatemia common in severe cases)
Creatinine should be included in prognostic models, as one mathematical model achieved 100% sensitivity and 91% specificity for predicting death when serum creatinine was added to AST, ALT, and INR 6.