Laboratory Monitoring in Acetaminophen Overdose
In acetaminophen overdose, immediately obtain serum acetaminophen level (drawn at 4 hours post-ingestion or later), AST, ALT, INR/PT, creatinine, and electrolytes to assess hepatotoxicity risk and guide N-acetylcysteine (NAC) treatment decisions. 1, 2
Essential Initial Laboratory Tests
Acetaminophen Level
- Draw serum acetaminophen concentration at 4 hours post-ingestion or as soon as possible thereafter if presentation is later 3
- Plot the level on the Rumack-Matthew nomogram to determine risk category (probable risk, possible risk, or no risk) 4, 2
- Normal/treatment threshold: Levels above the treatment line (starting at 150 mg/L or 993 µmol/L at 4 hours, declining to 4.7 mg/L or 31 µmol/L at 24 hours) require NAC treatment 2
- For repeated supratherapeutic ingestions, treat if acetaminophen level is ≥10 mg/L (66 µmol/L) 2
Hepatic Transaminases (AST/ALT)
- Obtain baseline AST and ALT immediately to assess for developing hepatotoxicity 4, 2
- Normal range: AST and ALT <50 IU/L 4
- Hepatotoxicity threshold: AST or ALT >50 IU/L indicates need for NAC treatment in suspected overdose 2
- Severe hepatotoxicity: AST or ALT >1,000 IU/L indicates severe liver injury requiring ICU-level care and transplant hepatology consultation 4, 2
- Peak transaminase levels typically occur 48-96 hours after acute ingestion 5
Coagulation Studies (INR/PT)
- Obtain baseline INR or prothrombin time to assess hepatic synthetic function 2
- Normal INR: approximately 1.0-1.2 6
- Coagulopathy (elevated INR) indicates severe hepatotoxicity and requires ICU-level care 2
Renal Function (Creatinine)
- Obtain baseline serum creatinine as acute renal failure can occur independently of hepatic failure 7
- Monitor creatinine daily for the first week, as acute tubular necrosis can develop starting on day 4, even as liver function improves 7
- Normal creatinine at presentation and 12 hours identifies very low-risk patients who may be candidates for shortened NAC protocols 6
Serial Monitoring Protocol
For Patients Receiving NAC Treatment
- Repeat AST, ALT, INR, and creatinine at 12 hours after starting NAC 6
- Continue monitoring every 12-24 hours until transaminases are declining and INR normalizing 2
- In low-risk patients (normal ALT, creatinine, and acetaminophen <20 mg/L at 12 hours), NAC can potentially be discontinued after 12 hours 6
For Late Presentations (>24 Hours)
- The nomogram does NOT apply to patients presenting >24 hours post-ingestion 2
- Treatment decisions must be based on acetaminophen levels, liver function tests, and clinical presentation rather than nomogram placement 2
- Administer NAC immediately without waiting for laboratory confirmation if hepatotoxicity is suspected 2
Critical Treatment Thresholds in Canadian Units
Acetaminophen Levels (µmol/L)
- Treatment line at 4 hours: 993 µmol/L (150 mg/L) 2
- Treatment line at 8 hours: 497 µmol/L (75 mg/L) 2
- Treatment line at 12 hours: 248 µmol/L (37.5 mg/L) 2
- Treatment line at 24 hours: 31 µmol/L (4.7 mg/L) 2
Hepatotoxicity Markers
- Mild elevation: AST/ALT 50-1,000 IU/L (15% hepatotoxicity risk, 2% mortality) 4
- Severe hepatotoxicity: AST/ALT >1,000 IU/L (14% mortality risk) 4
Common Pitfalls to Avoid
- Do not rely solely on the nomogram - patients may develop elevated transaminases despite "no risk" classification due to inaccurate history or increased susceptibility 2
- Do not wait for 4-hour level if presentation is delayed - start NAC immediately in suspected overdose with elevated transaminases 2
- Do not forget to monitor renal function - acute renal failure can occur even with improving liver function, typically starting day 4 7
- Do not assume safety in therapeutic dosing - even 4 g/day for 14 days can cause ALT elevations >3 times normal in 31-41% of healthy adults 1