What is the treatment for a patient with suspected paracetamol (acetaminophen) poisoning, particularly those with pre-existing liver disease or impaired liver function?

Treatment of Paracetamol Poisoning in Patients with Pre-existing Liver Disease

Administer N-acetylcysteine (NAC) immediately to all patients with suspected paracetamol poisoning, regardless of liver disease status, as it is the only proven antidote that reduces mortality and prevents liver failure—and patients with pre-existing liver disease require even more aggressive treatment with lower thresholds for intervention. 1

Immediate Management Algorithm

First-Line Actions (Within Minutes of Presentation)

• Give activated charcoal (1 g/kg orally) immediately if the patient presents within 4 hours of ingestion, just prior to starting NAC, provided the airway is protected and the patient can swallow safely 1, 2
• Start NAC without waiting for laboratory confirmation in any patient with suspected paracetamol overdose—treatment delay directly correlates with mortality 1
• Obtain serum paracetamol level, AST, ALT, INR, creatinine, and electrolytes immediately, but do not delay NAC while awaiting results if ingestion history suggests risk 1, 2

NAC Dosing Protocol

Use the standard 21-hour IV protocol (preferred over oral due to reliability and reduced treatment time): 2, 3

• Loading dose: 150 mg/kg IV over 15 minutes (diluted in 200 mL D5W or normal saline)
• Second dose: 50 mg/kg IV over 4 hours (diluted in 500 mL)
• Third dose: 100 mg/kg IV over 16 hours (diluted in 1000 mL)

For patients with pre-existing liver disease, consider the newer two-bag regimen (200 mg/kg over 4 hours, then 100 mg/kg over 16 hours), which has similar efficacy but significantly reduced adverse reactions 3

Risk Stratification Based on Timing and Paracetamol Levels

If Presentation is Within 4-24 Hours AND Time of Ingestion is Known

• Plot the paracetamol level (drawn ≥4 hours post-ingestion) on the Rumack-Matthew nomogram 1, 2
• Treat with NAC if the level plots at or above the "possible toxicity" line (150 mcg/mL at 4 hours or 37.5 mcg/mL at 12 hours) 1
• Critical caveat: Levels drawn before 4 hours are unreliable and must be repeated at 4 hours 1

If Presentation is >24 Hours Post-Ingestion

• The nomogram does NOT apply—base treatment decisions on paracetamol levels, transaminases, and clinical presentation 1
• Administer NAC immediately if any of the following are present: 1, 2
  • Detectable paracetamol level (any value)
  • AST or ALT >50 IU/L
  • Any coagulopathy (elevated INR)
  • Clinical signs of hepatotoxicity

Special Scenarios Requiring Immediate NAC (Regardless of Nomogram)

• Hepatic failure or acute liver injury with suspected paracetamol involvement (AST/ALT >1000 IU/L)—NAC reduces mortality from 80% to 52% even when started late 1
• Unknown time of ingestion with detectable paracetamol level 1
• Repeated supratherapeutic ingestions (≥10 g or 200 mg/kg in 24 hours, OR ≥6 g or 150 mg/kg per day for ≥48 hours) 1, 2
• Extended-release paracetamol formulations (≥10 g or 200 mg/kg)—obtain serial levels at 4 hours and again at 8-10 hours 1, 2

Critical Modifications for Pre-existing Liver Disease

Lower Treatment Thresholds

Patients with chronic liver disease, including cirrhosis, have significantly increased susceptibility to paracetamol hepatotoxicity and should be treated even with levels in the "non-toxic" range on the nomogram. 1, 4

• Maximum safe daily dose in liver disease: 2-3 grams per day (compared to 4 grams in healthy adults) 4
• Severe hepatotoxicity documented with doses as low as 4-5 g/day in high-risk patients 5, 4
• Treat with NAC if serum paracetamol ≥10 mg/mL OR if AST/ALT >50 IU/L, even if nomogram suggests non-toxic levels 1

Chronic Alcoholics Require Special Consideration

• Chronic alcohol consumption significantly lowers the toxicity threshold—severe hepatotoxicity and 33% mortality documented with doses of 5-20 g/day 5
• Even therapeutic doses (4 g/day) can cause severe hepatotoxicity in alcoholics 5, 4
• Treat alcoholic patients with NAC even if levels are below the nomogram treatment line 1

Malnourished Patients with Liver Disease

• Malnourished patients have depleted glutathione stores, making them more vulnerable even at therapeutic doses 4
• Stay at the lower end of dosing recommendations (2 grams/day maximum) 4
• Ensure adequate nutritional support including thiamine and micronutrients 4

Extended NAC Treatment Criteria

Continue NAC beyond the standard 21-hour protocol if any of the following persist after completion: 1, 2

• Detectable paracetamol level
• Rising AST or ALT
• Elevated INR
• Delayed presentation (>24 hours)
• Massive overdose (>30 g or 500 mg/kg)
• Pre-existing liver disease

For massive overdoses with paracetamol levels more than double the nomogram line, increase the NAC dose 3

Timing and Efficacy Data

The evidence demonstrates a clear time-dependent benefit: 1

• 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
• Treatment 16-24 hours: 41% develop hepatotoxicity (but still better than untreated 58%)

However, NAC should NEVER be withheld even in late presentations (>24 hours), as it still reduces mortality and complications in established hepatic failure. 1, 6

Monitoring Requirements

Initial Assessment

• Paracetamol level (repeat at 4 hours if initially drawn <4 hours post-ingestion) 2
• AST, ALT, bilirubin, INR 1, 2
• Creatinine and BUN (acute tubular necrosis can occur) 2, 7
• Electrolytes, glucose 2

During NAC Treatment

• Monitor hepatic and renal function throughout the 21-hour infusion 2
• Repeat labs after completion of NAC: if paracetamol still detectable OR AST/ALT still rising OR INR elevated, continue NAC and contact poison control 2

Severe Hepatotoxicity Indicators Requiring ICU Care

• AST or ALT >1000 IU/L (defines severe hepatotoxicity) 1
• Any coagulopathy 1
• Encephalopathy, renal failure, or metabolic derangements 1
• Contact liver transplant center immediately if any evidence of liver failure 1

Common Pitfalls to Avoid

• Do not wait for paracetamol levels if presentation is delayed or timing uncertain—start NAC immediately 1
• Do not rely on patient-reported dose—history is often inaccurate, and patients may underreport intake 8, 2
• Do not stop NAC at 21 hours if labs are abnormal—continue until paracetamol undetectable and transaminases declining 1, 2
• Do not assume low/absent paracetamol levels rule out poisoning if ingestion was remote or occurred over several days 1, 4
• Do not use the nomogram for repeated supratherapeutic ingestions, extended-release formulations, or presentations >24 hours 1, 2
• Very high transaminases (AST/ALT >3500 IU/L) are highly correlated with paracetamol poisoning even without clear overdose history—treat empirically 1, 4

Disposition

• Admit to ICU: severe hepatotoxicity (AST >1000 IU/L), coagulopathy, or any signs of liver failure 1
• Admit to monitored bed: all patients receiving NAC, especially those with pre-existing liver disease 1
• Psychiatric evaluation: all intentional overdoses before discharge 9