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

All patients with suspected paracetamol poisoning should receive N-acetylcysteine (NAC) immediately, regardless of pre-existing liver disease, as NAC reduces mortality from 80% to 52% in fulminant hepatic failure and should never be withheld even in late presentations. 1

Immediate Management Algorithm

Step 1: Initiate Treatment Without Delay

• Administer NAC immediately upon suspicion of paracetamol overdose in patients with liver disease—do not wait for laboratory confirmation. 1
• Give activated charcoal (1 g/kg) if the patient presents within 4 hours of ingestion and can protect their airway. 1, 2
• The critical window is 0-8 hours post-ingestion, where NAC provides maximal hepatoprotection with only 2.9% developing severe hepatotoxicity when treated within 8 hours. 1

Step 2: NAC Dosing Regimen

Use the standard intravenous protocol regardless of pre-existing liver disease: 1, 2

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes (or 200 mg/kg over 4 hours per updated two-bag regimen) 1, 3
• Second dose: 50 mg/kg over 4 hours (three-bag) or continue 100 mg/kg over 16 hours (two-bag) 1, 3
• Third dose: 100 mg/kg over 16 hours (three-bag regimen) 1

The newer two-bag regimen (200 mg/kg over 4 hours, then 100 mg/kg over 16 hours) has similar efficacy but significantly reduced adverse reactions compared with the three-bag regimen. 3

Special Considerations for Patients with Pre-existing Liver Disease

Lower Treatment Threshold

• Patients with chronic liver disease should be treated with NAC even with paracetamol levels in the "non-toxic" range on the Rumack-Matthew nomogram. 1
• Severe hepatotoxicity can occur with doses as low as 3-4 g/day in patients with liver disease, compared to the typical toxic threshold of >10 g/day. 1, 4
• The Rumack-Matthew nomogram may underestimate risk in patients with pre-existing hepatic impairment. 1

Extended NAC Treatment

Continue NAC beyond the standard 21-hour protocol in patients with pre-existing liver disease if: 1, 2

• Paracetamol levels remain detectable after the standard course 2
• AST/ALT continue to rise or remain elevated 2
• INR remains elevated or worsens 2
• Any clinical signs of worsening hepatotoxicity develop 1

Monitoring Requirements

Obtain the following laboratories immediately and serially: 1, 2

• Paracetamol serum concentration (if <4 hours post-ingestion, repeat at 4 hours) 2
• AST, ALT, bilirubin 1, 2
• INR/PT 1, 2
• Creatinine and BUN (acute renal failure can complicate paracetamol poisoning) 2, 5
• Blood glucose and electrolytes 2

Critical Scenarios Requiring Immediate NAC

Established Hepatotoxicity

• Any patient with elevated transaminases (AST or ALT >50 IU/L) and suspected paracetamol exposure must receive NAC immediately, regardless of time since ingestion. 1
• Transaminases "in the thousands" are highly correlated with paracetamol poisoning and mandate immediate NAC treatment. 1
• Severe hepatotoxicity is defined as AST or ALT >1,000 IU/L. 1

Acute-on-Chronic Liver Failure

• Patients presenting with acute deterioration and extensive paracetamol use should receive NAC immediately, even if they have underlying chronic liver disease (e.g., chronic hepatitis B). 1
• Low or absent paracetamol levels do NOT rule out paracetamol poisoning if ingestion was remote or occurred over several days. 1

Unknown Time of Ingestion

• All patients with detectable paracetamol levels and unknown time of ingestion should receive NAC. 1, 2
• If there is any uncertainty about the patient's risk of developing hepatotoxicity, administer a complete treatment course. 2

Repeated Supratherapeutic Ingestions (RSI)

The Rumack-Matthew nomogram does NOT apply to RSI—use clinical and laboratory criteria instead: 1, 2

• Treat with NAC if serum paracetamol ≥10 mg/mL 1
• Treat with NAC if AST or ALT >50 IU/L 1
• Treat if ≥10 g or 200 mg/kg (whichever is less) during a single 24-hour period 1
• Treat if ≥6 g or 150 mg/kg (whichever is less) per 24-hour period for ≥48 hours 1

Massive Overdoses

For massive overdoses (paracetamol concentrations more than double the nomogram line or ingestions ≥30 g or ≥500 mg/kg): 1, 3

• Increase NAC dosing beyond standard protocol 1
• Consider extended treatment duration 1, 2
• Contact a regional poison center (1-800-222-1222) or special assistance line (1-800-525-6115) for dosing guidance 2

Common Pitfalls and Caveats

Do Not Delay Treatment

• NAC efficacy diminishes progressively after 8 hours: severe hepatotoxicity develops in 26.4% when treatment begins 10-24 hours post-ingestion, compared to only 6.1% when started within 10 hours. 1
• Liver damage and death are associated with admission later than 15 hours after intake. 6
• Even when treatment is delayed beyond 24 hours, NAC still provides benefit and should never be withheld. 1

Avoid These Errors

• Do not wait for paracetamol levels if the patient presents with established hepatotoxicity—start NAC immediately. 1
• Do not stop NAC prematurely in patients with pre-existing liver disease—continue until paracetamol is undetectable AND transaminases are declining AND INR normalizes. 1, 2
• Do not use the nomogram for delayed presentations (>24 hours), extended-release formulations, or repeated supratherapeutic ingestions. 1, 2
• Do not routinely correct coagulopathy unless there is active bleeding. 7

ICU-Level Care Indications

Patients with severe hepatotoxicity (AST >1,000 IU/L) or coagulopathy require: 1

• ICU-level monitoring 1
• Early consultation with transplant hepatology 1
• Contact liver transplant center immediately if any evidence of liver failure develops 1

Monitor for Complications

Watch for signs of acute liver failure: 1, 8

• Encephalopathy 1
• Coagulopathy 1
• Renal failure (acute tubular necrosis can occur and may require temporary dialysis) 5
• Metabolic derangements 1