What is the dosage and administration protocol for acetylcysteine (N-acetylcysteine) tablets in a patient with a potential acetaminophen overdose?

N-Acetylcysteine (NAC) Tablet Dosing for Acetaminophen Overdose

For oral acetylcysteine treatment of acetaminophen overdose, administer a loading dose of 140 mg/kg followed by 70 mg/kg every 4 hours for 17 additional doses (total 72-hour protocol), ideally initiated within 8 hours of ingestion to maximize hepatoprotection. 1

Immediate Treatment Algorithm

Step 1: Initiate Treatment Without Delay

• Start NAC immediately if ≤24 hours have elapsed from ingestion, regardless of acetaminophen level availability 1
• Do not wait for laboratory confirmation when acetaminophen overdose is suspected 2, 3
• The critical window is 0-8 hours post-ingestion, where severe hepatotoxicity develops in only 2.9% of treated patients 3

Step 2: Gastrointestinal Decontamination (If Applicable)

• Administer activated charcoal 1 g/kg (50g standard adult dose) if patient presents within 4 hours of ingestion 2, 4
• If activated charcoal was given, perform gastric lavage before starting NAC, as charcoal adsorbs acetylcysteine and may reduce effectiveness 1
• Do not delay NAC administration even if charcoal has been given 2

Step 3: Standard Oral NAC Protocol

Loading Dose:

• 140 mg/kg orally as a single dose 2, 1
• Dilute 20% NAC solution to 5% concentration using diet cola or diet soft drink 1
• If using gastric tube, water may be used as diluent 1

Maintenance Doses:

• 70 mg/kg every 4 hours for 17 additional doses 2, 1
• Total treatment duration: 72 hours 1
• First maintenance dose given 4 hours after loading dose 1

Risk Stratification Using Rumack-Matthew Nomogram

When to Use the Nomogram

• Single acute ingestion with known time of ingestion 5, 3
• Acetaminophen level drawn 4-24 hours post-ingestion 5, 3
• The nomogram does NOT apply to: repeated supratherapeutic ingestions, extended-release formulations, or presentations >24 hours post-ingestion 3

Treatment Decisions Based on Nomogram

• Administer NAC if level plots at or above the "possible toxicity" line 5, 2
• Do NOT administer NAC if level clearly falls below the treatment line in low-risk patients 5
• For high-risk patients (chronic alcohol use, fasting, enzyme-inducing drugs), treat even with levels in "non-toxic" range 2, 3

Special Clinical Scenarios Requiring Mandatory Treatment

Treat Immediately Regardless of Nomogram:

• Established hepatic failure from acetaminophen (reduces mortality from 80% to 52%) 2, 3
• Elevated transaminases (AST/ALT >50 IU/L) with suspected acetaminophen exposure 3
• Unknown time of ingestion with detectable acetaminophen levels 2, 3
• Extended-release acetaminophen formulations 2, 3
• Repeated supratherapeutic ingestions: ≥10g or 200 mg/kg per 24 hours, or ≥6g or 150 mg/kg per 24 hours for ≥48 hours 3

High-Risk Populations Requiring Lower Treatment Threshold:

• Chronic alcohol users: treat even with "non-toxic" levels, as hepatotoxicity occurs with doses as low as 4g/day 3
• Patients taking enzyme-inducing medications 3
• Prolonged fasting states 2

Treatment Efficacy by Timing

Optimal Window (0-8 hours):

• Severe hepatotoxicity rate: 2.9% 3
• Maximum hepatoprotection achieved 5, 3

Acceptable Window (8-10 hours):

• Severe hepatotoxicity rate: 6.1% 5, 3
• Still highly effective 5

Late Treatment (10-24 hours):

• Severe hepatotoxicity rate: 26.4% 3
• Still provides significant benefit compared to no treatment (58% hepatotoxicity in untreated patients) 5

Very Late Presentation (>24 hours):

• NAC should still be administered—it reduces mortality and hepatotoxicity even with delayed treatment 2, 3
• Treatment decisions based on acetaminophen levels, liver function tests, and clinical presentation rather than nomogram 3

Managing Treatment Complications

Vomiting (Common Adverse Effect):

• If patient vomits within 1 hour of any dose, repeat that dose 1
• Dilution to 5% concentration minimizes vomiting propensity 1
• For persistent vomiting, consider duodenal intubation for administration 1
• Nausea and vomiting are expected adverse effects of oral NAC 1

Other Adverse Effects:

• Generalized urticaria (rare): discontinue only if allergic symptoms cannot be controlled 1
• Rash with or without mild fever (rare) 1

Monitoring During Treatment

Baseline Laboratory Studies:

• Acetaminophen level 1
• AST, ALT, bilirubin 1
• Prothrombin time/INR 1
• Creatinine, BUN 1
• Blood glucose, electrolytes 1

Serial Monitoring:

• Repeat AST, ALT, bilirubin, PT/INR, creatinine, BUN, glucose, and electrolytes daily if acetaminophen level is in toxic range 1
• For extended-release formulations, obtain serial acetaminophen levels as late increases may occur at 14 hours or beyond 3

When to Discontinue or Extend NAC

Criteria for Stopping at 72 Hours:

• Acetaminophen level undetectable 3
• Liver function tests remain normal 3
• No coagulopathy 3

Mandatory Extended Treatment Beyond 72 Hours:

• Delayed presentation (>24 hours post-ingestion) 3
• Extended-release acetaminophen 2, 3
• Repeated supratherapeutic ingestions 3
• Any elevation in AST or ALT above normal 3
• Rising transaminases 3
• Any coagulopathy present 3
• Detectable acetaminophen levels 3

Critical Red Flags Requiring Immediate ICU Transfer:

• AST/ALT >1000 IU/L (severe hepatotoxicity) 3
• Coagulopathy development 3
• Contact liver transplant center immediately for any evidence of liver failure 3

Critical Pitfalls to Avoid

• Never delay NAC while awaiting acetaminophen levels if strong suspicion exists 2
• Do not assume low/absent acetaminophen levels rule out poisoning if ingestion was remote or occurred over several days 3
• Do not stop NAC at 72 hours if any red flags are present (elevated transaminases, coagulopathy, detectable acetaminophen) 3
• Remember that even therapeutic doses (4g/day for 14 days) can cause ALT elevations >3x normal in 31-41% of healthy adults 3
• For chronic alcohol users, treat even with "non-toxic" nomogram levels 3

Preparation Instructions

• Dilute 20% NAC solution to 5% final concentration 1
• Use diet cola or other diet soft drinks for oral administration 1
• Water may be used if administering via gastric or duodenal tube 1
• Prepare dilutions freshly and use within 1 hour 1