What is the basic NAC regimen for acetaminophen overdose (repeated for emphasis)?

• A. 150 mg/kg over 60 min, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours
• B. 150 mg/kg over 60 min, then 50 mg/kg over 16 hours, then 100 mg/kg over 4 hours
• C. 100 mg/kg over 60 min, then 50 mg/kg over 4 hours, then 200 mg/kg over 16 hours
• D. 200 mg/kg over 60 min, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours

Answer: (A)

The basic concept here is delivering N-acetylcysteine in a schedule that rapidly achieves therapeutic levels and then maintains them to detoxify the harmful metabolite from acetaminophen overdose. The loading dose of 150 mg/kg given over one hour quickly raises NAC concentrations in the blood, allowing NAC to replenish glutathione stores and enable conjugation of NAPQI. The next dose, 50 mg/kg over four hours, sustains those levels so detoxification can continue as the initial shock dissipates. The final maintenance dose, 100 mg/kg over sixteen hours, keeps NAC present long enough to support ongoing protection of the liver during the critical period after overdose. Altogether this regimen balances rapid onset with sustained exposure to NAC, optimizing hepatoprotective effect while staying within safe dosing limits.

Other regimens that alter the dose amounts or the infusion durations would either fail to achieve rapid, adequate NAC concentrations or not maintain protective levels long enough, reducing the effectiveness of the antidote.