Analyzing the serum acetaminophen concentration is essential in all cases of acute overdose (see Fig. 45.1). A level prior to 4 h is difficult to interpret. High potential for toxicity exists when serum concentration is >200 μg/mL at 4 h, 50 μg/mL at 12 h and 7 μg/mL at 24 h after ingestion.

N-acetylcysteine (NAC) should be administered as soon as possible within the first 24 h of ingestion. However, antidotal therapy is optimal when given within 12 h of acetaminophen ingestion. NAC should be given if the patient has ingested more than 140 mg/kg (or 10 g) acetaminophen, if the serum level is above 140 μg/mL, or if the serum level is in the toxic range. The dose of N-acetylcysteine is 140 mg/kg as an initial oral loading dose, followed by 70 mg/kg every 4 h for a total of 17 doses. Nausea and vomiting are reported in 33 % of APAP overdoses before NAC and in an estimated 51 % during oral NAC therapy. In 2004, Acetadote became the first NAC solution approved by the FDA for IV use, allowing the United States to join the rest of the industrialized world, which has been using IV NAC since its introduction in 1977 [8]. A 72-h oral, 48-h IV, and 20-h IV protocol have been reported. These protocols have been compared by retrospective study and through meta-analysis [9]. When started within 8 h of ingestion, no protocol shows advantage over another. However, the 20-h IV protocol is generally preferred; this is given as a loading dose of 150 mg/kg over 15 min, followed by 50 mg/kg infused over 4 h and 100 mg/kg administered over 16 h as a constant infusion. Although there is general consensus that IV administration is preferable in the face of intractable vomiting, no study shows clear evidence that IV therapy is more or less effective than oral NAC therapy.