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A single dose of activated charcoal given within 1 hour of acetaminophen ingestion can reduce absorption and the need for antidotal therapy.
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Acetylcysteine (NAC) helps replenish glutathione and restores the liver's ability to detoxify NAPQI. Its use prevents hepatic injury and death. There are several protocols for NAC therapy with the most prevalent being 20-hour intravenous and 72-hour oral protocols.4 It is most effective if started within 8 hours after an acute overdose4 but remains beneficial even if started very late when hepatotoxicity is evident.5 The efficacy of NAC therapy after 8 hours is highly time-sensitive.6 However, current recommendations favor individualizing treatment duration, and continuing treatment until specific clinical and biochemical end-points have been satisfied.7 This particularly important for patients with massive acetaminophen overdose.
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The oral NAC protocol long used in the United States for treating APAP toxicity consisted of a loading dose of 140 mg/kg followed by 17 additional doses of 70 mg/kg given at 4-hour intervals. The 20% solution is unpalatable and should be diluted with three parts fruit juice or soda. Vomiting is common, and when it occurs within 1 hour of treatment, the dose is repeated with metoclopramide (0.25 mg/kg IV over 5 minutes) or ondansetron (0.15 mg/kg over 5 minutes). If necessary, NAC can be given via a nasogastric tube. If activated charcoal has been administered, the usual dose of NAC does not need to be increased.
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Intravenous NAC had been used for decades in the rest of the world, and in 2004 the Food and Drug Administration approved an intravenous formulation for use in the United States. Unlike the oral route, intravenous administration is not limited by vomiting and patient cooperation. The Edinburgh protocol is most widely used and is shown with slight modification in Table 113-1. Originally crafted as a 20-hour protocol, treatment should be continued in cases with hepatic failure (Table 113-2).
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Anaphylactoid reactions with urticaria, flushing and mild wheezing can occur especially during the initial intravenous load, and are easily treated by halting the infusion temporarily and administering antihistamines. Because such reactions are more common in patients with lower serum acetaminophen concentrations, they represent another reason to avoid empirically administering antidote in small children believed to have ingested acetaminophen but who ultimately have low or undetectable serum concentrations. Following an anaphylactoid reaction, it is prudent to verify the indication for antidote, its dilution and infusion rate. However, it is essential to resume the antidote if clinically indicated. Withholding the antidote when indicated because of an anaphylactoid reaction, or history of prior reaction, is unwarranted.
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Children under the age of 6 years rarely require NAC therapy. Most of them are brought to the hospital shortly after the discovery of possible ingestion. Thus, there is sufficient time to wait for the result of a serum acetaminophen concentration. Measurement is indicated if the potential for ingestion of greater than 200 mg/kg exists. If the result is above the treatment line, NAC dosing and dilution should be verified carefully. Ten-fold NAC dosing errors can be fatal. Care should be given to the volume of fluid administered to young children. Guidelines for dilution of NAC are found in Table 113-1.