2008年7月16日 星期三

NAC for Acetaminophen Poisoning

N-Acetylcysteine and Acetaminophen Poisoning
N-acetylcysteine prevents hepatic injury primarily by restoring hepatic glutathione. The primary pathways for acetaminophen metabolism are glucuronidation and sulfation to nontoxic metabolites. Approximately 5% of a therapeutic dose is metabolized by cytochrome P450 2E1 to the electrophile N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is extremely toxic to the liver. Ordinarily, NAPQI is rapidly detoxified by interaction with glutathione to form cysteine and mercapturic acid conjugates. If glutathione is depleted, NAPQI interacts with various macromolecules, leading to hepatocyte injury and death. As long as sufficient glutathione is present, the liver is protected from injury.

Dosing of N-Acetylcysteine
The choice of oral or intravenous administration of N-acetylcysteine depends on the clinical scenario. For the treatment of acute acetaminophen ingestion, oral N-acetylcysteine is given as a loading dose of 140 mg per kilogram of body weight, with maintenance doses of 70 mg per kilogram that are repeated every 4 hours for a total of 17 doses. The intravenous loading dose is 150 mg per kilogram over a period of 15 to 60 minutes, followed by an infusion of 12.5 mg per kilogram per hour over a 4-hour period, and finally an infusion of 6.25 mg per kilogram per hour over a 16-hour period.

Q: What is the maximum recommended dose of acetaminophen for an adult in one day?
A: The maximum recommended dose of acetaminophen is 4 g per day.

Q: What are the side effects of N-acetylcysteine?
A: N-acetylcysteine has an unpleasant smell and taste, and vomiting is common with oral administration. The most commonly reported adverse effects of intravenous N-acetylcysteine are anaphylactoid reactions, including rash, pruritus, angioedema, bronchospasm, tachycardia, and hypotension. Kerr et al. reported that approximately 15% of patients who were treated with intravenous N-acetylcysteine had an anaphylactoid reaction within 2 hours after the initial infusion and that increasing the infusion time from 15 to 60 minutes did not alter the rate of adverse events.

The Rumack–Matthew Nomogram

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New England Journal of Medicine - Vol. 359, No. 3, July 17, 2008

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