A 250mg/kg, 12-hour N-acetylcysteine (NAC) protocol was as effective as the usual 300mg/kg, 20-hour protocol in patients at lower risk for hepatotoxicity.
Why does this matter?
What if it was safe to medically clear a potential APAP overdose in 12 hours instead of 24? That would be good, but is it safe?
Stop the NAC
This was a cluster RCT with about 50 patients per group. To be enrolled in the study, they had to have a 4-hour level of at least 150mg/L but be considered low risk for hepatotoxicity, with “normal serum alanine transaminase (ALT) and creatinine on presentation and at 12 hours, and less than 20 mg/L acetaminophen at 12 hours.” Exclusions included: “pregnancy, acetaminophen modified-release ingestion, and other supratherapeutic ingestions (i.e., unintentional ingestions of more than 10 g or more than 200 mg/kg over 24 hours, more than 6 g/day over 48 hours).”
Patients received a fairly standard 20-hour 300mg/kg NAC protocol (consisting of 200 mg/kg over 4 hours followed by a further 100 mg/kg over 16 hours) or an abbreviated 12-hour 250mg/kg NAC protocol. The truncated protocol held the last 8 hours (50mg/kg) of the infusion if the serum ALT was <40, creatinine was normal, and acetaminophen was < 20 mg/L. There was no difference in the primary outcome of hepatic injury at 20 hours, defined as a doubling of the ALT and peak >100. There was also no difference in secondary outcomes, including ALT > 1,000, peak INR, or adverse drug reaction. Zero patients had hepatic injury in each group; none had delayed hepatic injury; none died; all were well at phone follow up on day 14.
I saw this article first in the excellent publication – Journal Watch.
The NACSTOP Trial: A Multicenter, Cluster-Controlled Trial of Early Cessation of Acetylcysteine in Acetaminophen Overdose. Hepatology. 2019 Feb;69(2):774-784. doi: 10.1002/hep.30224. Epub 2019 Jan 19.
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