|
Historically, acetylcysteine has been delivered at a fixed dose and duration of 300 mg/kg over 20 hours to nearly every patient deemed to be at any risk for hepatotoxicity following acetaminophen overdose. We investigated a 12-hour treatment regimen for selected low-risk patients. This was a multicenter, open-label, cluster-controlled trial at six metropolitan emergency departments. We enrolled subjects following single or staggered acetaminophen overdose with normal serum alanine transaminase (ALT) and creatinine on presentation and at 12 hours, and acetaminophen <20mg/L at 12 hours. Patients were allocated to intervention (250 mg/kg over 12-hour) or control (300 mg/kg over 20-hour) regimens by site. incidence of "hepatic injury" 20 hours post-initiation of acetylcysteine treatment; defined as ALT doubling and peak ALT > 100 IU/L, indicating the need for further antidotal treatment. Secondary outcomes included incidence of hepatotoxicity (ALT > 1000 IU/L), peak INR and adverse drug reactions. Of 449 acetaminophen overdoses receiving acetylcysteine, 100 were recruited to the study. Time to acetylcysteine (median 7 hours [IQR 6,12] vs 7 hours [6,10]) and initial acetaminophen (124 mg/L [58,171] vs 146 mg/L [66,204]) were similar between intervention and control groups. There was no difference in ALT (18 IU/L [13,22] vs 16 IU/L [13,21]) or INR (1.2 vs 1.2) 20 hours after starting acetylcysteine between groups. No patients developed hepatic injury or hepatotoxicity in either group (OR 1·0 [95% CI 0.02,50]). No patients re-presented with liver injury, none died and 96/96 were well at 14-day telephone follow-up. Discontinuing acetylcysteine based on laboratory testing after 12 hours of treatment is feasible and likely safe in selected patients at very low risk of liver injury from acetaminophen overdose. This article is protected by copyright. All rights reserved. |
|
