Medical News Stories
Reduction of Adverse Effects from Intravenous Acetylcysteine Treatment for Paracetamol Poisoning: a Randomized Controlled Trial
Study Question: Does a modified 12-hour IV acetylcysteine regimen result in fewer adverse effects (AE) than a standard 21-hour protocol for acetaminophen (referred to in the study as “paracetamol”) poisoning?
Study Description: This was a multicenter, randomized trial of hospitalized adults in the United Kingdom with acute acetaminophen poisoning. The study had a 2x2 factorial design wherein individuals received ondansetron or placebo pretreatment and either a modified (100 mg/kg over 2 hours, 200 mg/kg over 10 hours) or standard (150 mg/kg over 15 min, 50 mg/kg over 4 hours, 100 mg/kg over 16 hours) IV acetylcysteine regimen. Providers were masked to the antiemetic regimens but unmasked to the acetylcysteine regimens (in regard to the latter, the investigators cited “ethical and practical concerns”). The primary outcome measured the absence of vomiting/use of rescue antiemetics within 2 hours of acetylcysteine initiation.
Results: The study included 222 individuals, 6% of screened acetaminophen overdoses. No difference in hepatotoxicity was noted between acetylcysteine groups. In the primary outcome analysis, the modified regimen resulted in significantly less vomiting/use of rescue antiemetics compared to the standard regimen (39% vs. 71%; adjusted OR 0.26, 97.5% CI 0.13-0.52, p < 0.0001). No interaction was noted between the antiemetic and acetylcysteine treatment arms (p = 0.69). Severe anaphylactoid reactions occurred in 5% and 31% of modified and standard treatment arms, respectively.
Conclusion(s): A modified 12-hour IV acetylcysteine regimen yielded fewer AE than a standard 21-hour regimen for acute acetaminophen toxicity without a negative impact on efficacy.
Perspective: Valid concerns exist about the errors associated with multistage IV acetylcysteine regimens, AE, and cost. This study provides information about a relatively effective and simpler approach, yet three factors may affect the results’ interpretation and clinical utility. First, few of the screened patients were included in this study, which may have implications for broad generalizability. Second, regimens were unmasked, which may have altered rescue antiemetic use, an essential component of the composite primary endpoint. Finally, the standard regimen used differed from the FDA-approved dosing strategy with a 15-minute loading dose instead of the traditional 1 hour. It is unclear whether this alteration affected the results, but the early divergence of the anaphylactoid Kaplan-Meier curves between treatment arms may suggest the duration of loading dose infusion may have had an equal or even greater influence on the study’s results relative to total infusion time.