A Risk Quantification Instrument for Acute Acetaminophen Overdose Patients Treated With N-Acetylcysteine - 18/08/11
, Mark C. Yarema, MD, David N. Juurlink, MD, PhD, Angela M. Good, MD, David W. Johnson, MD
Address for correspondence: Marco Sivilotti, MD, MSc, Department of Emergency Medicine, Queen's University, 76 Stuart Street, Kingston, Ontario, Canada, K7L 2V7; 613-548-2368, fax 613-548-1374SEE EDITORIAL, P. 272.
Abstract |
Study objective |
The risk of hepatotoxicity after acute acetaminophen overdose varies with timed serum acetaminophen concentration and delay to treatment. The ability to accurately predict hepatotoxicity is needed to reduce confusion about the optimal treatment regimen for individual patients and the effects of risk modifiers such as ethanol. We quantitatively estimate the risk of hepatotoxicity based on the degree and duration of pretreatment exposure to supratherapeutic concentrations of acetaminophen.
Methods |
We examined all hospitalizations for acute acetaminophen overdose within a retrospective multicenter Canadian registry. We used a previously developed composite measure incorporating timed serum acetaminophen concentration and time to N-acetylcysteine treatment into a single parameter. We then modeled hepatotoxicity on this parameter, as well as age, sex, and ethanol use. Hepatotoxicity was defined as peak aminotransferase level of 1,000 IU/L or greater at 24 hours or longer.
Results |
Of 1,270 admitted patients treated mostly with intravenous N-acetylcysteine for less than 24 hours, our model accurately identified the 94 patients who developed hepatotoxicity (discriminatory index 0.93). Hepatotoxicity occurred in none of the 313 patients (95% confidence interval [CI] 0% to 1.0%) above the traditional 150 μg/mL treatment line who were classified as low risk (<1%) using our instrument. After adjustment for severity of exposure, the risk of hepatotoxicity was considerably higher in the absence of coingested ethanol (median hepatotoxic dose 16.5 mmol/L × hour [95% CI 8.74 to 31.0 mmol/L × hour] versus 27.1 mmol/L × hour [95% CI 11.1 to 66.3 mmol/L × hour]), particularly among alcoholics (4.79 mmol/L × hour [95% CI 2.13 to 10.8 mmol/L × hour]).
Conclusion |
Our risk prediction instrument identifies a large group of low-risk patients for whom 20-hour intravenous N-acetylcysteine therapy is sufficient. Our results suggest that acute and chronic ethanol use dramatically influences acetaminophen toxicity. This work may facilitate the evaluation of individualized treatment strategies for higher-risk patients.
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| Supervising editor: G. Randall Bond, MD Author contributions: MLAS had the original idea for the study. MCY and DWJ planned and coordinated the Canadian Acetaminophen Overdose Study and oversaw data collection. DNJ assisted in the analysis and interpretation of the results. AMG piloted and helped refine the methodology. All authors were involved in the writing of the manuscript. MLAS takes responsibility for the paper as a whole. Funding and support: Supported by the physicians of Ontario through the P.S.I. Foundation (MLAS grant 02-38); the Canadian Association of Emergency Physicians (MCY, DWJ); the Centre for Advancement of Health, Foothills Hospital Calgary AB (MCY, DWJ); a Canadian Institute of Health Research New Investigator Award (DNJ) and Student Research Award (AMG); and an Alberta Heritage Foundation Studentship (DWJ). Presented at the North American Congress of Clinical Toxicology, September 2003, Chicago, IL. Reprints not available from the authors. |
Vol 46 - N° 3
P. 263-271 - septembre 2005 Retour au numéro
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