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A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine.
Ann Emerg Med 2005; 46(3):263-71AE

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 mug/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 x hour [95% CI 8.74 to 31.0 mmol/L x hour] versus 27.1 mmol/L x hour [95% CI 11.1 to 66.3 mmol/L x hour]), particularly among alcoholics (4.79 mmol/L x hour [95% CI 2.13 to 10.8 mmol/L x 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.

Authors+Show Affiliations

Department of Emergency Medicine, Queen's University, Kingston, Ontario, Canada. sivilotm@meds.queensu.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16126138

Citation

Sivilotti, Marco L A., et al. "A Risk Quantification Instrument for Acute Acetaminophen Overdose Patients Treated With N-acetylcysteine." Annals of Emergency Medicine, vol. 46, no. 3, 2005, pp. 263-71.
Sivilotti ML, Yarema MC, Juurlink DN, et al. A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine. Ann Emerg Med. 2005;46(3):263-71.
Sivilotti, M. L., Yarema, M. C., Juurlink, D. N., Good, A. M., & Johnson, D. W. (2005). A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine. Annals of Emergency Medicine, 46(3), pp. 263-71.
Sivilotti ML, et al. A Risk Quantification Instrument for Acute Acetaminophen Overdose Patients Treated With N-acetylcysteine. Ann Emerg Med. 2005;46(3):263-71. PubMed PMID: 16126138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine. AU - Sivilotti,Marco L A, AU - Yarema,Mark C, AU - Juurlink,David N, AU - Good,Angela M, AU - Johnson,David W, PY - 2004/08/27/received PY - 2005/03/11/revised PY - 2005/04/01/accepted PY - 2005/8/30/pubmed PY - 2006/2/1/medline PY - 2005/8/30/entrez SP - 263 EP - 71 JF - Annals of emergency medicine JO - Ann Emerg Med VL - 46 IS - 3 N2 - 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 mug/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 x hour [95% CI 8.74 to 31.0 mmol/L x hour] versus 27.1 mmol/L x hour [95% CI 11.1 to 66.3 mmol/L x hour]), particularly among alcoholics (4.79 mmol/L x hour [95% CI 2.13 to 10.8 mmol/L x 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. SN - 1097-6760 UR - https://www.unboundmedicine.com/medline/citation/16126138/A_risk_quantification_instrument_for_acute_acetaminophen_overdose_patients_treated_with_N_acetylcysteine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-0644(05)00409-9 DB - PRIME DP - Unbound Medicine ER -