A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine
A risk quantification instrument for acute acetaminophen overdose patients treated with N-acetylcysteine
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DOI：
10.1016/j.annemergmed.2005.04.004
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发表时间：
2005-09-01
影响因子：
6.2
通讯作者：
Johnson, DW
中科院分区：
文献类型：
--
作者：
Sivilotti, MLA;Yarema, MC;Johnson, DW
试验目的：急性对乙酰氨基酚过量后肝毒性的风险随时间血清对乙酰氨基酚浓度和治疗延迟而变化。需要准确预测肝毒性的能力，以减少对个体患者最佳治疗方案以及乙醇等风险调节剂影响的困惑。我们定量估计的程度和持续时间的基础上的预处理暴露于超治疗浓度的acetaminophen.Methods的肝毒性的风险：我们研究了所有的急性对乙酰氨基酚过量的回顾性多中心加拿大注册表中的住院治疗。我们使用了以前开发的复合措施，将定时血清对乙酰氨基酚浓度和N-乙酰半胱氨酸治疗时间纳入一个单一的参数。然后，我们模拟肝毒性，在这个参数，以及年龄，性别和乙醇的使用。肝毒性被定义为峰值转氨酶水平为1,000 IU/L或更高，在24 hours or longer.Results：1,270入院的患者治疗大多与静脉注射N-乙酰半胱氨酸少于24小时，我们的模型准确地确定了94例肝毒性（判别指数0.93）。高于传统150 μ g/mL治疗线的313名患者（95%置信区间[CI] 0%至1.0%）均未发生肝毒性，使用我们的仪器将这些患者归类为低风险（< 1%）。在调整暴露的严重程度后，在没有同时摄入乙醇的情况下，肝毒性的风险显著升高（中位肝毒性剂量16.5 mmol/L x小时[95% CI 8.74至31.0 mmol/L x小时] vs 27.1 mmol/L x小时[95% CI 11.1至66.3 mmol/L x小时]），特别是在酗酒者中（4.79 mmol/L x h [95%CI 2.13 - 10.8 mmol/L x h]）。结论：我们的风险预测工具确定了一个大的低风险患者群体，对于他们来说，20小时静脉注射N-乙酰半胱氨酸治疗就足够了。我们的研究结果表明，急性和慢性乙醇使用显着影响对乙酰氨基酚的毒性。这项工作可能有助于评估高风险患者的个性化治疗策略。
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 mu g/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.