a Department of Medicine , School of Clinical Sciences, Monash University , Victoria , Australia.
b Austin Toxicology Service and Victorian Poisons Information Centre, Austin Health , Victoria , Australia.
Clin Toxicol (Phila). 2018 Mar;56(3):182-188. doi: 10.1080/15563650.2017.1355058. Epub 2017 Jul 31.
Paracetamol concentration is a highly accurate risk predictor for hepatotoxicity following overdose with known time of ingestion. However, the paracetamol-aminotransferase multiplication product can be used as a risk predictor independent of timing or ingestion type. Validated in patients treated with the traditional, "three-bag" intravenous acetylcysteine regimen, we evaluated the accuracy of the multiplication product in paracetamol overdose treated with a two-bag acetylcysteine regimen.
We examined consecutive patients treated with the two-bag regimen from five emergency departments over a two-year period. We assessed the predictive accuracy of initial multiplication product for the primary outcome of hepatotoxicity (peak alanine aminotransferase ≥1000IU/L), as well as for acute liver injury (ALI), defined peak alanine aminotransferase ≥2× baseline and above 50IU/L).
Of 447 paracetamol overdoses treated with the two-bag acetylcysteine regimen, 32 (7%) developed hepatotoxicity and 73 (16%) ALI. The pre-specified cut-off points of 1500 mg/L × IU/L (sensitivity 100% [95% CI 82%, 100%], specificity 62% [56%, 67%]) and 10,000 mg/L × IU/L (sensitivity 70% [47%, 87%], specificity of 97% [95%, 99%]) were highly accurate for predicting hepatotoxicity. There were few cases of hepatotoxicity irrespective of the product when acetylcysteine was administered within eight hours of overdose, when the product was largely determined by a high paracetamol concentration but normal aminotransferase.
The multiplication product accurately predicts hepatotoxicity when using a two-bag acetylcysteine regimen, especially in patients treated more than eight hours post-overdose. Further studies are needed to assess the product as a method to adjust for exposure severity when testing efficacy of modified acetylcysteine regimens.
在已知摄入时间的情况下，对乙酰氨基酚浓度是预测过量服用后肝毒性的高度准确风险预测因子。然而，对乙酰氨基酚-氨基转移酶乘积可以作为独立于时间或摄入类型的风险预测因子。该乘积在接受传统的“三袋”静脉乙酰半胱氨酸治疗方案的患者中得到了验证，我们评估了该乘积在接受两袋乙酰半胱氨酸治疗方案治疗的对乙酰氨基酚过量患者中的准确性。
我们检查了两年内来自五个急诊部门的接受两袋方案治疗的连续患者。我们评估了初始乘积对主要结局（丙氨酸氨基转移酶峰值≥1000IU/L）的肝毒性以及急性肝损伤（定义为峰值丙氨酸氨基转移酶≥2×基线且高于 50IU/L）的预测准确性。
在接受两袋乙酰半胱氨酸治疗方案治疗的 447 例对乙酰氨基酚过量患者中，有 32 例（7%）发生肝毒性，73 例（16%）发生急性肝损伤。预定义的截断点为 1500mg/L×IU/L（敏感性 100%[95%CI 82%，100%]，特异性 62%[56%，67%]）和 10000mg/L×IU/L（敏感性 70%[47%，87%]，特异性 97%[95%，99%]）对于预测肝毒性非常准确。当乙酰半胱氨酸在过量后 8 小时内给予时，无论产物如何，肝毒性的病例都很少，此时产物主要由高浓度的对乙酰氨基酚但正常的氨基转移酶决定。
使用两袋乙酰半胱氨酸方案时，乘积可准确预测肝毒性，尤其是在过量后 8 小时以上接受治疗的患者。需要进一步研究该产品作为在测试改良乙酰半胱氨酸方案疗效时调整暴露严重程度的方法。
