急性高危扑热息痛（对乙酰氨基酚）摄入时高剂量乙酰半胱氨酸的评估。
Assessment of high-dose acetylcysteine in acute high-risk paracetamol (acetaminophen) ingestion.
机构信息
UT Poison Control Center, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
Department of Emergency Medicine, University of Utah, Salt Lake City, UT, USA.
出版信息
Clin Toxicol (Phila). 2024 Aug;62(8):519-525. doi: 10.1080/15563650.2024.2377268. Epub 2024 Jul 25.
BACKGROUND
Prompt acetylcysteine treatment with standard doses (300 mg/kg over 21 h in divided doses) is almost universally effective in preventing hepatotoxicity after paracetamol (acetaminophen) overdose. However, hepatotoxicity is reported despite early treatment when paracetamol concentrations exceed 300 mg/L (1,985 μmol/L) at 4 h. Prior studies evaluating high-dose acetylcysteine to treat high-risk ingestions have shown mixed results. We compared outcomes in patients with high-risk ingestions receiving standard or high-dose acetylcysteine.
METHODS
Records from a single poison center were reviewed from 1 January 2017 to 31 December 2022. We included cases of acute paracetamol ingestion treated with intravenous acetylcysteine with an initial paracetamol concentration above the "300 mg/L" (1,985 μmol/L) line on the Rumack-Matthew nomogram. We compared standard and high-dose acetylcysteine groups by odds ratios and multivariable logistic regression. We defined hepatotoxicity as aminotransferase activity >1,000 U/L.
RESULTS
We included 190 cases. Fifty-six percent received standard-dose acetylcysteine while 44% received high-dose acetylcysteine. Treatment within 8 h yielded no difference in hepatotoxicity between groups (odds ratio 1.67, 95% CI 0.067-42.3). Among patients treated after 8 h, hepatoxicity was more common in the high-dose group (odds ratio 3.39, 95% CI 1.25-9.2) though odds of liver failure were similar (odds ratio 2.78, 95% CI 0.89-8.69). Eighty-eight percent of patients with hepatotoxicity had elevated aminotransferase activity at presentation. No patient died or received a liver transplant.
DISCUSSION
Rates of hepatotoxicity were low in patients treated within 8 h regardless of acetylcysteine dose. Unexpectedly, high-dose acetylcysteine treatment was associated with an increased odds of hepatoxicity in those treated after 8 h, but most had abnormal aminotransferase activities at presentation and there was no difference in rates of liver failure. Limitations include the use of retrospective, voluntarily reported poison center data.
CONCLUSIONS
Prompt treatment with acetylcysteine, regardless of dose, prevented hepatotoxicity in high-risk paracetamol ingestion.
背景
在对乙酰氨基酚（扑热息痛）过量后，及时给予标准剂量（21 小时内分 3 次给予 300mg/kg）的乙酰半胱氨酸治疗，几乎可以完全预防肝毒性。然而，尽管在 4 小时内对乙酰氨基酚浓度超过 300mg/L（1985μmol/L）时进行了早期治疗，仍有肝毒性的报道。先前评估高剂量乙酰半胱氨酸治疗高危摄入的研究结果喜忧参半。我们比较了接受标准剂量或高剂量乙酰半胱氨酸治疗的高危摄入患者的结局。
方法
我们回顾了 2017 年 1 月 1 日至 2022 年 12 月 31 日期间一家中毒中心的记录。我们纳入了使用静脉内乙酰半胱氨酸治疗的急性对乙酰氨基酚摄入病例，这些病例的初始对乙酰氨基酚浓度高于 Rumack-Matthew 列线图上的“300mg/L”（1985μmol/L）线。我们通过比值比和多变量逻辑回归比较了标准剂量和高剂量乙酰半胱氨酸组。我们将肝毒性定义为转氨酶活性>1000U/L。
结果
我们纳入了 190 例病例。56%的患者接受了标准剂量乙酰半胱氨酸治疗，而 44%的患者接受了高剂量乙酰半胱氨酸治疗。在 8 小时内进行治疗，两组之间的肝毒性无差异（比值比 1.67，95%CI 0.067-42.3）。在 8 小时后接受治疗的患者中，高剂量组肝毒性更常见（比值比 3.39，95%CI 1.25-9.2），尽管肝功能衰竭的几率相似（比值比 2.78，95%CI 0.89-8.69）。88%的肝毒性患者在就诊时转氨酶活性升高。没有患者死亡或接受肝移植。
讨论
无论乙酰半胱氨酸剂量如何，在 8 小时内接受治疗的患者中，肝毒性的发生率均较低。出乎意料的是，在 8 小时后接受治疗的患者中，高剂量乙酰半胱氨酸治疗与肝毒性发生的几率增加相关，但大多数患者在就诊时转氨酶活性异常，肝功能衰竭的发生率无差异。局限性包括使用回顾性、自愿报告的中毒中心数据。
结论
及时给予乙酰半胱氨酸治疗，无论剂量如何，均可预防高危对乙酰氨基酚摄入后的肝毒性。
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