对乙酰氨基酚控释制剂过量：一项前瞻性观察研究（ATOM-3）。
Modified release paracetamol overdose: a prospective observational study (ATOM-3).
机构信息
a Clinical Toxicology Unit/Emergency Department , Prince of Wales Hospital , Randwick , NSW , Australia.
b Department of Pharmacology, School of Medical Sciences , University of Sydney , Sydney , NSW , Australia.
出版信息
Clin Toxicol (Phila). 2018 Sep;56(9):810-819. doi: 10.1080/15563650.2018.1439950. Epub 2018 Feb 16.
BACKGROUND
Modified-release (MR) paracetamol is available in many countries as 665 mg tablets of which 69% is MR and 31% is immediate release. There are concerns that MR paracetamol overdose has higher rates of liver injury despite standard treatment algorithms. The objective of this study was to describe the clinical characteristics and outcomes of acute MR paracetamol overdose.
METHODS
Prospective observational study, recruiting patients from January 2013 to June 2017, from five clinical toxicology units and calls to two Poisons Information Centres in Australia. Included were patients >14 years who ingested ≥10 g or 200 mg/kg (whichever is less) of MR paracetamol. Data collected included demographics, ingestion history, pathology results, treatments, and outcomes including hepatotoxicity (ALT >1000 U/L).
RESULTS
In total, 116 patients were recruited, 85(73%) were female. The median dose ingested was 32 g (IQR: 20-49 g) and median time to presentation was 3 h (IQR: 2-9 h). 78(67%) had an initial paracetamol concentration above the nomogram line (150 mg/L at 4 h). A further 12(10%) crossed the nomogram after repeat paracetamol measurements, of which five crossed after two non-toxic levels 4 h apart. Six had a double paracetamol peak, in three occurring >24 h post-ingestion. 113(97%) received acetylcysteine of which 67 received prolonged treatment beyond the standard 21 h. This was because of an elevated paracetamol concentration at the completion of acetylcysteine in 39 (median paracetamol concentration 25 mg/L, IQR: 16-62 mg/L). 21 (18%) developed hepatotoxicity, including six treated within 8 h of ingestion. Activated charcoal and double doses of acetylcysteine did not significantly decrease the risk of hepatotoxicity.
CONCLUSIONS
Drug regulatory authorities are considering restrictions on MR paracetamol preparations. Following an acute MR paracetamol overdose, this study found that many patients had a persistently elevated paracetamol concentrations, many required prolonged treatment and some developed liver injury despite early acetylcysteine treatment. Furthermore, activated charcoal and increased acetylcysteine did not appear to significantly alter the risk of liver injury. Hence, research into better treatment strategies is required.
TRIAL REGISTRATION
Australian Toxicology Monitoring (ATOM) Study - Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.
背景
在许多国家， 都有控释（MR）扑热息痛， 有 665 毫克的片剂， 其中 69%是 MR 制剂， 31%是速释制剂。 尽管有标准治疗方案， 但人们担心 MR 扑热息痛过量会导致更高的肝损伤率。 本研究的目的是描述急性 MR 扑热息痛过量的临床特征和结果。
方法
这是一项前瞻性观察性研究， 从 2013 年 1 月至 2017 年 6 月， 在澳大利亚的五个临床毒理学单位和两个毒物信息中心进行患者招募。 纳入标准为摄入≥ 10 g 或 200 mg/kg（以较小者为准） MR 扑热息痛的年龄大于 14 岁的患者。 收集的数据包括人口统计学、 摄入史、 病理学结果、 治疗和结局， 包括肝毒性（ALT＞ 1000 U/L）。
结果
共纳入 116 例患者， 85 例（73%）为女性。 中位摄入剂量为 32 g（IQR： 20-49 g）， 中位就诊时间为 3 h（IQR： 2-9 h）。 78 例（67%）的初始扑热息痛浓度超过了列线图的线（4 h 时 150 mg/L）。 另外 12 例（10%）在重复扑热息痛测量后越过了列线图， 其中 5 例在相隔 4 h 的两次非毒性水平后越过。 6 例有双重扑热息痛高峰， 其中 3 例发生在摄入后 24 小时以上。 113 例（97%）接受了乙酰半胱氨酸治疗， 其中 67 例接受了标准 21 小时以外的延长治疗。 这是因为在乙酰半胱氨酸治疗结束时， 39 例（中位扑热息痛浓度为 25 mg/L， IQR： 16-62 mg/L）的扑热息痛浓度升高。 21 例（18%）发生了肝毒性， 其中 6 例在摄入后 8 小时内接受了治疗。 活性炭和乙酰半胱氨酸的双倍剂量并没有显著降低肝毒性的风险。
结论
药品监管机构正在考虑限制 MR 扑热息痛制剂的使用。 在急性 MR 扑热息痛过量后， 本研究发现， 许多患者的扑热息痛浓度持续升高， 许多患者需要延长治疗， 尽管早期使用了乙酰半胱氨酸， 但仍有部分患者发生了肝损伤。 此外， 活性炭和增加乙酰半胱氨酸似乎并没有显著改变肝损伤的风险。 因此， 需要研究更好的治疗策略。
试验注册
澳大利亚毒理学监测（ATOM）研究-澳大利亚扑热息痛项目：ACTRN12612001240831（ANZCTR）注册日期：2012 年 11 月 23 日。
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