Department of Clinical Pharmacology, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Basic Clin Pharmacol Toxicol. 2024 Sep;135(3):285-294. doi: 10.1111/bcpt.14051. Epub 2024 Jul 14.
N-acetylcysteine (NAC) is regarded as an effective treatment of paracetamol overdoses. However, in cases of "massive" paracetamol overdoses, recent studies indicate that patients may not be sufficiently treated with the standard dose of NAC (300 mg/kg over 20-21 h). The subject is further complicated because "massive overdoses" and "high-risk" are defined differently; some studies use the ingested amount (e.g., >40 g), and some studies use blood concentrations of paracetamol and transaminases. This narrative review investigates whether high-dose NAC significantly decreases the risk of hepatotoxicity in patients with massive paracetamol overdoses. Three observational studies were analysed; one study with 373 patients found no significant difference (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.49-3.29). One study with 79 patients found a significant difference (OR: 0.27, 95% CI: 0.08-0.94). The third study with 89 patients found a significant difference in hepatoxicity between the groups (p = 0.043). There are no solid evidence to support that treatment with high-dose NAC significantly reduces the rate of hepatotoxicity in patients presenting with massive paracetamol overdoses. Differences in inclusion criteria in the included studies make the studies incomparable. This paper shows that standardized inclusion is needed to determine whether a high-dose NAC regimen should be included in clinical practice.
N-乙酰半胱氨酸（NAC）被认为是治疗对乙酰氨基酚过量的有效方法。然而，在“大剂量”对乙酰氨基酚过量的情况下，最近的研究表明，标准剂量的 NAC（20-21 小时内 300mg/kg）可能不足以治疗患者。由于“大剂量”和“高风险”的定义不同，情况变得更加复杂；一些研究使用摄入的量（例如，>40g），而一些研究使用对乙酰氨基酚和转氨酶的血液浓度。本综述研究了高剂量 NAC 是否能显著降低大剂量对乙酰氨基酚过量患者发生肝毒性的风险。分析了三项观察性研究；一项纳入 373 例患者的研究未发现显著差异（比值比 [OR]：1.27，95%置信区间 [CI]：0.49-3.29）。一项纳入 79 例患者的研究发现存在显著差异（OR：0.27，95% CI：0.08-0.94）。第三项纳入 89 例患者的研究发现两组之间的肝毒性存在显著差异（p=0.043）。目前没有确凿的证据支持高剂量 NAC 治疗可显著降低大剂量对乙酰氨基酚过量患者肝毒性的发生率。纳入研究的纳入标准存在差异，使研究不可比。本文表明，需要标准化纳入标准，以确定高剂量 NAC 方案是否应纳入临床实践。
