Evaluation and treatment of acetaminophen toxicity.
Evaluation and treatment of acetaminophen toxicity.
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DOI：
10.1016/bs.apha.2018.12.004
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Curry, Steven C
中科院分区：
文献类型：
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作者：
Fisher, Erik S;Curry, Steven C
对乙酰氨基酚中毒的典型临床过程，诊断和治疗的审查。对于急性过量，大多数成年人必须摄入约12克或更多的对乙酰氨基酚（APAP），才有严重肝毒性的风险。血清APAP浓度与摄入后数小时的列线图可以帮助确定肝损伤的风险和治疗需求。然而，关于服药时间和服药量的病史通常是不可靠的。血清转氨酶活性的峰值通常出现在急性摄入后48- 96小时。患者可能在摄入后几天出现肝功能衰竭，血清APAP浓度无法检测。长期摄入过量APAP剂量并发生肝毒性的患者通常会出现这种情况，肾衰竭在这一人群中更常见。目前的治疗集中在N-乙酰半胱氨酸（NAC）的管理，以防止肝毒性，虽然NAC也改善了急性肝衰竭患者的结果。当在摄入APAP后早期给予时，NAC的主要作用机制是维持细胞内谷胱甘肽储存，从而使亲电APAP代谢物NAPQI解毒。NAC在静脉给药时通常耐受性良好，主要问题是过敏样反应。这些反应通常发生在负荷剂量期间，并且很容易通过停止NAC输注、给予抗组胺药，然后以较慢的输注速率重新开始负荷剂量来治疗。人们担心目前的NAC剂量不足以充分治疗大的APAP摄入。急性肝功能衰竭的患者可能是原位肝移植的候选者。
A review of the typical clinical course, diagnosis and treatment of acetaminophen toxicity is provided. For an acute overdose, most adults must ingest about 12g or more acetaminophen (APAP) before risk of serious hepatotoxicity is of concern. A nomogram of serum APAP concentration vs hours post-ingestion can assist in determining risk of liver injury and need for treatment. However, histories concerning the time of ingestion and the amount of drug ingested are usually unreliable. Peak serum transaminase activities usually occur 48-96h after acute ingestion. It is possible for patients to present in liver failure days after ingestion with undetectable serum APAP concentrations. Patients who have chronically ingested excessive APAP doses and develop hepatotoxicity usually present with such, and renal failure is more common in this population. Current treatment centers on administration of N-acetylcysteine (NAC) to prevent hepatotoxicity, though NAC also improves outcomes in patients who present with acute liver failure. When given early after APAP ingestion, NAC's main mechanism of action is to maintain intracellular glutathione stores so to detoxify the electrophilic APAP metabolite, NAPQI. NAC is generally well-tolerated when given intravenously, with the main concern being anaphylactoid reactions. These reactions usually occur during loading doses and are easily treated with discontinuation of the NAC infusion, administration of antihistamines, and then restarting the loading dose at a slower infusion rate. There is concern that current NAC dosing is not large enough to adequately treat large APAP ingestions. Patients with acute liver failure may be candidates for orthotopic liver transplantation.