Sandilands E A, Bateman D N
NPIS Edinburgh - SPIB, Royal Infirmary of Edinburgh, UK.
Clin Toxicol (Phila). 2009 Feb;47(2):81-8. doi: 10.1080/15563650802665587.
Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians.
A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine.
A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose.
This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and treatment of adverse reactions to acetylcysteine and identifies particular "at-risk" patient groups. Given the commonality of adverse reactions associated with acetylcysteine, it is important to ensure that any adverse event does not preclude patients from receiving maximal hepatic protection, particularly in the context of significant paracetamol ingestion. Further work on mechanisms should allow specific therapies to be developed.
对乙酰氨基酚是自我中毒事件中最常被故意摄入的药物之一，也是西方世界急性肝衰竭的主要原因。乙酰半胱氨酸被广泛认为是对乙酰氨基酚中毒的首选解毒剂，但其使用并非毫无风险。不良反应，常常导致治疗延迟，在静脉注射和口服乙酰半胱氨酸时都经常出现，是治疗医生普遍关注的问题。
一项系统的文献综述，调查与乙酰半胱氨酸相关的不良反应的发生率、临床特征和机制。
已描述了对乙酰半胱氨酸的多种不良反应，从恶心到死亡，后者大多是由于给药错误。口服和静脉给药的反应模式不同，但报告的口服反应频率至少与静脉注射一样高。静脉制剂的反应导致与真正过敏反应相似的临床特征，包括皮疹、瘙痒、血管性水肿、支气管痉挛，很少有低血压，但由非免疫机制引起。这种反应的确切性质仍不清楚。组胺现在似乎是该反应的重要介质，有证据表明患者易感性存在差异，女性以及有哮喘或特应性病史的人尤其易感。通过血清对乙酰氨基酚浓度测量的对乙酰氨基酚摄入量也很重要，因为较高的对乙酰氨基酚浓度可保护患者免受类过敏反应的影响。大多数类过敏反应发生在乙酰半胱氨酸治疗开始时，此时浓度最高。乙酰半胱氨酸还会影响凝血因子活性，这会影响在对乙酰氨基酚过量情况下国际标准化比值轻微异常的解读。
本综述讨论了乙酰半胱氨酸不良反应的发生率、临床特征、潜在病理生理机制和治疗方法，并确定了特定的“高危”患者群体。鉴于与乙酰半胱氨酸相关的不良反应很常见，重要的是要确保任何不良事件都不会妨碍患者获得最大程度的肝脏保护，特别是在大量摄入对乙酰氨基酚的情况下。对机制的进一步研究应有助于开发特定的治疗方法。
