Pakravan Nasrin, Waring W Stephen, Sharma Sushma, Ludlam Christopher, Megson Ian, Bateman D Nicholas
National Poisons Information Service Edinburgh, University ofEdinburgh, Edinburgh, UK.
Clin Toxicol (Phila). 2008 Sep;46(8):697-702. doi: 10.1080/15563650802245497.
Adverse effects to N-acetylcysteine (NAC) are well recognized, but their etiology and incidence are unclear.
The nature and severity of adverse effects were prospectively studied in 169 patients and potential reaction mediators studied in 22 patients.
Adverse effects were minimal in 101 (59.8%), moderate in 51 (30.2%), and severe in 17 (10.1%). Features were nausea (70.4%), vomiting (60.4%), flushing (24.9%), pruritus (20.1%), dyspnea (13.6%), chest pain (7.1%), dizziness (7.7%), fever (4.7%), wheeze and bronchospasm (7.1%), and rash and urticaria (3.6%). Serum acetaminophen concentration was lower in patients with severe adverse effects: median (IQR) 46 mg/L (0 to 101 mg/L), moderate 108 mg/L (54 to 178 mg/L), and minimal 119 mg/L (77 to 174 mg/L), p = 0.002. Family history of allergy and female gender were independent risk factors for adverse effects. Severity of adverse effects was associated with histamine release: AUC for change from baseline histamine was -6 ng/mL min (-60 to 11 ng/mL min) in the minimal group, 26 ng/mL min (3-129 ng/mL min) in the moderate group, and 49 ng/mL min (21-68 ng/mL min) in the severe group (p = 0.01). There was no increase in tryptase and no differences between groups for NAC concentrations or hemostatic and inflammatory variables (factors II, VII, IX, X, vWF, tPA, IL6, and CRP).
Severity of adverse effects correlates with the extent of histamine release. Histamine release appears independent of tryptase suggesting a non-mast cell source. Acetaminophen is protective against adverse effects of NAC, and mechanisms by which acetaminophen might lessen histamine release require further attention.
N-乙酰半胱氨酸（NAC）的不良反应已得到充分认识，但其病因和发生率尚不清楚。
对169例患者的不良反应性质和严重程度进行前瞻性研究，并对22例患者的潜在反应介质进行研究。
101例（59.8%）不良反应轻微，51例（30.2%）中度，17例（10.1%）严重。症状包括恶心（70.4%）、呕吐（60.4%）、潮红（24.9%）、瘙痒（20.1%）、呼吸困难（13.6%）、胸痛（7.1%）、头晕（7.7%）、发热（4.7%）、喘息和支气管痉挛（7.1%）以及皮疹和荨麻疹（3.6%）。严重不良反应患者的血清对乙酰氨基酚浓度较低：中位数（四分位间距）为46 mg/L（0至101 mg/L），中度为108 mg/L（54至178 mg/L），轻微为119 mg/L（77至174 mg/L），p = 0.002。过敏家族史和女性是不良反应的独立危险因素。不良反应的严重程度与组胺释放有关：轻微组组胺从基线变化的曲线下面积（AUC）为-6 ng/mL·min（-60至11 ng/mL·min），中度组为26 ng/mL·min（3至129 ng/mL·min），严重组为49 ng/mL·min（21至68 ng/mL·min）（p = 0.01）。类胰蛋白酶没有增加，各组之间的NAC浓度或止血和炎症变量（因子II、VII、IX、X、血管性血友病因子、组织型纤溶酶原激活剂、白细胞介素6和C反应蛋白）没有差异。
不良反应的严重程度与组胺释放程度相关。组胺释放似乎独立于类胰蛋白酶，提示非肥大细胞来源。对乙酰氨基酚对NAC的不良反应有保护作用，对乙酰氨基酚减轻组胺释放的机制需要进一步关注。
