Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
Clin Toxicol (Phila). 2022 Nov;60(11):1251-1265. doi: 10.1080/15563650.2022.2098139. Epub 2022 Sep 21.
poisoning causes severe liver damage which may be potentially fatal. Several treatments are available, but their effectiveness has not been systematically evaluated. We performed a systematic review to investigate the effect of the most commonly used therapies: N-acetylcysteine (NAC), benzylpenicillin (PEN), and silibinin (SIL) on patient outcomes. In addition, other factors contributing to patient outcomes are identified.
We searched MEDLINE and Embase for case series and case reports that described patient outcomes after poisoning with amanitin-containing mushrooms. We extracted clinical characteristics, treatment details, and outcomes. We used the liver item from the Poisoning Severity Score (PSS) to categorize intoxication severity.
We included 131 publications describing a total of 877 unique cases. The overall survival rate of all patients was 84%. Patients receiving only supportive care had a survival rate of 59%. The use of SIL or PEN was associated with a 90% (OR 6.40 [3.14-13.04]) and 89% (OR 5.24 [2.87-9.56]) survival rate, respectively. NAC/SIL combination therapy was associated with 85% survival rate (OR 3.85 [2.04, 7.25]). NAC/PEN/SIL treatment group had a survival rate of 76% (OR 2.11 [1.25, 3.57]). Due to the limited number of cases, the use of NAC alone could not be evaluated. Additional analyses in 'proven cases' (amanitin detected), 'probable cases' (mushroom identified by mycologist), and 'possible cases' (neither amanitin detected nor mushroom identified) showed comparable results, but the results did not reach statistical significance. Transplantation-free survivors had significantly lower peak values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total serum bilirubin (TSB), and international normalized ratio (INR) compared to liver transplantation survivors and patients with fatal outcomes. Higher peak PSS was associated with increased mortality.
Based on data available, no statistical differences could be observed for the effects of NAC, PEN or SIL in proven poisonings with amanitin-containing mushrooms. However, monotherapy with SIL or PEN and combination therapy with NAC/SIL appear to be associated with higher survival rates compared to supportive care alone. AST, ALT, TSB, and INR values are possible predictors of potentially fatal outcomes.
中毒可导致严重的肝损伤，可能危及生命。目前已有多种治疗方法，但尚未对其疗效进行系统评估。本研究旨在通过系统评价，调查最常用的三种疗法（N-乙酰半胱氨酸[NAC]、青霉素[PEN]和水飞蓟素[SIL]）对患者预后的影响，并确定影响患者预后的其他因素。
我们检索了 MEDLINE 和 Embase 中描述含鹅膏蕈碱蘑菇中毒患者结局的病例系列和病例报告。我们提取了临床特征、治疗细节和结局。我们使用中毒严重程度评分（PSS）的肝脏项目对中毒严重程度进行分类。
共纳入 131 篇文献，描述了 877 例独特的病例。所有患者的总体生存率为 84%。仅接受支持治疗的患者生存率为 59%。使用 SIL 或 PEN 治疗的患者生存率分别为 90%（OR 6.40[3.14-13.04]）和 89%（OR 5.24[2.87-9.56]）。NAC/SIL 联合治疗的生存率为 85%（OR 3.85[2.04,7.25]）。NAC/PEN/SIL 治疗组的生存率为 76%（OR 2.11[1.25,3.57]）。由于病例数量有限，无法评估 NAC 单独使用的效果。在“确诊病例”（检测到鹅膏蕈碱）、“疑似病例”（经真菌学家鉴定的蘑菇）和“可能病例”（未检测到鹅膏蕈碱且未鉴定蘑菇）中的进一步分析显示了类似的结果，但未达到统计学意义。与肝移植幸存者和死亡结局患者相比，无肝移植幸存者的天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、总血清胆红素（TSB）和国际标准化比值（INR）的峰值显著降低。较高的 PSS 峰值与死亡率增加相关。
基于现有数据，无法观察到 NAC、PEN 或 SIL 对含鹅膏蕈碱蘑菇中毒的疗效差异。然而，与单独支持治疗相比，SIL 或 PEN 单药治疗以及 NAC/SIL 联合治疗似乎与更高的生存率相关。AST、ALT、TSB 和 INR 值可能是潜在致命结局的预测指标。
