BACKGROUND 5-Fluorouracil (5-FU)-induced hyperammonaemic encephalopathy is a rare but serious 5-FU adverse drug reaction (ADR). Given the growing number of cancers treated with 5-FU and the paucity of data regarding this ADR, we performed a retrospective national survey to better characterise 5-FU-induced hyperammonaemic encephalopathy. PATIENTS AND METHODS Since inception of the French pharmacovigilance database, we identified all patients who experienced 5-FU-induced hyperammonaemic encephalopathy. Variables regarding demographics, characteristics, management and outcome of patients were collected. RESULTS From 1986 to 2018, 30 patients were included. 5-FU-induced hyperammonaemic encephalopathy started 2 [1-4] days after 5-FU infusion onset. Most common neurological disorders were consciousness impairment, seizures and confusion. hyperammonaemia tended to be higher in patients with the lowest Glasgow score and admitted in intensive care unit (ICU) compared to non-ICU patients (250 [133-522] versus 139 [68-220] μmol/L respectively, p = NS). Dihydropyrimidine dehydrogenase deficiency was found in 27% of tested patients (n = 3/11). Encephalopathy-induced mortality was 17%, 57% of patients were admitted in ICU and 70% had a complete neurological recovery within 5 [2-10] days. A 5-FU rechallenge was considered in 14 (67%) patients with neurological recovery and a relapse was observed in 57% of them. No 5-FU-induced hyperammonaemic encephalopathy relapse was observed as long as 5-FU rechallenge was performed with decreased 5-FU dosage. CONCLUSION We report the largest cohort of 5-FU-induced hyperammonaemic encephalopathy cases so far. This ADR should be suspected and ammonaemia measured in all patients experiencing neurological disorders after 5-FU administration. In patients with complete neurological recovery, a 5-FU rechallenge could be cautiously considered.

中文翻译：

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5-氟尿嘧啶引起的高氨血症性脑病：一项法国国家调查。

背景技术5-氟尿嘧啶（5-FU）诱导的高氨血症性脑病是一种罕见但严重的5-FU不良药物反应（ADR）。鉴于用5-FU治疗的癌症数量不断增加，并且关于该ADR的数据很少，我们进行了一项回顾性全国调查，以更好地表征5-FU诱发的高氨血症性脑病。患者和方法自法国药物警戒数据库建立以来，我们确定了所有经历过5-FU诱发的高氨血症性脑病的患者。收集有关人口统计学，特征，治疗和结果的变量。结果从1986年至2018年，共纳入30例患者。5-FU输注开始后2 [1-4]天开始发生5-FU引起的高氨血症性脑病。最常见的神经系统疾病是意识障碍，癫痫发作和神志不清。与非ICU患者相比，格拉斯哥评分最低且被重症监护病房（ICU）入院的患者的高氨血症倾向更高（分别为250 [133-522]和139 [68-220]μmol/ L，p = NS） 。在27％的测试患者中发现二氢嘧啶脱氢酶缺乏症（n = 3/11）。脑病引起的死亡率为17％，ICU收治了57％的患者，而70％的患者在5 [2-10]天内完全恢复了神经。14例（67％）神经功能恢复患者考虑进行5-FU再挑战，其中57％观察到复发。只要减少5-FU剂量进行5-FU再挑战，就没有观察到5-FU引起的高氨血症性脑病复发。结论我们报道了迄今为止最大的5-FU诱发的高氨血症性脑病病例。在所有接受5-FU给药后出现神经系统疾病的患者中，均应怀疑该ADR并测量其氨血症。在神经功能完全恢复的患者中，应谨慎考虑5-FU再挑战。