NSW Poisons, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia.
Clin Toxicol (Phila). 2011 Jun;49(5):385-90. doi: 10.3109/15563650.2011.587126.
Brodifacoum is a widely available superwarfarin used as a commercial rodenticide. Toxicity from long-acting anticoagulant rodenticides, primarily from uncontrolled bleeding, has been reported. Very little published toxicokinetic data are available for human brodifacoum poisoning. Management is also contentious with uncertainty over the dose, frequency, and duration of antidote treatment with vitamin K. The role of brodifacoum levels in guiding management is not entirely established.
A novel, highly sensitive method was developed for measuring all commercially available rodenticide-hydroxycoumarin anti-coagulants. Monthly brodifacoum levels were performed in two patients to determine half-life and expected time for levels to fall below 10 μg/L.
We report two concurrent cases at our clinical toxicology service that required prolonged treatment with oral vitamin K to achieve normalisation of coagulation studies. Brodifacoum elimination appears to follow first-order kinetics. Case 1 had a brodifacoum elimination half-life of 33 days and was treated with vitamin K (100 mg) for 6 months. Case 2 was treated with vitamin K (100 mg) for 3 months with a half-life of 15 days.
Our cases illustrate the positive experience in the utility of brodifacoum levels to confirm diagnosis and aid in directing antidote therapy. Large ingestions of brodifacoum-containing rodenticides are likely to require high-dose oral vitamin K administered daily. A brodifacoum level below 10 μg/L was associated with a normal coagulation profile following completion of vitamin K(1) therapy in our cases; this level may prove to be a safe treatment cessation threshold.
Brodifacoum 是一种广泛使用的超级杀鼠剂,用作商业杀鼠剂。已报道因长效抗凝血杀鼠剂(主要因不受控制的出血)引起的毒性。人类摄入 brodifacoum 中毒的毒代动力学数据非常少。由于维生素 K 拮抗剂治疗的剂量、频率和持续时间存在争议,因此管理也存在争议。brodifacoum 水平在指导管理中的作用尚未完全确定。
开发了一种新型、高灵敏度的方法来测量所有市售的杀鼠剂-羟基香豆素抗凝血剂。对两名患者进行每月一次的 brodifacoum 水平检测,以确定半衰期和水平降至 10μg/L 以下的预期时间。
我们报告了在我们的临床毒理学服务中同时发生的两例病例,这些病例需要长期口服维生素 K 治疗才能使凝血研究正常化。Brodifacoum 的消除似乎遵循一级动力学。病例 1 的 brodifacoum 消除半衰期为 33 天,用维生素 K(100mg)治疗 6 个月。病例 2 用维生素 K(100mg)治疗 3 个月,半衰期为 15 天。
我们的病例说明了 brodifacoum 水平在确认诊断和指导解毒剂治疗方面的积极经验。摄入大量含 brodifacoum 的杀鼠剂可能需要每天给予高剂量的口服维生素 K。在我们的病例中,维生素 K(1)治疗完成后,当 brodifacoum 水平低于 10μg/L 时,凝血谱正常;这一水平可能被证明是一个安全的治疗停止阈值。