Craig Simon
Emergency Registrar, Monash Medical Centre, Clayton, Victoria, Australia.
Neurocrit Care. 2005;3(2):161-70. doi: 10.1385/NCC:3:2:161.
Phenytoin toxicity may result from intentional overdose, dosage adjustments, drug interactions, or alterations in physiology. Intoxication manifests predominantly as nausea, central nervous system dysfunction (particularly confusion, nystagmus, and ataxia), with depressed conscious state, coma, and seizures occurring in more severe cases. Cardiac complications such as arrhythmias and hypotension are rare in cases of phenytoin ingestion, but they may be seen in parenteral administration of phenytoin or fosphenytoin. Deaths are unlikely after phenytoin intoxication alone. A greatly increased half-life in overdose due to zero-order pharmacokinetics can result in a prolonged duration of symptoms and thus prolonged hospitalization with its attendant complications. The mainstay of therapy for a patient with phenytoin intoxication is supportive care. Treatment includes attention to vital functions, management of nausea and vomiting, and prevention of injuries due to confusion and ataxia. There is no antidote, and there is no evidence that any method of gastrointestinal decontamination or enhanced elimination improves outcome. Activated charcoal should be considered if the patient presents early; however, the role of multiple-dose activated charcoal is controversial. Experimental studies have proven increased clearance rates, but this effect has not been translated into clinical benefit. There is no evidence that any invasive method of enhanced elimination (such as plasmapheresis, hemodialysis, or hemoperfusion) provides any benefit. This article provides an overview of phenytoin pharmacokinetics and the clinical manifestations of toxicity, followed by a detailed review of the various treatment modalities.
苯妥英钠中毒可能由故意过量用药、剂量调整、药物相互作用或生理改变引起。中毒主要表现为恶心、中枢神经系统功能障碍(尤其是意识模糊、眼球震颤和共济失调),在更严重的情况下会出现意识状态降低、昏迷和癫痫发作。在苯妥英钠摄入病例中,心律失常和低血压等心脏并发症很少见,但在静脉注射苯妥英钠或磷苯妥英钠时可能会出现。单独苯妥英钠中毒后不太可能死亡。由于零级药代动力学,过量用药时半衰期大幅延长,可导致症状持续时间延长,从而延长住院时间及其伴随的并发症。苯妥英钠中毒患者的主要治疗方法是支持性护理。治疗包括关注生命体征、处理恶心和呕吐,以及预防因意识模糊和共济失调导致的损伤。没有解毒剂,也没有证据表明任何胃肠道净化或强化清除方法能改善预后。如果患者就诊早,应考虑使用活性炭;然而,多剂量活性炭的作用存在争议。实验研究已证明清除率增加,但这种效果尚未转化为临床益处。没有证据表明任何侵入性强化清除方法(如血浆置换、血液透析或血液灌流)有任何益处。本文概述了苯妥英钠的药代动力学和中毒的临床表现,随后详细回顾了各种治疗方式。