Introduction: Patients in the emergency department (ED) often require IV loading of anticonvulsants for seizures. Phenytoin is a first line agent for status epilepticus, however rapid administration is associated with cardiogenic shock believed to be due to the diluent, propylene glycol. Fosphenytoin was developed as a safer alternative, however cardiotoxicity still occurs. We present a case of cardiotoxicity from therapeutic IV fosphenytoin loading despite use of the recommended infusion rate.
Case Report: A 49 yo man with a history of coronary artery disease (CAD) and seizure disorder arrived to the ED in status epilepticus. Blood glucose was 128 mg/dL. His medications included carvedilol and amlodipine. His seizures were refractory to 2 mg of lorazepam, thus he was given an 18 PE/kg dose of fosphenytoin IV over 15 min. Immediately after the fosphenytoin dose he had 4 apneic episodes and was intubated. His heart rate (HR) and blood pressure, respectively, fell from 114 to 40 and 151/102 to 75/52, One mg of atropine was given with improvement of his HR only to 60. Repeat ECG revealed junctional rhythm at a rate of 62 bpm, with no change in QRS (100 ms) or QTc (384 ms) and completely normal ST segments and T-waves. An echocardiogram (echo) revealed an ejection fraction (EF) 20% with globally decreased function; an echo from 1 year previous showed an EF of 70%. A dopamine drip was started that was titrated to 15 mcg/kg/min; after 6 hours it was weaned off. Troponin I peaked at 0.085 ng/ml (99% reference, 0.034). An echo after the patient was extubated revealed no significant changes from his baseline.
Discussion: Fosphenytoin is a water-soluble molecule developed to address some of the undesirable effects of phenytoin, including impaired myocardial contractility, decreased peripheral vascular resistance and depressed myocardial conduction. Despite the lack of propylene glycol, cardiovascular complications have also been described with rapid and/or supratherapeutic IV administration of fosphenytoin. Our case is unique, however, in that cardiogenic shock occurred despite a therapeutic dose at the recommended rate of 150 PE/min. While a prevailing theory is toxicity from fast cardiac sodium channel blockade, in our case QRS widening was not observed on ECG, making another uncertain mechanism more plausible. With no evidence of focal ischemia on ECG or echo, our patient's CAD is very unlikely to have contributed to his cardiogenic shock, however it is conceivable his antihypertensives may have rendered him more susceptible.
Conclusion: IV fosphenytoin can result in bradycardia, hypotension, and cardiogenic shock. Providers who administer IV fosphenytoin should be aware of these rare but life-threatening side effects.