Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD, 21287, USA.
Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, USA.
Crit Care. 2018 Jun 7;22(1):153. doi: 10.1186/s13054-018-2066-1.
The incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting. When a new anticonvulsant is initiated, drug factors, such as onset of action and side effects, and patient factors, such as age, renal, and hepatic function, should be taken into account. It is important to note that the altered physiology of critically ill patients as well as pharmacological and nonpharmacological interventions such as renal replacement therapy, extracorporeal membrane oxygenation, and target temperature management may lead to therapeutic failure or toxicity. This may be even more challenging with the availability of newer antiepileptics where the evidence for their use in critically ill patients is limited.
This article reviews the pharmacokinetics and pharmacodynamics of antiepileptics as well as application of these principles when dosing antiepileptics and monitoring serum levels in critically ill patients. The selection of the most appropriate anticonvulsant to treat seizure and status epileptics as well as the prophylactic use of these agents in this setting are also discussed. Drug-drug interactions and the effect of nonpharmacological interventions such as renal replacement therapy, plasma exchange, and extracorporeal membrane oxygenation on anticonvulsant removal are also included.
Optimal management of antiepileptic drugs in the intensive care unit is challenging given altered physiology, polypharmacy, and nonpharmacological interventions, and requires a multidisciplinary approach where appropriate and timely assessment, diagnosis, treatment, and monitoring plans are in place.
重症监护病房中癫痫发作的发生率为 3.3%至 34%。因此,在此情况下经常需要开始或继续使用抗癫痫药物。当开始使用新的抗癫痫药物时,应考虑药物因素,如作用开始时间和副作用,以及患者因素,如年龄、肾功能和肝功能。需要注意的是,危重症患者的生理学改变以及肾替代治疗、体外膜氧合和目标温度管理等药理学和非药理学干预可能导致治疗失败或毒性。对于新的抗癫痫药物,由于其在危重症患者中的使用证据有限,情况可能更加具有挑战性。
本文综述了抗癫痫药物的药代动力学和药效动力学,以及在危重症患者中给药和监测血清水平时应用这些原则的情况。还讨论了选择最合适的抗癫痫药物来治疗癫痫发作和癫痫持续状态,以及在这种情况下预防性使用这些药物。还包括药物相互作用以及肾替代治疗、血浆置换和体外膜氧合等非药理学干预对抗癫痫药物清除的影响。
鉴于生理学改变、多种药物治疗和非药理学干预,重症监护病房中抗癫痫药物的最佳管理具有挑战性,需要采取多学科方法,在适当和及时的评估、诊断、治疗和监测计划的基础上进行。