Pharmacotherapy for Nonconvulsive Seizures and Nonconvulsive Status Epilepticus

Most seizures in critically ill patients are nonconvulsive. A significant number of neurological and medical conditions can be complicated by nonconvulsive seizures (NCSs) and nonconvulsive status epilepticus (NCSE), with brain infections, hemorrhages, global hypoxia, sepsis, and recent neurosurgery being the most prominent etiologies. Prolonged NCSs and NCSE can lead to adverse neurological outcomes. Early recognition requires a high degree of suspicion and rapid and appropriate duration of continuous electroencephalogram (cEEG) monitoring. Although high quality research evaluating treatment with antiseizure medications and long-term outcome is still lacking, it is probable that expeditious pharmacological management of NCSs and NCSE may prevent refractoriness and further neurological injury. There is limited evidence on pharmacotherapy for NCSs and NCSE, although a few clinical trials encompassing both convulsive and NCSE have demonstrated similar efficacy of different intravenous (IV) antiseizure medications (ASMs), including levetiracetam, valproate, lacosamide and fosphenytoin. The choice of specific ASMs lies on tolerability and safety since critically ill patients frequently have impaired renal and/or hepatic function as well as hematological/hemodynamic lability. Treatment frequently requires more than one ASM and occasionally escalation to IV anesthetic drugs. When multiple ASMs are required, combining different mechanisms of action should be considered. There are several enteral ASMs that could be used when IV ASM options have been exhausted. Refractory NCSE is not uncommon, and its treatment requires a very judicious selection of ASMs aiming at reducing seizure burden along with management of the underlying condition.