Ketamine and Levetiracetam as Second-line Antiseizure Medication for Status Epilepticus in Children

Generalized convulsive status epilepticus (GCSE) is the most common pediatric neurological emergency. Benzodiazepines (BDZs) are the recommended first-line anti-seizure medication (ASM) for GCSE, but they fail to halt seizures in about 40% of cases. Moreover, approximately 50% of BDZ-refractory GCSE are not terminated by second-line ASMs, including levetiracetam, valproate, and phenytoin. Continuous GCSE for a longer duration is associated with progressive brain injury and a higher risk of mortality, epilepsy, and permanent neurodevelopmental impairment. Therefore, early control of GCSE is pivotal for improving patients' outcomes.

A potential approach for early control of GCSE is the use of early ASM polytherapy. Ketamine is a promising option to be combined with standard ASMs for more rapid control of seizures. Ketamine has been used for decades for pediatric procedural analgosedation due to its excellent safety profile and wide therapeutic index. Ketamine works as a noncompetitive antagonist for N-methyl-D-aspartate (NMDA) receptors, which are progressively upregulated by way of receptor trafficking during ongoing seizure activity. Ketamine administration is associated with termination or attenuation of refractory SE (RSE) and super-refractory SE (SRSE). Multiple observational studies have reported the efficacy of ketamine in the pre-hospital emergency treatment of BZD-refractory status epilepticus. Furthermore, the recently published Ket-Mid study demonstrated that the ketamine-midazolam combination was more effective than midazolam alone in the initial treatment of pediatric GCSE. However, the value of combining ketamine with levetiracetam for the treatment of BZD-refractory status epilepticus has not been well investigated.

The present study (Ketamine and Levetiracetam as Second-line antiseizure medication for Status Epilepticus in Children, KLaSSEC) aims to investigate the efficacy of ketamine-levetiracetam combination vs. levetiracetam alone for treating children with BDZ-refractory GCSE. The findings could help earlier control of seizures and better clinical outcomes for children with status epilepticus

• Number of participants with cessation of seizures at 5-minute [Срок оценки: 5 minutes]
• Number of participants with sustained cessation of seizures [Срок оценки: From 20 minutes to 60 minutes]
• Number of participants with recurrence of seizures [Срок оценки: From 20 minutes to 4 hours]
• Number of participants underwent endotracheal intubation [Срок оценки: 60 minutes]
• Number of participants with severe hypotension [Срок оценки: 60 minutes]
• Number of participants with severe hypertension [Срок оценки: 60 minutes]
• Number of participants with severe cardiac arrhythmia [Срок оценки: 60 minutes]
• Number of participants with emergence reactions [Срок оценки: 4 hours]
• Number of participants admitted to Pediatric Intensive Care Unit [Срок оценки: 24 hours]
• Mortality [Срок оценки: 24 hours]