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Japanese guidelines for treatment of pediatric status epilepticus - 2023
Kenjiro Kikuchi1, Ichiro Kuki2, Masahiro Nishiyama3
1Working Group for the Revision of Treatment Guidelines for Pediatric Status Epilepticus/Convulsive Status Epilepticus, Japanese Society of Child Neurology, Tokyo, Japan; Division of Neurology, Pediatric Epilepsy Center, Saitama Children 's Medical Center, Saitama, Japan.
Insights
The updated Japanese guidelines recommend buccal midazolam for pre-hospital and in-hospital pediatric status epilepticus (SE) treatment. Intravenous benzodiazepines are preferred if possible, with lorazepam showing fewer respiratory issues than diazepam.
Area of Science:
- Neurology
- Pediatric Epilepsy
- Clinical Guidelines
Background:
- The 2015 International League Against Epilepsy definition of status epilepticus (SE) emphasized early treatment.
- Clinical challenges persist in Japan regarding appropriate drug selection for pediatric SE.
- A revised guideline, "Japanese Guidelines for the Treatment of Pediatric Status Epilepticus 2023" (GL2023), addresses these concerns.
Purpose of the Study:
- To provide updated recommendations for the treatment of pediatric status epilepticus in Japan.
- To clarify drug choices for pre-hospital and in-hospital management of SE.
- To address emerging clinical issues in pediatric SE treatment.
Main Methods:
- Review and synthesis of current evidence and clinical practices for pediatric SE.
- Development of evidence-based recommendations for drug selection and treatment strategies.
- Inclusion of specific recommendations for different treatment settings (pre-hospital, in-hospital, established SE).
Main Results:
- Buccal midazolam is recommended for pre-hospital treatment and when intravenous access is unavailable in-hospital.
- Intravenous benzodiazepines (midazolam, lorazepam, diazepam) are recommended if intravenous access is obtainable.
- Lorazepam demonstrated a lower incidence of respiratory depression compared to diazepam, with similar seizure cessation rates.
- Phenytoin/fosphenytoin and phenobarbital are options for established pediatric SE; levetiracetam is restricted to adults in Japan.
- Coma therapy is recommended for refractory SE, but no specific treatment is recommended for super-refractory SE.
- The guideline acknowledges a lack of recommendations for nonconvulsive SE (NCSE) in children.
Conclusions:
- GL2023 provides updated guidance for pediatric SE treatment in Japan, prioritizing buccal midazolam and intravenous benzodiazepines.
- The guidelines highlight the comparative safety profiles of different benzodiazepines.
- Further research is needed to establish effective treatments and improve outcomes for pediatric nonconvulsive SE.
Abstract:
The updated definition of status epilepticus (SE) by the International League Against Epilepsy in 2015 included two critical time points (t1: at which the seizure should be regarded as an "abnormally prolonged seizure"; and t2: beyond which the ongoing seizure activity can pose risk of long-term consequences) to aid in diagnosis and management and highlights the importance of early treatment of SE more clearly than ever before. Although Japan has witnessed an increasing number of pre-hospital drug treatment as well as first- and second-line treatments, clinical issues have emerged regarding which drugs are appropriate. To address these clinical concerns, a revised version of the "Japanese Guidelines for the Treatment of Pediatric Status Epilepticus 2023" (GL2023) was published. For pre-hospital treatment, buccal midazolam is recommended. For in-hospital treatment, if an intravenous route is unobtainable, buccal midazolam is also recommended. If an intravenous route can be obtained, intravenous benzodiazepines such as midazolam, lorazepam, and diazepam are recommended. However, the rates of seizure cessation were reported to be the same among the three drugs, but respiratory depression was less frequent with lorazepam than with diazepam. For established SE, phenytoin/fosphenytoin and phenobarbital can be used for pediatric SE, and levetiracetam can be used in only adults in Japan. Coma therapy is recommended for refractory SE, with no recommended treatment for super-refractory SE. GL2023 lacks adequate recommendations for the treatment of nonconvulsive status epilepticus (NCSE). Although electrographic seizure and electrographic SE may lead to brain damages, it remains unclear whether treatment of NCSE improves outcomes in children. We plan to address this issue in an upcoming edition of the guideline.
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