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Year : 2023  |  Volume : 10  |  Issue : 1  |  Page : 3-4

Choice of antiepileptic in benzodiazepines refractory convulsive status epilepticus in children

1 Department of Pediatrics and Intensive Care, INHS Asvini, Mumbai, Maharashtra, India
2 Department of Pediatrics, INHS Asvini, Mumbai, Maharashtra, India

Date of Submission12-Dec-2022
Date of Acceptance19-Dec-2022
Date of Web Publication20-Jan-2023

Correspondence Address:
Dr. Bal Mukund
Department of Pediatrics and Intensive Care, INHS Asvini, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcc.jpcc_97_22

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How to cite this article:
Mukund B, Bhat V. Choice of antiepileptic in benzodiazepines refractory convulsive status epilepticus in children. J Pediatr Crit Care 2023;10:3-4

How to cite this URL:
Mukund B, Bhat V. Choice of antiepileptic in benzodiazepines refractory convulsive status epilepticus in children. J Pediatr Crit Care [serial online] 2023 [cited 2023 Mar 24];10:3-4. Available from: http://www.jpcc.org.in/text.asp?2023/10/1/3/368240

Acute seizure and status epilepticus (SE) constitute one of the major medical emergencies in children. The incidence in developing countries is higher than developed countries because of infections.[1] The definition of SE is based on the duration of seizures, the operational definition is to treat any child who is brought seizering to the emergency room, as SE. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic–clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. Robust data are yet not available for other forms of seizures with time points.[2] To avoid associated mortality and morbidity, timely termination of convulsive SE is the primary goal in the management. Time points (t2) if known may guide us to treat aggressively if SE crosses this time point to prevent long-term consequences.

Currently benzodiazepines namely, lorazepam, midazolam, or diazepam is used as first-line agent to terminate SE.[3] After failure of benzodiazepines in 40%–60% of convulsive SEs, phenytoin has been recommended since 1970s.[4] Current guidelines recommend phenytoin, levetiracetam, and valproate for the management of benzodiazepines refractory SE. Recently, the Indian academy of pediatrics guidelines on evaluation and management of SE-2022 has recommended the first line – injection of benzodiazepines and second line – intravenous (i. v) phenytoin or fosphenytoin 20 mg/kg of phenytoin equivalent at 3 mg/kg/min, if seizures persists then either i. v levetiracetam or i. v phenobarbitone or i. v valproate, followed by general anesthesia to achieve burst suppression. The systemic side effects of phenytoin such as hypotension, arrhythmia, or phlebitis are not seen with levetiracetam; however, their safety and efficacy in SE in children have been limited. A recent meta-analysis of seven trials with 1028 participants of levetiracetam versus phenytoin in established SE in children and adults concluded that levetiracetam was not significantly superior in seizure cessation in patients with established SE.[5]

In the current issue of the Journal of Pediatric Critical Care, Anupama et al. compared levetiracetam with fosphenytoin as a second-line drug in convulsive SE in children.[6] It is an open-label randomized controlled trial from a single tertiary care institute from south India. It was a Clinical Trial Registry of India registered trial between 1 month and 12 years of age. It was a simple randomization in 100 patients. Both drugs were used in standard dosage and primary outcomes were measured in the next 20 min. The seizure control was similar in both groups, the mean time for control in the fosphenytoin group was 11.16 + 3.58 min and in the leviteracetam group was 12.78 + 3.07 min (P = 0.059). Similarly, seizure recurrence and time to seizure recurrences were similar. In the secondary outcome, side effects and mean time to regain full sensorium were similar. Similarly, the duration of pediatric intensive care unit stay and mortality were not statistically significant. The authors found similar results as mentioned in other similar studies quoted in discussion. The limitations of this study are open-label single-center study with simple randomization, slow delivery of levetiracetam over 20 min instead of 5 min, and lack of electroencephalogram usage during the study. A meta-analysis published recently also failed to depict the superiority of levetiracetam over fosphenytoin.[5] A large multicentric study with robust design and in varied etiological profiles may give a better insight in future.

  References Top

Sasidaran K, Singhi S, Singhi P. Management of acute seizure and status epilepticus in pediatric emergency. Indian J Pediatr 2012;79:510-7.  Back to cited text no. 1
Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus – Report of the ILAE task force on classification of status epilepticus. Epilepsia 2015;56:1515-23.  Back to cited text no. 2
Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, et al. Evidence-based guideline: Treatment of convulsive status epilepticus in children and adults: Report of the guideline committee of the American epilepsy society. Epilepsy Curr 2016;16:48-61.  Back to cited text no. 3
Brigo F, Bragazzi NL, Lattanzi S, Nardone R, Trinka E. A critical appraisal of randomized controlled trials on intravenous phenytoin in convulsive status epilepticus. Eur J Neurol 2018;25:451-63.  Back to cited text no. 4
Li L, Zhang Y, Jia L, Jia D, Faramand A, Chong W, et al. Levetiracetam versus phenytoin for the treatment of established status epilepticus: A systematic review and meta-analysis of randomized controlled trials. Seizure 2020;78:43-8.  Back to cited text no. 5
Anupama S, Poovazhagi V, Nisha R, Suresh Kumar S, Sathya J. Comparison of levetiracetam as second-line drug with fosphenytoin in convulsive status epilepticus among children: A single center, open-label randomized controlled trial. J Pediatr Crit Care 2023;10:18-23.  Back to cited text no. 6
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