Skip to main content

Anticonvulsive Drug Use in Status Treatment in Children

  • Living reference work entry
  • First Online:
NeuroPsychopharmacotherapy

Abstract

Status epilepticus is one of the most common life-threatening neurological emergencies in childhood with a mortality rate of up to 3%. Treatment becomes more difficult as a status epilepticus continues indicating the importance of early effective therapeutic approaches. Management guidelines for the pediatric population often rely on expert opinions, and only few randomized-controlled trials (RCT) exist. Here, we summarize the current data on treatment of a convulsive status epilepticus in childhood and propose a treatment algorithm.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Abend NS, Dlugos DJ. Treatment of refractory status epilepticus: literature review and a proposed protocol. Pediatr Neurol. 2008;38(6):377–90.

    Article  PubMed  Google Scholar 

  • Abend NS, Bearden D, Helbig I, McGuire J, Narula S, Panzer JA, et al. Status epilepticus and refractory status epilepticus management. Semin Pediatr Neurol. 2014;21(4):263–74.

    Article  PubMed  PubMed Central  Google Scholar 

  • Agarwal P, Kumar N, Chandra R, Gupta G, Antony AR, Garg N. Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure. 2007;16(6):527–32.

    Article  PubMed  Google Scholar 

  • Appavu B, Vanatta L, Condie J, Kerrigan JF, Jarrar R. Ketogenic diet treatment for pediatric super-refractory status epilepticus. Seizure. 2016;41:62–5.

    Article  PubMed  Google Scholar 

  • Appleton R, Sweeney A, Choonara I, Robson J, Molyneux E. Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. Dev Med Child Neurol. 1995;37(8):682–8.

    Article  CAS  PubMed  Google Scholar 

  • Appleton R, Choonara I, Martland T, Phillips B, Scott R, Whitehouse W. The treatment of convulsive status epilepticus in children. The status epilepticus working party, members of the status epilepticus working party. Arch Dis Child. 2000;83(5):415–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Appleton R, Macleod S, Martland T. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev. 2008;3:CD001905.

    Google Scholar 

  • Brigo F, Nardone R, Tezzon F, Trinka E. Nonintravenous midazolam versus intravenous or rectal diazepam for the treatment of early status epilepticus: a systematic review with meta-analysis. Epilepsy Behav EB. 2015;49:325–36.

    Article  Google Scholar 

  • Brigo F, Bragazzi NL, Bacigaluppi S, Nardone R, Trinka E. Is intravenous lorazepam really more effective and safe than intravenous diazepam as first-line treatment for convulsive status epilepticus? A systematic review with meta-analysis of randomized controlled trials. Epilepsy Behav EB. 2016;64(Pt A):29–36.

    Article  Google Scholar 

  • Brigo F, Lattanzi S, Nardone R, Trinka E. Intravenous Brivaracetam in the treatment of status epilepticus: a systematic review. CNS Drugs. 2019;33(8):771–81.

    Article  CAS  PubMed  Google Scholar 

  • Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3–23.

    Article  PubMed  Google Scholar 

  • Capovilla G, Beccaria F, Beghi E, Minicucci F, Sartori S, Vecchi M. Treatment of convulsive status epilepticus in childhood: recommendations of the Italian League Against Epilepsy. Epilepsia. 2013;54(Suppl 7):23–34.

    Article  CAS  PubMed  Google Scholar 

  • Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y. A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care. 1997;13(2):92–4.

    Article  CAS  PubMed  Google Scholar 

  • Chin RFM, Neville BGR, Peckham C, Bedford H, Wade A, Scott RC, et al. Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet Lond Engl. 2006;368(9531):222–9.

    Article  Google Scholar 

  • Crawford TO, Mitchell WG, Fishman LS, Snodgrass SR. Very-high-dose phenobarbital for refractory status epilepticus in children. Neurology. 1988;38(7):1035–40.

    Article  PubMed  Google Scholar 

  • Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet Lond Engl. 2019;393(10186):2135–45.

    Article  CAS  Google Scholar 

  • DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 1996;46(4):1029–35.

    Article  CAS  PubMed  Google Scholar 

  • Dham BS, Hunter K, Rincon F. The epidemiology of status epilepticus in the United States. Neurocrit Care. 2014;20(3):476–83.

    Article  PubMed  Google Scholar 

  • Elia M, Klepper J, Leiendecker B, Hartmann H. Ketogenic diets in the treatment of epilepsy. Curr Pharm Des. 2017;23(37):5691–701.

    Article  CAS  PubMed  Google Scholar 

  • Fişgin T, Gurer Y, Teziç T, Senbil N, Zorlu P, Okuyaz C, et al. Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. J Child Neurol. 2002;17(2):123–6.

    Article  PubMed  Google Scholar 

  • Gaínza-Lein M, Sánchez Fernández I, Jackson M, Abend NS, Arya R, Brenton JN, et al. Association of time to treatment with short-term outcomes for pediatric patients with refractory convulsive status epilepticus. JAMA Neurol. 2018;75(4):410–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gaspard N, Hirsch LJ, Sculier C, Loddenkemper T, van Baalen A, Lancrenon J, et al. New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES): state of the art and perspectives. Epilepsia. 2018;59(4):745–52.

    Article  PubMed  Google Scholar 

  • Gathwala G, Goel M, Singh J, Mittal K. Intravenous diazepam, midazolam and lorazepam in acute seizure control. Indian J Pediatr. 2012;79(3):327–32.

    Article  PubMed  Google Scholar 

  • Giang DW, McBride MC. Lorazepam versus diazepam for the treatment of status epilepticus. Pediatr Neurol. 1988;4(6):358–61.

    Article  CAS  PubMed  Google Scholar 

  • Gilad R, Izkovitz N, Dabby R, Rapoport A, Sadeh M, Weller B, et al. Treatment of status epilepticus and acute repetitive seizures with i.v. valproic acid vs phenytoin. Acta Neurol Scand. 2008;118(5):296–300.

    Article  CAS  PubMed  Google Scholar 

  • 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(1):48–61.

    Article  PubMed  PubMed Central  Google Scholar 

  • Höfler J, Rohracher A, Kalss G, Zimmermann G, Dobesberger J, Pilz G, et al. (S)-Ketamine in refractory and super-refractory status epilepticus: a retrospective study. CNS Drugs. 2016;30(9):869–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Holsti M, Sill BL, Firth SD, Filloux FM, Joyce SM, Furnival RA. Prehospital intranasal midazolam for the treatment of pediatric seizures. Pediatr Emerg Care. 2007;23(3):148–53.

    Article  PubMed  Google Scholar 

  • Kadel J, Bauer S, Hermsen AM, Immisch I, Kay L, Klein KM, et al. Use of emergency medication in adult patients with epilepsy: a multicentre cohort study from Germany. CNS Drugs. 2018;32(8):771–81.

    Article  PubMed  Google Scholar 

  • Kellinghaus C, Lang N, Rossetti AO, Rüegg S, Tilz C, Trinka E, et al. Making SENSE–sustained effort network for treatment of status epilepticus as a multicenter prospective registry. BMC Neurol. 2015;15:230.

    Article  PubMed  PubMed Central  Google Scholar 

  • Koo CM, Kang H-C. Could Cannabidiol be a treatment option for intractable childhood and adolescent epilepsy? J Epilepsy Res. 2017;7(1):16–20.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lang N, Lange M, Schmitt FC, Bös M, Weber Y, Evers S, et al. Intravenous lacosamide in clinical practice-results from an independent registry. Seizure. 2016;39:5–9.

    Article  PubMed  Google Scholar 

  • Lee WK, Liu KT, Young BWY. Very-high-dose phenobarbital for childhood refractory status epilepticus. Pediatr Neurol. 2006;34(1):63–5.

    Article  PubMed  Google Scholar 

  • Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet Lond Engl. 2019;393(10186):2125–34.

    Article  CAS  Google Scholar 

  • Malamiri RA, Ghaempanah M, Khosroshahi N, Nikkhah A, Bavarian B, Ashrafi MR. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. 2012;16(5):536–41.

    Article  Google Scholar 

  • Maytal J, Shinnar S, Moshé SL, Alvarez LA. Low morbidity and mortality of status epilepticus in children. Pediatrics. 1989;83(3):323–31.

    CAS  PubMed  Google Scholar 

  • McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet Lond Engl. 2005;366(9481):205–10.

    Article  CAS  Google Scholar 

  • McMullan J, Sasson C, Pancioli A, Silbergleit R. Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis. Acad Emerg Med Off J Soc Acad Emerg Med. 2010;17(6):575–82.

    Article  Google Scholar 

  • McTague A, Martland T, Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev. 2018a;10(1):CD001905.

    Google Scholar 

  • McTague A, Martland T, Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev. 2018b;10(1):CD001905.

    Google Scholar 

  • Meurer WJ, Silbergleit R, Nicholas KS, Burke JF, Durkalski V. Accounting for repeat enrollments during an emergency clinical trial: the Rapid Anticonvulsant Medications Prior to Arrival Trial (RAMPART). Acad Emerg Med Off J Soc Acad Emerg Med. 2015;22(3):373–7.

    Article  Google Scholar 

  • Misra UK, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus: a pilot study. Neurology. 2006;67(2):340–2.

    Article  CAS  PubMed  Google Scholar 

  • Mpimbaza A, Ndeezi G, Staedke S, Rosenthal PJ, Byarugaba J. Comparison of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children: a randomized clinical trial. Pediatrics. 2008;121(1):e58–64.

    Article  PubMed  Google Scholar 

  • Ngampoopun M, Suwanpakdee P, Jaisupa N, Nabangchang C. Effectiveness and adverse effect of intravenous Lacosamide in nonconvulsive status epilepticus and acute repetitive seizures in children. Neurol Res Int. 2018;2018:8432859.

    Article  PubMed  PubMed Central  Google Scholar 

  • Noureen N, Khan S, Khursheed A, Iqbal I, Maryam M, Sharib SM, et al. Clinical efficacy and safety of injectable Levetiracetam versus phenytoin as second-line therapy in the management of generalized convulsive status epilepticus in children: an open-label randomized controlled trial. J Clin Neurol Seoul Korea. 2019;15(4):468–72.

    Article  Google Scholar 

  • Rajaraman RR, Sankar R, Hussain SA. Successful use of pure cannabidiol for the treatment of super-refractory status epilepticus. Epilepsy Behav Case Rep. 2018;10:141–4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Raspall-Chaure M, Chin RFM, Neville BG, Scott RC. Outcome of paediatric convulsive status epilepticus: a systematic review. Lancet Neurol. 2006;5(9):769–79.

    Article  PubMed  Google Scholar 

  • Riviello JJ, Claassen J, LaRoche SM, Sperling MR, Alldredge B, Bleck TP, et al. Treatment of status epilepticus: an international survey of experts. Neurocrit Care. 2013;18(2):193–200.

    Article  PubMed  Google Scholar 

  • Rosati A, Ilvento L, L’Erario M, De Masi S, Biggeri A, Fabbro G, et al. Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01). BMJ Open. 2016;6(6):e011565.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sánchez Fernández I, Vendrame M, Kapur K, Klehm J, Uysal S, Gedik M, et al. Comparison of pediatric patients with status epilepticus lasting 5-29 min versus ≥30 min. Epilepsy Behav EB. 2014;37:1–6.

    Article  Google Scholar 

  • Sánchez Fernández I, Gaínza-Lein M, Loddenkemper T. Nonintravenous rescue medications for pediatric status epilepticus: a cost-effectiveness analysis. Epilepsia. 2017;58(8):1349–59.

    Article  PubMed  CAS  Google Scholar 

  • Sánchez Fernández I, Gaínza-Lein M, Abend NS, Anderson AE, Arya R, Brenton JN, et al. Factors associated with treatment delays in pediatric refractory convulsive status epilepticus. Neurology. 2018;90(19):e1692–701.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sánchez Fernández I, Goodkin HP, Scott RC. Pathophysiology of convulsive status epilepticus. Seizure. 2019;68:16–21.

    Article  PubMed  Google Scholar 

  • Santamarina E, Parejo Carbonell B, Sala J, Gutiérrez-Viedma Á, Miró J, Asensio M, et al. Use of intravenous brivaracetam in status epilepticus: a multicenter registry. Epilepsia. 2019;60(8):1593–601.

    Article  CAS  PubMed  Google Scholar 

  • Schubert-Bast S, Zöllner JP, Ansorge S, Hapfelmeier J, Bonthapally V, Eldar-Lissai A, et al. Burden and epidemiology of status epilepticus in infants, children, and adolescents: a population-based study on German health insurance data. Epilepsia. 2019;60(5):911–20.

    Article  PubMed  Google Scholar 

  • Scott LJ, Lyseng-Williamson KA, Garnock-Jones KP. Oromucosal midazolam: a guide to its use in paediatric patients with prolonged acute convulsive seizures. CNS Drugs. 2012;26(10):893–7.

    Article  CAS  PubMed  Google Scholar 

  • Seinfeld S, Shinnar S, Sun S, Hesdorffer DC, Deng X, Shinnar RC, et al. Emergency management of febrile status epilepticus: results of the FEBSTAT study. Epilepsia. 2014;55(3):388–95.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shah I, Deshmukh CT. Intramuscular midazolam vs intravenous diazepam for acute seizures. Indian J Pediatr. 2005;72(8):667–70.

    Article  PubMed  Google Scholar 

  • Silbergleit R, Lowenstein D, Durkalski V, Conwit R, NETT Investigators. Lessons from the RAMPART study--and which is the best route of administration of benzodiazepines in status epilepticus. Epilepsia. 2013;54(Suppl 6):74–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh RK, Stephens S, Berl MM, Chang T, Brown K, Vezina LG, et al. Prospective study of new-onset seizures presenting as status epilepticus in childhood. Neurology. 2010;74(8):636–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh A, Stredny CM, Loddenkemper T. Pharmacotherapy for pediatric convulsive status epilepticus. CNS Drugs. 2020;34(1):47–63.

    Article  CAS  PubMed  Google Scholar 

  • Smith DM, McGinnis EL, Walleigh DJ, Abend NS. Management of Status Epilepticus in children. J Clin Med. 2016;5(4)

    Google Scholar 

  • Sreenath TG, Gupta P, Sharma KK, Krishnamurthy S. Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: a randomized controlled trial. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. 2010;14(2):162–8.

    Article  CAS  Google Scholar 

  • Stewart WA, Harrison R, Dooley JM. Respiratory depression in the acute management of seizures. Arch Dis Child. 2002;87(3):225–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strzelczyk A, Zöllner JP, Willems LM, Jost J, Paule E, Schubert-Bast S, et al. Lacosamide in status epilepticus: systematic review of current evidence. Epilepsia. 2017;58(6):933–50.

    Article  CAS  PubMed  Google Scholar 

  • Strzelczyk A, Kay L, Bauer S, Immisch I, Klein KM, Knake S, et al. Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus. Epilepsia. 2018;59(8):1549–56.

    Article  CAS  PubMed  Google Scholar 

  • Tasker RC, Vitali SH. Continuous infusion, general anesthesia and other intensive care treatment for uncontrolled status epilepticus. Curr Opin Pediatr. 2014;26(6):682–9.

    Article  CAS  PubMed  Google Scholar 

  • Tiamkao S, Mayurasakorn N, Suko P, Jitpimolmard S, Arunpongpaisal S, Phuttharak W, et al. Very high dose phenobarbital for refractory status epilepticus. J Med Assoc Thail Chotmaihet Thangphaet. 2007;90(12):2597–600.

    Google Scholar 

  • 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(10):1515–23.

    Article  PubMed  Google Scholar 

  • Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super-refractory status epilepticus. Seizure. 2019;68:62–71.

    Article  PubMed  Google Scholar 

  • Watanabe S, Okumura Y, Aiba H. A case of acute encephalitis with refractory repetitive partial seizures successfully controlled by very-high-dose phenobarbital therapy found in a boy. No Hattatsu Brain Dev. 2014;46(6):443–6.

    Google Scholar 

  • Wilkes R, Tasker RC. Pediatric intensive care treatment of uncontrolled status epilepticus. Crit Care Clin. 2013;29(2):239–57.

    Article  PubMed  Google Scholar 

  • Wu YW, Shek DW, Garcia PA, Zhao S, Johnston SC. Incidence and mortality of generalized convulsive status epilepticus in California. Neurology. 2002;58(7):1070–6.

    Article  CAS  PubMed  Google Scholar 

  • Yoshikawa H, Yamazaki S, Abe T, Oda Y. Midazolam as a first-line agent for status epilepticus in children. Brain and Development. 2000;22(4):239–42.

    Article  CAS  PubMed  Google Scholar 

  • Zeiler FA, Zeiler KJ, Teitelbaum J, Gillman LM, West M. Modern inhalational anesthetics for refractory status epilepticus. Can J Neurol Sci J Can Sci Neurol. 2015;42(2):106–15.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Angela M. Kaindl .

Editor information

Editors and Affiliations

Section Editor information

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Kaindl, A.M., Gratopp, A., Prager, C. (2020). Anticonvulsive Drug Use in Status Treatment in Children. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_373-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-56015-1_373-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56015-1

  • Online ISBN: 978-3-319-56015-1

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics