Skip to main content
SpringerLink
Log in

Pediatric Status Epilepticus: Treat Early and Avoid Delays

  • Review Article
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Pediatric convulsive status epilepticus (cSE) is a neurologic emergency with potential for morbidity and mortality. Rapid treatment and escalation of therapies to achieve early seizure control is paramount in preventing complications and providing the best patient outcomes. Although guidelines recommend early treatment, cessation of out-of-hospital SE is undermined by treatment delay and inadequate dosing. Logistical challenges include prompt seizure recognition, first-line benzodiazepine (BZD) availability, comfort and expertise in administration of BZD, and timely arrival of emergency personnel. In-hospital, SE onset is additionally impacted by delays to first- and second-line treatment and availability of resources. This review presents an evidence-based, clinically oriented review of pediatric cSE, including its definitions and treatments. It provides evidence and rationale for timely treatment of first-line BZD treatment followed by prompt escalation to second-line antiseizure medication therapies for established SE. Treatment delays and barriers to care are discussed, with practical considerations for opportunities for areas of improvement in the initial treatment of cSE.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Chin RF, Neville BG, Peckham C, et al. Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet. 2006;368(9531):222–9. https://doi.org/10.1016/S0140-6736(06)69043-0.

    Article  PubMed  Google Scholar 

  2. DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 1996;46(4):1029–35. https://doi.org/10.1212/WNL.46.4.1029.

    Article  CAS  PubMed  Google Scholar 

  3. Pallin DJ, Goldstein JN, Moussally JS, et al. Seizure visits in US emergency departments: epidemiology and potential disparities in care. Int J Emerg Med. 2008;1(2):97–105. https://doi.org/10.1007/s12245-008-0024-4.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sánchez Fernández I, Amengual-Gual M, Barcia Aguilar C, et al. Descriptive epidemiology and health resource utilization for status epilepticus in the emergency department in the United States of America. Seizure. 2012;87:7–16. https://doi.org/10.1016/j.seizure.2021.02.020.

    Article  Google Scholar 

  5. DeLorenzo RJ, Garnett LK, Towne AR, et al. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia. 1999. https://doi.org/10.1111/j.1528-1157.1999.tb02070.x.

    Article  PubMed  Google Scholar 

  6. Raspall-Chaure M, Chin RFM, Neville BG, et al. Outcome of paediatric convulsive status epilepticus: a systematic review. Lancet Neurol. 2006;5(9):769–79. https://doi.org/10.1016/S1474-4422(06)70546-4.

    Article  PubMed  Google Scholar 

  7. Glauser T, Shinnar S, Gloss D, 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. https://doi.org/10.5698/1535-7597-16.1.48.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Brophy GM, Bell R, Claasen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012. https://doi.org/10.1007/s12028-012-9695-z.

    Article  PubMed  Google Scholar 

  9. Shinnar S, Berg AT, Moshe SL, et al. How long do new-onset seizures in children last? Ann Neurol. 2001;49(5):659–64.

    Article  CAS  PubMed  Google Scholar 

  10. Goodkin HP, Kapur J. Responsiveness of status epilepticus to treatment with diazepan decreases rapidly as seizure duration increases. Epilepsy Curr. 2003;3(1):11–2. https://doi.org/10.1046/j.1535-7597.2003.03104.x.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sánchez Fernández I, Abend NS, Amengual-Gual M, et al. Association of guideline publication and delays to treatment in pediatric status epilepticus. Neurology. 2020. https://doi.org/10.1212/WNL.0000000000010174.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sanchez Fernandez I, Abend NS, Agadi S, et al. Time from convulsive status epilepticus onset to anticonvulsant administration in children. Neurology. 2015;84(23):2304–11. https://doi.org/10.1212/WNL.0000000000001673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Seinfeld S, Shinnar S, Sun S, et al. Emergency management of febrile status epilepticus: results of the FEBSTAT study. Epilepsia. 2014;55(3):388–95. https://doi.org/10.1111/epi.12526.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sheehan T, et al. Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus. Epilepsia. 2021;62(11):2766–77. https://doi.org/10.1111/epi.17043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vasquez A, Gaínza-Lein M, Abend NS, et al. First-line medication dosing in pediatric refractory status epilepticus. Neurology. 2020;95(19):e2683–96. https://doi.org/10.1212/WNL.0000000000010828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Vossler DG, Bainbridge JL, Boggs JG, et al. Treatment of refractory convulsive status epilepticus: a comprehensive review by the American Epilepsy Society Treatments Committee. Epilepsy Curr. 2020;20(5):245–64. https://doi.org/10.1177/1535759720928269.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ochoa JG, Dougherty M, Papanastassiou A, et al. Treatment of super-refractory status epilepticus: a review. Epilepsy Curr. 2021;21(6):1535759721999670. https://doi.org/10.1177/1535759721999670.

    Article  PubMed  Google Scholar 

  18. Chin RFM, Neville BGR, Scott RC. A systematic review of the epidemiology of status epilepticus. Eur J Neurol. 2004;11(12):800–10. https://doi.org/10.1111/j.1468-1331.2004.00943.x.

    Article  CAS  PubMed  Google Scholar 

  19. Chen JWY, Wasterlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol. 2006;5(3):246–56. https://doi.org/10.1016/S1474-4422(06)70374-X.

    Article  PubMed  Google Scholar 

  20. Sánchez Fernández I, Vendrame M, Kapur K, et al. Comparison of pediatric patients with status epilepticus lasting 5–29 min versus ≥ 30 min. Epilepsy Behav. 2014;37:1–6. https://doi.org/10.1016/j.yebeh.2014.05.018.

    Article  PubMed  Google Scholar 

  21. Pujar S, Scott RC. Long-term outcomes after childhood convulsive status epilepticus. Curr Opin Pediatr. 2019;31(6):763–8. https://doi.org/10.1097/MOP.0000000000000825.

    Article  PubMed  Google Scholar 

  22. Pujar SS, Martinos MM, Cortina-Borja M, et al. Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study. Lancet Child Adolesc Health. 2018;2(2):103–11. https://doi.org/10.1016/S2352-4642(17)30174-8.

    Article  PubMed  Google Scholar 

  23. Martinos MM, Pujar S, O’Reilly H, et al. Intelligence and memory outcomes within 10 years of childhood convulsive status epilepticus. Epilepsy Behav. 2019;95:18–25. https://doi.org/10.1016/j.yebeh.2019.03.039.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1981;22(4):489–501. https://doi.org/10.1111/j.1528-1157.1981.tb06159.x.

  25. Meldrum BS, Horton RW. Physiology of status epilepticus in primates. Arch Neurol. 1973;28(1):1–9. https://doi.org/10.1001/archneur.1973.00490190019001.

    Article  CAS  PubMed  Google Scholar 

  26. Joshi S, Goodkin HP. The need to intervene before time point 2: evidence from clinical and animal data that status epilepticus damages the brain. J Clin Neurophysiol. 2020;37(5):375–80. https://doi.org/10.1097/WNP.0000000000000711.

    Article  PubMed  Google Scholar 

  27. Lothman E. The biochemical basis and pathophysiology of status epilepticus. Neurology. 1990;40(5 Suppl 2):13–23.

    CAS  PubMed  Google Scholar 

  28. Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia. 1999;40(1):120–2. https://doi.org/10.1111/j.1528-1157.1999.tb02000.x.

    Article  CAS  PubMed  Google Scholar 

  29. Trinka E, Cock H, Hesdorffer D, 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. https://doi.org/10.1111/epi.13121.

    Article  PubMed  Google Scholar 

  30. Goodkin HP, Kapur J. The impact of diazepam’s discovery on the treatment and understanding of status epilepticus. Epilepsia. 2009;50(9):2011–8. https://doi.org/10.1111/j.1528-1167.2009.02257.x.

    Article  CAS  PubMed  Google Scholar 

  31. Deeb TZ, Maguire J, Moss SJ. Possible alterations in GABAA receptor signaling that underlie benzodiazepine-resistant seizures. Epilepsia. 2012;53(Suppl 9):79–88. https://doi.org/10.1111/epi.12037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rajasekaran K, Joshi S, Kozhemyakin M, et al. Receptor trafficking hypothesis revisited: plasticity of AMPA receptors during established status epilepticus. Epilepsia. 2013;54(Suppl 6):14–6. https://doi.org/10.1111/epi.12266.

    Article  PubMed  Google Scholar 

  33. Ferlisi M, Shorvon S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain. 2012;135(Pt 8):2314–28. https://doi.org/10.1093/brain/aws091.

    Article  PubMed  Google Scholar 

  34. Trinka E, Kälviäinen R. 25 years of advances in the definition, classification and treatment of status epilepticus. Seizure. 2017;44:65–73. https://doi.org/10.1016/j.seizure.2016.11.001.

    Article  PubMed  Google Scholar 

  35. Trinka E, Leitinger M. Management of status epilepticus, refractory status epilepticus, and super-refractory status epilepticus. Continuum Lifelong Learn Neurol. 2022;28(2):559–602. https://doi.org/10.1212/CON.0000000000001103.

    Article  Google Scholar 

  36. Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super-refractory status epilepticus. Seizure. 2019;68:62–71. https://doi.org/10.1016/j.seizure.2018.05.012.

    Article  PubMed  Google Scholar 

  37. National Institute for Health and Care Excellence (NICE). Epilepsies in children, young people and adults. London; NICE; 2022.

  38. Bacon M, Appleton R, Bangalore H, et al. Review of the new APLS guideline (2022): Management of the convulsing child. Arch Dis Child Educ Pract Ed. 2023;108(1):43–8. https://doi.org/10.1136/archdischild-2021-323351.

    Article  PubMed  Google Scholar 

  39. Lombroso CT. Treatment of status epilepticus with diazepam. Neurology. 1966;16(7):629–34. https://doi.org/10.1212/wnl.16.7.629.

    Article  CAS  PubMed  Google Scholar 

  40. Kapur J. Prehospital treatment of status epilepticus with benzodiazepines is effective and safe. Epilepsy Curr. 2002;2(4):121–4. https://doi.org/10.1046/j.1535-7597.2002.00045.x.

    Article  PubMed  PubMed Central  Google Scholar 

  41. McIntyre J, Robertson S, Norris E, et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet. 2005;366(9481):205–10. https://doi.org/10.1016/S0140-6736(05)66909-7.

    Article  CAS  PubMed  Google Scholar 

  42. Kapoor M, Cloyd JC, Siegel RA. A review of intranasal formulations for the treatment of seizure emergencies. J Control Release. 2016;237:147–59. https://doi.org/10.1016/j.jconrel.2016.07.001.

    Article  CAS  PubMed  Google Scholar 

  43. Tsze DS, Ieni M, Fenster DB, et al. Optimal volume of administration of intranasal midazolam in children: a randomized clinical trial. Ann Emerg Med. 2017;69(5):600–9. https://doi.org/10.1016/j.annemergmed.2016.08.450.

    Article  PubMed  Google Scholar 

  44. MAD Nasal Device Procedure Guide. Teleflex, IN. Morrisville, NC. https://teleflex.com/usa/en/product-areas/anesthesia/atomization/mad-nasal-device/AN_ATM_Anesthesia-MAD-Nasal-User-Guide_MC_MC-001925_Rev1.pdf#search='mad%20nasal%20device%20procedure%20guide. Accessed 17 Mar 2023.

  45. Valtoco Package Insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211635s000lbl.pdf. Accessed 17 Mar 2023.

  46. Getzoff N. Clinical Review NDA 211635 Valtoco (Diazepam nasal spray). Center for Drug Evaluation and Research; 2020. p. 1–49.

  47. Hogan RE, Gidal BE, Koplowitz B, et al. Bioavailability and safety of diazepam intranasal solution compared to oral and rectal diazepam in healthy volunteers. Epilepsia. 2020;61(3):455–64. https://doi.org/10.1111/epi.16449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. NAYZILAM® (midazolam) nasal spray, CIV n.d. https://www-accessdata-fda-gov.offcampus.lib.washington.edu/drugsatfda_docs/label/2019/211321s000lbl.pdf. Accessed 17 Mar 2023.

  49. Freilich ER. Clinical Review. NDA 211321 Nayzilam (Intranasal midazolam). Center for Drug Evaluation and Research; 2019. p. 1–89.

  50. Detyniecki K, van Ess PJ, Sequeira DJ, et al. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters—a randomized, double-blind, placebo-controlled trial. Epilepsia. 2019;60(9):1797–808. https://doi.org/10.1111/epi.15159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bouw MR, Chung SS, Gidal B, et al. Clinical pharmacokinetic and pharmacodynamic profile of midazolam nasal spray. Epilepsy Res. 2021;171: 106567. https://doi.org/10.1016/j.eplepsyres.2021.106567.

    Article  CAS  PubMed  Google Scholar 

  52. McTagueA, Martland T, Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev. 2018:(1):CD001905. https://doi.org/10.1002/14651858.CD001905.pub3.

  53. Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001;345(9):631–7. https://doi.org/10.1056/NEJMoa002141.

    Article  CAS  PubMed  Google Scholar 

  54. Chamberlain JM, Okada P, Holsti M, et al. Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial. JAMA. 2014;311(16):1652–60. https://doi.org/10.1001/jama.2014.2625.

    Article  CAS  PubMed  Google Scholar 

  55. Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366(7):591–600. https://doi.org/10.1056/NEJMoa1107494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mpimbaza A, Ndeezi G, Staedke S, et al. 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. https://doi.org/10.1542/peds.2007-0930.

    Article  PubMed  Google Scholar 

  57. Chhabra R, Gupta R, Gupta LK. Intranasal midazolam versus intravenous/rectal benzodiazepines for acute seizure control in children: a systematic review and meta-analysis. Epilepsy Behav. 2021;125: 108390. https://doi.org/10.1016/j.yebeh.2021.108390.

    Article  PubMed  Google Scholar 

  58. Zhao Z-Y, Wang H-Y, Wen B, et al. A comparison of midazolam, lorazepam, and diazepam for the treatment of status epilepticus in children: a network meta-analysis. J Child Neurol. 2016;31(9):1093–107. https://doi.org/10.1177/0883073816638757.

    Article  PubMed  Google Scholar 

  59. Chamberlain JM, Kapur J, Shinnar S, et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020;395(10231):1217–24. https://doi.org/10.1016/S0140-6736(20)30611-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dalziel SR, Borland ML, Furyk J, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (andomi): an open-label, multicentre, andomized controlled trial. Lancet. 2019;393(10186):2135–45. https://doi.org/10.1016/S0140-6736(19)30722-6.

    Article  CAS  PubMed  Google Scholar 

  61. Lyttle MD, Rainford NEA, Gamble C, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019;393(10186):2125–34. https://doi.org/10.1016/S0140-6736(19)30724-X.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Burman RJ, Ackermann S, Shapson-Coe A, et al. A comparison of parenteral phenobarbital vs. parenteral phenytoin as second-line management for pediatric convulsive status epilepticus in a resource-limited setting. Front Neurol. 2019. https://doi.org/10.3389/fneur.2019.00506.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Sánchez Fernández I, Gaínza-Lein M, Lamb N, et al. Meta-analysis and cost-effectiveness of second-line antiepileptic drugs for status epilepticus. Neurology. 2019;92(20):e2339–48. https://doi.org/10.1212/WNL.0000000000007503.

    Article  PubMed  Google Scholar 

  64. Malamiri RA, Ghaempanah M, Khosroshahi N, et al. 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. 2012;16(5):536–41. https://doi.org/10.1016/j.ejpn.2012.01.012.

    Article  PubMed  Google Scholar 

  65. Pellock JM. Treatment considerations: traditional antiepileptic drugs. Epilepsy Behav. 2002;3(6):18–23. https://doi.org/10.1016/S1525-5050(02)00538-3.

    Article  PubMed  Google Scholar 

  66. Garbovsky LA, Drumheller BC, Perrone J. Purple glove syndrome after phenytoin or fosphenytoin administration: review of reported cases and recommendations for prevention. J Med Toxicol. 2015;11(4):445–59. https://doi.org/10.1007/s13181-015-0490-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Touchette DR, Rhoney DH. Cost-minimization analysis of phenytoin and fosphenytoin in the emergency department. Pharmacotherapy. 2000;20(8):908–16. https://doi.org/10.1592/phco.20.11.908.35269.

    Article  CAS  PubMed  Google Scholar 

  68. DeToledo JC, Ramsay RE. Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs. Drug Saf. 2000;22(6):459–66. https://doi.org/10.2165/00002018-200022060-00004.

    Article  CAS  PubMed  Google Scholar 

  69. Feng Y, Chen Y, Jia Y, et al. Efficacy and safety of levetiracetam versus (fos)phenytoin for second-line treatment of epilepticus: a meta-analysis of latest randomized controlled trials. Seizure. 2021;91:339–45. https://doi.org/10.1016/j.seizure.2021.07.012.

    Article  PubMed  Google Scholar 

  70. Xue T, Wei L, Shen X, et al. Levetiracetam versus phenytoin for the pharmacotherapy of benzodiazepine-refractory status epilepticus: a systematic review and meta-analysis of randomized controlled trials. CNS Drugs. 2020;34(12):1205–15. https://doi.org/10.1007/s40263-020-00770-0.

    Article  CAS  PubMed  Google Scholar 

  71. Klowak JA, Hewitt M, Catenacci V, et al. Levetiracetam versus phenytoin or fosphenytoin for second-line treatment of pediatric status epilepticus: a meta-analysis. Pediatr Crit Care Med. 2021;22(9):e480–91. https://doi.org/10.1097/PCC.0000000000002703.

    Article  PubMed  Google Scholar 

  72. Angurana SK, Suthar R. Efficacy and safety of levetiracetam vs. phenytoin as second line antiseizure medication for pediatric convulsive status epilepticus: a systematic review and meta-analysis of randomized controlled trials. J Trop Pediatr. 2021. https://doi.org/10.1093/tropej/fmab014.

    Article  PubMed  Google Scholar 

  73. Zhang Y, Liu Y, Liao Q, Liu Z. Preferential antiseizure medications in pediatric patients with convulsive status epilepticus: a systematic review and network meta-analysis. Clin Drug Investig. 2021;41(1):1–17. https://doi.org/10.1007/s40261-020-00975-7.

    Article  PubMed  Google Scholar 

  74. Vignesh V, Rameshkumar R, Mahadevan S. Comparison of phenytoin, valproate and levetiracetam in pediatric convulsive status epilepticus: a randomized double-blind controlled clinical trial. Indian Pediatr. 2020;57(3):222–7.

    Article  PubMed  Google Scholar 

  75. Strzelczyk A, Zöllner JP, Willems LM, et al. Lacosamide in status epilepticus: systematic review of current evidence. Epilepsia. 2017;58(6):933–50. https://doi.org/10.1111/epi.13716.

    Article  CAS  PubMed  Google Scholar 

  76. Misra UK, Dubey D, Kalita J. Comparison of lacosamide versus sodium valproate in status epilepticus: a pilot study. Epilepsy Behav. 2017;76:110–3. https://doi.org/10.1016/j.yebeh.2017.07.005.

    Article  PubMed  Google Scholar 

  77. Panda PK, Panda P, Dawman L, et al. Efficacy of lacosamide and phenytoin in status epilepticus: a systematic review. Acta Neurol Scand. 2021;144(4):366–74. https://doi.org/10.1111/ane.13469.

    Article  PubMed  Google Scholar 

  78. Jackson MC, Vasquez A, Ojo O, et al. Identifying barriers to care in the pediatric acute seizure care pathway. Int J Integr Care. 2022;22(1):28. https://doi.org/10.5334/ijic.5598.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Neville KL, McCaffery H, Baxter Z, et al. Implementation of a standardized seizure action plan to improve communication and parental education. Pediatr Neurol. 2020;112:56–63. https://doi.org/10.1016/j.pediatrneurol.2020.04.005.

    Article  PubMed  Google Scholar 

  80. Gaínza-Lein M, Benjamin R, Stredny C, et al. Rescue medications in epilepsy patients: a family perspective. Seizure. 2017;52:188–94. https://doi.org/10.1016/j.seizure.2017.10.007.

    Article  PubMed  Google Scholar 

  81. Penovich P, Glauser T, Becker D, et al. Recommendations for development of acute seizure action plans (ASAPs) from an expert panel. Epilepsy Behav. 2021;123: 108264. https://doi.org/10.1016/j.yebeh.2021.108264.

    Article  PubMed  Google Scholar 

  82. Roundy LM, Filloux FM, Kerr L, et al. Seizure action plans do not reduce health care utilization in pediatric epilepsy patients. J Child Neurol. 2016;31(4):433–8. https://doi.org/10.1177/0883073815597755.

    Article  PubMed  Google Scholar 

  83. Albert DVF, Moreland JJ, Salvator A, et al. Seizure action plans for pediatric patients with epilepsy: a randomized controlled trial. J Child Neurol. 2019;34(11):666–73. https://doi.org/10.1177/0883073819846810.

    Article  PubMed  Google Scholar 

  84. Dean P, O’Hara K, Brooks L, et al. Managing acute seizures: new rescue delivery option and resources to assist school nurses. NASN Sch Nurse. 2021;36(6):346–54. https://doi.org/10.1177/1942602X211026333.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Hartman AL, Devore CDL, Section on Neurology, American Academy of Pediatrics: Council on School Health, American Academy of Pediatrics, Doerrer SC. Rescue medicine for epilepsy in education settings. Pediatrics. 2016. https://doi.org/10.1542/peds.2015-3876.

    Article  PubMed  Google Scholar 

  86. Cohen NT. Toward the adoption of a Federal seizure action plan. Epilepsy Behav. 2021;114(Pt A): 107649. https://doi.org/10.1016/j.yebeh.2020.107649.

    Article  PubMed  Google Scholar 

  87. Wallace A, Wirrell E, Payne E. Seizure rescue medication use among US pediatric epilepsy providers: a survey of the pediatric epilepsy research consortium. J Pediatr. 2019;212:111–6. https://doi.org/10.1016/j.jpeds.2019.05.034.

    Article  PubMed  Google Scholar 

  88. Terry D, Paolicchi J, Karn M. Acceptance of the use of diazepam rectal gel in school and day care settings. J Child Neurol. 2007;22(9):1135–8. https://doi.org/10.1177/0883073807306254.

    Article  PubMed  Google Scholar 

  89. Kaune A, Schumacher PM, Hope SC, et al. Administration of anticonvulsive rescue medication in children-discrepancies between parents’ self-reports and limited practical performance. Eur J Pediatr. 2016;175(9):1139–46. https://doi.org/10.1007/s00431-016-2750-6.

    Article  CAS  PubMed  Google Scholar 

  90. Stredny CM, Abend NS, Loddenkemper T. Towards acute pediatric status epilepticus intervention teams: do we need ‘seizure codes’? Seizure. 2018;58:133–40. https://doi.org/10.1016/j.seizure.2018.04.011.

    Article  PubMed  Google Scholar 

  91. Pellock JM, Marmarou A, DeLorenzo R. Time to treatment in prolonged seizure episodes. Epilepsy Behav. 2004;5(2):192–6. https://doi.org/10.1016/j.yebeh.2003.12.012.

    Article  PubMed  Google Scholar 

  92. Srivastava K, Suryawanshi VR, Yerrapalam N, et al. Compliance with status epilepticus management protocol and effect on clinical outcomes in children with status epilepticus. Eur J Hosp Pharm. 2023;30(3):147–52. https://doi.org/10.1136/ejhpharm-2021-002721.

    Article  PubMed  Google Scholar 

  93. Uppal P, Cardamone M, Webber C, et al. Management of status epilepticus in children prior to medical retrieval: deviations from the guidelines. J Paediatr Child Health. 2019;55(12):1458–62. https://doi.org/10.1111/jpc.14448.

    Article  PubMed  Google Scholar 

  94. Uppal P, Cardamone M, Fonseca B, et al. The need for improved management of status epilepticus in children in Australia: time from seizure onset to treatment is consistently delayed. J Paediatr Child Health. 2022;58(2):261–6. https://doi.org/10.1111/jpc.15697.

    Article  PubMed  Google Scholar 

  95. Eriksson K, Metsäranta P, Huhtala H, et al. Treatment delay and the risk of prolonged status epilepticus. Neurology. 2005;65(8):1316–8. https://doi.org/10.1212/01.wnl.0000180959.31355.92.

    Article  CAS  PubMed  Google Scholar 

  96. Lewena S, Young S. When benzodiazepines fail: how effective is second line therapy for status epilepticus in children? Emerg Med Australas. 2006;18(1):45–50. https://doi.org/10.1111/j.1742-6723.2006.00807.x.

    Article  PubMed  Google Scholar 

  97. Gaínza-Lein M, Sánchez Fernández I, Jackson M, et al. Association of time to treatment with short-term outcomes for pediatric patients with refractory convulsive status epilepticus. JAMA Neurol. 2018. https://doi.org/10.1001/jamaneurol.2017.4382.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Chin RFM, Neville BGR, Peckham C, et al. Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol. 2008;7(8):696–703. https://doi.org/10.1016/S1474-4422(08)70141-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Alldredge BK, Wall DB, Ferriero DM. Effect of prehospital treatment on the outcome of status epilepticus in children. Pediatr Neurol. 1995;12(3):213–6. https://doi.org/10.1016/0887-8994(95)00044-g.

    Article  CAS  PubMed  Google Scholar 

  100. Shah MI, Macia CG, Dayan PS, et al. An evidence-based guideline for pediatric prehospital seizure management using GRADE methodology. Prehosp Emerg Care. 2014;18(Suppl 1):15–24. https://doi.org/10.3109/10903127.2013.844874.

    Article  PubMed  Google Scholar 

  101. Silverman EC, Sporer KA, Lemieux JM, et al. Prehospital care for the adult and pediatric seizure patient: current evidence-based recommendations. West J Emerg Med. 2017;18(3):419–36. https://doi.org/10.5811/westjem.2016.12.32066.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Betjemann JP, Josephson SA, Lowenstein DH, et al. Emergency medical services protocols for generalized convulsive status epilepticus. JAMA. 2019;321(12):1216–7. https://doi.org/10.1001/jama.2019.0441.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Carey JM, Studnek JR, Browne LR, et al. Paramedic-identified enablers of and barriers to pediatric seizure management: a multicenter, qualitative study. Prehosp Emerg Care. 2019;23(6):870–81. https://doi.org/10.1080/10903127.2019.1595234.

    Article  PubMed  Google Scholar 

  104. Guterman EL, Burke JF, Sporer KA. Prehospital treatment of status epilepticus in the United States. JAMA. 2021;326(19):1970–1. https://doi.org/10.1001/jama.2021.15964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Han EJ, Chuck CC, Martin TJ, et al. Statewide emergency medical services protocols for status epilepticus management. Ann Neurol. 2021;89(3):604–9. https://doi.org/10.1002/ana.2598.

    Article  CAS  PubMed  Google Scholar 

  106. Shah AN, Frush K, Luo X, et al. Effect of an intervention standardization system on pediatric dosing and equipment size determination: a crossover trial involving simulated resuscitation events. Arch Pediatr Adolesc Med. 2003;157(3):229–36. https://doi.org/10.1001/archpedi.157.3.229.

    Article  PubMed  Google Scholar 

  107. Luten R, Wears RL, Broselow J, et al. Managing the unique size-related issues of pediatric resuscitation: reducing cognitive load with resuscitation aids. Acad Emerg Med. 2002;9(8):840–7. https://doi.org/10.1111/j.1553-2712.2002.tb02175.x.

    Article  PubMed  Google Scholar 

  108. Woods B, Lang B, Blayney C, et al. Medic One Pediatric (MOPed) cards: standardising paramedic paediatric resuscitation. BMJ Open Qual. 2019;8(3): e000534. https://doi.org/10.1136/bmjoq-2018-000534.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Keene JC, Woods B, Wainwright M, et al. Optimized benzodiazepine treatment of pediatric status epilepticus through a standardized emergency medical services resuscitation tool. Pediatr Neurol. 2022;126:50–5. https://doi.org/10.1016/j.pediatrneurol.2021.10.001.

    Article  PubMed  Google Scholar 

  110. M. Shah. Pediatric Dose Optimization for Seizures in Emergency Medical Services (PediDOSE). 2021. https://www.clinicaltrials.gov/ct2/show/NCT05121324.

  111. Seattle Children’s Hospital, Morgan L, Abrams L, et al. Seizure critical care pathway. 2021. https://www.seattlechildrens.org/pdf/seizure-pathway.pdf.

  112. Ostendorf AP, Merison K, Wheeler TA, et al. Decreasing seizure treatment time through quality improvement reduces critical care utilization. Pediatr Neurol. 2018. https://doi.org/10.1016/j.pediatrneurol.2018.05.012.

    Article  PubMed  Google Scholar 

  113. Trau SP, Sterrett EC, Feinstein L, et al. Institutional pediatric convulsive status epilepticus protocol decreases time to first and second line anti-seizure medication administration. Seizure. 2020;81:263–8. https://doi.org/10.1016/j.seizure.2020.08.011.

    Article  PubMed  Google Scholar 

  114. Vidaurre J, Albert DVF, Parker W, et al. Improving time for administration of second-line antiseizure medications for children with generalized convulsive status epilepticus using quality improvement methodology. Epilepsia. 2021;62(10):2496–504. https://doi.org/10.1111/epi.17026.

    Article  CAS  PubMed  Google Scholar 

  115. Cassel-Choudhury G, Beal J, Longani N, et al. Protocol-driven management of convulsive status epilepticus at a tertiary children’s hospital. Pediatr Crit Care Med. 2019. https://doi.org/10.1097/PCC.0000000000001816.

    Article  PubMed  Google Scholar 

  116. Vasquez A, Gaínza-Lein M, Sánchez Fernández I, et al. Hospital emergency treatment of convulsive status epilepticus: comparison of pathways from ten pediatric research centers. Pediatr Neurol. 2018. https://doi.org/10.1016/j.pediatrneurol.2018.06.004.

    Article  PubMed  Google Scholar 

  117. Sathe AG, Underwood E, Coles LD, et al. Underdosing of benzodiazepines in patients with status epilepticus enrolled in established status epilepticus treatment trial. Acad Emerg Med. 2019;26(8):940–3. https://doi.org/10.1111/acem.13811.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Spatola M, Alvarez V, Rossetti AO. Benzodiazepine overtreatment in status epilepticus is related to higher need of intubation and longer hospitalization. Epilepsia. 2013;54(8):e99–102. https://doi.org/10.1111/epi.12235.

    Article  CAS  PubMed  Google Scholar 

  119. Tirupathi S, McMenamin JB, Webb DW. Analysis of factors influencing admission to intensive care following convulsive status epilepticus in children. Seizure. 2009;18(9):630–3. https://doi.org/10.1016/j.seizure.2009.07.006.

    Article  PubMed  Google Scholar 

  120. Lee B, Asian Status Epilepticus Survey Group. Treatment gap for convulsive status epilepticus in resource-poor countries. Epilepsia. 2018;59(Suppl 2):135–9. https://doi.org/10.1111/epi.14484.

    Article  PubMed  Google Scholar 

  121. Marshall C, Olaniyah T, Jalloh AA, et al. Survey of the perceived treatment gap in status epilepticus care across Sub-Saharan countries from the perspective of healthcare providers. Epilepsy Behav. 2021;125: 108408. https://doi.org/10.1016/j.yebeh.2021.108408.

    Article  PubMed  Google Scholar 

  122. Burman RJ, Rosch RE, Wilmshurst JM, et al. Why won’t it stop? The dynamics of benzodiazepine resistance in status epilepticus. Nat Rev Neurol. 2022;18(7):428–41. https://doi.org/10.1038/s41582-022-00664-3.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Neurology, Department of Neurology, University of Washington, 4800 Sand Point Way NE, Neurology, MB.7.420, Seattle, WA, 98105, USA

    Lindsey A. Morgan

  2. Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, USA

    Lindsey A. Morgan

  3. Quality and Clinical Effectiveness, Center for Quality and Patient Safety, Seattle Children’s Hospital, Seattle, WA, USA

    Jennifer B. Hrachovec

  4. Departments of Neurology and Pediatrics, University of Virginia Health System, Charlottesville, VA, USA

    Howard P. Goodkin

Authors
  1. Lindsey A. Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer B. Hrachovec
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Howard P. Goodkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lindsey A. Morgan.

Ethics declarations

Funding

Funding was not received for the publication of this review article.

Conflict of interest

Lindsey A. Morgan, Jennifer B. Hrachovec, and Howard P. Goodkin declare that they have no conflicts of interest.

Availability of data and material

Not applicable.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Code availability

Not applicable.

Author contributions

Lindsey A. Morgan and Howard P. Goodkin developed the idea and participated equally in the drafting of this review. Jennifer B. Hrachovec provided critical revisions and edits. All authors read and approved the final version.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morgan, L.A., Hrachovec, J.B. & Goodkin, H.P. Pediatric Status Epilepticus: Treat Early and Avoid Delays. Pediatr Drugs 25, 411–424 (2023). https://doi.org/10.1007/s40272-023-00570-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40272-023-00570-1

Search

Navigation