Status epilepticus

EVIDENCE REPOSITORIES

This evidence repository is a collection of best available resources and evidence collated by a knowledge synthesis team at Alberta Research for Health Evidence (ARCHE) and the clinical content team. The knowledge synthesis team utilizes a pyramid-shaped framework, built upon the “4S” hierarchy of evidence model, to provide detailed evidence appropriate to meet stakeholders’ needs. They search a combination of databases (Cochrane Library, PubMed, TRIP Database) and web-based search engines (Google, Google Scholar) to locate evidence for the knowledge pyramids. Publication types sought in the initial topic searches are organized into five levels that determine the order in which resources are presented: (2)

(3)

Overviews and Summaries of

(5)

Where applicable resources for families and parents are also listed. The knowledge synthesis team collaborates with the clinical content team to select the most relevant guidelines, reviews, and key studies, which can be found below. This evidence repository is not intended to be an exhaustive list of resources for a topic, but rather a curated list of current, evidence-based resources, based on expert consensus of relevance and usability for a general emergency department setting. Every effort is made to identify resources that are open access (i.e. publicly available, free of charge, not requiring a subscription). More information about the creation of our evidence repositories can be found here.

Thank you to the following clinical content experts and Knowledge Synthesis team who led the development of this evidence repository.

1. National Institute for Health and Care Excellence. Epilepsies in children, young people and adults. 2022.
2. McKenzie KC, Hahn CD, Friedman JN. Emergency management of the paediatric patient with convulsive status epilepticus. Paediatr Child Health. 2021 Jan 21;26(1):50-66.
3. 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.
4. 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;16(1):48-61.
5. Shah MI, Macias 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.
6. Mishra D, Sharma S, Sankhyan N, et al. Consensus guidelines on management of childhood convulsive status epilepticus. Indian Pediatr. 2014;51(12):975-90.
7. Abend NS, Loddenkemper T. Management of pediatric status epilepticus. Curr Treat Options Neurol. 2014;16(7):301.
8. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3-23.
9. Friedman J. Emergency management of the paediatric patient with generalized convulsive status epilepticus. Paediatr Child Health. 2011;16(2):91-104.
10. Kälviäinen R. Status epilepticus treatment guidelines. Epilepsia. 2007;48 Suppl 8:99-102.
11. Appleton R, Choonara I, Martland T, et al. 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.

1. Ferretti A, Riva A, Fabrizio A, et al. Best practices for the management of febrile seizures in children. Ital J Pediatr. 2024;50(1):95.
2. Singh A, Stredny CM, Loddenkemper T. Pharmacotherapy for pediatric convulsive status epilepticus. CNS Drugs. 2020;34(1):47-63.
3. Stahl-Timmins W. Managing febrile seizures. BMJ. 2015.
4. Patel N, Ram D, Swiderska N, et al. Clinical review: Febrile seizures. BMJ. 2015.
5. Hampers LC, Spina LA. Evaluation and management of pediatric febrile seizures in the emergency department. Emerg Med Clin North Am. 2011;29(1):83-93.

1. Corsello A, Marangoni MB, Macchi M, et al. Febrile seizures: A systematic review of different guidelines. Pediatr Neurol. 2024;155:141-8.
2. Zhang Q, Peng S, Wei Z, et al. Comparative efficacy and safety of second-line medications for status epilepticus: A network meta-analysis. Medicine (Baltimore). 2024;103(46):e40333.
3. Specchio N, Auvin S, Strzelczyk A, et al. Efficacy and safety of stiripentol in the prevention and cessation of status epilepticus: A systematic review. Epilepsia Open. 2024;9(6):2017-36.
4. Au YK, Kananeh MF, Rahangdale R, et al. Treatment of refractory status epilepticus with continuous intravenous anesthetic drugs: A systematic review. JAMA Neurol. 2024;81(5):534-48.
5. Cao Y, Li H, Chen M, et al. Evaluation and systematic review of guidance documents for status epilepticus. Epilepsy Behav. 2024;150:109555.
6. Chiriboga N, Spentzas T, Abu-Sawwa R. A systematic review and meta-analysis of ketamine in pediatric status epilepticus. Epilepsia. 2024;65(8):2200-12.
7. Aldharman SS, Alayed FT, Almutairi FA, et al. Intramuscular versus intravenous treatment of status epilepticus: A systematic review. Cureus. 2023;15(4):e38212.
8. Jain P, Aneja S, Cunningham J, et al. Treatment of benzodiazepine-resistant status epilepticus: Systematic review and network meta-analyses. Seizure. 2022;102:74-82.
9. Hashimoto R, Suto M, Tsuji M, et al. Use of antipyretics for preventing febrile seizure recurrence in children: A systematic review and meta-analysis. Eur J Pediatr. 2021;180(4):987-97.
10. 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.
11. McTague A, Martland T, Appleton R. Drug management for acute tonic‐clonic convulsions including convulsive status epilepticus in children. Cochrane Database of Systematic Reviews. 2018(1).
12. Poblete R, Sung G. Status epilepticus and beyond: A clinical review of status epilepticus and an update on current management strategies in super-refractory status epilepticus. Korean J Crit Care Med. 2017;32(2):89-105.
13. Whelan H, Harmelink M, Chou E, et al. Complex febrile seizures-a systematic review. Dis Mon. 2017;63(1):5-23.
14. Au CC, Branco RG, Tasker RC. Management protocols for status epilepticus in the pediatric emergency room: Systematic review article. J Pediatr (Rio J). 2017;93 Suppl 1:84-94.
15. Paul SP, Rogers E, Wilkinson R, Paul B. Management of febrile convulsion in children. Emerg Nurse. 2015;23(2):18-25.
16. Kimia AA, Bachur RG, Torres A, Harper MB. Febrile seizures: Emergency medicine perspective. Curr Opin Pediatr. 2015;27(3):292-7.
17. Prasad M, Krishnan PR, Sequeira R, Al‐Roomi K. Anticonvulsant therapy for status epilepticus. Cochrane Database of Systematic Reviews. 2014(9).
18. Najaf-Zadeh A, Dubos F, Hue V, et al. Risk of bacterial meningitis in young children with a first seizure in the context of fever: A systematic review and meta-analysis. PLoS One. 2013;8(1):e55270.
19. Riviello JJ, Jr., Ashwal S, Hirtz D, et al. Practice parameter: Diagnostic assessment of the child with status epilepticus (an evidence-based review): Report of the quality standards subcommittee of the American academy of neurology and the practice committee of the child neurology society. Neurology. 2006;67(9):1542-50.

1. Shah MI, Ostermayer DG, Browne LR, et al. Multicenter evaluation of prehospital seizure management in children. Prehosp Emerg Care. 2021;25(4):475-86.
2. Zeidan S, Rohaut B, Outin H, et al. Not all patients with convulsive status epilepticus intubated in pre-hospital settings meet the criteria for refractory status epilepticus. Seizure. 2021;88:29-35.
3. Kim D, Kim JM, Cho YW, et al. Antiepileptic drug therapy for status epilepticus. J Clin Neurol. 2021;17(1):11-9.
4. Vespa PM, Olson DM, John S, et al. Evaluating the clinical impact of rapid response electroencephalography: The decide multicenter prospective observational clinical study. Crit Care Med. 2020;48(9):1249-57.
5. Vasquez A, Gaínza-Lein M, Abend NS, et al. First-line medication dosing in pediatric refractory status epilepticus. Neurology. 2020;95(19):e2683-e96.
6. Lee SK. Diagnosis and treatment of status epilepticus. J Epilepsy Res. 2020;10(2):45-54.
7. Handral A, Veerappa BG, Gowda VK, et al. Levetiracetam versus fosphenytoin in pediatric convulsive status epilepticus: A randomized controlled trial. J Pediatr Neurosci. 2020;15(3):252-6.
8. Guterman EL, Sanford JK, Betjemann JP, et al. Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus. Neurology. 2020;95(24):e3203-e12.
9. Chamberlain JM, Kapur J, Shinnar S, et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group: A double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020;395(10231):1217-24.
10. Appleton RE, Rainford NE, Gamble C, et al. Levetiracetam as an alternative to phenytoin for second-line emergency treatment of children with convulsive status epilepticus: The eclipse RCT. Health Technol Assess. 2020;24(58):1-96.
11. Amorim E, McGraw CM, Westover MB. A theoretical paradigm for evaluating risk-benefit of status epilepticus treatment. J Clin Neurophysiol. 2020;37(5):385-92.
12. Yazbeck M, Sra P, Parvizi J. Rapid response electroencephalography for urgent evaluation of patients in community hospital intensive care practice. J Neurosci Nurs. 2019;51(6):308-12.
13. 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.
14. Kapur J, Elm J, Chamberlain JM, et al. Randomized trial of three anticonvulsant medications for status epilepticus. N Engl J Med. 2019;381(22):2103-13.
15. Dalziel SR, Borland ML, Furyk J, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (consept): An open-label, multicentre, randomised controlled trial. Lancet. 2019;393(10186):2135-45.
16. 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.
17. 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;86:33-41.
18. Marino MC, Ostermayer DG, Mondragon JA, et al. Improving prehospital protocol adherence using bundled educational interventions. Prehosp Emerg Care. 2018;22(3):361-9.

epilepticus (se): A prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam–pilot study. Epilepsy Res. 2015;114:52-8.

1. Momen AA, Azizi Malamiri R, Nikkhah A, et al. Efficacy and safety of intramuscular midazolam versus rectal diazepam in controlling status epilepticus in children. Eur J Paediatr Neurol. 2015;19(2):149-54.
2. Khongkhatithum C, Thampratankul L, Wiwattanadittakul N, Visudtibhan A. Intravenous levetiracetam in thai children and adolescents with status epilepticus and acute repetitive seizures. Eur J Paediatr Neurol. 2015;19(4):429-34.
3. Kämppi L, Mustonen H, Soinila S. Factors related to delays in pre-hospital management of status epilepticus. Neurocrit Care. 2015;22(1):93-104.
4. Harini C, Nagarajan E, Kimia AA, et al. Utility of initial EEG in first complex febrile seizure. Epilepsy Behav. 2015;52(Pt A):200-4.
5. Alford EL, Wheless JW, Phelps SJ. Treatment of generalized convulsive status epilepticus in pediatric patients. J Pediatr Pharmacol Ther. 2015;20(4):260-89.
6. 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.
7. Kim JS, Lee JH, Ryu HW, et al. Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus. Pediatr Emerg Care. 2014;30(8):525-8.
8. 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.
9. Thakker A, Shanbag P. A randomized controlled trial of intranasal-midazolam versus intravenous- diazepam for acute childhood seizures. J Neurol. 2013;260(2):470-4.
10. Silbergleit R, Lowenstein D, Durkalski V, Conwit R. Lessons from the rampart study–and which is the best route of administration of benzodiazepines in status epilepticus. Epilepsia. 2013;54 Suppl 6(0 6):74-7.
11. 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.
12. Nordli DR, Jr., Moshé SL, Shinnar S, et al. Acute EEG findings in children with febrile status epilepticus: Results of the FEBSTAT study. Neurology. 2012;79(22):2180-6.
13. Misra UK, Kalita J, Maurya PK. Levetiracetam versus lorazepam in status epilepticus: A randomized, open labeled pilot study. J Neurol. 2012;259(4):645-8.
14. McTague A, Kneen R, Kumar R, et al. Intravenous levetiracetam in acute repetitive seizures and status epilepticus in children: Experience from a children's hospital. Seizure. 2012;21(7):529-34.
15. 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.
16. Javadzadeh M, Sheibani K, Hashemieh M, Saneifard H. Intranasal midazolam compared with intravenous diazepam in patients suffering from acute seizure: A randomized clinical trial. Iran J Pediatr. 2012;22(1):1-8.
17. Silbergleit R, Lowenstein D, Durkalski V, Conwit R. Rampart (rapid anticonvulsant medication prior to arrival trial): A double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics. Epilepsia. 2011;52 Suppl 8(Suppl 8):45-7.
18. Shearer P, Riviello J. Generalized convulsive status epilepticus in adults and children: Treatment guidelines and protocols. Emerg Med Clin North Am. 2011;29(1):51-64.
19. Arya R, Gulati S, Kabra M, et al. Intranasal versus intravenous lorazepam for control of acute seizures in children: A randomized open-label study. Epilepsia. 2011;52(4):788-93.
20. 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. 2010;14(2):162-8.
21. Lewena S, Pennington V, Acworth J, et al. Emergency management of pediatric convulsive status epilepticus: A multicenter study of 542 patients. Pediatr Emerg Care. 2009;25(2):83-7.
22. 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.
23. Chin RF, Neville BG, Peckham C, et al. Treatment of community-onset, childhood convulsive status epilepticus: A prospective, population-based study. Lancet Neurol. 2008;7(8):696-703.
24. Mehta V, Singhi P, Singhi S. Intravenous sodium valproate versus diazepam infusion for the control of refractory status epilepticus in children: A randomized controlled trial. J Child Neurol. 2007;22(10):1191-7.
25. Agarwal P, Kumar N, Chandra R, et al. Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure. 2007;16(6):527-32.
26. Teng D, Dayan P, Tyler S, et al. Risk of intracranial pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children. Pediatrics. 2006;117(2):304-8.
27. Tay SK, Hirsch LJ, Leary L, et al. Nonconvulsive status epilepticus in children: Clinical and EEG characteristics. Epilepsia. 2006;47(9):1504-9.
28. Misra UK, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus: A pilot study. Neurology. 2006;67(2):340-2.
29. Shah I, Deshmukh CT. Intramuscular midazolam vs intravenous diazepam for acute seizures. Indian J Pediatr. 2005;72(8):667-70.
30. 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.
31. Chin RF, Neville BG, Scott RC. Meningitis is a common cause of convulsive status epilepticus with fever. Arch Dis Child. 2005;90(1):66-9.
32. Mahmoudian T, Zadeh MM. Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy Behav. 2004;5(2):253-5.
33. Yu KT, Mills S, Thompson N, Cunanan C. Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures. Epilepsia. 2003;44(5):724-6.
34. Fişgin T, Gurer Y, Teziç T, 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.
35. Lahat E, Goldman M, Barr J, et al. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: Prospective randomised study. BMJ. 2000;321(7253):83-6.

1. Stahl-Timmins W. Managing febrile seizures. BMJ. 2015.
2. Richer L, Mikrogianakis A, Helman A. Emergency medicine cases podcast: Emergency management of pediatric seizures – guidance and podcast. Emergency Medicine Cases. 2015.