2,146
Views
64
CrossRef citations to date
0
Altmetric
Reviews

Pharmacologic treatment of status epilepticus

, , , , &
Pages 513-534 | Received 11 Sep 2015, Accepted 30 Nov 2015, Published online: 09 Feb 2016

References

  • Dobesberger J, Ristic AJ, Walser G, et al. Duration of focal complex, secondarily generalized tonic-clonic, and primarily generalized tonic-clonic seizures - A video-EEG analysis. Epilepsy Behav. 2015 Aug;49:111–117. PubMed PMID: 25935513.
  • Theodore WH, Porter RJ, Albert P, et al. The secondarily generalized tonic-clonic seizure: a videotape analysis. Neurology. 1994;44(8):1403–1407.
  • Jenssen S, Gracely EJ, Sperling MR. How long do most seizures last? A systematic comparison of seizures recorded in the epilepsy monitoring unit. Epilepsia. 2006 Sep;47(9):1499–1503. PubMed PMID: 16981866.
  • Shinnar S, Berg AT, Moshe SL, et al. How long do new-onset seizures in children last? Ann Neurol. 2001 May;49(5):659–664. PubMed PMID: 11357957.
  • 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 Oct;56(10):1515–1523. PubMed PMID: 26336950.
  • Prasad K, Krishnan PR, Al Roomi K, et al. Anticonvulsant therapy for status epilepticus. Br J Clin Pharmacol. 2007;63(6):640–647.
  • Prasad M, Krishnan PR, Sequeira R, et al. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev. 2014;9:CD003723. PubMed PMID: 25207925.
  • Brigo F, Nardone R, Tezzon F, et al. A common reference-based indirect comparison meta-analysis of buccal versus intranasal midazolam for early status epilepticus. CNS Drugs. 2015 Sep;29(9):741–757. PubMed PMID: 26293745.
  • Brigo F, Nardone R, Tezzon F, et al. Nonintravenous midazolam versus intravenous or rectal diazepam for the treatment of early status epilepticus: a systematic review with meta-analysis. Epilepsy Behav. 2015 Aug;49:325–336. PubMed PMID: 25817929.
  • McMullan J, Sasson C, Pancioli A, et al. Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis. Acad Emerg Med. 2010 Jun;17(6):575–582. PubMed PMID: 20624136.
  • Sofou K, Kristjansdottir R, Papachatzakis NE, et al. Management of prolonged seizures and status epilepticus in childhood: a systematic review. J Child Neurol. 2009 Aug;24(8):918–926. PubMed PMID: 19332572.
  • Brigo F, Storti M, Del Felice A, et al. IV Valproate in generalized convulsive status epilepticus: a systematic review. Eur J Neurol. 2012 Sep;19(9):1180–1191. PubMed PMID: 22182304.
  • Trinka E, Hofler J, Zerbs A, et al. Efficacy and safety of intravenous valproate for status epilepticus: a systematic review. CNS Drugs. 2014 Jul;28(7):623–639. PubMed PMID: 24806973.
  • Shorvon S, Baulac M, Cross H, et al. The drug treatment of status epilepticus in Europe: consensus document from a workshop at the first London Colloquium on Status Epilepticus. Epilepsia. 2008;49(7):1277–1285.
  • Meierkord H, Boon P, Engelsen B, et al. EFNS guideline on the management of status epilepticus in adults. Eur J Neurol. 2010 Mar;17(3):348–355. PubMed PMID: 20050893.
  • Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocritical Care. 2012 Aug;17(1):3–23. PubMed PMID: 22528274.
  • Capovilla G, Beccaria F, Beghi E, et al. Treatment of convulsive status epilepticus in childhood: recommendations of the Italian League Against Epilepsy. Epilepsia. 2013 Oct;54(Suppl 7):23–34. PubMed PMID: 24099053.
  • Beniczky S, Hirsch LJ, Kaplan PW, et al. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia. 2013 Sep;54(Suppl 6):28–29. PubMed PMID: 24001066.
  • Leitinger M, Beniczky S, Rohracher A, et al. Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus - approach to clinical application. Epilepsy Behav. 2015 Aug;49:158–163. PubMed PMID: 26092326.
  • Trinka E, Leitinger M. Which EEG patterns in coma are nonconvulsive status epilepticus? Epilepsy Behav. 2015 Aug;49:203–222. PubMed PMID: 26148985.
  • Prasad K, Al Roomi K, Krishnan PR, et al. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev. 2005;(4):CD003723.
  • Haynes RB. Of studies, syntheses, synopses, summaries, and systems: the “5S” evolution of information services for evidence-based healthcare decisions. Evid Based Med. 2006 Dec;11(6):162–164. PubMed PMID: 17213159.
  • Trinka E, Brigo F. Benzodiazepines used in the treatment of epilepsy. In: Shorvon S, Perucca E, Engel J, editors. The treatment of epilepsy. 4th ed. Chichester (UK): Wyley; 2015. p. 398–417.
  • Schütz H. Benzodiazepines II. A handbook. Basic data, analytical methods, pharmacokonetics, and comprehensive literature. Heidelberg: Springer; 1989.
  • Greenblatt DJ, Divoll M. Diazepam versus lorazepam: relationship of drug distribution to duration of clinical action. In: Escueta AVD, Wasterlain CG, Treiman DM, et al., editors. Status epileptics mechanisms of brain damage and treatment advances in neruology. Vol. 34. New York (NY): Raven Press; 1983. p. 487–491.
  • Leppik IE, Derivan AT, Homan RW, et al. Double-blind study of lorazepam and diazepam in status epilepticus. J Am Med Assoc. 1983;249:1452–1454.
  • Appleton R, Sweeney A, Choonara I, et al. Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. Dev Med Child Neurol. 1995;37(8):682–688.
  • 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):631–637.
  • Chamberlain JM, Okada P, Holsti M, et al. Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial. Jama. 2014 Apr 23–30;311(16):1652–1660. PubMed PMID: 24756515.
  • Anderson M, Tambe P, Sammons H, et al. Pharmacokinetics of buccal and intranasal lorazepam in healthy adult volunteers. Eur J Clin Pharmacol. 2012 Feb;68(2):155–159. PubMed PMID: 21837394.
  • 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 Apr;52(4):788–793. PubMed PMID: 21275979.
  • Greenblatt DJ, Shader RI, Franke K, et al. Pharmacokinetics and bioavailability of intravenous, intramuscular and oral lorazepam in humans. Pharmacological Sci. 1979;68:57–63.
  • Friedman H, Ochs HR, Greenblat DJ, et al. Tissue distrubtion of diazepam and its metabolite desmethyldiazepam: a human autopsy study. J Clin Pharmacol. 1985;25:613–615.
  • Lamson MJ, Sitki-Green D, Wannarka GL, et al. Pharmacokinetics of diazepam administered intramuscularly by autoinjector versus rectal gel in healthy subjects: a phase I, randomized, open-label, single-dose, crossover, single-centre study. Clin Drug Investig. 2011;31(8):585–597. PubMed PMID: 21721594.
  • Leppik IE, Patel SI. Intramuscular and rectal therapies of acute seizures. Epilepsy Behav. 2015 Aug;49:307–312. PubMed PMID: 26071998.
  • Cereghino JJ, Cloyd JC, Kuzniecky RI. Rectal diazepam gel for treatment of acute repetitive seizures in adults. Arch Neurol. 2002;59(12):1915–1920.
  • Dreifuss FE, Rosman NP, Cloyd JC, et al. A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med. 1998;338(26):1869–1875.
  • Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012 Feb 16;366(7):591–600. PubMed PMID: 22335736. Pubmed Central PMCID: 3307101.
  • Welch RD, Nicholas K, Durkalski-Mauldin VL, et al. Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population. Epilepsia. 2015 Feb;56(2):254–262. PubMed PMID: 25597369. Pubmed Central PMCID: 4386287.
  • Bottomley DM, Hanks GW. Subcutaneous midazolam infusion in palliative care. J Pain Symptom Manage. 1990 Aug;5(4):259–261. PubMed PMID: 2384705.
  • Gremaud G, Zulian GB. Indications and limitations of intravenous and subcutaneous midazolam in a palliative care center. J Pain Symptom Manage. 1998 Jun;15(6):331–333. PubMed PMID: 9670632.
  • Berlin A, Dahlstrom H. Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration. Eur J Clin Pharmacol. 1975;9(2–3):155–159.
  • Dreifuss FE, Penry JK, Rose SW, et al. Serum clonazepam concentrations in children with absence seizures. Neurology. 1975;25:255–258.
  • Congdon PJ, Forysthe WI. Intravenous clonazepam in the treatment of status epilepticus in children. Epilepsia. 1980;21:97–102.
  • Singh AN, Le Morvan P. Treatment of status epilepticus with intravenous clonazepam. Prog Neuropsychopharmacol Biol Psychiatry. 1982;6(4–6):539–542. PubMed PMID: 6819599.
  • Crevoisier C, Delisle MC, Joseph I, et al. Comparative single-dose pharmacokinetics of clonazepam following intravenous, intramuscular and oral administration to healthy volunteers. Eur Neurol. 2003;49(3):173–177. PubMed PMID: 12646763.
  • Greenblatt DJ, Blaskovich PD, Nuwayser ES, et al. Clonazepam pharmacokinetics: comparison of subcutaneous microsphere injection with multiple-dose oral administration. J Clin Pharmacol. 2005 Nov;45(11):1288–1293. PubMed PMID: 16239362.
  • Kapur J, Macdonald RL. Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity of hippocampal dentate granule cell GABAA receptors. J Neurosci. 1997;17(19):7532–7540.
  • Mazarati AM, Baldwin RA, Sankar R, et al. Time-dependent decrease in the effectiveness of antiepileptic drugs during the course of self-sustaining status epilepticus. Brain Res. 1998;814(1–2):179–185.
  • Naylor DE, Liu H, Wasterlain CG. Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci. 2005;25(34):7724–7733.
  • Wang J, Liu S, Haditsch U, et al. Interaction of calcineurin and type-A GABA receptor gamma 2 subunits produces long-term depression at CA1 inhibitory synapses. J Neurosci. 2003 Feb 1;23(3):826–836. PubMed PMID: 12574411.
  • Naylor DE, Liu H, Niquet J, et al. Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus. Neurobiol Dis. 2013 Jun;54:225–238. PubMed PMID: 23313318.
  • Wasterlain CG, Naylor DE, Liu H, et al. Trafficking of NMDA receptors during status epilepticus: therapeutic implications. Epilepsia. 2013 Sep;54(Suppl 6):78–80. PubMed PMID: 24001081. Pubmed Central PMCID: 4551407.
  • Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998;339(12):792–798.
  • Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011 Oct;134(Pt 10):2802–2818. PubMed PMID: 21914716.
  • Jones S, Pahl C, Trinka E, et al. A protocol for the inhospital emergency drug management of convulsive status epilepticus in adults. Pract Neurol. 2014 Jun;14(3):194–197. PubMed PMID: 24810377.
  • Trinka E, Hofler J, Leitinger M, et al. Pharmacotherapy for Status Epilepticus. Drugs. 2015 Sep;75(13):1499–1521. PubMed PMID: 26310189.
  • Hofler J, Trinka E. Lacosamide as a new treatment option in status epilepticus. Epilepsia. 2013 Mar;54(3):393–404. PubMed PMID: 23293881.
  • Hofler J, Unterberger I, Dobesberger J, et al. Intravenous lacosamide in status epilepticus and seizure clusters. Epilepsia. 2011 Oct;52(10):e148–152. PubMed PMID: 21801171.
  • Hauptmann A. Luminal bei Epilepsie. Münchner Medizinische Wochenschrift. 1912 Aug 27;35:1907–1909.
  • Janz D. Historical vignette: medical treatment of status epilepticus. Epilepsia. 2013 Sep;54(Suppl 6):3–10. PubMed PMID: 24001060.
  • Yasiry Z, Shorvon SD. How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years. Epilepsia. 2012 Dec;53(Suppl 8):26–39. PubMed PMID: 23205960.
  • Hosgood JR, Kimbrel JM, Protus BM, et al. Evaluation of subcutaneous phenobarbital administration in hospice patients. Am J Hosp Palliat Care. 2014 Dec 3:pii: 1049909114555157. PubMed PMID: 25473092. [Epub ahead of print]
  • Shaner DM, McCurdy SA, Herring MO, et al. Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology. 1988;38:202–207.
  • Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies. Seizure. 2014 Mar;23(3):167–174. PubMed PMID: 24433665.
  • Brigo F, Igwe SC, Nardone R, et al. A common reference-based indirect comparison meta-analysis of intravenous valproate versus intravenous phenobarbitone for convulsive status epilepticus. Epileptic Disorders. 2013 Sep;15(3):314–323. PubMed PMID: 23981687.
  • Murphy JT, Schwab RS. Diphenylhydantoin (dilantin) sodium used parenterally in control of convulsions; a five-year report. J Am Med Assoc. 1956 Feb 4;160(5):385–388. PubMed PMID: 13278209.
  • Carter C. Use of parenteral diphenylhydantoin (Dilantin) sodium in control of status epilepticus. Arch Neurol Psychiatry. 1958;79:136–137.
  • Pilz C, Dreyer R. Ergebnisse der parenteralen Behandlung des Status epilepticus mit Diphenylhydantoin in den Jahren 1959–1965 [Results of parenteral diphenylhydantoin therapy of status epilepticus from the years 1959–1965]. Archiv Fur Psychiatrie Und Nervenkrankheiten. 1969;212(3):254–270. PubMed PMID: 4981258.
  • Appleton RE, Gill A. Adverse events associated with intravenous phenytoin in children: a prospective study. Seizure. 2003 Sep;12(6):369–372. PubMed PMID: 12915082.
  • Wallis W, Kutt H, McDowell F. Intravenous diphenyl hydantoin treatment of acute repetitive seizures. Neurology. 1968;18:513–525.
  • Wilder BJ, Ramsay RE, Willmore LJ, et al. Efficacy of intravenous phenytoin in the treatment of status epilepticus: kinetics of central nervous system penetration. Ann Neurol. 1977;1:511–518.
  • Cranford RE, Leppik IE, Patrick B, et al. Intravenous phenytoin in acute treatment of seizures. Neurology. 1979;29(11):1474–1479.
  • Leppik IE, Patrick BK, Cranford RE. Treatment of acute seizures and status epilepticus with intravenous phenytoin. In: Escueta AVD, Wasterlain CG, Treiman DM, et al., editors. Status epileptics mechaisms of brain damage and treatment advances in neurology. Vol. 34. New York (NY): Raven Press; 1983. p. 447–452.
  • Misra UK, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus: a pilot study. Neurology. 2006;67(2):340–342.
  • Gilad R, Izkovitz N, Dabby R, et al. Treatment of status epilepticus and acute repetitive seizures with i.v. valproic acid vs phenytoin. Acta Neurol Scand. 2008 Nov;118(5):296–300. PubMed PMID: 18798830.
  • Agarwal P, Kumar N, Chandra R, et al. Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure. 2007;16(6):527–532.
  • Alvarez V, Januel JM, Burnand B, et al. Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam. Epilepsia. 2011 Jul;52(7):1292–1296. PubMed PMID: 21480881.
  • Burneo JG, Anandan JV, Barkley GL. A prospective study of the incidence of the purple glove syndrome. Epilepsia. 2001;42(9):1156–1159.
  • Chhabra P, Gupta N, Kaushik A. Compartment syndrome as a spectrum of purple glove syndrome following intravenous phenytoin administration in a young male: a case report and review of literature. Neurol India. 2013 Jul-Aug;61(4):419–420. PubMed PMID: 24005736.
  • O’Brien TJ, Cascino GD, So EL, et al. Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin. Neurology. 1998;51(4):1034–1039.
  • Boucher BA. Fosphenytoin: a novel phenytoin prodrug. Pharmacotherapy. 1996 Sep-Oct;16(5):777–791. PubMed PMID: 8888074.
  • Boucher BA, Feler CA, Dean JC, et al. The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. Pharmacotherapy. 1996 Jul-Aug;16(4):638–645. PubMed PMID: 8840370.
  • Fischer JH, Patel TV, Fischer PA. Fosphenytoin: clinical pharmacokinetics and comparative advantages in the acute treatment of seizures. Clin Pharmacokinet. 2003;42(1):33–58. PubMed PMID: 12489978.
  • DeToledo JC, Ramsay RE. Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs. Drug Saf. 2000 Jun;22(6):459–466. PubMed PMID: 10877039.
  • Armstrong EP, Sauer KA, Downey MJ. Phenytoin and fosphenytoin: a model of cost and clinical outcomes. Pharmacotherapy. 1999 Jul;19(7):844–853. PubMed PMID: 10417033.
  • Rudis MI, Touchette DR, Swadron SP, et al. Cost-effectiveness of oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin in the emergency department. Ann Emerg Med. 2004 Mar;43(3):386–397. PubMed PMID: 14985668.
  • Trinka E. The Use of Valproate and New Antiepileptic Drugs in Status Epilepticus. Epilepsia. 2007;48(Suppl 8):49–51.
  • Trinka E. What is the evidence to use new intravenous AEDs in status epilepticus? Epilepsia. 2011 Oct;52(Suppl 8):35–38. PubMed PMID: 21967358.
  • Trinka E. What is the relative value of the standard anticonvulsants: Phenytoin and fosphenytoin, phenobarbital, valproate, and levetiracetam? Epilepsia. 2009 Dec;50(Suppl 12):40–43. PubMed PMID: 19941522.
  • Giroud M, Gras D, Escousse A, et al. Use of injectable valproic acid in status epilepticus. A pilot study. Drug Invest. 1993;5(3):154–159.
  • Limdi NA, Knowlton RK, Cofield SS, et al. Safety of rapid intravenous loading of valproate. Epilepsia. 2007;48(3):478–483.
  • Sinha S, Naritoku DK. Intravenous valproate is well tolerated in unstable patients with status epilepticus. Neurology. 2000;55(5):722–724.
  • Limdi NA, Faught E. The safety of rapid valproic acid infusion. Epilepsia. 2000;41(10):1342–1345.
  • Limdi NA, Shimpi AV, Faught E, et al. Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology. 2005;64(2):353–355.
  • Kramer G, Bergmann A, Deshpande LS, et al. Current Place of Intravenous Valproic Acid in the Treatment of Generalized Tonic-Clonic Status Epilepticus. Aktuelle Neurologie. 2005;32(5):263–274.
  • Trinka E, Dobesberger J, Brîssner G, et al. Treatment of Status Epilepticus. A Retrospective Analysis of 248 Patients. Epilepsia. 2006;47(s3):16.
  • Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs. 2002;16(10):695–714.
  • Konig SA, Elger CE, Vassella F, et al. [Recommendations for blood studies and clinical monitoring in early detection of valproate-associated liver failure. Results of a consensus conferences 9 May - 11 May 1997 in Berlin]. Nervenarzt. 1998;69(10):835–840.
  • Konig SA, Schenk M, Sick C, et al. Fatal liver failure associated with valproate therapy in a patient with Friedreich’s disease: review of valproate hepatotoxicity in adults. Epilepsia. 1999;40(7):1036–1040.
  • Embacher N, Karner E, Wanschitz J, et al. Acute encephalopathy after intravenous administration of valproate in nonconvulsive status epilepticus. Eur J Neurol. 2006;13(10):e5–e6.
  • Gidal BE, Baltes E, Otoul C, et al. Effect of levetiracetam on the pharmacokinetics of adjunctive antiepileptic drugs: a pooled analysis of data from randomized clinical trials. Epilepsy Res. 2005;64(1–2):1–11.
  • Patsalos PN. Clinical pharmacokinetics of levetiracetam. ClinPharmacokinet. 2004;43(11):707–724.
  • Schulze-Bonhage A, Hefft S, Oehl B. Termination of complex partial status epilepticus by intravenous levetiracetam - a case report. J Neurol Neurosurg Psychiatry. 2009 Aug;80(8):931–933.
  • Broessner G, Dobesberger J, Seppi K, et al. Intravenous levetiracetam in seizure emergency situations including status epilepticus. Epilepsia. 2007;48(s8):103–104.
  • Trinka E, Dobesberger J. New treatment options in status epilepticus: a critical review on intravenous levetiracetam. Ther Adv Neurol Disord. 2009 Mar;2(2):79–91. PubMed PMID: 21180643. Pubmed Central PMCID: 3002622.
  • Zelano J, Kumlien E. Levetiracetam as alternative stage two antiepileptic drug in status epilepticus: a systematic review. Seizure. 2012 May;21(4):233–236. PubMed PMID: 22321334.
  • Atmaca MM, Orhan EK, Bebek N, et al. Intravenous levetiracetam treatment in status epilepticus: a prospective study. Epilepsy Res. 2015 Aug;114:13–22. PubMed PMID: 26088881.
  • Misra UK, Kalita J, Maurya PK. Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled pilot study. J Neurol. 2012 Apr;259(4):645–648. PubMed PMID: 21898137.
  • Mundlamuri RC, Sinha S, Subbakrishna DK, et al. Management of generalised convulsive status 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 Aug;114:52–58. PubMed PMID: 26088885.
  • Chakravarthi S, Goyal MK, Modi M, et al. Levetiracetam versus phenytoin in management of status epilepticus. J Clin Neurosci. 2015 Jun;22(6):959–963. PubMed PMID: 25899652.
  • Cock HR, Group E. Established status epilepticus treatment trial (ESETT). Epilepsia. 2011 Oct;52(Suppl 8):50–52. PubMed PMID: 21967363.
  • Bleck T, Cock H, Chamberlain J, et al. The established status epilepticus trial 2013. Epilepsia. 2013 Sep;54(Suppl 6):89–92. PubMed PMID: 24001084.
  • Remi C, Lorenzl S, Vyhnalek B, et al. Continuous subcutaneous use of levetiracetam: a retrospective review of tolerability and clinical effects. J Pain Palliat Care Pharmacother. 2014 Dec;28(4):371–377. PubMed PMID: 25313924.
  • Beyreuther BK, Freitag J, Heers C, et al. Lacosamide: a review of preclinical properties. CNS Drug Rev. 2007 Spring;13(1):21–42. PubMed PMID: 17461888.
  • Biton V, Rosenfeld WE, Whitesides J, et al. Intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures. Epilepsia. 2008 Mar;49(3):418–424. PubMed PMID: 17888078.
  • Chung S, Ben-Menachem E, Sperling MR, et al. Examining the clinical utility of lacosamide: pooled analyses of three phase II/III clinical trials. CNS Drugs. 2010 Dec;24(12):1041–1054. PubMed PMID: 21090838.
  • Ben-Menachem E. Lacosamide: an investigational drug for adjunctive treatment of partial-onset seizures. Drugs Today. 2008 Jan;44(1):35–40. PubMed PMID: 18301802.
  • Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007 Jul;48(7):1308–1317. PubMed PMID: 17635557.
  • Krauss G, Ben-Menachem E, Mameniskiene R, et al. Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures. Epilepsia. 2010 Jun;51(6):951–957. PubMed PMID: 20041945.
  • Sutter R, Marsch S, Ruegg S. Safety and efficacy of intravenous lacosamide for adjunctive treatment of refractory status epilepticus: a comparative cohort study. CNS Drugs. 2013 Apr;27(4):321–329. PubMed PMID: 23533010.
  • Krause LU, Brodowski KO, Kellinghaus C. Atrioventricular block following lacosamide intoxication. Epilepsy Behav. 2011 Apr;20(4):725–727. PubMed PMID: 21411374.
  • Garces M, Villanueva V, Mauri JA, et al. Factors influencing response to intravenous lacosamide in emergency situations: LACO-IV study. Epilepsy Behav. 2014 Jul;36:144–152. PubMed PMID: 24922617.
  • Mayer SA, Claassen J, Lokin J, et al. Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol. 2002;59(2):205–210.
  • Holtkamp M, Othman J, Buchheim K, et al. Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosurg Psychiatry. 2005;76(4):534–539.
  • Ferlisi M, Hocker S, Grade M, et al., International Steering Committee of the StEp A. Preliminary results of the global audit of treatment of refractory status epilepticus. Epilepsy Behav. 2015 Aug;49:318–324. PubMed PMID: 25952268.
  • Ferlisi M, Shorvon S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain. 2012 Aug;135(Pt 8):2314–2328. PubMed PMID: 22577217.
  • Singhi S, Murthy A, Singhi P, et al. Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. J Child Neurol. 2002;17(2):106–110.
  • Fernandez A, Lantigua H, Lesch C, et al. High-dose midazolam infusion for refractory status epilepticus. Neurology. 2014 Jan 28;82(4):359–365. PubMed PMID: 24363133. Pubmed Central PMCID: 3929199.
  • Naritoku DK, Sinha S. Prolongation of midazolam half-life after sustained infusion for status epilepticus. Neurology. 2000;54(6):1366–1368.
  • Zhan RZ, Qi S, Wu C, et al. Intravenous anesthetics differentially reduce neurotransmission damage caused by oxygen-glucose deprivation in rat hippocampal slices in correlation with N-methyl-D-aspartate receptor inhibition. Crit Care Med. 2001 Apr;29(4):808–813. PubMed PMID: 11373474.
  • Wood PR, Browne GPR, Pugh S. Propofol infusion for the treatment of status epilepticus. Lancet. 1988;i:480–481.
  • Claassen J, Hirsch LJ, Emerson RG, et al. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia. 2002;43(2):146–153.
  • Prasad A, Worrall BB, Bertram EH, et al. Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia. 2001;42(3):380–386.
  • Begemann M, Rowan AJ, Tuhrim S. Treatment of refractory complex-partial status epilepticus with propofol: case report. Epilepsia. 2000;41(1):105–109.
  • Stecker MM, Kramer TH, Raps EC, et al. Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia. 1998 Jan;39(1):18–26. PubMed PMID: 9578008.
  • Brown LA, Levin GM. Role of propofol in refractory status epilepticus. Ann Pharmacother. 1998 Oct;32(10):1053–1059. PubMed PMID: 9793598.
  • Yanny HF, Christmas D. Propofol infusions for status epilepticus. Anaesthesia. 1988;43:514.
  • Mirrakhimov AE, Voore P, Halytskyy O, et al. Propofol infusion syndrome in adults: a clinical update. Crit Care Res Pract. 2015;2015:260385. PubMed PMID: 25954513. Pubmed Central PMCID: 4410753.
  • Rossetti AO, Milligan TA, Vulliemoz S, et al. A randomized trial for the treatment of refractory status epilepticus. Neurocritical Care. 2011 Feb;14(1):4–10. PubMed PMID: 20878265.
  • Lowenstein DH, Aminoff MJ, Simon RP. Barbiturate anesthesia in the treatment of status epilepticus: clinical experience of 14 patients. Neurology. 1988;38:395–400.
  • Stover JF, Lenzlinger PM, Stocker R, et al. Thiopental in CSF and serum correlates with prolonged loss of cortical activity. Eur Neurol. 1998;39(4):223–228. PubMed PMID: 9635473.
  • Pugin D, Foreman B, De Marchis GM, et al. Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study. Crit Care. 2014;18(3):R103. PubMed PMID: 24886712. Pubmed Central PMCID: 4095579.
  • Melamed R, Bar-Yosef S, Shakhar G, et al. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003 Nov;97(5):1331–1339. PubMed PMID: 14570648.
  • Stover JF, Stocker R. Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury. Eur J Clin Pharmacol. 1998 Sep;54(7):529–534. PubMed PMID: 9832294.
  • Tian J, Chau C, Hales TG, et al. GABA(A) receptors mediate inhibition of T cell responses. J Neuroimmunol. 1999 Apr 1;96(1):21–28. PubMed PMID: 10227421.
  • Zeiler FA, Zeiler KJ, Teitelbaum J, et al. Modern inhalational anesthetics for refractory status epilepticus. Can J Neurol Sci / Le journal canadien des sciences neurologiques. 2015 Mar;42(2):106–115. PubMed PMID: 25572922.
  • Rossetti AO. Novel anesthetics and other treatment strategies for refractory status epilepticus. Epilepsia. 2009 Dec;50(Suppl 12):51–53. PubMed PMID: 19941525.
  • Yeoman P, Hutchinson A, Byrne A, et al. Etomidate infusions for the control of refractory status epilepticus. Intensive Care Med. 1989;15:255–259.
  • Thompson Bastin ML, Baker SN, Weant KA. Effects of etomidate on adrenal suppression: a review of intubated septic patients. Hosp Pharm. 2014 Feb;49(2):177–183. PubMed PMID: 24623871. Pubmed Central PMCID: 3940683.
  • Bensalem MK, Fakhoury TA. Topiramate and status epilepticus: report of three cases. Epilepsy Behav. 2003;4(6):757–760.
  • Kahriman M, Minecan D, Kutluay E, et al. Efficacy of topiramate in children with refractory status epilepticus. Epilepsia. 2003;44(10):1353–1356.
  • Blumkin L, Lerman-Sagie T, Houri T, et al. Pediatric refractory partial status epilepticus responsive to topiramate. J Child Neurol. 2005;20(3):239–241.
  • Bragatti JA, Torres CM, Netto CB, et al. Topiramate is effective for status epilepticus and seizure control in neuraminidase deficiency. Arquivos de neuro-psiquiatria. 2011 Jun;69(3):565–566. PubMed PMID: 21755142.
  • Perry MS, Holt PJ, Sladky JT. Topiramate loading for refractory status epilepticus in children. Epilepsia. 2006;47(6):1070–1071.
  • Akyildiz BN, Kumandas S. Treatment of pediatric refractory status epilepticus with topiramate. Childs Nerv Syst. 2011 Sep;27(9):1425–1430. PubMed PMID: 21442269.
  • Hottinger A, Sutter R, Marsch S, et al. Topiramate as an adjunctive treatment in patients with refractory status epilepticus: an observational cohort study. CNS Drugs. 2012 Sep 1;26(9):761–772. PubMed PMID: 22823481.
  • Goodwin H, Hinson HE, Shermock KM, et al. The use of lacosamide in refractory status epilepticus. Neurocritical Care. 2011 Jun;14(3):348–353. PubMed PMID: 21249530.
  • Swisher CB, Doreswamy M, Gingrich KJ, et al. Phenytoin, levetiracetam, and pregabalin in the acute management of refractory status epilepticus in patients with brain tumors. Neurocritical Care. 2012 Feb;16(1):109–113. PubMed PMID: 21882056.
  • Rohracher A, Hofler J, Kalss G, et al. Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit. Epilepsy Behav. 2015 Aug;49:354–358. PubMed PMID: 25962657.
  • Redecker J, Wittstock M, Benecke R, et al. Efficacy of perampanel in refractory nonconvulsive status epilepticus and simple partial status epilepticus. Epilepsy Behav. 2015 Apr;45:176–179. PubMed PMID: 25819947.
  • Rosche J, Kampf C, Benecke R. Possible effect of perampanel on focal status epilepticus after generalized tonic-clonic status epilepticus. Acta Neurol Belg. 2014 Sep;114(3):243–244. PubMed PMID: 23801431.
  • Conway JM, Birnbaum AK, Kriel RL, et al. Relative bioavailability of topiramate administered rectally. Epilepsy Res. 2003 May;54(2–3):91–96. PubMed PMID: 12837560.
  • Fujikawa DG. Neuroprotective effect of ketamine administered after status epilepticus onset. Epilepsia. 1995;36(2):186–195.
  • Borris DJ, Bertram EH, Kapur J. Ketamine controls prolonged status epilepticus. Epilepsy Res. 2000;42(2–3):117–122.
  • Mazarati AM, Wasterlain CG. N-methyl-D-asparate receptor antagonists abolish the maintenance phase of self-sustaining status epilepticus in rat. NeurosciLett. 1999;265(3):187–190.
  • Gaspard N, Foreman B, Judd LM, et al. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Epilepsia. 2013 Aug;54(8):1498–1503. PubMed PMID: 23758557. Pubmed Central PMCID: 3731413.
  • Synowiec AS, Singh DS, Yenugadhati V, et al. Ketamine use in the treatment of refractory status epilepticus. Epilepsy Res. 2013 Jul;105(1–2):183–188. PubMed PMID: 23369676.
  • Basha MM, Alqallaf A, Shah AK. Drug-induced EEG pattern predicts effectiveness of ketamine in treating refractory status epilepticus. Epilepsia. 2015 Apr;56(4):e44–48. PubMed PMID: 25759241.
  • Walker MC, Howard RS, Smith SJ, et al. Diagnosis and treatment of status epilepticus on a neurological intensive care unit. QJM. 1996;89(12):913–920.
  • Kofke WA, Bloom MJ, Van Cott A, et al. Electrographic tachyphylaxis to etomidate and ketamine used for refractory status epilepticus controlled with isoflurane. J Neurosurg Anesthesiol. 1997 Jul;9(3):269–272. PubMed PMID: 9239591.
  • Ubogu EE, Sagar SM, Lerner AJ, et al. Ketamine for refractory status epilepticus: a case of possible ketamine-induced neurotoxicity. Epilepsy Behav. 2003;4(1):70–75.
  • Robakis TK, Hirsch LJ. Literature review, case report, and expert discussion of prolonged refractory status epilepticus. Neurocrit Care. 2006;4(1):35–46.
  • Pruss H, Holtkamp M. Ketamine successfully terminates malignant status epilepticus. Epilepsy Res. 2008 Dec;82(2–3):219–222. PubMed PMID: 18804344.
  • Yeh PS, Shen HN, Chen TY. Oral ketamine controlled refractory nonconvulsive status epilepticus in an elderly patient. Seizure. 2011 Nov;20(9):723–726. PubMed PMID: 21724423.
  • Kramer AH. Early ketamine to treat refractory status epilepticus. Neurocritical Care. 2012 Apr;16(2):299–305. PubMed PMID: 22237581.
  • Zeiler FA, Kaufmann AM, Gillman LM, et al. Ketamine for medically refractory status epilepticus after elective aneurysm clipping. Neurocritical Care. 2013 Aug;19(1):119–124. PubMed PMID: 23702695.
  • Shrestha GS, Joshi P, Chhetri S, et al. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: a report of two cases. Indian J Crit Care Med. 2015 May;19(5):283–285. PubMed PMID: 25983437. Pubmed Central PMCID: 4430749.
  • Hsieh CY, Sung PS, Tsai JJ, et al. Terminating prolonged refractory status epilepticus using ketamine. Clin Neuropharmacol. 2010 May;33(3):165–167. PubMed PMID: 20098301
  • Duley L, Gulmezoglu AM, Henderson-Smart DJ, et al. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010;(11):CD000025. PubMed PMID: 21069663.
  • Duley L, Henderson-Smart DJ, Chou D. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev. 2010;(10):CD000128. PubMed PMID: 20927719.
  • Nowak L, Bregestovski P, Ascher P, et al. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2–8;307(5950):462–465. PubMed PMID: 6320006.
  • Nowak LM, Wright JM. Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg(2+)-free solutions. Neuron. 1992 Jan;8(1):181–187. PubMed PMID: 1370371.
  • Visser NA, Braun KP, Leijten FS, et al. Magnesium treatment for patients with refractory status epilepticus due to POLG1-mutations. J Neurol. 2011 Feb;258(2):218–222. PubMed PMID: 20803213. Pubmed Central PMCID: 3036811.
  • Yang YC, Huang CS, Kuo CC. Lidocaine, carbamazepine, and imipramine have partially overlapping binding sites and additive inhibitory effect on neuronal Na+ channels. Anesthesiology. 2010 Jul;113(1):160–174. PubMed PMID: 20526191.
  • Zeiler FA, Zeiler KJ, Teitelbaum J, et al. Lidocaine for status epilepticus in pediatrics. Can J Neurol Sci / Le journal canadien des sciences neurologiques. 2015 Nov;42(6):414–426. PubMed PMID: 26303341.
  • Zeiler FA, Zeiler KJ, Kazina CJ, et al. Lidocaine for status epilepticus in adults. Seizure. 2015 Sep;31:41–48. PubMed PMID: 26362376.
  • Bernhard CG, Bohm E, Hojeberg S. A new treatment of status epilepticus; intravenous injections of a local anesthetic (lidocaine). AMA Arch Neurol Psychiatry. 1955 Aug;74(2):208–214. PubMed PMID: 14397899.
  • Vezzani A, Ruegg S. The pivotal role of immunity and inflammatory processes in epilepsy is increasingly recognized: introduction. Epilepsia. 2011 May;52(Suppl 3):1–4. PubMed PMID: 21542838.
  • Rogawski MA, Loya CM, Reddy K, et al. Neuroactive steroids for the treatment of status epilepticus. Epilepsia. 2013 Sep;54(Suppl 6):93–98. PubMed PMID: 24001085. Pubmed Central PMCID: 3772544.
  • Broomall E, Natale JE, Grimason M, et al. Pediatric super-refractory status epilepticus treated with allopregnanolone. Ann Neurol. 2014 Dec;76(6):911–915. PubMed PMID: 25363147. Pubmed Central PMCID: 4534165.
  • Trinka E, Dobesberger J. New treatment options in status epilepticus: a critical review on levetiracetam. Therap Adv Neurol Dis. 2009;2(2):79–91.
  • 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):1191–1197.
  • Chen WB, Gao R, Su YY, et al. Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study. Eur J Neurol. 2011 Dec;18(12):1391–1396. PubMed PMID: 21557791.
  • 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 Sep;16(5):536–541. PubMed PMID: 22326977.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.