Skip to main content

Advertisement

SpringerLink
Log in

Intravenous levetiracetam as treatment for status epilepticus

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

There are established drugs for the treatment of status epilepticus (SE) but their potentially hazardous side-effects are well known. Levetiracetam (LEV) is a novel anticonvulsant available for intravenous (i.v.) application. It could be an alternative when standard drugs fail or should be avoided. We retrospectively identified patients from two German teaching hospitals who were treated with LEV i.v. for SE. Their charts were reviewed regarding sociodemographic data, type, etiology, onset and duration of SE, dose of LEV, concurrent antiepileptic drugs (AED) treatment, tolerability, and outcome. Thirty-two patients (15 female) were found who were treated with i.v. LEV for SE (median age 71 years). Two patients were exclusively treated with LEV. Eight received a low and further 20 patients a high dose of benzodiazepines before LEV. Two patients were treated with LEV to enable discontinuation of narcosis. SE was generalized convulsive in five, nonconvulsive in 20, and simple focal in seven patients. Etiology was acute 13 times and remote symptomatic 16 times; three SE were of unknown etiology. Therapy was initiated within a median time of 3 h and LEV i.v. was applied within a median time of 6 h. Median LEV bolus was 2,000 mg; median total dose on day 1 was 3,500 mg. Benzodiazepines plus i.v. LEV terminated SE in 23 patients without application of additional anticonvulsants, 10 within 30 min. LEV could not terminate SE in seven patients. We documented nausea and emesis in one and elevation of liver enzymes in another patient that were likely to be attributed to LEV. LEV i.v. seems to be safe with relevant efficiency for the treatment of SE in elderly and multimorbid patients when comorbidity and respiratory insufficiency precludes high doses of benzodiazepines or phenytoin.

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

Similar content being viewed by others

References

  1. Abend NS, Florance N, Finkel RS, Licht DJ, Dlugos DJ (2008) Intravenous levetiracetam terminates refractory focal status epilepticus. Neurocrit Care 10:83–86

    Article  Google Scholar 

  2. Agarwal P, Kumar N, Chandra R, Gupta G, Antony AR, Garg N (2007) Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure 16:527–532

    Article  PubMed  Google Scholar 

  3. Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O’Neil N, Neuhaus JM, Segal MR, Lowenstein DH (2001) A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 345:631–637

    Article  PubMed  CAS  Google Scholar 

  4. Altenmüller DM, Kuhn A, Surges R, Schulze-Bonhage A (2008) Termination of absence status epilepticus by low-dose intravenous levetiracetam. Epilepsia 49:1289–1290

    Article  PubMed  Google Scholar 

  5. Aminoff MJ, Simon RP (1980) Status epilepticus. Causes, clinical features and consequences in 98 patients. Am J Med 69:657–666

    Article  PubMed  CAS  Google Scholar 

  6. Baulac M, Brodie MJ, Elger CE, Krakow K, Stockis A, Meyvisch P, Falter U (2007) Levetiracetam intravenous infusion as an alternative to oral dosing in patients with partial-onset seizures. Epilepsia 48:589–592

    Article  PubMed  CAS  Google Scholar 

  7. Bernhard CG, Bohm E, Hojeberg S (1955) A new treatment of status epilepticus; intravenous injections of a local anesthetic (lidocaine). AMA Arch Neurol Psychiatry 74:208–214

    PubMed  CAS  Google Scholar 

  8. Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T (2007) Progress report on new antiepileptic drugs: a summary of the eigth Eilat conference (EILAT VIII). Epilepsy Res 73:1–52

    Article  PubMed  Google Scholar 

  9. Chen JW, Wasterlain CG (2006) Status epilepticus: pathophysiology and management in adults. Lancet Neurol 5:246–256

    Article  PubMed  Google Scholar 

  10. Commission on Classification, Terminology of the International League Against Epilepsy (1981) Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 22:489–501

    Article  Google Scholar 

  11. Custer KL, Austin NS, Sullivan JM, Bajjalieh SM (2006) Synaptic vesicle protein 2 enhances release probability at quiescent synapses. J Neurosci 26:1303–1313

    Article  PubMed  CAS  Google Scholar 

  12. De Smedt T, Raedt R, Vonck K, Boon P (2007) Levetiracetam: the profile of a novel anticonvulsant drug—part I: preclinical data. CNS Drug Rev 13:43–56

    Article  PubMed  Google Scholar 

  13. DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L, Garnett L, Fortner CA, Ko D (1996) A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 46:1029–1035

    PubMed  CAS  Google Scholar 

  14. Duron RM, Medina MT, Martinez-Juarez IE, Bailey JN, Perez-Gosiengfiao KT, Ramos-Ramirez R, Lopez-Ruiz M, Alonso ME, Ortega RH, Pascual-Castroviejo I, Machado-Salas J, Mija L, Delgado-Escueta AV (2005) Seizures of idiopathic generalized epilepsies. Epilepsia 46(Suppl 9):34–47

    Article  PubMed  Google Scholar 

  15. Eckert M, Besser R (2008) Rapid intravenous infusion of levetiracetam. Akt Neurol 35:211–213

    Article  Google Scholar 

  16. Falip M, Carreno M, Amaro S, Donaire A, Delgado R, Toledo M, Maestro I (2006) Use of levetiracetam in hospitalized patients. Epilepsia 47:2186–2188

    Article  PubMed  CAS  Google Scholar 

  17. Farooq MU, Naravetla B, Majid A, Gupta R, Pysh JJ, Kassab MY (2007) IV levetiracetam in the management of non-convulsive status epilepticus. Neurocrit Care 7:36–39

    Article  PubMed  Google Scholar 

  18. Gastaut H (1969) Classification of the epilepsies. Proposal for an international classification. Epilepsia 10:14–21

    PubMed  Google Scholar 

  19. Grant R, Shorvon SD (2000) Efficacy and tolerability of 1000–4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy. Epilepsy Res 42:89–95

    Article  PubMed  CAS  Google Scholar 

  20. Hamano S, Sugiyama N, Yamashita S, Tanaka M, Hayakawa M, Minamitani M, Yoshinari S, Eto Y (2006) Intravenous lidocaine for status epilepticus during childhood. Dev Med Child Neurol 48:220–222

    Article  PubMed  Google Scholar 

  21. Hattori H, Yamano T, Hayashi K, Osawa M, Kondo K, Aihara M, Haginoya K, Hamano S, Izumi T, Kaneko K, Kato I, Matsukura M, Minagawa K, Miura T, Ohtsuka Y, Sugai K, Takahashi T, Yamanouchi H, Yamamoto H, Yoshikawa H (2008) Effectiveness of lidocaine infusion for status epilepticus in childhood: a retrospective multi-institutional study in Japan. Brain Dev 30:504–512

    Article  PubMed  Google Scholar 

  22. Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA (1998) Incidence of status epilepticus in Rochester, Minnesota, 1965–1984. Neurology 50:735–741

    PubMed  CAS  Google Scholar 

  23. Jackson MJ (2008) Should we accept the status quo? Time for new trials in status epilepticus. J Neurol Neurosurg Psychiatry 79:490

    Article  PubMed  Google Scholar 

  24. Knake S, Gruener J, Hattemer K, Klein KM, Bauer S, Oertel WH, Hamer HM, Rosenow F (2008) Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus. J Neurol Neurosurg Psychiatry 79:588–589

    Article  PubMed  CAS  Google Scholar 

  25. Knake S, Rosenow F, Vescovi M, Oertel WH, Mueller HH, Wirbatz A, Katsarou N, Hamer HM (2001) Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia 42:714–718

    Article  PubMed  CAS  Google Scholar 

  26. Larch J, Trinka E (2006) Intravenous valproate in status epilepticus: a systematic review of evidence. Epilepsia 47(Suppl 3):39

    Google Scholar 

  27. Leppik IE, Derivan AT, Homan RW, Walker J, Ramsay RE, Patrick B (1983) Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 249:1452–1454

    Article  PubMed  CAS  Google Scholar 

  28. Limdi NA, Shimpi AV, Faught E, Gomez CR, Burneo JG (2005) Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology 64:353–355

    PubMed  CAS  Google Scholar 

  29. Lowenstein DH, Bleck T, Macdonald RL (1999) It’s time to revise the definition of status epilepticus. Epilepsia 40:120–122

    Article  PubMed  CAS  Google Scholar 

  30. Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B (2004) The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci USA 101:9861–9866

    Article  PubMed  CAS  Google Scholar 

  31. Olsen KB, Tauboll E, Gjerstad L (2007) Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults. Acta Neurol Scand Suppl 187:51–54

    Article  PubMed  CAS  Google Scholar 

  32. Pascual J, Ciudad J, Berciano J (1992) Role of lidocaine (lignocaine) in managing status epilepticus. J Neurol Neurosurg Psychiatry 55:49–51

    Article  PubMed  CAS  Google Scholar 

  33. Patel NC, Landan IR, Levin J, Szaflarski J, Wilner AN (2006) The use of levetiracetam in refractory status epilepticus. Seizure 15:137–141

    Article  PubMed  Google Scholar 

  34. Patsalos PN (2000) Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther 85:77–85

    Article  PubMed  CAS  Google Scholar 

  35. Patsalos PN (2004) Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet 43:707–724

    Article  PubMed  CAS  Google Scholar 

  36. Peters CN, Pohlmann-Eden B (2005) Intravenous valproate as an innovative therapy in seizure emergency situations including status epilepticus—experience in 102 adult patients. Seizure 14:164–169

    Article  PubMed  Google Scholar 

  37. Ramael S, Daoust A, Otoul C, Toublanc N, Troenaru M, Lu ZS, Stockis A (2006) Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and pharmacokinetic study. Epilepsia 47:1128–1135

    Article  PubMed  CAS  Google Scholar 

  38. Ramael S, De Smedt F, Toublanc N, Otoul C, Boulanger P, Riethuisen JM, Stockis A (2006) Single-dose bioavailability of levetiracetam intravenous infusion relative to oral tablets and multiple-dose pharmacokinetics and tolerability of levetiracetam intravenous infusion compared with placebo in healthy subjects. Clin Ther 28:734–744

    Article  PubMed  CAS  Google Scholar 

  39. Rosenow F, Knake S (2008) Intravenöse Valproattherapie zur Statusbehandlung. In: Valproinsäure: Pharmakologie, klinischer Einsatz, Nebenwirkungen. Springer, Berlin, pp 200–206

  40. Rossetti AO, Bromfield EB (2005) Levetiracetam in the treatment of status epilepticus in adults: a study of 13 episodes. Eur Neurol 54:34–38

    Article  PubMed  CAS  Google Scholar 

  41. Rossetti AO, Bromfield EB (2006) Determinants of success in the use of oral levetiracetam in status epilepticus. Epilepsy Behav 8:651–654

    Article  PubMed  Google Scholar 

  42. Rowan AJ, Scott DF (1970) Major status epilepticus. A series of 42 patients. Acta Neurol Scand 46:573–584

    Article  PubMed  CAS  Google Scholar 

  43. Ruegg S, Naegelin Y, Hardmeier M, Winkler DT, Marsch S, Fuhr P (2008) Intravenous levetiracetam: treatment experience with the first 50 critically ill patients. Epilepsy Behav 12:477–480

    Article  PubMed  Google Scholar 

  44. Rupprecht S, Franke K, Fitzek S, Witte OW, Hagemann G (2007) Levetiracetam as a treatment option in non-convulsive status epilepticus. Epilepsy Res 73:238–244

    Article  PubMed  CAS  Google Scholar 

  45. Schulze-Bonhage A, Hefft S, Oehl B (2007) Termination of complex partial status epilepticus by intravenous levetiracetam—a case report. J Neurol Neurosurg Psychiatry. [Epub ahead of print]

  46. Sinha S, Naritoku DK (2000) Intravenous valproate is well tolerated in unstable patients with status epilepticus. Neurology 55:722–724

    PubMed  CAS  Google Scholar 

  47. Theodore WH, Porter RJ, Albert P, Kelley K, Bromfield E, Devinsky O, Sato S (1994) The secondarily generalized tonic-clonic seizure: a videotape analysis. Neurology 44:1403–1407

    PubMed  CAS  Google Scholar 

  48. Thomas P (2007) How urgent is the treatment of nonconvulsive status epilepticus? Epilepsia 48(Suppl 8):44–45

    Article  PubMed  Google Scholar 

  49. Towne AR, Pellock JM, Ko D, DeLorenzo RJ (1994) Determinants of mortality in status epilepticus. Epilepsia 35:27–34

    Article  PubMed  CAS  Google Scholar 

  50. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, Handforth A, Faught E, Calabrese VP, Uthman BM, Ramsay RE, Mamdani MB (1998) A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med 339:792–798

    Article  PubMed  CAS  Google Scholar 

  51. Trinka E (2007) The use of valproate and new antiepileptic drugs in status epilepticus. Epilepsia 48(Suppl 8):49–51

    Article  PubMed  CAS  Google Scholar 

  52. Vignatelli L, Rinaldi R, Galeotti M, de Carolis P, D’Alessandro R (2005) Epidemiology of status epilepticus in a rural area of northern Italy: a 2-year population-based study. Eur J Neurol 12:897–902

    Article  PubMed  CAS  Google Scholar 

  53. Vignatelli L, Tonon C, D’Alessandro R (2003) Incidence and short-term prognosis of status epilepticus in adults in Bologna, Italy. Epilepsia 44:964–968

    Article  PubMed  Google Scholar 

  54. Waterhouse EJ, DeLorenzo RJ (2001) Status epilepticus in older patients: epidemiology and treatment options. Drugs Aging 18:133–142

    Article  PubMed  CAS  Google Scholar 

  55. Yildiz B, Citak A, Ucsel R, Karabocuoglu M, Aydinli N, Uzel N (2008) Lidocaine treatment in pediatric convulsive status epilepticus. Pediatr Int 50:35–39

    Article  PubMed  CAS  Google Scholar 

  56. Yu KT, Mills S, Thompson N, Cunanan C (2003) Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures. Epilepsia 44:724–726

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest statement

Dr. Berning has received travel support from UCB. Dr. Kellinghaus has received travel support or honoraria from UCB, Janssen-Cilag, Eisai, Sanofi-Aventis, Pfizer, and Novartis. Dr. Boesebeck has received travel support or honoraria from UCB, Eisai, Janssen-Cilag, and Pfizer. UCB financially supported the data collection and the writing of the manuscript. UCB was allowed to comment on the first draft of this article but neither had any influence on data collection and interpretation nor on writing of this article.

Author information

Authors and Affiliations

  1. Department of Neurology, Klinikum Osnabrück, Am Finkenhügel 1, 49076, Osnabrück, Germany

    Sascha Berning & Christoph Kellinghaus

  2. Department of Neurology, Diakoniekrankenhaus Rotenburg/Wümme, Rotenburg (Wümme), Germany

    Frank Boesebeck

  3. Department of Neuropediatrics, University Medical Center Schleswig-Hostein, Campus Kiel, Kiel, Germany

    Andreas van Baalen

Authors
  1. Sascha Berning
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frank Boesebeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreas van Baalen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christoph Kellinghaus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sascha Berning.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berning, S., Boesebeck, F., van Baalen, A. et al. Intravenous levetiracetam as treatment for status epilepticus. J Neurol 256, 1634–1642 (2009). https://doi.org/10.1007/s00415-009-5166-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-009-5166-7

Keywords

Search

Navigation