Download PDF
Semin Neurol 2008; 28(3): 342-354
DOI: 10.1055/s-2008-1079339
© Thieme Medical Publishers

Treatment of Status Epilepticus

Hiba Arif1 , Lawrence J. Hirsch1
  • 1Comprehensive Epilepsy Center, Columbia University, New York, New York
Further Information

Publication History

Publication Date:
24 July 2008 (online)

    Permissions and Reprints

ABSTRACT

Status epilepticus (SE) is a neurological emergency that requires prompt diagnosis and treatment, as delay is associated with a higher likelihood of poor response to treatment and worse outcome. Lorazepam has been well established as a first-line therapy. Subsequent steps are less established, and there are many reasonable options, including intravenous fosphenytoin, valproate, midazolam, propofol, and phenobarbital. If intravenous access is not immediately available, rectal diazepam or nasal or buccal midazolam should be given; this can also be used as out-of-hospital treatment to prevent or treat SE. For refractory SE, continuous intravenous midazolam and propofol, separately or in combination, are rapidly effective, with pentobarbital remaining the gold standard for prolonged cases. If a patient does not awaken after treatment, urgent electroencephalogram (EEG) should be obtained to rule out nonconvulsive seizure activity. In refractory SE, continuous EEG monitoring is required to recognize recurrence of seizure activity, as most seizures will be nonconvulsive.

KEYWORDS

Status epilepticus - seizure - nonconvulsive status epilepticus - epilepsy - continuous EEG monitoring

REFERENCES

  • 1 Logroscino G, Hesdorffer D C, Cascino G et al.. Time trends in incidence, mortality, and case-fatality after first episode of status epilepticus.  Epilepsia. 2001;  42 1031-1035
    CrossrefPubMedGoogle Scholar
  • 2 Claassen J, Lokin J K, Fitzsimmons B F et al.. Predictors of functional disability and mortality after status epilepticus.  Neurology. 2002;  58 139-142
    PubMedGoogle Scholar
  • 3 DeLorenzo R J, Hauser W A, Towne A R et al.. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia.  Neurology. 1996;  46 1029-1035
    CrossrefPubMedGoogle Scholar
  • 4 Lowenstein D H, Alldredge B K. Status epilepticus.  N Engl J Med. 1998;  338 970-976
    CrossrefPubMedGoogle Scholar
  • 5 Lowenstein D H, Bleck T, Macdonald R L. It's time to revise the definition of status epilepticus.  Epilepsia. 1999;  40 120-122
    CrossrefPubMedGoogle Scholar
  • 6 Jenssen S, Gracely E J, Sperling M R. How long do most seizures last? A systematic comparison of seizures recorded in the epilepsy monitoring unit.  Epilepsia. 2006;  47 1499-1503
    CrossrefPubMedGoogle Scholar
  • 7 DeLorenzo R J, Waterhouse E J, Towne A R et al.. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus.  Epilepsia. 1998;  39 833-840
    CrossrefPubMedGoogle Scholar
  • 8 Claassen J, Mayer S A, Kowalski R G et al.. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients.  Neurology. 2004;  62 1743-1748
    CrossrefPubMedGoogle Scholar
  • 9 Jordan K G. Continuous EEG monitoring in the neuroscience intensive care unit and emergency department.  J Clin Neurophysiol. 1999;  16 14-39
    CrossrefPubMedGoogle Scholar
  • 10 Vespa P M, Nuwer M R, Nenov V et al.. Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring.  J Neurosurg. 1999;  91 750-760
    CrossrefPubMedGoogle Scholar
  • 11 Towne A R, Waterhouse E J, Boggs J G et al.. Prevalence of nonconvulsive status epilepticus in comatose patients.  Neurology. 2000;  54 340-345
    CrossrefPubMedGoogle Scholar
  • 12 Claassen J, Jette N, Chum F et al.. Electrographic seizures and periodic discharges after intracerebral hemorrhage.  Neurology. 2007;  69 1356-1365
    CrossrefPubMedGoogle Scholar
  • 13 Vespa P M, O'Phelan K, Shah M et al.. Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome.  Neurology. 2003;  60 1441-1446
    CrossrefPubMedGoogle Scholar
  • 14 Young G B, Jordan K G, Doig G S. An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality.  Neurology. 1996;  47 83-89
    CrossrefPubMedGoogle Scholar
  • 15 Lowenstein D H, Alldredge B K. Status epilepticus at an urban public hospital in the 1980s.  Neurology. 1993;  43(3 Pt 1) 483-488
    CrossrefPubMedGoogle Scholar
  • 16 Mazarati A M, Baldwin R A, 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
    CrossrefPubMedGoogle Scholar
  • 17 Claassen J, Hirsch L J, Mayer S A. Treatment of status epilepticus: a survey of neurologists.  J Neurol Sci. 2003;  211(1–2) 37-41
    CrossrefPubMedGoogle Scholar
  • 18 Treiman D M, Meyers P D, Walton N Y et al.. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group.  N Engl J Med. 1998;  339 792-798
    CrossrefPubMedGoogle Scholar
  • 19 Hirsch L J, Arif H. Status epilepticus.  Continuum: Lifelong Learning Neurol. 2007;  13 121-151
    PubMedGoogle Scholar
  • 20 Misra U K, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus: a pilot study.  Neurology. 2006;  67 340-342
    CrossrefPubMedGoogle Scholar
  • 21 Sinha S, Naritoku D K. Intravenous valproate is well tolerated in unstable patients with status epilepticus.  Neurology. 2000;  55 722-724
    CrossrefPubMedGoogle Scholar
  • 22 Limdi N A, Shimpi A V, Faught E et al.. Efficacy of rapid IV administration of valproic acid for status epilepticus.  Neurology. 2005;  64 353-355
    CrossrefPubMedGoogle Scholar
  • 23 Peters C N, Pohlmann-Eden B. Intravenous valproate as an innovative therapy in seizure emergency situations including status epilepticus: experience in 102 adult patients.  Seizure. 2005;  14 164-169
    CrossrefPubMedGoogle Scholar
  • 24 Agarwal P, Kumar N, Chandra R et al.. Randomized study of intravenous valproate and phenytoin in status epilepticus.  Seizure. 2007;  16 527-532
    CrossrefPubMedGoogle Scholar
  • 25 Alldredge B K, Gelb A M, Isaacs S M et al.. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.  N Engl J Med. 2001;  345 631-637
    CrossrefPubMedGoogle Scholar
  • 26 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 83-86
    CrossrefPubMedGoogle Scholar
  • 27 Scott R C, Besag F M, Neville B G. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial.  Lancet. 1999;  353 623-626
    CrossrefPubMedGoogle Scholar
  • 28 Baysun S, Aydin O F, Atmaca E et al.. A comparison of buccal midazolam and rectal diazepam for the acute treatment of seizures.  Clin Pediatr (Phila). 2005;  44 771-776
    CrossrefPubMedGoogle Scholar
  • 29 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;  366 205-210
    CrossrefPubMedGoogle Scholar
  • 30 Claassen J, Hirsch L J, Emerson R G et al.. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review.  Epilepsia. 2002;  43 146-153
    PubMedGoogle Scholar
  • 31 Claassen J, Hirsch L J, Emerson R G et al.. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus.  Neurology. 2001;  57 1036-1042
    PubMedGoogle Scholar
  • 32 Rossetti A O, Reichhart M D, Schaller M D et al.. Propofol treatment of refractory status epilepticus: a study of 31 episodes.  Epilepsia. 2004;  45 757-763
    CrossrefPubMedGoogle Scholar
  • 33 Robakis T K, Hirsch L J. Literature review, case report, and expert discussion of prolonged refractory status epilepticus.  Neurocrit Care. 2006;  4 35-46
    CrossrefPubMedGoogle Scholar
  • 34 Rossetti A O, Bromfield E B. Levetiracetam in the treatment of status epilepticus in adults: a study of 13 episodes.  Eur Neurol. 2005;  54 34-38
    CrossrefPubMedGoogle Scholar
  • 35 Towne A R, Garnett L K, Waterhouse E J et al.. The use of topiramate in refractory status epilepticus.  Neurology. 2003;  60 332-334
    CrossrefPubMedGoogle Scholar
  • 36 Niebauer M, Gruenthal M. Topiramate reduces neuronal injury after experimental status epilepticus.  Brain Res. 1999;  837(1–2) 263-269
    CrossrefPubMedGoogle Scholar
  • 37 Klitgaard H. Levetiracetam: the preclinical profile of a new class of antiepileptic drugs?.  Epilepsia. 2001;  42(S4) 13-18
    CrossrefPubMedGoogle Scholar
  • 38 Ramael S, Daoust A, Otoul C et al.. Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and pharmacokinetic study.  Epilepsia. 2006;  47 1128-1135
    CrossrefPubMedGoogle Scholar
  • 39 Farooq M U, Naravetla B, Majid A et al.. IV levetiracetam in the management of non-convulsive status epilepticus.  Neurocrit Care. 2007;  7 36-39
    CrossrefPubMedGoogle Scholar
  • 40 Knake S, Gruener J, Hattemer K et al.. Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus.  J Neurol Neurosurg Psychiatry. 2008;  79 588-589
    CrossrefPubMedGoogle Scholar
  • 41 DeLorenzo R J, Pellock J M, Towne A R et al.. Epidemiology of status epilepticus.  J Clin Neurophysiol. 1995;  12 316-325
    CrossrefPubMedGoogle Scholar
  • 42 Chin R F, Neville B G, Peckham C et al.. Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study.  Lancet. 2006;  368 222-229
    CrossrefPubMedGoogle Scholar
  • 43 Hesdorffer D C, Logroscino G, Cascino G et al.. Incidence of status epilepticus in Rochester, Minnesota, 1965–1984.  Neurology. 1998;  50 735-741
    CrossrefPubMedGoogle Scholar
  • 44 Shinnar S, Pellock J M, Moshe S L et al.. In whom does status epilepticus occur: age-related differences in children.  Epilepsia. 1997;  38 907-914
    CrossrefPubMedGoogle Scholar
  • 45 Jette N, Claassen J, Emerson R G et al.. Frequency and predictors of nonconvulsive seizures during continuous electroencephalographic monitoring in critically ill children.  Arch Neurol. 2006;  63 1750-1755
    CrossrefPubMedGoogle Scholar
  • 46 Eriksson K, Kälviäinen R. Pharmacologic management of convulsive status epilepticus in childhood.  Expert Rev Neurother. 2005;  5 777-783
    CrossrefPubMedGoogle Scholar
  • 47 Hanna J P, Ramundo M L. Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children.  Neurology. 1998;  50 301-303
    PubMedGoogle Scholar
  • 48 van Gestel J P, Blusse van Oud-Alblas H J, Malingre M et al.. Propofol and thiopental for refractory status epilepticus in children.  Neurology. 2005;  65 591-592
    CrossrefPubMedGoogle Scholar
  • 49 Hayashi K, Osawa M, Aihara M et al.. Efficacy of intravenous midazolam for status epilepticus in childhood.  Pediatr Neurol. 2007;  36 366-372
    CrossrefPubMedGoogle Scholar
  • 50 Tay S K, Hirsch L J, Leary L et al.. Nonconvulsive status epilepticus in children: clinical and EEG characteristics.  Epilepsia. 2006;  47 1504-1509
    CrossrefPubMedGoogle Scholar
  • 51 Gilbert D L, Gartside P S, Glauser T A. Efficacy and mortality in treatment of refractory generalized convulsive status epilepticus in children: a meta-analysis.  J Child Neurol. 1999;  14 602-609
    CrossrefPubMedGoogle Scholar
  • 52 Sahin M, Menache C C, Holmes G L et al.. Outcome of severe refractory status epilepticus in children.  Epilepsia. 2001;  42 1461-1467
    CrossrefPubMedGoogle Scholar
  • 53 Kim S J, Lee D Y, Kim J S. Neurologic outcomes of pediatric epileptic patients with pentobarbital coma.  Pediatr Neurol. 2001;  25 217-220
    CrossrefPubMedGoogle Scholar
  • 54 Sahin M, Menache C C, Holmes G L et al.. Prolonged treatment for acute symptomatic refractory status epilepticus: outcome in children.  Neurology. 2003;  61 398-401
    PubMedGoogle Scholar
  • 55 Krishnamurthy K B, Drislane F W. Relapse and survival after barbiturate anesthetic treatment of refractory status epilepticus.  Epilepsia. 1996;  37 863-867
    CrossrefPubMedGoogle Scholar
  • 56 Hesdorffer D C, Logroscino G, Cascino G D et al.. Recurrence of afebrile status epilepticus in a population-based study in Rochester, Minnesota.  Neurology. 2007;  69 73-78
    CrossrefPubMedGoogle Scholar
  • 57 Krishnamurthy K B, Drislane F W. Depth of EEG suppression and outcome in barbiturate anesthetic treatment for refractory status epilepticus.  Epilepsia. 1999;  40 759-762
    CrossrefPubMedGoogle Scholar
  • 58 Rossetti A O, Logroscino G, Bromfield E B. Refractory status epilepticus: effect of treatment aggressiveness on prognosis.  Arch Neurol. 2005;  62 1698-1702
    CrossrefPubMedGoogle Scholar
  • 59 Jordan K G, Hirsch L J. Nonconvulsive status epilepticus (NCSE), treat to burst-suppression: pro and con.  Epilepsia. 2006;  47(suppl l) 41-45
    PubMedGoogle Scholar
  • 60 Jirsch J, Hirsch L J. Nonconvulsive seizures: developing a rational approach to the diagnosis and management in the critically ill population.  Clin Neurophysiol. 2007;  118 1660-1670
    CrossrefPubMedGoogle Scholar
  • 61 Litt B, Wityk R J, Hertz S H et al.. Nonconvulsive status epilepticus in the critically ill elderly.  Epilepsia. 1998;  39 1194-1202
    CrossrefPubMedGoogle Scholar
  • 62 DeGiorgio C M, Heck C N, Robinowicz A L, Gott P S, Smith T, Correale J. Serum neuron-specific enolase in the major subtypes of status epilepticus.  Neurolgy. 1999;  52 746-749
    PubMedGoogle Scholar

Lawrence J HirschM.D. 

Associate Clinical Professor of Neurology, Comprehensive Epilepsy Center, Columbia University, Neurological Institute

Box NI-135, 710 West 168th Street, New York, NY 10032

Email: ljh3@columbia.edu