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)

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.

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
  • 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
  • 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
  • 4 Lowenstein D H, Alldredge B K. Status epilepticus.  N Engl J Med. 1998;  338 970-976
  • 5 Lowenstein D H, Bleck T, Macdonald R L. It's time to revise the definition of status epilepticus.  Epilepsia. 1999;  40 120-122
  • 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
  • 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
  • 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
  • 9 Jordan K G. Continuous EEG monitoring in the neuroscience intensive care unit and emergency department.  J Clin Neurophysiol. 1999;  16 14-39
  • 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
  • 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
  • 12 Claassen J, Jette N, Chum F et al.. Electrographic seizures and periodic discharges after intracerebral hemorrhage.  Neurology. 2007;  69 1356-1365
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 19 Hirsch L J, Arif H. Status epilepticus.  Continuum: Lifelong Learning Neurol. 2007;  13 121-151
  • 20 Misra U K, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus: a pilot study.  Neurology. 2006;  67 340-342
  • 21 Sinha S, Naritoku D K. Intravenous valproate is well tolerated in unstable patients with status epilepticus.  Neurology. 2000;  55 722-724
  • 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
  • 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
  • 24 Agarwal P, Kumar N, Chandra R et al.. Randomized study of intravenous valproate and phenytoin in status epilepticus.  Seizure. 2007;  16 527-532
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 36 Niebauer M, Gruenthal M. Topiramate reduces neuronal injury after experimental status epilepticus.  Brain Res. 1999;  837(1–2) 263-269
  • 37 Klitgaard H. Levetiracetam: the preclinical profile of a new class of antiepileptic drugs?.  Epilepsia. 2001;  42(S4) 13-18
  • 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
  • 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
  • 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
  • 41 DeLorenzo R J, Pellock J M, Towne A R et al.. Epidemiology of status epilepticus.  J Clin Neurophysiol. 1995;  12 316-325
  • 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
  • 43 Hesdorffer D C, Logroscino G, Cascino G et al.. Incidence of status epilepticus in Rochester, Minnesota, 1965–1984.  Neurology. 1998;  50 735-741
  • 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
  • 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
  • 46 Eriksson K, Kälviäinen R. Pharmacologic management of convulsive status epilepticus in childhood.  Expert Rev Neurother. 2005;  5 777-783
  • 47 Hanna J P, Ramundo M L. Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children.  Neurology. 1998;  50 301-303
  • 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
  • 49 Hayashi K, Osawa M, Aihara M et al.. Efficacy of intravenous midazolam for status epilepticus in childhood.  Pediatr Neurol. 2007;  36 366-372
  • 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
  • 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
  • 52 Sahin M, Menache C C, Holmes G L et al.. Outcome of severe refractory status epilepticus in children.  Epilepsia. 2001;  42 1461-1467
  • 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
  • 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
  • 55 Krishnamurthy K B, Drislane F W. Relapse and survival after barbiturate anesthetic treatment of refractory status epilepticus.  Epilepsia. 1996;  37 863-867
  • 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
  • 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
  • 58 Rossetti A O, Logroscino G, Bromfield E B. Refractory status epilepticus: effect of treatment aggressiveness on prognosis.  Arch Neurol. 2005;  62 1698-1702
  • 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
  • 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
  • 61 Litt B, Wityk R J, Hertz S H et al.. Nonconvulsive status epilepticus in the critically ill elderly.  Epilepsia. 1998;  39 1194-1202
  • 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

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

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