Skip to main content Accessibility help
  • Print publication year: 2019
  • Online publication date: July 2019

Chapter 15 - Status Epilepticus in the Neurocritical Care Unit


Status epilepticus (SE) is defined as continuous or repetitive seizure activity persisting for at least five minutes without recovery to baseline between attacks [1,2]. SE may be classified into convulsive and nonconvulsive, based on the presence of rhythmic jerking of the extremities. Refractory status epilepticus (RSE) is defined as ongoing seizures failing to respond to first- and second-line anticonvulsant drug therapy. Among these patients, 10 to 15% [3] fail to respond to third-line therapy, and are considered to have super-refractory SE (SRSE) [4].

1.Brophy, GM, Bell, R, Claassen, J, et al. (2012). Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 17(1): 323.
2.Lowenstein, DH, Alldredge, BK (1993). Status epilepticus at an urban public hospital in the 1980s. Neurology 43(3 Pt 1): 483488.
3.Novy, J, Logroscino, G, Rossetti, AO (2010). Refractory status epilepticus: a prospective observational study. Epilepsia 51(2): 251256.
4.Foreman, B, Hirsch, LJ (2012). Epilepsy emergencies: diagnosis and management. Neurol Clin 30: 1141.
5.Claassen, J, Silbergleit, R, Weingart, SD, Smith, WS (2012). Emergency neurological life support: status epilepticus. Neurocrit Care 17 Suppl 1: S73S78.
6.Pallin, DJ, Goldstein, JN, Moussally, JS, et al. (2008). Seizure visits in US emergency departments: epidemiology and potential disparities in care. Int J Emerg Med.;1(2): 97105.
7.Pitts, S, Niska, RW, Xu, J, Burt, CW (2008). National Hospital Ambulatory Medical Care Survey: 2006 emergency department summary. Natl Health Stat Report (7): 138.
8.Alldredge, BK, Gelb, AM, Isaacs, SM, et al. (2001). A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 345(9): 631637.
9.Oddo, M, Carrera, E, Claassen, J, Mayer, SA, Hirsch, LJ (2009). Continuous electroencephalography in the medical intensive care unit. Crit Care Med 37(6): 20512056.
10.Young, GB, Jordan, KG, Doig, GS (1996). An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality. Neurology 47(1): 8389.
11.Claassen, J, Mayer, SA, Kowalski, RG, et al. (2004). Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 62(10): 17431748.
12.Kurtz, P, Gaspard, N, Wahl, AS, et al. (2014). Continuous electroencephalography in a surgical intensive care unit. Intensive Care Med 40(2): 228234.
13.DeLorenzo, RJ, Pellock, JM, Towne, AR, Boggs, JG (1995). Epidemiology of status epilepticus. J Clin Neurophysiol 12(4): 316325.
14.DeLorenzo, RJ, Waterhouse, EJ, Towne, AR, et al. (1998). Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia 39(8): 833840.
15.Mayer, S, Claassen, J, Lokin, J, et al. (2002). Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 59(2): 205210.
16.Trinka, E, Hofler, J, Zerbs, A (2012). Causes of status epilepticus. Epilepsia 53 Suppl 4: 127138.
17.Hesdorffer, DC, Logroscino, G, Cascino, G, Annegers, JF, Hauser, WA (1998). Incidence of status epilepticus in Rochester, Minnesota, 1965–1984. Neurology 50(3): 735741.
18.DeLorenzo, RJ, Hauser, WA, Towne, AR, et al. (1996). A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 46(4): 10291035.
19.Shinnar, S, Pellock, JM, Moshé, SL, et al. (1997). In whom does status epilepticus occur: age-related differences in children. Epilepsia 38(8): 907914.
20.NLSTEPSS Collaborative Group, Chin, RF, Neville, BG, Peckham, C, et al. (2006). Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet 368(9531): 222229.
21.American Academy of Neurology Subcommittee; Practice Committee of the Child Neurology Society, Riviello, JJ Jr., Ashwal, S, Hirtz, D, et al. (2006). 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 67(9): 15421550.
22.Theodore, WH, Porter, RJ, Albert, P, et al. (1994). The secondarily generalized tonic-clonic seizure: a videotape analysis. Neurology 44(8): 14031407.
23.Sutter, R, Kaplan, PW (2012). Electroencephalographic criteria for nonconvulsive status epilepticus: synopsis and comprehensive survey. Epilepsia 53 (Suppl 3): 151.
24.Beniczky, S, Hirsch, LJ, Kaplan, PW, et al. (2013). Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia 54 (Suppl 6): 2829.
25.Jirsch, J, Hirsch, LJ (2007). Nonconvulsive seizures: developing a rational approach to the diagnosis and management in the critically ill population. Clin Neurophysiol 118(8): 16601670.
26.Walker, M, Cross, H, Smith, S, et al. (2005). Nonconvulsive status epilepticus: Epilepsy Research Foundation workshop reports. Epileptic Disord 7(3): 253296.
27.Husain, AM, Horn, GJ, Jacobson, MP (2003). Non-convulsive status epilepticus: usefulness of clinical features in selecting patients for urgent EEG. J Neurol Neurosurg Psychiatry 74(2): 189191.
28.Lowenstein, DH, Aminoff, MJ (1992). Clinical and EEG features of status epilepticus in comatose patients. Neurology 42(1): 100104.
29.Simon, RP, Aminoff, MJ (1986). Electrographic status epilepticus in fatal anoxic coma. Ann Neurol 20(3): 351355.
30.Goodkin, HP, Yeh, JL, Kapur, J (2005). Status epilepticus increases the intracellular accumulation of GABAA receptors. . J Neurosci 25(23): 55115520.
31.Naylor, DE, Liu, H, Wasterlain, CG (2005). Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci 25: 77247733.
32.Meierkord, H, Boon, P, Engelsen, B, et al. (2010). EFNS guideline on the management of status epilepticus in adults. Eur J Neurol 17(3): 348355.
33.Claassen, J, Hirsch, LJ, Emerson, RG, Mayer, SA (2002). Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 43(2): 146153.
34.Prasad, A, Worrall, BB, Bertram, EH, Bleck, TP (2001). Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 42(3): 380386.
35.Westover, MB, Shafi, MM, Bianchi, MT, et al. (2014). The probability of seizures during EEG monitoring in critically ill adults. Clin Neurophysiol 126(3): 463-471.
36.Szabó, CA, Lancaster, JL, Lee, S, et al. (2006). MR imaging volumetry of subcortical structures and cerebellar hemispheres in temporal lobe epilepsy Am J Neuroradiology 27(10): 21552160.
37.Briellmann, RS, Wellard, RM, Jackson, GD (2005). Seizure-associated abnormalities in epilepsy: evidence from MR imaging. Epilepsia 46(5): 760766.
38.Vespa, PM, McArthur, DL, Xu, Y, et al. (2010). Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy. Neurology 75(9): 792798.
39.Parmar, H, Lim, SH, Tan, NC, Lim, CC (2006). Acute symptomatic seizures and hippocampus damage: DWI and MRS findings. Neurology 66(11):17321735.
40.Donaire, A, Carreno, M, Gómez, B, et al. (2006). Cortical laminar necrosis related to prolonged focal status epilepticus. J Neurol Neurosurg Psychiatry 77(1): 104106.
41.Lowenstein, DH (1999). Status epilepticus: an overview of the clinical problem. Epilepsia 40 (Suppl 1): S3S8; discussion S21–S22.
42.Silbergleit, R, Durkalski, V, Lowenstein, D, et al. (2012). Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med 366(7): 591600.
43.Treiman, DM, Meyers, PD, Walton, NY, et al. (1998). A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med 339(12): 792798.
44.Leppik, IE, Derivan, AT, Homan, RW, et al. (1983). Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 249(11): 14521454.
45.Misra, UK, Kalita, J, Patel, R (2006). Sodium valproate vs phenytoin in status epilepticus: a pilot study. Neurology 67(2): 340342.
46.Moddel, G, Bunten, S, Dobis, C, et al. (2009). Intravenous levetiracetam: a new treatment alternative for refractory status epilepticus. J Neurol Neurosurg Psychiatry 80(6): 689692.
47.Albers, JM, Möddel, G, Dittrich, R, et al. (2011). Intravenous lacosamide–an effective add-on treatment of refractory status epilepticus. Seizure 20: 428430.
48.Höfler, J, Trinka, E (2013). Lacosamide as a new treatment option in status epilepticus. Epilepsia 54(3): 393404.
49.Goodwin, H, Hinson, HE, Shermock, KM, et al. (2011). The use of lacosamide in refractory status epilepticus. Neurocrit Care 14(3): 348353.
50.Sutter, R, Marsch, S, Fuhr, P, Kaplan, PW, Rüegg, S (2014). Anesthetic drugs in status epilepticus: risk or rescue? A 6-year cohort study. Neurology 82(8): 656664.
51.Kowalski, RG, Ziai, WC, Rees, RN, et al. (2012). Third-line antiepileptic therapy and outcome in status epilepticus: the impact of vasopressor use and prolonged mechanical ventilation. Crit Care Med 40(9): 26772684.
52.Rossetti, AO, Milligan, TA, Vulliemoz, S, et al. (2011). A randomized trial for the treatment of refractory status epilepticus. Neurocrit Care 14(1): 410.
53.Iyer, VN, Hoel, R, Rabinstein, AA (2009). Propofol infusion syndrome in patients with refractory status epilepticus: an 11-year clinical experience. Crit Care Med 37(12): 30243030.
54.Fernandez, A, Lantigua, H, Lesch, C, et al. (2014). High-dose midazolam infusion for refractory status epilepticus. Neurology 82(4): 359365.
55.Claassen, J, Hirsch, LJ, Emerson, RG, et al. (2001). Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 57(6): 10361042.
56.Shafer, A (1998). Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens. Crit Care Med 26(5): 947956.
57.Shafer, A, Doze, VA, White, PF (1990). Pharmacokinetic variability of midazolam infusions in critically ill patients. Crit Care Med 18(9): 10391041.
58.Finley, GA, MacManus, B, Sampson, SE, Fernandez, CV, Retallick, R (1993). Delayed seizures following sedation with propofol. Can J Anaesth 40(9): 863865.
59.Kam, PC, Cardone, D (2007). Propofol infusion syndrome. Anaesthesia 62(7): 690701.
60.Huff, JS, Bleck, TP (1996). Propofol and midazolam in status epilepticus. Acad Emerg Med 3(2): 179.
61.Bleck, T (1995). Critical Care Medicine: Principles of Diagnosis and Management. Chicago: Mosby.
62.Pugin, D, Foreman, B, De Marchis, GM, et al. (2014). Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study. Crit Care 18(3): R103.
63.Yaffe, K, Lowenstein, DH (1993). Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus. Neurology 43(5): 895900.
64.Devlin, E, Clarke, RS, Mirakhur, RK, McNeill, TA (1994). Effect of four i.v. induction agents on T-lymphocyte proliferations to PHA in vitro. Br J Anaesth 73(3): 315317.
65.Kramer, AH (2012). Early ketamine to treat refractory status epilepticus. Neurocrit Care 16(2): 299305.
66.Gaspard, N, Foreman, B, Judd, LM, et al. (2013). Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Epilepsia 54(8): 14981503.
67.Zeiler, FA, Teitelbaum, J, Gillman, LM, West, M (2014). NMDA antagonists for refractory seizures. Neurocrit Care. 20(3): 502513.
68.Martin, B, Kapur, J (2008). A combination of ketamine and diazepam synergistically controls refractory status epilepticus induced by cholinergic stimulation. Epilepsia 49(2): 248255.
69.Hsieh, C, Sung, PS, Tsai, JJ, Huang, CW (2010). Terminating prolonged refractory status epilepticus using ketamine. Clin Neuropharmacol 33(3): 165167.
70.Mewasingh, L, Sékhara, T, Aeby, A, Christiaens, FJ, Dan, B (2003). Oral ketamine in paediatric non-convulsive status epilepticus. Seizure 12(7): 483489.
71.Swisher, CB, Doreswamy, M, Gingrich, KJ, Vredenburgh, JJ, Kolls, BJ (2012). Phenytoin, levetiracetam, and pregabalin in the acute management of refractory status epilepticus in patients with brain tumors. Neurocrit Care 16(1): 109113.
72.Kossoff, EH, Zupec-Kania, BA, Amark, PE, et al. (2009). Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia 50(2): 304317.
73.Thakur, KT, Probasco, JC, Hocker, SE, et al. (2014). Ketogenic diet for adults in super-refractory status epilepticus. Neurology 82(8): 665-670.
74.Mirsattari, SM, Sharpe, MD, Young, GB (2004). Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane. Arch Neurol 61(8): 12541259.
75.Fugate, JE, Burns, JD, Wijdicks, EF, et al. (2010). Prolonged high-dose isoflurane for refractory status epilepticus: is it safe? Anesth Analg 111(6): 15201524.
76.Kofke, WA, Young, RS, Davis, P, et al. (1989). Isoflurane for refractory status epilepticus: a clinical series. Anesthesiology 71(5):653659.
77.Shorvon, S, Ferlisi, M (2011). The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 134(Pt 10): 28022818.
78.Claassen, J, Albers, D, Schmidt, JM, et al. (2014). Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome. Ann Neurol 75(5): 771781.
79.Corry, JJ, Dhar, R, Murphy, T, Diringer, MN (2008). Hypothermia for refractory status epilepticus. Neurocrit Care 9(2): 189197.
80.Lambrecq, V, Villéga, F, Marchal, C, et al. (2012). Refractory status epilepticus: electroconvulsive therapy as a possible therapeutic strategy. Seizure 21(9): 661664.
81.Kamel, H, Cornes, SB, Hegde, M, Hall, SE, Josephson, SA (2010). Electroconvulsive therapy for refractory status epilepticus: a case series. Neurocrit Care 12(2): 204210.
82.Lhatoo, SD, Alexopoulos, AV (2007). The surgical treatment of status epilepticus. Epilepsia 48 (Suppl 8): 6165.
83.O’Neill, BR, Valeriano, J, Synowiec, A, et al. (2011). Refractory status epilepticus treated with vagal nerve stimulation: case report. Neurosurgery 69(5): E1172E1175.
84.Legriel, S, Bruneel, F, Dalle, L, et al. (2008). Recurrent takotsubo cardiomyopathy triggered by convulsive status epilepticus. Neurocrit Care 9(1): 118121.
85.Legriel, S, Azoulay, E, Resche-Rigon, M, et al. (2010). Functional outcome after convulsive status epilepticus. Crit Care Med 38(12): 22952303.
86.Scholtes, FB, Renier, WO, Meinardi, H (1994). Generalized convulsive status epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia 35(5):11041112.
87.Bleck, TP (1991). Convulsive disorders: status epilepticus. Clin Neuropharmacol 14(3): 191198.
88.Chen, JW, Wasterlain, CG (2006). Status epilepticus: pathophysiology and management in adults. Lancet Neurol 5(3): 246256.
89.Mazarati, AM, Baldwin, RA, Sankar, R, Wasterlain, CG (1998). Time-dependent decrease in the effectiveness of antiepileptic drugs during the course of self-sustaining status epilepticus. Brain Res 814(1–2): 179185.
90.Payne, T, Bleck, TP (1997). Status epilepticus. Crit Care Clin 13(1): 1738.
91.Aminoff, MJ, Simon, RP (1980). Status epilepticus. Causes, clinical features and consequences in 98 patients. Am J Med 69(5): 657666.
92.Claassen, J, Lokin, JK, Fitzsimmons, BF, Mendelsohn, FA, Mayer, SA (2002). Predictors of functional disability and mortality after status epilepticus. Neurology 58(1): 139142.
93.Logroscino, G, Hesdorffer, DC, Cascino, G, Annegers, JF, Hauser, WA (1997). Short-term mortality after a first episode of status epilepticus. Epilepsia 38(12): 13441349.
94.Logroscino, G, Hesdorffer, DC, Cascino, GD, et al. (2002). Long-term mortality after a first episode of status epilepticus. Neurology 58(4):537541.
95.Krishnamurthy, KB, Drislane, FW (1999). Depth of EEG suppression and outcome in barbiturate anesthetic treatment for refractory status epilepticus. Epilepsia 40(6): 759762.
96.Rossetti, AO, Reichhart, MD, Schaller, MD, Despland, PA, Bogousslavsky, J (2004). Propofol treatment of refractory status epilepticus: a study of 31 episodes. Epilepsia 45(7): 757763.
97.Rossetti, AO, Logroscino, G, Bromfield, EB (2005). Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol 62(11): 16981702.
98.Koubeissi, M, Alshekhlee, A (2007). In-hospital mortality of generalized convulsive status epilepticus: a large US sample. Neurology 69(9): 886893.
99.Rossetti, AO, Hurwitz, S, Logroscino, G, Bromfield, EB (2006). Prognosis of status epilepticus: role of aetiology, age, and consciousness impairment at presentation. J Neurol Neurosurg Psychiatry 77(5): 611615.
100.Logroscino, G, Hesdorffer, DC, Cascino, G, Annegers, JF, Hauser, WA (2001). Time trends in incidence, mortality, and case-fatality after first episode of status epilepticus. Epilepsia 42(8): 10311035.
101.Cooper, AD, Britton, JW, Rabinstein, AA (2009). Functional and cognitive outcome in prolonged refractory status epilepticus. Arch Neurol 66(12): 15051509.
102.Hesdorffer, D, Logroscino, G, Cascino, GD, Hauser, WA (2007). Recurrence of afebrile status epilepticus in a population-based study in Rochester, Minnesota. Neurology 69(1): 7378.