Concepts for Prehospital and Initial In-hospital Therapy of Status Epilepticus

Abstract

Status epilepticus is a major neurological emergency requiring immediate anticonvulsive treatment. Rapid and sufficient treatment is essential for optimizing outcome and reducing mortality. Here, we give an overview on concepts for acute prehospital and initial in-hospital treatment of status epilepticus. Options for initial therapy in settings without intensive care monitoring are presented in detail.

• References

• 1 Betjemann JP, Lowenstein DH. Status epilepticus in adults. Lancet Neurol 2015; 14: 615-624
• 2 Knake S, Rosenow F, Vescovi M. et al. Incidence of status epilepticus in adults in Germany: A prospective, population-based study. Epilepsia 2001; 42: 714-718
• 3 Kortland LM, Alfter A, Bähr O. et al. Costs and cost-driving factors for acute treatment of adults with status epilepticus: A multicenter cohort study from Germany. Epilepsia 2016; 57: 2056-2066
• 4 Strzelczyk A, Knake S, Oertel WH. et al. Inpatient treatment costs of status epilepticus in adults in Germany. Seizure 2013; 22: 882-885
• 5 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; 56: 1515-1523
• 6 Rosenow F. Status epilepticus im Erwachsenenalter. In: Diener HC, Weimar C. (Hrsg.) Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme Verlag; 2012
• 7 Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia 1999; 40: 120-122
• 8 Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology 1993; 43: 483-488
• 9 Kapur J, Macdonald RL. Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity of hippocampal dentate granule cell GABAA receptors. J Neurosci 1997; 17: 7532-7540
• 10 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: 631-637
• 11 Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: A critical review of available therapies and a clinical treatment protocol. Brain 2011; 134: 2802-2818
• 12 Holtkamp M, Othman J, Buchheim K. et al. A “malignant” variant of status epilepticus. Arch Neurol 2005; 62: 1428-1431
• 13 Strzelczyk A, Kortland LM, Knake S. et al. Stiripentol for the treatment of super-refractory status epilepticus. Acta Neurol Scand 2015; 132: 435-439
• 14 Thakur KT, Probasco JC, Hocker SE. et al. Ketogenic diet for adults in super-refractory status epilepticus. Neurology 2014; 82: 665-670
• 15 Rohracher A, Höfler J, Kalss G. et al. Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit. Epilepsy Behav 2015; 49: 354-358
• 16 Broomall E, Natale JE, Grimason M. et al. Pediatric super-refractory status epilepticus treated with allopregnanolone. Ann Neurol 2014; 76: 911-915
• 17 Levesque M, Herrington R, Leclerc L. et al. Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy. Neuropharmacology 2017; 121: 12-19
• 18 Chen JW, Wasterlain CG. Status epilepticus: Pathophysiology and management in adults. Lancet Neurol 2006; 5: 246-256
• 19 Prasad M, Krishnan PR, Sequeira R. et al. Anticonvulsant therapy for status epilepticus. Cochrane database of systematic reviews 2014; CD003723
• 20 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: 173-177
• 21 Alvarez V, Lee JW, Drislane FW. et al. Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison. Epilepsia 2015; 56: 1275-1285
• 22 Silbergleit R, Lowenstein D, Durkalski V. et al. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): A double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics. Epilepsia 2011; 52 (Suppl. 08) 45-47
• 23 Silbergleit R, Durkalski V, Lowenstein D. et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med 2012; 366: 591-600
• 24 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; 56: 254-262
• 25 Silbergleit R, Lowenstein D, Durkalski V. et al. Lessons from the RAMPART study–and which is the best route of administration of benzodiazepines in status epilepticus. Epilepsia 2013; 54 (Suppl. 06) 74-77
• 26 Crawford TO, Mitchell WG, Snodgrass SR. Lorazepam in childhood status epilepticus and serial seizures: Effectiveness and tachyphylaxis. Neurology 1987; 37: 190-195
• 27 Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: A randomised trial. Lancet 1999; 353: 623-626
• 28 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
• 29 Fisgin T, Gurer Y, Tezic T. et al. Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: Prospective randomized study. J Child Neurol 2002; 17: 123-126
• 30 Mahmoudian T, Zadeh MM. Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy Behav 2004; 5: 253-255
• 31 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
• 32 Ashrafi MR, Khosroshahi N, Karimi P. et al. Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children. Eur J Paediatr Neurol 2010; 14: 434-438
• 33 de Haan GJ, van der Geest P, Doelman G. et al. A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations. Epilepsia 2010; 51: 478-482
• 34 Holsti M, Dudley N, Schunk J. et al. Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures in pediatric patients with epilepsy. Arch Pediatr Adolesc Med 2010; 164: 747-753
• 35 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; 52: 788-793
• 36 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; 17: 575-582
• 37 Thakker A, Shanbag P. A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures. J Neurol 2013; 260: 470-474
• 38 Kay L, Reif PS, Belke M. et al. Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures. Epilepsia 2015; 56: 1408-1414
• 39 Kriel RL, Cloyd JC, Hadsall RS. et al. Home use of rectal diazepam for cluster and prolonged seizures: Efficacy, adverse reactions, quality of life, and cost analysis. Ped Neurol 1991; 7: 13-17
• 40 Timmerman A, Jennekens-Schinkel A, Oostrom KJ. et al. Stesolid emergency treatment: Cave social fear!. Seizure 2008; 17: 333-338
• 41 Tatum IW. Adult patient perceptions of emergency rectal medications for refractory seizures. Epilepsy Behav 2002; 3: 535-538
• 42 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; 29: 741-757
• 43 Trinka E, Brigo F, Shorvon S. Recent advances in status epilepticus. Curr Op Neurology 2016; 29: 189-198
• 44 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: 792-798
• 45 Kuruvilla T, Bharucha NE. Cerebellar atrophy after acute phenytoin intoxication. Epilepsia 1997; 38: 500-502
• 46 Rohracher A, Reiter DP, Brigo F. et al. Status epilepticus in the elderly-A retrospective study on 120 patients. Epilepsy Res 2016; 127: 317-323
• 47 Sutter R, Marsch S, Fuhr P. et al. Anesthetic drugs in status epilepticus: Risk or rescue? A 6-year cohort study. Neurology 2014; 82: 656-664
• 48 Kellinghaus C, Stogbauer F. Treatment of status epilepticus in a large community hospital. Epilepsy Behav 2012; 23: 235-240
• 49 Ertl J, Hapfelmeier J, Peckmann T. et al. Guideline conform initial monotherapy increases in patients with focal epilepsy: A population-based study on German health insurance data. Seizure 2016; 41: 9-15
• 50 Strzelczyk A, Bergmann A, Biermann V. et al. Neurologist adherence to clinical practice guidelines and costs in patients with newly diagnosed and chronic epilepsy in Germany. Epilepsy Behav 2016; 64: 75-82
• 51 Bede P, Lawlor D, Solanki D. et al. Carbapenems and valproate: A consumptive relationship. Epilepsia Open 2017; 2: 107-111
• 52 Strzelczyk A, Zöllner JP, Willems LM. et al. Lacosamide in status epilepticus: Systematic review of current evidence. Epilepsia 2017; 58: 933-950
• 53 Höfler J, Unterberger I, Dobesberger J. et al. Intravenous lacosamide in status epilepticus and seizure clusters. Epilepsia 2011; 52: e148-e152
• 54 Kellinghaus C, Berning S, Immisch I. et al. Intravenous lacosamide for treatment of status epilepticus. Acta Neurol Scand 2011; 123: 137-141
• 55 Lang N, Lange M, Schmitt FC. et al. Intravenous lacosamide in clinical practice-Results from an independent registry. Seizure 2016; 39: 5-9
• 56 Strzelczyk A, Steinig I, Willems LM. et al. Treatment of refractory and super-refractory status epilepticus with brivaracetam: A cohort study from two German university hospitals. Epilepsy Behav 2017; 70(pt A): 177-181
• 57 Steinig I, von Podewils F, Möddel G. et al. Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicentre cohort study from Germany. Epilepsia 2017; 58: 1208-1216
• 58 Yates SL, Fakhoury T, Liang W. et al. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav 2015; 52: 165-168
• 59 Brandt C, May TW, Bien CG. Brivaracetam as adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy: The current evidence base. Ther Adv Neurol Dis 2016; 9: 474-482
• 60 Strzelczyk A, Klein KM, Willems LM. et al. Brivaracetam in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus. Expert Rev Clinical Pharmacol 2016; 9: 637-645
• 61 Nicolas JM, Hannestad J, Holden D. et al. Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 2016; 57: 201-209
• 62 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; 14: 194-197
• 63 Neues Rezeptur-Formularium. Midazolam-Rezepturen. ABDA – Bundesvereinigung Deutscher Apothekerverbände 2002