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Description : Current guidance (2019) with regards to the pharmacological Mx. and Tx. of Status Epilepticus with 2nd. line anti-epileptic drugs (AED's)

Tags : Status Epilepticus, Pharmacology, Epilepsy, Emergency Nursing, Neurological disorders,Pharmacological,Second line Treatment

Published on : May 11, 2021 | Views : 2113 | Downloads : 1

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Slide 1-

Levetiracetam, Valproate or Phenytoin? An Overview and Evaluation of current Pharmacological Second line Treatment options in Status Epilepticus Darren Freeman RN
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Learning Objectives What is a Seizure? Terminology Incidence and Mortality of Status Epilepticus Definition of Status Epilepticus Stages of Status Epilepticus The ‘stepwise’ approach to Tx. & Mx. Current 2nd Line Anti-epileptic Drug (AED) Therapies Review of recent literature including ESETT, ConSEPT & EcLiPSE trials Implications for practice?
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2 1 What is a Seizure? ‘Paroxysmal alteration of neurologic function caused by the excessive, hypersynchronous discharge of neurons in the brain.’ (Stafstrom and Carmant, 2015) https://youtu.be/WqtERCawzC4
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Terminology and Classification of Seizures (ILAE, 2017)
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Incidence and Mortality of Status Epilepticus Annual worldwide incidence of approx. 81.1/100 000 adults according to a recent systematic reviews of population-based studies Actual incidence rates are difficult to determine due to…. Under/over reporting depending on country of origin Misdiagnosis – PNES, NEAD Whether or not reversible causes are included in Diagnosis of SE? Overall Mortality of approx. 20%
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Definition of Status Epilepticus (SE) ‘A condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally prolonged seizures (after time point +1). It is a condition which can have long-term consequences (after time point +2) including neuronal death, neuronal injury and alteration of neuronal networks, depending on the type and duration of seizures.’ (ILAE, 2015)
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ILAE Recommended Tx. Windows (ILAE, 2015) Reversible Causes Systemic Hypoglycaemia,Hypo Na+,Hypo Ca+, Hyper K+ Hypertensive Crisis, Intracranial - Infection, Bleed, Raised ICP ?? Cause- trauma, intracranial mass
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Stages of Status Epilepticus (ILAE, 2015)
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Benzodiazipine Refractory SE Why 1st Line Benzo’s Fail….. About 30-40% of SE cases fail to respond to Benzodiazipines requiring a 2nd line AED Lab studies on rats indicate GABA-A ‘receptor trafficking’ involved After repeated stimulation by GABA agonist drugs (benzo’s) GABA-A receptors become coated in clathrin substance and then undergo apoptosis Less GABA-A receptors now available Predominance of excitory N-methyl-d-aspartate (NMDA) pathway producing glutamate
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(Web MD, 2019) (Niquet et al., 2016)
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Current 2nd line AED Therapies Phenytoin/Fosphenytoin
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Current 2nd line AED Therapies Sodium Valproate
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Current 2nd line AED Therapies Levetiracetam (Keppra)
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‘Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial’ ConSEPT
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EcLiPSE ‘Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial’
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ESETT
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ESETT
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Cost Effectiveness In order of Effectiveness in terminating SE as 2nd line AED Phenobarbital (USD $96.25) Valproate (USD $20.00) Lacsomide (USD $127.20) Levetiracetam (USD $11.50) Phenytoin (USD $33.00) Sánchez - Fernández, I., Gaínza-Lein, M., Lamb, N., & Loddenkemper, T. (2019)
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Implications for Practice?? Benzodiazipines alone were able to terminate seizures in 40-60% of SE cases No clinically significant difference between choice of 2nd line AED and rate of seizure cessation or safety (ESETT) However is a Primary Outcome of: ‘Absence of clinically evident seizures and improvement in level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication’ As defined by the authors of the ESETT trial acceptable??? The pharmacological safety profiles and potential risk of adverse events, depending on the choice of 2nd. Line AED should be weighed up What clinical setting will the patient most likely be cared for in? 2nd Line AED cost and availability
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www.poweredtemplates.com Thank You!
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References Betjemann, J. P., & Lowenstein, D. H. (2015). Status epilepticus in adults. The Lancet Neurology, 14(6), 615-624. doi:https://doi.org/10.1016/S1474-4422(15)00042-3 SDHB (2018). Drug Therapy in Status Epilepticus - Adult (District). (MIDAS ID: 24212). Retrieved from https://vpn.southerndhb.govt.nz/+CSCO+0h75676763663A2F2F63687966722E666268677572656171756F2E746269672E616D++/sites/MIDASpub/SitePages/ViewDoc.aspx?doc=24212 Brigo, F., Bragazzi, N., Nardone, R., & Trinka, E. (2016). Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus. Epilepsy & Behavior, 64. doi:https://doi.org/10.1016/j.yebeh.2016.09.030. Dalziel, S. R., Borland, M. L., Furyk, J., Bonisch, M., Neutze, J., Donath, S., . . . Babl, F. E. (2019). Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. The Lancet, 393(10186), 2135-2145. doi:https://doi.org/10.1016/S0140-6736(19)30722-6E International League Against Epilepsy (2015). A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia, 65(10). doi:https://doi.org/10.1111/epi.13121
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Trinka, E. & Kalviainen, R (2016). 25 years of advances in the definition, classification and treatment of status epilepticus. Seizure, 44, P65-73. doi:https://doi.org/10.1016/j.seizure.2016.11.001 Esmail., S. (2018). Intravenous Levetiracetam versus Phenytoin in the Management of Status Epilepticus in Adults: A Systematic Review of Randomised-Controlled Trials. Journal of Neurological Disorders, 7(399). doi:10.4172/2329-6895.1000399 National Institute for Health and Clinical Excellence [NICE] (2012). Epilepsies: diagnosis and management, Clinical guideline [CG137]. Retrieved from https://www.nice.org.uk/guidance/cg137/chapter/Appendix-F-Protocols-for-treating-convulsive-status-epilepticus-in-adults-and-children-adults-published-in-2004-and-children-published-in-2011 Fisher, R. S., Cross, J. H., D'Souza, C., French, J. A., Haut, S. R., Higurashi, N., . . . Zuberi, S. M. (2017). Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia, 58(4), 531-542. doi:10.1111/epi.13671 Kapur, J., Elm, J., Chamberlain, J. M., Barsan, W., Cloyd, J., Lowenstein, D., . . . Silbergleit, R. (2019). Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. The New England Journal of Medicine, 381(22), 2103–2113. doi:10.1056/NEJMoa1905795
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Laing, S., Fenwick, R., & Yates, J (Hosts). (2016-present). Seizures: Roadside to Resus (Podcast). Retrieved from https://theresusroom.co.uk/seizures/ Leitinger, M., Trinka, E., Zimmermann, G.,Granbichler, C., Kobulashvili, T. & Siebert, U (2020). Epidemiology of status epilepticus in adults: Apples, pears, and oranges — A critical review. Epilepsy and Behaviour, 103(106720). doi:https://doi.org/10.1016/j.yebeh.2019.106720 Mahmoud, S., Marette, V., Lindqvist, T., & Ahmed, S. (2019). Critical Care Management of Status Epilepticus at a Tertiary Care University Hospital. Canadian Journal of Neurological Sciences, 46(6), 702-710. doi:10.1017/cjn.2019.278 Mc Candless, D. W. (1986). Status epilepticus-induced changes in primate cortical energy metabolism. American Journal of Physiology: Cell Physiology, 250(5). Web MD (2019). What happens in your brain during a seizure. Retrieved from https://youtu.be/WqtERCawzC4 Meierkord, H., Boon, P., Engelsen, B., Göcke, K., Shorvon, S., Tinuper, P., & Holtkamp, M. (2010). EFNS guideline on the management of status epilepticus in adults. European Journal of Neurology, 17(3), 348-355. doi:https://doi.org/10.1111/j.1468-1331.2009.02917.x
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Niquet, J., Baldwin, R., Suchomelova, L., Lumley, L., Naylor, D., Eavey, R., & Wasterlain, C. G. (2016). Benzodiazepine-refractory status epilepticus: pathophysiology and principles of treatment. Annals of the New York Academy of Sciences, 1378(1), 166–173. doi:https://doi.org/10.1111/nyas.13147 Smith, P. (2019). Management of Established Status Epilepticus. New England Journal of Medicine, 381(22), 2171-2172. doi: https://doi.org/10.1056/NEJMe1913775 Stafstrom, C. E., & Carmant, L. (2015). Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harbor perspectives in medicine, 5(6). doi: https://doi.org/10.1101/cshperspect.a022426 Sánchez - Fernández, I., Gaínza-Lein, M., Lamb, N., & Loddenkemper, T. (2019). Meta-analysis and cost-effectiveness of second-line antiepileptic drugs for status epilepticus. Neurology, 92(20). doi:10.1212/WNL.0000000000007503 Trinka, E., Höfler, J., Leitinger, M., & Brigo, F. (2015). Pharmacotherapy for Status Epilepticus. Drugs, 75(13), 1499–1521. doi: https://doi.org/10.1007/s40265-015-0454-2 Lyttle MD et al. (2019) Levetiracetam Versus Phenytoin for Second-Line Treatment of Paediatric Convulsive Status epilepticus (EcLiPSE): A Multicentre, Open-Label, Randomised Trial. The Lancet, 393 (10186), 2125-2134. doi: https://doi.org/10.1016/S0140-6736(19)30724-X