{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:53:31Z","timestamp":1785308011116,"version":"3.55.0"},"reference-count":74,"publisher":"National Institute for Health and Care Research","issue":"20","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["NIHR132153"],"award-info":[{"award-number":["NIHR132153"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"\n Background<\/jats:title>\n Convulsive status epilepticus is defined as \u2265\u20095 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting.<\/jats:p>\n <\/jats:sec>\n \n Data sources<\/jats:title>\n We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo\u00ae<\/jats:sup>, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020.<\/jats:p>\n <\/jats:sec>\n \n Review methods<\/jats:title>\n Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness.<\/jats:p>\n <\/jats:sec>\n \n Limitations<\/jats:title>\n The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting.<\/jats:p>\n <\/jats:sec>\n \n Study registration<\/jats:title>\n This study is registered as PROSPERO CRD42020201953.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment<\/jats:italic>; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.<\/jats:p>\n <\/jats:sec>","DOI":"10.3310\/rsvk2062","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T14:45:39Z","timestamp":1648219539000},"page":"1-76","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Pre-hospital and emergency department treatment of convulsive status epilepticus in adults: an evidence synthesis"],"prefix":"10.3310","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-884X","authenticated-orcid":true,"given":"Moira","family":"Cruickshank","sequence":"first","affiliation":[{"name":"Health Services Research Unit, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-0354","authenticated-orcid":true,"given":"Mari","family":"Imamura","sequence":"additional","affiliation":[{"name":"Health Services Research Unit, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5437-6789","authenticated-orcid":true,"given":"Corinne","family":"Booth","sequence":"additional","affiliation":[{"name":"Independent Consultant, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6277-7972","authenticated-orcid":true,"given":"Lorna","family":"Aucott","sequence":"additional","affiliation":[{"name":"Health Services Research Unit, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6622-7839","authenticated-orcid":true,"given":"Carl","family":"Counsell","sequence":"additional","affiliation":[{"name":"Institute of Applied Health Sciences, University of Aberdeen, UK"},{"name":"NHS Grampian, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1405-1795","authenticated-orcid":true,"given":"Paul","family":"Manson","sequence":"additional","affiliation":[{"name":"Health Services Research Unit, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5539-8819","authenticated-orcid":true,"given":"Graham","family":"Scotland","sequence":"additional","affiliation":[{"name":"Health Services Research Unit and Health Economics Research Unit, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7576-6751","authenticated-orcid":true,"given":"Miriam","family":"Brazzelli","sequence":"additional","affiliation":[{"name":"Health Services Research Unit, University of Aberdeen, Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2022,3]]},"reference":[{"key":"key20220322135620372_ref1-bib1","doi-asserted-by":"publisher","first-page":"E49","DOI":"10.3390\/jcm5050049","article-title":"Treatment of established status epilepticus","volume":"5","author":"Falco-Walter","year":"2016","journal-title":"J Clin Med"},{"key":"key20220322135620372_ref1-bib2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003723.pub3","article-title":"Anticonvulsant therapy for status epilepticus","volume":"9","author":"Prasad","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"key20220322135620372_ref1-bib3","volume-title":"Status Epilepticus: BMJ Best Practice","author":"Lesser","year":"2018"},{"key":"key20220322135620372_ref1-bib4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12028-012-9695-z","article-title":"Guidelines for the evaluation and management of status epilepticus","volume":"17","author":"Brophy","year":"2012","journal-title":"Neurocrit Care"},{"key":"key20220322135620372_ref1-bib5","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/epi.13670","article-title":"Operational classification of seizure types by the International League Against Epilepsy: position paper of the ILAE Commission for Classification and Terminology","volume":"58","author":"Fisher","year":"2017","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib6","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/j.1528-1157.1999.tb02000.x","article-title":"It\u2019s time to revise the definition of status epilepticus","volume":"40","author":"Lowenstein","year":"1999","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib7","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1056\/NEJM199804023381407","article-title":"Status epilepticus","volume":"338","author":"Lowenstein","year":"1998","journal-title":"N Engl J Med"},{"key":"key20220322135620372_ref1-bib8","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1111\/epi.13121","article-title":"A definition and classification of status epilepticus \u2013 report of the ILAE Task Force on Classification of Status Epilepticus","volume":"56","author":"Trinka","year":"2015","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1177\/0883073807303064","article-title":"Overview: definitions and classifications of seizure emergencies","volume":"22","author":"Pellock","year":"2007","journal-title":"J Child Neurol"},{"key":"key20220322135620372_ref1-bib10","first-page":"9","article-title":"Status epilepticus: epidemiologic considerations","volume":"40","author":"Hauser","year":"1990","journal-title":"Neurology"},{"key":"key20220322135620372_ref1-bib11","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1212\/wnl.55.5.693","article-title":"Incidence of status epilepticus in French-speaking Switzerland: (EPISTAR)","volume":"55","author":"Coeytaux","year":"2000","journal-title":"Neurology"},{"key":"key20220322135620372_ref1-bib12","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1212\/wnl.50.3.735","article-title":"Incidence of status epilepticus in Rochester, Minnesota, 1965\u20131984","volume":"50","author":"Hesdorffer","year":"1998","journal-title":"Neurology"},{"key":"key20220322135620372_ref1-bib13","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1046\/j.1528-1157.2001.01101.x","article-title":"Incidence of status epilepticus in adults in Germany: a prospective, population-based study","volume":"42","author":"Knake","year":"2001","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib14","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1136\/bmj.331.7518.673","article-title":"Status epilepticus: an evidence based guide","volume":"331","author":"Walker","year":"2005","journal-title":"BMJ"},{"key":"key20220322135620372_ref1-bib15","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/j.1528-1167.2009.02323.x","article-title":"Refractory status epilepticus: a prospective observational study","volume":"51","author":"Novy","year":"2010","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib16","unstructured":"Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and Management of Epilepsy in Adults: SIGN 143. Edinburgh: SIGN; 2015. URL: www.sign.ac.uk\/sign-143-diagnosis-and-management-of-epilepsy-in-adults (accessed July 2020)."},{"key":"key20220322135620372_ref1-bib17","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/j.1365-2044.1995.tb15095.x","article-title":"The intensive care treatment of convulsive status epilepticus in the UK. Results of a national survey and recommendations","volume":"50","author":"Walker","year":"1995","journal-title":"Anaesthesia"},{"key":"key20220322135620372_ref1-bib18","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1093\/qjmed\/89.12.913","article-title":"Diagnosis and treatment of status epilepticus on a neurological intensive care unit","volume":"89","author":"Walker","year":"1996","journal-title":"QJM"},{"key":"key20220322135620372_ref1-bib19","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1111\/j.1528-1157.1994.tb02562.x","article-title":"Generalized convulsive status epilepticus: causes, therapy, and outcome in 346 patients","volume":"35","author":"Scholtes","year":"1994","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib20","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1056\/NEJM199809173391202","article-title":"A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group","volume":"339","author":"Treiman","year":"1998","journal-title":"N Engl J Med"},{"key":"key20220322135620372_ref1-bib21","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1016\/S0196-0644(05)80120-9","article-title":"Refractory status epilepticus in adults","volume":"22","author":"Jagoda","year":"1993","journal-title":"Ann Emerg Med"},{"key":"key20220322135620372_ref1-bib22","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1056\/NEJMoa002141","article-title":"A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus","volume":"345","author":"Alldredge","year":"2001","journal-title":"N Engl J Med"},{"key":"key20220322135620372_ref1-bib23","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/epi.12284","article-title":"Lessons from the RAMPART study \u2013 and which is the best route of administration of benzodiazepines in status epilepticus","volume":"54","author":"Silbergleit","year":"2013","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib24","doi-asserted-by":"publisher","first-page":"48","DOI":"10.5698\/1535-7597-16.1.48","article-title":"Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society","volume":"16","author":"Glauser","year":"2016","journal-title":"Epilepsy Curr"},{"key":"key20220322135620372_ref1-bib25","unstructured":"National Institute for Health and Care Excellence (NICE). Epilepsies: Diagnosis and Management. Clinical Guideline [CG137]. London: NICE; 2012. URL: www.nice.org.uk\/guidance\/cg137 (accessed July 2020)."},{"key":"key20220322135620372_ref1-bib26","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1164\/rccm.201102-0273CI","article-title":"Sedation and analgesia in the mechanically ventilated patient","volume":"185","author":"Patel","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"key20220322135620372_ref1-bib27","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s12028-012-9790-1","article-title":"Treatment of status epilepticus: an international survey of experts","volume":"18","author":"Riviello","year":"2013","journal-title":"Neurocrit Care"},{"key":"key20220322135620372_ref1-bib28","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1097\/NRL.0000000000000281","article-title":"Treatment of status epilepticus: what are the guidelines and are we following them?","volume":"25","author":"Parsons","year":"2020","journal-title":"Neurologist"},{"key":"key20220322135620372_ref1-bib29","volume-title":"Proposed Algorithm for Convulsive Status Epilepticus 2016","author":"American Epilepsy Society"},{"key":"key20220322135620372_ref1-bib30","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1111\/j.1468-1331.2009.02917.x","article-title":"European Federation of Neurological Societies. EFNS guideline on the management of status epilepticus in adults","volume":"17","author":"Meierkord","year":"2010","journal-title":"Eur J Neurol"},{"key":"key20220322135620372_ref1-bib31","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.2165\/11636220-000000000-00000","article-title":"Sedation for critically ill or injured adults in the intensive care unit: a shifting paradigm","volume":"72","author":"Roberts","year":"2012","journal-title":"Drugs"},{"key":"key20220322135620372_ref1-bib32","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/00003246-200201000-00020","article-title":"Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult","volume":"30","author":"Jacobi","year":"2002","journal-title":"Crit Care Med"},{"key":"key20220322135620372_ref1-bib33","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1056\/NEJMra1208705","article-title":"Sedation and delirium in the intensive care unit","volume":"370","author":"Reade","year":"2014","journal-title":"N Engl J Med"},{"key":"key20220322135620372_ref1-bib34","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1097\/CCM.0b013e3182783b72","article-title":"Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit","volume":"41","author":"Barr","year":"2013","journal-title":"Crit Care Med"},{"key":"key20220322135620372_ref1-bib35","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/S0140-6736(95)91209-6","article-title":"Prolonged sedation due to accumulation of conjugated metabolites of midazolam","volume":"346","author":"Bauer","year":"1995","journal-title":"Lancet"},{"key":"key20220322135620372_ref1-bib36","first-page":"1","article-title":"Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability","volume":"42","author":"Alvarez","year":"1998","journal-title":"J Intellect Disabil Res"},{"key":"key20220322135620372_ref1-bib37","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1177\/0883073810368312","article-title":"Dissolving oral clonazepam wafers in the acute treatment of prolonged seizures","volume":"25","author":"Troester","year":"2010","journal-title":"J Child Neurol"},{"key":"key20220322135620372_ref1-bib38","doi-asserted-by":"publisher","first-page":"2644","DOI":"10.1001\/jama.298.22.2644","article-title":"Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial","volume":"298","author":"Pandharipande","year":"2007","journal-title":"JAMA"},{"key":"key20220322135620372_ref1-bib39","volume-title":"BUCCOLAM 2.5mg Oromucosal Solution","author":"Electronic Medicines Compendium","year":"2020"},{"key":"key20220322135620372_ref1-bib40","volume-title":"Diazepam RecTubes 10mg Rectal Solution","author":"Electronic Medicines Compendium","year":"2020"},{"key":"key20220322135620372_ref1-bib41","volume-title":"Diazemuls Emulsion","author":"Electronic Medicines Compendium","year":"2020"},{"key":"key20220322135620372_ref1-bib42","volume-title":"Ativan Injection","author":"Electronic Medicines Compendium","year":"2020"},{"key":"key20220322135620372_ref1-bib43","volume-title":"Keppra 100 mg\/ml Concentrate for Solution for Infusion","author":"Electronic Medicines Compendium","year":"2020"},{"key":"key20220322135620372_ref1-bib44","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1056\/NEJMoa1905795","article-title":"Randomized trial of three anticonvulsant medications for status epilepticus","volume":"381","author":"Kapur","year":"2019","journal-title":"N Engl J Med"},{"key":"key20220322135620372_ref1-bib45","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1345\/aph.10387","article-title":"Intravenous valproate in status epilepticus","volume":"35","author":"Hodges","year":"2001","journal-title":"Ann Pharmacother"},{"key":"key20220322135620372_ref1-bib46","volume-title":"Sodium Valproate 100mg\/ml Solution for Injection or Infusion","author":"Electronic Medicines Compendium","year":"2020"},{"key":"key20220322135620372_ref1-bib47","doi-asserted-by":"publisher","first-page":"4","DOI":"10.5863\/1551-6776-25.1.4","article-title":"Status epilepticus: the slow and agonizing death of phenytoin","volume":"25","author":"Hall","year":"2020","journal-title":"J Pediatr Pharmacol Ther"},{"key":"key20220322135620372_ref1-bib48","volume-title":"Phenytoin Hospira 50 mg\/ml Injection BP.","author":"Electronic Medicines Compendium","year":"2019"},{"key":"key20220322135620372_ref1-bib49","doi-asserted-by":"publisher","first-page":"3543","DOI":"10.29309\/TPMJ\/2020.27.07.3543","article-title":"Comparison of phenobarbital and sodium valproate for the treatment of status epilepticus in children","volume":"27","author":"Jamali","year":"2020","journal-title":"Professional Med"},{"key":"key20220322135620372_ref1-bib50","volume-title":"Phenobarbital Sodium 30mg\/ml Injection.","author":"Electronic Medicines Compendium","year":"2018"},{"key":"key20220322135620372_ref1-bib51","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.yebeh.2015.02.030","article-title":"Nonintravenous midazolam versus intravenous or rectal diazepam for the treatment of early status epilepticus: a systematic review with meta-analysis","volume":"49","author":"Brigo","year":"2015","journal-title":"Epilepsy Behav"},{"key":"key20220322135620372_ref1-bib52","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1111\/nyas.13147","article-title":"Benzodiazepine-refractory status epilepticus: pathophysiology and principles of treatment","volume":"1378","author":"Niquet","year":"2016","journal-title":"Ann N Y Acad Sci"},{"key":"key20220322135620372_ref1-bib53","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.seizure.2017.02.015","article-title":"Convulsive Status Epilepticus Study Group of the Uslcentro Toscana, Italy. Challenges in the treatment of convulsive status epilepticus","volume":"47","author":"Zaccara","year":"2017","journal-title":"Seizure"},{"key":"key20220322135620372_ref1-bib54","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0","author":"Higgins","year":"2011"},{"key":"key20220322135620372_ref1-bib55","doi-asserted-by":"publisher","first-page":"e123","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement","volume":"3","author":"Moher","year":"2009","journal-title":"Open Med"},{"key":"key20220322135620372_ref1-bib56","doi-asserted-by":"publisher","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"key20220322135620372_ref1-bib57","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S1474-4422(15)00296-3","article-title":"Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial","volume":"15","author":"Navarro","year":"2016","journal-title":"Lancet Neurol"},{"key":"key20220322135620372_ref1-bib58","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1056\/NEJMoa1107494","article-title":"NETT Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus","volume":"366","author":"Silbergleit","year":"2012","journal-title":"N Engl J Med"},{"key":"key20220322135620372_ref1-bib59","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1212\/wnl.38.2.202","article-title":"Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin","volume":"38","author":"Shaner","year":"1988","journal-title":"Neurology"},{"key":"key20220322135620372_ref1-bib60","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-10979-2","article-title":"Management of the first stage of convulsive status epilepticus in adults: a systematic review of current randomised evidence","author":"Cruickshank","year":"2022","journal-title":"J Neurol"},{"key":"key20220322135620372_ref1-bib61","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1474-4422(15)00333-6","article-title":"Dr No: double drug fails to eliminate status epilepticus","volume":"15","author":"Claassen","year":"2016","journal-title":"Lancet Neurol"},{"key":"key20220322135620372_ref1-bib62","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1093\/qjmed\/95.4.225","article-title":"A comparison of lorazepam and diazepam as initial therapy in convulsive status epilepticus","volume":"95","author":"Cock","year":"2002","journal-title":"QJM"},{"key":"key20220322135620372_ref1-bib63","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1111\/epi.13584","article-title":"Costs and cost-driving factors for acute treatment of adults with status epilepticus: a multicenter cohort study from Germany","volume":"57","author":"Kortland","year":"2016","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib64","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.yebeh.2018.09.046","article-title":"Cost of status epilepticus (SE): effects of delayed treatment and SE duration","volume":"89","author":"Santamarina","year":"2018","journal-title":"Epilepsy Behav"},{"key":"key20220322135620372_ref1-bib65","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1111\/j.1528-1167.2008.01706_3.x","article-title":"The drug treatment of status epilepticus in Europe: consensus document from a workshop at the first London Colloquium on Status Epilepticus","volume":"49","author":"Shorvon","year":"2008","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib66","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s40263-015-0271-x","article-title":"A common reference-based indirect comparison meta-analysis of buccal versus intranasal midazolam for early status epilepticus","volume":"29","author":"Brigo","year":"2015","journal-title":"CNS Drugs"},{"key":"key20220322135620372_ref1-bib67","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1111\/j.1553-2712.2010.00751.x","article-title":"Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis","volume":"17","author":"McMullan","year":"2010","journal-title":"Acad Emerg Med"},{"key":"key20220322135620372_ref1-bib68","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/S0197-2456(01)00120-9","article-title":"The PreHospital Treatment of Status Epilepticus (PHTSE) study: design and methodology","volume":"22","author":"Lowenstein","year":"2001","journal-title":"Control Clin Trials"},{"key":"key20220322135620372_ref1-bib69","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1056\/NEJM200112203452521","article-title":"Correction: a comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus","volume":"345","author":"Alldredge","year":"2001","journal-title":"New Engl J Med"},{"key":"key20220322135620372_ref1-bib70","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/j.1528-1167.2011.03236.x","article-title":"A prehospital randomized trial in convulsive status epilepticus","volume":"52","author":"Navarro","year":"2011","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib71","unstructured":"ClinicalTrials.gov. Study of Antiepileptic Drug in Generalised Convulsive Status Epilepticus. Bethesda, MD: National Library of Medicine; 2010. URL: www.cochranelibrary.com\/central\/doi\/10.1002\/central\/CN-02025411\/full (accessed 21 July 2020)."},{"key":"key20220322135620372_ref1-bib72","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1056\/NEJMx120016","article-title":"Correction: intramuscular versus intravenous therapy for prehospital status epilepticus","volume":"366","author":"Silbergleit","year":"2012","journal-title":"New Engl J Med"},{"key":"key20220322135620372_ref1-bib73","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1528-1167.2011.03235.x","article-title":"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","volume":"52","author":"Silbergleit","year":"2011","journal-title":"Epilepsia"},{"key":"key20220322135620372_ref1-bib74","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s12028-014-0106-5","article-title":"Endotracheal intubation in patients treated for prehospital status epilepticus","volume":"23","author":"Vohra","year":"2015","journal-title":"Neurocrit Care"}],"container-title":["Health Technology Assessment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/FXII0508","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/publications\/RSVK2062\/RSVK2062.xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/FXII0508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T15:50:49Z","timestamp":1692114649000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.journalslibrary.nihr.ac.uk\/hta\/RSVK2062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":74,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["10.3310\/RSVK2062"],"URL":"https:\/\/doi.org\/10.3310\/rsvk2062","relation":{},"ISSN":["1366-5278","2046-4924"],"issn-type":[{"value":"1366-5278","type":"print"},{"value":"2046-4924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"This content has been made freely available to all.","name":"free","label":"Free to read"},{"value":"7-2020","name":"contractual_start_date","label":"Contractual start date","group":{"name":"article_history","label":"Article History"}},{"value":"1-2021","name":"editorial_review_begun","label":"Editorial review begun","group":{"name":"article_history","label":"Article History"}},{"value":"5-2021","name":"accepted_for_publication","label":"Accepted for publication","group":{"name":"article_history","label":"Article History"}}]}}