{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:37:23Z","timestamp":1793356643860,"version":"4.5.0"},"reference-count":53,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"Importance<\/jats:title>Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthetic therapy or recurs on the reduction\/withdrawal of anesthesia. Current clinical knowledge of the disease and optimal treatment approach is sparse.<\/jats:p><\/jats:sec>Objective<\/jats:title>To systematically assess clinical characteristics, causes, outcomes, prognostic factors, and treatment approaches for patients with SRSE.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>In this systematic review and meta-analysis, all studies reporting adult patients (18 years or older) diagnosed with nonanoxic SRSE were considered for inclusion, irrespective of study design. The databases used were MEDLINE, Cochrane Library, EMBASE, and ClinicalTrials.org (database inception through May 5, 2022).<\/jats:p><\/jats:sec>Data extraction and synthesis<\/jats:title>The study complied with the PRISMA guidelines for reporting, data extraction, and data synthesis. Different tools were used to assess risk of bias. All available data were extracted and missing data were neither imputed nor completed by contacting the study authors.<\/jats:p><\/jats:sec>Main outcome and measures<\/jats:title>Successful treatment of SRSE, in-hospital mortality, and disability at discharge (estimated modified Rankin Scale).<\/jats:p><\/jats:sec>Results<\/jats:title>The study team identified a total of 95 articles and 30 conference abstracts reporting 1200 patients with nonanoxic SRSE (266 individual patients were available for meta-analysis). They had a mean SRSE duration of 36.3 days, mean age of 40.8 years, and equal sex distribution. Patients with SRSE had a distinct pattern of etiologies where acute cerebral events and unknown etiologies accounted for 41.6% and 22.3% of all etiologies, respectively. Reports of SRSE caused by, eg, alcohol, drugs, or tumors were rare. At discharge, only 26.8% had none to slight disability (none, 16 [8.4%]; nonsignificant and slight disability, 35 [18.4%]). In-hospital mortality was 24.1%. Mortality stabilized after long-term treatment (more than 28 days) but with increased rates of seizure cessation and moderate to severe disability. Established prognostic factors, such as age and etiology, were not associated with in-hospital mortality. Reported treatment with ketamine, phenobarbital, other barbiturates, vagus nerve stimulator, and ketogenic diet were not associated with outcome.<\/jats:p><\/jats:sec>Conclusion and Relevance<\/jats:title>Patients with SRSE are distinct due to their pattern of care (eg, long-term treatment to younger patients without negative prognostic factors and unknown\/nonmalignant etiologies) and their natural course of SE. Very long-term treatment was associated with lower mortality and high odds of cessation of SRSE but increased risk of moderate to severe disability.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.2407","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T15:34:40Z","timestamp":1690817680000},"page":"959","source":"Crossref","is-referenced-by-count":54,"title":["Outcomes and Treatment Approaches for Super-Refractory Status Epilepticus"],"prefix":"10.1001","volume":"80","author":[{"given":"Camilla Dyremose","family":"Cornwall","sequence":"first","affiliation":[{"name":"Department of Neurology, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kr\u00f8ig\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim Sejr Skovbo","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette Edemann","family":"Callesen","sequence":"additional","affiliation":[{"name":"Metodekonsulent Callesen, Silkeborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph Patrick","family":"Beier","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"},{"name":"OPEN, Open Patient data Explorative Network, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"Pt 10","key":"noi230053r1","doi-asserted-by":"publisher","first-page":"2802","DOI":"10.1093\/brain\/awr215","article-title":"The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol.","volume":"134","author":"Shorvon","year":"2011","journal-title":"Brain"},{"issue":"2","key":"noi230053r2","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1212\/CON.0000000000001103","article-title":"Management of status epilepticus, refractory status epilepticus, and super-refractory status epilepticus.","volume":"28","author":"Trinka","year":"2022","journal-title":"Continuum (Minneap Minn)"},{"issue":"1","key":"noi230053r3","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/ane.12605","article-title":"Refractory and super-refractory status epilepticus in adults: a 9-year cohort study.","volume":"135","author":"Delaj","year":"2017","journal-title":"Acta Neurol Scand"},{"key":"noi230053r4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.eplepsyres.2017.03.009","article-title":"Long-term outcome of refractory status epilepticus in adults: a retrospective population-based study.","volume":"133","author":"Kantanen","year":"2017","journal-title":"Epilepsy Res"},{"issue":"9","key":"noi230053r5","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1111\/epi.2017.58.issue-9","article-title":"Costs, length of stay, and mortality of super-refractory status epilepticus: a population-based study from Germany.","volume":"58","author":"Strzelczyk","year":"2017","journal-title":"Epilepsia"},{"issue":"1","key":"noi230053r6","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13054-017-1661-x","article-title":"Predictors of hospital and one-year mortality in intensive care patients with refractory status epilepticus: a population-based study.","volume":"21","author":"Kantanen","year":"2017","journal-title":"Crit Care"},{"issue":"71","key":"noi230053r7","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"issue":"s6","key":"noi230053r8","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/epi.2013.54.issue-s6","article-title":"The London-Innsbruck Status Epilepticus Colloquia 2007-2011, and the main advances in the topic of status epilepticus over this period.","volume":"54","author":"Shorvon","year":"2013","journal-title":"Epilepsia"},{"issue":"1","key":"noi230053r9","doi-asserted-by":"publisher","first-page":"139","DOI":"10.5005\/jp-journals-10071-24073","article-title":"Medium-chain triglyceride ketogenic diet as a treatment strategy for adult super-refractory status epilepticus.","volume":"26","author":"Dutta","year":"2022","journal-title":"Indian J Crit Care Med"},{"key":"noi230053r10","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3218231","article-title":"Super-refractory status epilepticus treated with high dose perampanel: case series and review of the literature.","volume":"2019","author":"Newey","year":"2019","journal-title":"Case Rep Crit Care"},{"issue":"4","key":"noi230053r11","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/epi.2017.58.issue-4","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"},{"issue":"10","key":"noi230053r12","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1007\/s00415-008-0989-1","article-title":"Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy.","volume":"255","author":"Rossetti","year":"2008","journal-title":"J Neurol"},{"issue":"4","key":"noi230053r13","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1111\/epi.1993.34.issue-4","article-title":"Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy.","volume":"34","year":"1993","journal-title":"Epilepsia"},{"issue":"4","key":"noi230053r14","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1111\/epi.2010.51.issue-4","article-title":"Recommendation for a definition of acute symptomatic seizure.","volume":"51","author":"Beghi","year":"2010","journal-title":"Epilepsia"},{"key":"noi230053r15","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.jclinepi.2017.04.026","article-title":"CARE guidelines for case reports: explanation and elaboration document.","volume":"89","author":"Riley","year":"2017","journal-title":"J Clin Epidemiol"},{"key":"noi230053r17","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":"noi230053r18","doi-asserted-by":"publisher","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"noi230053r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208","article-title":"The REDCap consortium: building an international community of software platform partners.","volume":"95","author":"Harris","year":"2019","journal-title":"J Biomed Inform"},{"issue":"6","key":"noi230053r20","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1111\/ane.v145.6","article-title":"Ketamine in adult super-refractory status epilepticus: efficacy analysis on a prospective registry.","volume":"145","author":"Caranzano","year":"2022","journal-title":"Acta Neurol Scand"},{"issue":"4","key":"noi230053r21","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1111\/ane.13061","article-title":"Perampanel for treatment of status epilepticus in Austria, Finland, Germany, and Spain.","volume":"139","author":"Strzelczyk","year":"2019","journal-title":"Acta Neurol Scand"},{"issue":"1","key":"noi230053r22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/ane.2015.132.issue-1","article-title":"Super-refractory status epilepticus in West China.","volume":"132","author":"Tian","year":"2015","journal-title":"Acta Neurol Scand"},{"issue":"4","key":"noi230053r23","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1111\/ane.2018.137.issue-4","article-title":"Stiripentol for the treatment of super-refractory status epilepticus with cross-sensitivity.","volume":"137","author":"Uchida","year":"2018","journal-title":"Acta Neurol Scand"},{"issue":"8","key":"noi230053r24","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1212\/WNL.0000000000000151","article-title":"Ketogenic diet for adults in super-refractory status epilepticus.","volume":"82","author":"Thakur","year":"2014","journal-title":"Neurology"},{"issue":"1","key":"noi230053r25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4103\/aian.AIAN_170_20","article-title":"Ketogenic diet for super-refractory status epilepticus: a case series and review of literature.","volume":"24","author":"Anand","year":"2021","journal-title":"Ann Indian Acad Neurol"},{"issue":"3","key":"noi230053r26","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1002\/ana.v82.3","article-title":"Brexanolone as adjunctive therapy in super-refractory status epilepticus.","volume":"82","author":"Rosenthal","year":"2017","journal-title":"Ann Neurol"},{"issue":"9","key":"noi230053r27","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/s40263-016-0371-2","article-title":"(S)-Ketamine in refractory and super-refractory status epilepticus: a retrospective study.","volume":"30","author":"H\u00f6fler","year":"2016","journal-title":"CNS Drugs"},{"issue":"3","key":"noi230053r28","doi-asserted-by":"publisher","first-page":"R103","DOI":"10.1186\/cc13883","article-title":"Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study.","volume":"18","author":"Pugin","year":"2014","journal-title":"Crit Care"},{"key":"noi230053r29","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.107929","article-title":"Predictors of outcome in super refractory status epilepticus.","volume":"118","author":"Jose","year":"2021","journal-title":"Epilepsy Behav"},{"key":"noi230053r30","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.yebeh.2015.04.065","article-title":"Incidence and mortality of super-refractory status epilepticus in adults.","volume":"49","author":"Kantanen","year":"2015","journal-title":"Epilepsy Behav"},{"key":"noi230053r31","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.106960","article-title":"Secondary hypothermia in patients with super-refractory status epilepticus managed with propofol and ketamine.","volume":"105","author":"Sabharwal","year":"2020","journal-title":"Epilepsy Behav"},{"issue":"4","key":"noi230053r32","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1684\/epd2.2015.17.issue-4","article-title":"Mega-dose phenobarbital therapy for super-refractory status epilepticus.","volume":"17","author":"Byun","year":"2015","journal-title":"Epileptic Disord"},{"issue":"6","key":"noi230053r33","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1684\/epd2.v23.6","article-title":"Pentobarbital coma therapy for super-refractory status epilepticus and in-hospital mortality: an observational study.","volume":"23","author":"Koh","year":"2021","journal-title":"Epileptic Disord"},{"key":"noi230053r34","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fneur.2019.00025","article-title":"The different clinical features between autoimmune and infectious status epilepticus.","volume":"10","author":"Lin","year":"2019","journal-title":"Front Neurol"},{"key":"noi230053r35","doi-asserted-by":"publisher","first-page":"636","DOI":"10.3389\/fneur.2017.00636","article-title":"A study of super refractory status epilepticus from India.","volume":"8","author":"Misra","year":"2017","journal-title":"Front Neurol"},{"issue":"10","key":"noi230053r36","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1001\/jamaneurol.2016.1572","article-title":"Progressive brain atrophy in super-refractory status epilepticus.","volume":"73","author":"Hocker","year":"2016","journal-title":"JAMA Neurol"},{"issue":"8","key":"noi230053r37","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1002\/jpen.v46.8","article-title":"Modified low ratio ketogenic therapy in the treatment of adults with super-refractory status epilepticus.","volume":"46","author":"Kaul","year":"2022","journal-title":"JPEN J Parenter Enteral Nutr"},{"issue":"3","key":"noi230053r38","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1007\/s12028-021-01395-x","article-title":"Quantitative EEG-based seizure estimation in super-refractory status epilepticus.","volume":"36","author":"Alkhachroum","year":"2021","journal-title":"Neurocrit Care"},{"key":"noi230053r39","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.seizure.2019.12.002","article-title":"New-onset refractory status epilepticus: a retrospective cohort study.","volume":"74","author":"Gugger","year":"2020","journal-title":"Seizure"},{"key":"noi230053r40","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.seizure.2020.12.020","article-title":"A retrospective cohort study of super-refractory status epilepticus in a tertiary neuro-ICU setting.","volume":"85","author":"Kerin","year":"2021","journal-title":"Seizure"},{"key":"noi230053r41","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.seizure.2017.09.003","article-title":"Factors associated with occurrence and outcome of super-refractory status epilepticus.","volume":"52","author":"Mad\u017ear","year":"2017","journal-title":"Seizure"},{"issue":"5","key":"noi230053r42","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1017\/cjn.2017.28","article-title":"Spectrum and predictors of refractory status epilepticus in a developing country.","volume":"44","author":"Dubey","year":"2017","journal-title":"Can J Neurol Sci"},{"issue":"10","key":"noi230053r43","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1007\/s00134-017-4837-6","article-title":"Super-refractory status epilepticus: epidemiology, early predictors, and outcomes.","volume":"43","author":"Chateauneuf","year":"2017","journal-title":"Intensive Care Med"},{"issue":"6","key":"noi230053r44","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1001\/jamaneurol.2022.0609","article-title":"Prediction of long-term survival after status epilepticus using the ACD score.","volume":"79","author":"Roberg","year":"2022","journal-title":"JAMA Neurol"},{"issue":"12","key":"noi230053r45","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1111\/epi.2016.57.issue-12","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"},{"issue":"1","key":"noi230053r46","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/epi.2019.60.issue-1","article-title":"Epidemiology of status epilepticus in adults: a population-based study on incidence, causes, and outcomes.","volume":"60","author":"Leitinger","year":"2019","journal-title":"Epilepsia"},{"issue":"2","key":"noi230053r47","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1136\/bmjebm-2017-110853","article-title":"Methodological quality and synthesis of case series and case reports.","volume":"23","author":"Murad","year":"2018","journal-title":"BMJ Evid Based Med"},{"issue":"1","key":"noi230053r48","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/epi.2019.60.issue-1","article-title":"High long-term mortality after incident status epilepticus in adults: results from a population-based study.","volume":"60","author":"Rodin","year":"2019","journal-title":"Epilepsia"},{"issue":"2","key":"noi230053r49","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/epi.2010.51.issue-2","article-title":"Refractory status epilepticus: a prospective observational study.","volume":"51","author":"Novy","year":"2010","journal-title":"Epilepsia"},{"issue":"2","key":"noi230053r50","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s12028-014-0080-y","article-title":"Epidemiology-based mortality score in status epilepticus (EMSE).","volume":"22","author":"Leitinger","year":"2015","journal-title":"Neurocrit Care"},{"issue":"22","key":"noi230053r51","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":"noi230053r52","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.106466","article-title":"Intravenous antiepileptic drugs in adults with benzodiazepine-resistant convulsive status epilepticus: a systematic review and network meta-analysis.","author":"Brigo","year":"2019","journal-title":"Epilepsy Behav"},{"issue":"25","key":"noi230053r53","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1056\/NEJMoa1608193","article-title":"Hypothermia for neuroprotection in convulsive status epilepticus.","volume":"375","author":"Legriel","year":"2016","journal-title":"N Engl J Med"},{"key":"noi230053r16","unstructured":"Wells? G, Shea? B, O\u2019Connell? D, . The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.? https:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2807605\/jamaneurology_cornwall_2023_oi_230053_1694018358.1359.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T15:01:48Z","timestamp":1694444508000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2807605"}},"subtitle":["A Systematic Review and Meta-Analysis"],"short-title":[],"issued":{"date-parts":[[2023,9,1]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2023.2407","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9,1]]}}}