{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:03:00Z","timestamp":1789970580967,"version":"4.0.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) are associated with substantial morbidity, mortality, and intensive care requirements. Ketamine has emerged as a potential adjunct because of its N-methyl-D-aspartate receptor antagonism and relatively favourable haemodynamic profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the effectiveness and safety of ketamine in RSE and SRSE resolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This systematic review followed PRISMA 2020 and was registered in PROSPERO (CRD42024625516). PubMed, Scopus, Web of Science, and Biblioteca Virtual en Salud were searched from inception to 20 November 2025. Two independent reviewers screened studies, extracted clinical, therapeutic, electroencephalographic, haemodynamic, and survival data, and assessed risk of bias using National Institutes of Health quality assessment tools. Meta-analysis was not performed because of substantial heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve studies comprising 491 patients were included. Ketamine was generally administered as part of multimodal therapy after failure of several antiseizure medications and intravenous anaesthetics. Infusion rates ranged from 0.05\u2005mg\/kg\/h to 10.5\u2005mg\/kg\/h, and treatment duration ranged from 6\u2005h to 29 days. Study-defined response rates following ketamine initiation ranged from 43.3% for complete electrographic seizure cessation to 100% for overall RSE\/SRSE resolution; however, the highest estimates often reflected combined treatment rather than ketamine alone. Short-term or hospital survival ranged from 45.8% to 81.8%. Immediate haemodynamic deterioration appeared uncommon, although attribution was limited by baseline instability and concomitant therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ketamine-containing regimens were associated with clinically relevant seizure reduction or cessation in RSE\/SRSE, without a consistent signal of acute haemodynamic harm. However, the independent effect of ketamine on sustained seizure control, survival, and functional recovery remains uncertain. Prospective comparative studies using standardised dosing, timing, and outcome definitions are required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>PROSPERO identifier CRD42024625516.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1959414","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:35:36Z","timestamp":1789968936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ketamine use in the refractory and super refractory status epilepticus: a systematic review"],"prefix":"10.3389","volume":"13","author":[{"given":"Betsab\u00e9","family":"Troya-C\u00f3rdova","sequence":"first","affiliation":[{"name":"Universidad UTE, Facultad Ciencias de la Salud Eugenio Espejo, Carrera Atenci\u00f3n Prehospitalaria y Emergencias, Grupo de Investigaci\u00f3n en Medicina Prehospitalaria (GRIMPE)","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo S.","family":"Pinto-Villalba","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad Ciencias de la Salud Eugenio Espejo, Carrera Atenci\u00f3n Prehospitalaria y Emergencias, Grupo de Investigaci\u00f3n en Medicina Prehospitalaria (GRIMPE)","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/J.SEIZURE.2016.11.001","article-title":"25 years of advances in the definition, classification and treatment of status epilepticus","volume":"44","author":"Trinka","year":"2017","journal-title":"Seizure"},{"key":"B2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/S42466-022-00199-4\/TABLES\/1","article-title":"Super-refractory status epilepticus in adults","volume":"4","author":"Malter","year":"2022","journal-title":"Neurol Res Pract"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1111\/EPI.17391","article-title":"International consensus recommendations for management of new onset refractory status epilepticus (NORSE) including febrile infection-related epilepsy syndrome (FIRES): summary and clinical tools","volume":"63","author":"Wickstr\u00f6m","year":"2022","journal-title":"Epilepsia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1001\/JAMANEUROL.2024.0108","article-title":"Treatment of refractory status epilepticus with continuous intravenous anesthetic drugs: a systematic review","volume":"81","author":"Au","year":"2024","journal-title":"JAMA Neurol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.4103\/neuroindia.NI_958_16","article-title":"Status epilepticus: refractory and super-refractory","volume":"65","author":"Dubey","year":"2017","journal-title":"Neurol India"},{"key":"B6","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1046\/J.1528-1157.2002.28501.X","article-title":"Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review","volume":"43","author":"Claassen","year":"2002","journal-title":"Epilepsia"},{"key":"B7","doi-asserted-by":"publisher","first-page":"E1191","DOI":"10.1212\/WNL.0000000000200818","article-title":"Management of refractory status epilepticus: an international cohort study (MORSE CODe) analysis of patients managed in the ICU","volume":"99","author":"Chiu","year":"2022","journal-title":"Neurology"},{"key":"B8","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":"B9","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/S1474-4422(15)00042-3","article-title":"Status epilepticus in adults","volume":"14","author":"Betjemann","year":"2015","journal-title":"Lancet Neurol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"108512","DOI":"10.1016\/j.yebeh.2021.108512","article-title":"The role of ketamine-induced beta activity in the treatment of refractory status epilepticus. Is the EEG useful to determine responder\u2019s rate? A retrospective study","volume":"127","author":"Machado","year":"2022","journal-title":"Epilepsy Behav"},{"key":"B11","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1111\/ANE.13610","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"},{"key":"B12","doi-asserted-by":"publisher","first-page":"5449","DOI":"10.1007\/S10072-024-07635-0","article-title":"Ketamine reduces seizure and interictal continuum activity in refractory status epilepticus: a multicenter in-person and teleneurocritical care study","volume":"45","author":"Harnicher","year":"2024","journal-title":"Neurol Sci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.seizure.2024.01.013","article-title":"Ketamine in the treatment of refractory and super-refractory status epilepticus: experience from two centres","volume":"117","author":"Garc\u00eda-Ruiz","year":"2024","journal-title":"Seizure"},{"key":"B14","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.yebeh.2015.07.040","article-title":"Propofol-ketamine combination therapy for effective control of super-refractory status epilepticus","volume":"52","author":"Sabharwal","year":"2015","journal-title":"Epilepsy Behav"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1111\/EPI.12247","article-title":"Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study","volume":"54","author":"Gaspard","year":"2013","journal-title":"Epilepsia"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.3390\/DIAGNOSTICS15172137","article-title":"From subtle signs to severe sequelae-A century of symptomatology and comorbidities in the diagnosis of GH-secreting pituitary neuroendocrine tumors: a systematic review","volume":"15","author":"Ayora","year":"2025","journal-title":"Diagnostics (Basel)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1726046","DOI":"10.3389\/FNEUR.2026.1726046\/TEXT","article-title":"Transcranial ultrasonography in the detection of cerebrovascular accident: a systematic review and bivariate random-effects meta-analysis","volume":"17","author":"Pinto-Villalba","year":"2026","journal-title":"Front Neurol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fmed.2023.1229053","article-title":"Reported adverse events during out-of-hospital mechanical ventilation and ventilatory support in emergency medical services and critical care transport crews: a systematic review","volume":"10","author":"Pinto-Villalba","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e44","DOI":"10.1111\/EPI.12947","article-title":"Drug-induced EEG pattern predicts effectiveness of ketamine in treating refractory status epilepticus","volume":"56","author":"Basha","year":"2015","journal-title":"Epilepsia"},{"key":"B20","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/J.EPLEPSYRES.2013.01.007","article-title":"Ketamine use in the treatment of refractory status epilepticus","volume":"105","author":"Synowiec","year":"2013","journal-title":"Epilepsy Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"E2286","DOI":"10.1212\/WNL.0000000000010611","article-title":"Ketamine to treat super-refractory status epilepticus","volume":"95","author":"Alkhachroum","year":"2020","journal-title":"Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1177\/1550059420942677","article-title":"Efficacy and safety of ketamine in refractory\/super-refractory nonconvulsive status epilepticus: single-center experience","volume":"52","author":"Dericioglu","year":"2021","journal-title":"Clin EEG Neurosci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/S12028-022-01578-0","article-title":"Factors associated with refractory status epilepticus termination following ketamine initiation: a multivariable analysis model","volume":"38","author":"Srinivas","year":"2023","journal-title":"Neurocrit Care"},{"key":"B24","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"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/S12028-010-9445-Z","article-title":"A randomized trial for the treatment of refractory status epilepticus","volume":"14","author":"Rossetti","year":"2011","journal-title":"Neurocrit Care"},{"key":"B26","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1001\/JAMANEUROL.2023.2407","article-title":"Outcomes and treatment approaches for super-refractory status epilepticus: a systematic review and meta-analysis","volume":"80","author":"Cornwall","year":"2023","journal-title":"JAMA Neurol"},{"key":"B27","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"},{"key":"B28","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/S13311-018-0640-5","article-title":"Treatment of refractory and super-refractory status epilepticus","volume":"15","author":"Rai","year":"2018","journal-title":"Neurotherapeutics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1007\/S40263-018-0569-6","article-title":"Ketamine for refractory Status epilepticus: a systematic review","volume":"32","author":"Rosati","year":"2018","journal-title":"CNS Drugs"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3942","DOI":"10.1007\/S00415-024-12453-7","article-title":"The efficacy and safety of ketamine in the treatment of super-refractory status epilepticus: a systematic review","volume":"271","author":"Yan","year":"2024","journal-title":"J Neurol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/EPI4.12627","article-title":"KETASER01 protocol: what went right and what went wrong","volume":"7","author":"Rosati","year":"2022","journal-title":"Epilepsia Open"},{"key":"B32","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1111\/EPI.17550","article-title":"Ketamine as advanced second-line treatment in benzodiazepine-refractory convulsive status epilepticus in children","volume":"64","author":"Buratti","year":"2023","journal-title":"Epilepsia"},{"key":"B33","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.pediatrneurol.2025.03.011","article-title":"Combined ketamine and midazolam versus midazolam alone for initial treatment of pediatric generalized convulsive status epilepticus (ket-mid study): a randomized controlled trial","volume":"167","author":"Othman","year":"2025","journal-title":"Pediatr Neurol"},{"key":"B34","author":"Kapur","year":""}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1959414\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:35:37Z","timestamp":1789968937000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1959414\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":34,"alternative-id":["10.3389\/fmed.2026.1959414"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1959414","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"article-number":"1959414"}}