Intravenous ketamine for the treatment of refractory status epilepticus: A retrospective multicenter study

• Type of Material: Article
• Authors: Nicolas Gaspard, Yale University; Brandon Foreman, Columbia University College of Physicians and Surgeons; Lilith Judd, Emory University; James N. Brenton, University of Virginia; Barnett R. Nathan, University of Virginia; Blathnaid M. McCoy, Hospital for Sick Children; Ali Al-Otaibi, Hospital for Sick Children; Ronan Kilbride, Massachusetts General Hospital; Ivan Sanchez Fernandez, Boston Children's Hospital; Lucy Mendoza, University of Cincinnati; Sophie Samuel, University of Texas Health Science Center; Asma Zakaria, University of Texas Health Science Center; Giridhar P. Kalamangalam, University of Texas Health Science Center; Benjamin Legros, ULB-Hôpital Erasme; Jerzy P. Szaflarski, University of Cincinnati; Tobias Loddenkemper, Boston Children's Hospital; Cecil D. Hahn, Hospital for Sick Children; Howard P. Goodkin, University of Virginia; Jan Claassen, Columbia University College of Physicians and Surgeons; Lawrence J. Hirsch, Yale University; Suzette M Laroche, Emory University
• Language: English
• Date: 2013-08-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 International League Against Epilepsy.
• Final Published Version (URL): http://dx.doi.org/10.1111/epi.12247
• Title of Journal or Parent Work: Epilepsia
• ISSN: 0013-9580
• Volume: 54
• Issue: 8
• Start Page: 1498
• End Page: 1503
• Grant/Funding Information: N.G. was the recipient of a Postdoctoral Research Fellowship from the Belgian American Education Foundation; and received research grant from the Commission for Educational Exchange between the USA and Belgium and the Belgian Neurological Society.; I. S.F. was funded by a grant for the study of Epileptic Encephalopathies from ‘Fundación Alfonso Martín Escudero’.; This study was performed as part of the Critical Care EEG Monitoring Research Consortium (CCEMRC), of which eight of the participating centers are members. The CCEMRC is supported by a Research Infrastructure Award from the American Epilepsy Society and the Epilepsy Foundation of America.; B.F. received funding from Pfizer’s Medical and Academic Partnerships Program.
• Keywords: Antiepileptic drugs; IMPACT; Refractory status epilepticus; Science & Technology; Anesthetics; ACIDOSIS; Life Sciences & Biomedicine; Ketamine; Treatment; Clinical Neurology; MIDAZOLAM; Neurosciences & Neurology
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience

Abstract

Purpose: To examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). Methods: Multicenter retrospective review of medical records and electroencephalography (EEG) reports in 10 academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE that were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury. Key Findings: Permanent control of RSE was achieved in 57% (34 of 60) of episodes. Ketamine was felt to have contributed to permanent control ("possible" or "likely" responses) in 32% (19 of 60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with postanoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9 mg/kg/h, when ketamine was introduced at least 8 days after SE onset, or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26 of 60), but was lower when SE was controlled within 24 h of ketamine initiation (16% vs. 56%, p = 0.0047). Significance: Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE.