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September 20, 2022; 99 (12) Research Article

Ketamine for Management of Neonatal and Pediatric Refractory Status Epilepticus

View ORCID ProfileMarin Jacobwitz, Caitlyn Mulvihill, View ORCID ProfileMichael C. Kaufman, Alexander K. Gonzalez, Karla Resendiz, Jennifer M. MacDonald, Conall Francoeur, View ORCID ProfileIngo Helbig, Alexis A. Topjian, Nicholas S. Abend
First published July 11, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200889
Marin Jacobwitz
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Caitlyn Mulvihill
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Michael C. Kaufman
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Alexander K. Gonzalez
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Karla Resendiz
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Jennifer M. MacDonald
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Conall Francoeur
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Ingo Helbig
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Alexis A. Topjian
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Nicholas S. Abend
From the Department of Pediatrics (Division of Neurology) (M.J., C.M., M.C.K., A.K.G., I.H., N.S.A.), Children's Hospital of Philadelphia; The Epilepsy NeuroGenetics Initiative (ENGIN) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia; Department of Biomedical and Health Informatics (DBHi) (M.C.K., A.K.G., I.H.), Children's Hospital of Philadelphia, PA; Department of Anesthesia and Critical Care Medicine (K.R., A.A.T., N.S.A.), Children's Hospital of Philadelphia; Department of Pharmacy Services (K.R.), Children's Hospital of Philadelphia, PA; Division of Critical Care (J.M.M.), Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH; Division of Critical Care (C.F.), Quebec, Department of Pediatrics, CHU de Québec–University of Laval Research Center; Departments of Neurology and Pediatrics (I.H., N.S.A.), University of Pennsylvania Perelman School of Medicine; and Department of Anesthesia & Critical Care (A.A.T.), University of Pennsylvania Perelman School of Medicine.
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Citation
Ketamine for Management of Neonatal and Pediatric Refractory Status Epilepticus
Marin Jacobwitz, Caitlyn Mulvihill, Michael C. Kaufman, Alexander K. Gonzalez, Karla Resendiz, Jennifer M. MacDonald, Conall Francoeur, Ingo Helbig, Alexis A. Topjian, Nicholas S. Abend
Neurology Sep 2022, 99 (12) e1227-e1238; DOI: 10.1212/WNL.0000000000200889

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Abstract

Background and Objectives Few data are available regarding the use of anesthetic infusions for refractory status epilepticus (RSE) in children and neonates, and ketamine use is increasing despite limited data. We aimed to describe the impact of ketamine for RSE in children and neonates.

Methods Retrospective single-center cohort study of consecutive patients admitted to the intensive care units of a quaternary care children's hospital treated with ketamine infusion for RSE.

Results Sixty-nine patients were treated with a ketamine infusion for RSE. The median age at onset of RSE was 0.7 years (interquartile range 0.15–7.2), and the cohort included 13 (19%) neonates. Three patients (4%) had adverse events requiring intervention during or within 12 hours of ketamine administration, including hypertension in 2 patients and delirium in 1 patient. Ketamine infusion was followed by seizure termination in 32 patients (46%), seizure reduction in 19 patients (28%), and no change in 18 patients (26%).

Discussion Ketamine administration was associated with few adverse events, and seizures often terminated or improved after ketamine administration. Further data are needed comparing first-line and subsequent anesthetic medications for treatment of pediatric and neonatal RSE.

Classification of Evidence This study provides Class IV evidence on the therapeutic utility of ketamine for treatment of RSE in children and neonates.

Glossary

CEEG=
continuous electroencephalographic monitoring;
CHD=
congenital heart disease;
CICU=
SE in the cardiac;
ECMO=
extracorporeal membrane oxygenation;
FIRES=
febrile infection–related epilepsy syndrome;
ICP=
intracranial pressure;
ICU=
intensive care unit;
IQR=
interquartile range;
IIC=
ictal-interictal continuum;
NICU=
SE in the neonatal;
PICU=
SE in the pediatric;
RSE=
refractory SE;
SE=
status epilepticus

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Renee Shellhaas, MD, MS.

  • Class of Evidence: NPub.org/coe

  • CME Course: NPub.org/cmelist

  • Received January 11, 2022.
  • Accepted in final form May 11, 2022.
  • © 2022 American Academy of Neurology
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