title: Feasibility Study Evaluating Therapeutic Hypothermia for Refractory Status Epilepticus in Children.
abstract: Pediatric refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality, which lacks consensus regarding diagnosis and treatment(s). Therapeutic hypothermia (TH) is an effective treatment for RSE in preclinical models and small series. In addition, TH is a standard care for adults after cardiac arrest and neonates with hypoxic-ischemic encephalopathy. The purpose of this study was to identify the feasibility of a study of pediatric RSE within a research group (Pediatric Neurocritical Care Research Group [PNCRG]). Pediatric intensive care unit (PICU) admissions at seven centers were prospectively screened from October 2012 to July 2013 for RSE. Experts within the PNCRG estimated that clinicians would be unwilling to enroll a child, unless the child required at least two different antiepileptic medications and a continuous infusion of another antiepileptic medication with ongoing electrographic seizure activity for ≥2 hours after continuous infusion initiation. Data for children meeting the above inclusion criteria were collected, including the etiology of RSE, history of epilepsy, and maximum dose of continuous antiepileptic infusions. There were 8113 PICU admissions over a cumulative 52 months (October 2012-July 2013) at seven centers. Of these, 69 (0.85%) children met inclusion criteria. Twenty children were excluded due to acute diagnoses affected by TH, contraindications to TH, or lack of commitment to aggressive therapies. Sixteen patients had seizure cessation within 2 hours, resulting in 33 patients who had inadequate seizure control after 2 hours and a continuous antiepileptic infusion. Midazolam (21/33, 64%) and pentobarbital (5/33, 15%) were the most common infusions with a wide maximum dose range. More than one infusion was required for seizure control in four patients. There are substantial numbers of subjects at clinical sites within the PNCRG with RSE that would meet the proposed inclusion criteria for a study of TH. The true feasibility of such a study depends on the sample size necessary to achieve therapeutic effects on justifiable clinical outcomes.
authors.affiliation: 1 Division of Critical Care Medicine, Department of Child Health, Phoenix Children's Hospital, University of Arizona College of Medicine Phoenix , Phoenix, Arizona.
authors.forename: Sandra D W
authors.initials: SD
authors.lastname: Buttram
authors.affiliation: 2 Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Au
authors.affiliation: 3 Division of Critical Care Medicine, Children's Medical Center of Dallas, University of Texas Southwestern , Dallas, Texas.
authors.forename: Joshua
authors.initials: J
authors.lastname: Koch
authors.affiliation: 4 Rainbow Babies and Children's Hospital, Case Western Reserve University , Cleveland, Ohio.
authors.forename: Karen
authors.initials: K
authors.lastname: Lidsky
authors.affiliation: 5 Department of Neurology, The Hospital for Sick Children , Toronto, Canada .
authors.forename: Kristin
authors.initials: K
authors.lastname: McBain
authors.affiliation: 6 Division of Critical Care Medicine, Nationwide Children's Hospital, The Ohio State University , Columbus, Ohio.
authors.forename: Nicole
authors.initials: N
authors.lastname: O'Brien
authors.affiliation: 7 Division of Child Neurology, Departments of Pediatrics and Neurology, Primary Children's Medical Center, University of Utah , Salt Lake City, Utah.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Zielinski
authors.affiliation: 2 Division of Pediatric Critical Care Medicine, Department of Critical Care Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bell
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D001291:Attitude of Health Personnel; D001833:Body Temperature Regulation; D001921:Brain / Q000503:physiopathology*; D058256:Brain Waves; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004569:Electroencephalography; D005240:Feasibility Studies; D006801:Humans; D007036:Hypothermia, Induced; D015278:Intensive Care Units, Pediatric; D009656:North America; D018579:Patient Selection; D011446:Prospective Studies; D012107:Research Design; D018401:Sample Size; D013226:Status Epilepticus / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants