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Pediatr Crit Care Med. 2016 Oct;17(10):968-975.

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.

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1The Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA.2The Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.3The Departments of Neurology and Pediatrics, The University of Virginia Health System, Charlottesville, VA.4The Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.5The Departments of Pediatrics and Neurology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO.6The Division of Neurology, The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.7The Comprehensive Epilepsy Center and Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.8The Department of Epilepsy, Neurophysiology, and Critical Care Neurology, Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC.9Division of Neurology and Critical Care, The Department of Pediatrics, Ann & Robert H Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL.10The Division of Pediatric Neurology, Duke University Medical Center, Duke University, Durham, NC.11The Departments of Neurology and Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.12The Department of Pediatric Neurology, Phoenix Children's Hospital and Barrow Neurological Institute, Phoenix, AZ.



To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control.


Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent.


Nine pediatric hospitals in the United States.


In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment.


The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies.


Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter multinational study.

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