Lack of association of first and second-line medication dosing and progression to refractory status epilepticus in children
Authors
Cristina Barcia Aguilar, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Pediatric Neurology Unit, Department of Pediatrics, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: cristinabarciaaguilar@gmail.com.
Marta Amengual-Gual, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Pediatric Neurology Unit, Department of Pediatrics, Hospital Universitari Son Espases, Universitat de les Illes Balears, Palma, Spain. Electronic address: marta.amengual.gual@gmail.com.
J Nicholas Brenton, Department of Neurology and Pediatrics, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: jnb8h@virginia.edu.
Kevin E. Chapman, Department of Neurosciences, Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA. Electronic address: kchapman@phoenixchildrens.com.
Justice Clark, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jmclark219@gmail.com.
William D. Gaillard, Center for Neuroscience, Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. Electronic address: WGAILLAR@childrensnational.org.
Joshua L. Goldstein, Davee Pediatric Neurocritical Care Program, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: j-goldstein4@northwestern.edu.
Howard P. Goodkin, Department of Neurology and Pediatrics, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: HPG9V@hscmail.mcc.virginia.edu.
Robert Kahoud, Division of Pediatric Critical Care Medicine, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address: Kahoud.Robert@mayo.edu.
Yi-Chen Lai, Section of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Electronic address: ylai@bcm.edu.
Mohamad A. Mikati, Division of Pediatric Neurology, Duke University Medical Center, Duke University, Durham, NC, USA. Electronic address: mohamad.mikati@duke.edu.
Lindsey A. Morgan, Division of Pediatric Neurology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA. Electronic address: Lindsey.Morgan@seattlechildrens.org.
Eric T. Payne, Division of Neurology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada. Electronic address: eric.payne@precisionbrain.ca.
Craig A. Press, Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: pressca@chop.edu.
Latania Reece, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: reecelatania@gmail.com.
Tristan T. Sands, Division of Child Neurology, Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA. Electronic address: tts27@cumc.columbia.edu.
Kumar Sannagowdara, Advocate Health - MidwestFollow
Theodore Sheehan, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: teddysheehan01@gmail.com.
Renée A. Shellhaas, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: rshellhaas@wustl.edu.
Robert C. Tasker, Department of Neurology, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: robert.tasker@childrens.harvard.edu.
Mark S. Wainwright, Division of Pediatric Neurology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA. Electronic address: Mark.Wainwright@seattlechildrens.org.
Bo Zhang, Department of Neurology, Department of ICCTR Biostatistics and Research Design Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Bo.Zhang@childrens.harvard.edu.
Tobias Loddenkemper, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: tobias.loddenkemper@childrens.harvard.edu.
Recommended Citation
Barcia Aguilar C, Amengual-Gual M, Brenton JN, et al. Lack of association of first and second-line medication dosing and progression to refractory status epilepticus in children. Seizure. 2024;123:133-141. doi:10.1016/j.seizure.2024.10.017
Abstract
Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children.
Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given as the first single-dose) using a logistic regression model, adjusting for confounders such as time to ASMs. The proportion of patients receiving low first non-benzodiazepine ASM doses was calculated and a logistic regression model was used to evaluate risk factors for low dosing of the first non-benzodiazepine ASM.
Results: Among 320 children, 170 (53.1 %) developed RSE, and 150 (46.9 %) responded to the first non-benzodiazepine ASM dose (non-RSE). One hundred thirty-seven (42.8 %) received a low total benzodiazepine dose, and 128 (40 %) received a low first non-benzodiazepine ASM dose. The odds of developing RSE were not higher after a low total benzodiazepine dose (OR=0.76, 95 %CI 0.47-1.23, p = 0.27) or low first non-benzodiazepine ASM dose (OR=0.85, 95 %CI 0.42-1.71, p = 0.65). Receiving a low first non-benzodiazepine ASM dose was independently associated with having received a low total benzodiazepine dose (OR=1.65, 95 %CI 1.01-2.70, p = 0.04).
Conclusion: For most patients, dosing variability in first and second-line medications for SE was not the sole clinical feature predicting progression to RSE in this cohort of benzodiazepine-resistant patients. Identification of additional modifiable clinical biomarkers that predict progression to RSE is needed. Though lower ASM doses did not predict RSE in this model, the administration of ASMs at doses likely to prevent RSE remains crucial in SE treatment.
