Lack of association of first and second-line medication dosing and progression to refractory status epilepticus in children

Cristina Barcia Aguilar; Marta Amengual-Gual; J Nicholas Brenton; Kevin E Chapman; Justice Clark; William D Gaillard; Joshua L Goldstein; Howard P Goodkin; Robert Kahoud; Yi-Chen Lai; Mohamad A Mikati; Lindsey A Morgan; Eric T Payne; Craig A Press; Latania Reece; Tristan T Sands; Kumar Sannagowdara; Theodore Sheehan; Renée A Shellhaas; Robert C Tasker; Mark S Wainwright; Bo Zhang; Tobias Loddenkemper; pSERG

doi:10.1016/j.seizure.2024.10.017

Lack of association of first and second-line medication dosing and progression to refractory status epilepticus in children

Seizure. 2024 Oct 28:123:133-141. doi: 10.1016/j.seizure.2024.10.017. Online ahead of print.

Authors

Cristina Barcia Aguilar¹, Marta Amengual-Gual², J Nicholas Brenton³, Kevin E Chapman⁴, Justice Clark⁵, William D Gaillard⁶, Joshua L Goldstein⁷, Howard P Goodkin⁸, Robert Kahoud⁹, Yi-Chen Lai¹⁰, Mohamad A Mikati¹¹, Lindsey A Morgan¹², Eric T Payne¹³, Craig A Press¹⁴, Latania Reece¹⁵, Tristan T Sands¹⁶, Kumar Sannagowdara¹⁷, Theodore Sheehan¹⁸, Renée A Shellhaas¹⁹, Robert C Tasker²⁰, Mark S Wainwright²¹, Bo Zhang²², Tobias Loddenkemper²³; pSERG

Affiliations

¹ 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: [email protected].
² 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: [email protected].
³ Department of Neurology and Pediatrics, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: [email protected].
⁴ Department of Neurosciences, Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA. Electronic address: [email protected].
⁵ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
⁶ Center for Neuroscience, Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC, USA. Electronic address: [email protected].
⁷ Davee Pediatric Neurocritical Care Program, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: [email protected].
⁸ Department of Neurology and Pediatrics, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: [email protected].
⁹ Division of Pediatric Critical Care Medicine, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address: [email protected].
¹⁰ Section of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Electronic address: [email protected].
¹¹ Division of Pediatric Neurology, Duke University Medical Center, Duke University, Durham, NC, USA. Electronic address: [email protected].
¹² Division of Pediatric Neurology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA. Electronic address: [email protected].
¹³ Division of Neurology, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada. Electronic address: [email protected].
¹⁴ 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: [email protected].
¹⁵ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
¹⁶ 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: [email protected].
¹⁷ Department of Pediatric Neurology & Epilepsy, Advocate Aurora Health Care, Greenfield, WI, USA. Electronic address: [email protected].
¹⁸ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
¹⁹ Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: [email protected].
²⁰ Department of Neurology, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
²¹ Division of Pediatric Neurology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA. Electronic address: [email protected].
²² 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: [email protected].
²³ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].

PMID: 39550933
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.

Keywords: All epilepsy/seizures; Antiepileptic drugs; Outcome research; Pediatric; Status epilepticus.