Abstract
Objective: To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation. Methods: This was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation. Results: We included 289 patients (55.7% male) with a median age of 4.3 (1.3-9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18-3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05-1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23-3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24-3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57-0.95). Conclusion: BZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation.Classification of evidenceThis study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E2683-E2696 |
| Journal | Neurology |
| Volume | 95 |
| Issue number | 19 |
| DOIs | |
| State | Published - Nov 10 2020 |
Funding
A. Vasquez, M. Gaínza-Lein, and N.S. Abend report no disclosures relevant to the manuscript. M. Gaínza-Lein was funded by a grant for the study of status epilepticus from “Fundación Alfonso Martín Escudero.” A. Anderson and R. Arya report no disclosures relevant to the manuscript. J.N. Brenton has served as a consultant for Novartis. J.L. Carpenter, K. Chapman, J. Clark, R. Farias-Moeller, W.D. Gaillard, T. Glauser, J.L. Goldstein, H.P. Goodkin, R.M. Guerriero, K. Kapur, Y.C. Lai, T.L. McDonough, M.A. Mikati, and L.A. Morgan report no disclosures relevant to the manuscript. E. Novotny is on the professional advisory board of the Epilepsy Foundation of America. A.P. Ostendorf, E.T. Payne, K. Peariso, and J. Piantino report no disclosures relevant to the manuscript. J.J. Riviello is a member of a data safety monitoring board for GW Pharmaceuticals. His spouse is an editor for UptoDate. K. Sannagowdara and R.C. Tasker report no disclosures relevant to the manuscript. D. Tchapyjnikov receives research funding from Children's Miracle Network Hospitals and has previously received consultation fees from Gerson Lehrman Group, Guidepoint, IQVIA, and bioStrategies Group. A. Topjian reports no disclosures relevant to the manuscript. M.S. Wainwright is a member of Clinical Advisory Board for Sage Therapeutics. A. Wilfong and K. Williams reports no disclosures relevant to the manuscript. T. Loddenkemper serves on the Council of the American Clinical Neurophysiology Society, as founder and consortium principal investigator of the pSERG, as an associate editor for Wyllie's Treatment of Epilepsy 6th edition and 7th editions (Elsevier), and as a member of the NORSE Institute and Critical Care EEG Monitoring Research Consortium. He served as associate editor of Seizure (Elsevier) and served on the Laboratory Accreditation Board for Long Term (Epilepsy and Intensive Care Unit) Monitoring and American Board of Clinical Neurophysiology in the past. He is part of patent applications to detect and predict clinical outcomes and to detect, manage, diagnose, and treat neurologic conditions, epilepsy, and seizures. T. Loddenkemper is coinventor of the TriVox Health technology, and Dr. Loddenkemper and Boston Children's Hospital might receive financial benefits from this technology in the form of compensation in the future. He received research support from the Epilepsy Research Fund, NIH, Center for Integration of Medicine & Innovative Technology/Department of Defense, Patient-Centered Outcomes Research Institute, the Epilepsy Foundation of America, the American Epilepsy Society, the Epilepsy Therapy Project, the Pediatric Epilepsy Research Foundation, the Danny Did Foundation, Cure, and the HHV6 Foundation, and received research grants from Lundbeck, Eisai, Upsher-Smith, Mallinckrodt, Sunovion, Sage, Empatica, Acorda, and Pfizer, including past device donations from various companies, including Empatica, SmartWatch, and Neuro-electrics. In the past, he served as a consultant for Eisai, Lundbeck, UCB, Amzell, Sunovion, Upsher Smith, and Zogenix. He performs video EEG long-term and ICU monitoring, EEGs, and other electrophysiologic studies at Boston Children's Hospital and affiliated hospitals and bills for these procedures, and he evaluates pediatric neurology patients and bills for clinical care. He has received speaker honorariums/grand round travel support from national/international societies and national/international academic centers. Some of Dr. Loddenkemper's trainees received salary support from international foundations/societies and academic centers while working in his laboratory. His wife, Dr. Karen Stannard, is a pediatric neurologist; performs video-EEG long-term and ICU monitoring, EEGs, and other electrophysiologic studies and bills for these procedures; and evaluates pediatric neurology patients and bills for clinical care. Go to Neurology.org/N for full disclosures. This study and consortium were funded by the Epilepsy Foundation of America (EF- 213583, Targeted Initiative for Health Outcomes), by the American Epilepsy Society/Epilepsy Foundation of America Infrastructure Award, by the Pediatric Epilepsy Research Foundation and by the Epilepsy Research Fund.
ASJC Scopus subject areas
- Clinical Neurology