TY - JOUR
T1 - Association of time to treatment with short-term outcomes for pediatric patients with refractory convulsive status epilepticus
AU - Gaínza-Lein, Marina
AU - Fernández, Iván Sánchez
AU - Jackson, Michele
AU - Abend, Nicholas S.
AU - Arya, Ravindra
AU - Nicholas Brenton, J.
AU - Carpenter, Jessica L.
AU - Chapman, Kevin E.
AU - Gaillard, William D.
AU - Glauser, Tracy A.
AU - Goldstein, Joshua L.
AU - Goodkin, Howard P.
AU - Kapur, Kush
AU - Mikati, Mohamad A.
AU - Peariso, Katrina
AU - Tasker, Robert C.
AU - Tchapyjnikov, Dmitry
AU - Topjian, Alexis A.
AU - Wainwright, Mark S.
AU - Wilfong, Angus
AU - Williams, Korwyn
AU - Loddenkemper, Tobias
AU - Loddenkemper, Tobias
AU - Gaínza-Lein, Marina
AU - Tasker, Robert C.
AU - Sánchez Fernández, Iván
AU - Clark, Justice
AU - Jackson, Michele
AU - Kapur, Kush
AU - Abend, Nicolas S.
AU - Topjian, Alexis A.
AU - Gaillard, William D.
AU - Carpenter, Jessica
AU - Wainstein, Steven
AU - Dean, Nathan
AU - Sperberg, Katherine
AU - Glauser, Tracy A.
AU - Peariso, Katrina
AU - Arya, Ravindra
AU - Clark, Peggy
AU - Chapman, Kevin E.
AU - Mikati, Mohamad A.
AU - Tchapyjnikov, Dmrity
AU - Helseth, Ashley
AU - Cornet, Karen
AU - Turner, David
AU - Wainwright, Mark S.
AU - Goldstein, Joshua L.
AU - Rusie, Allison
AU - Payne, Eric
AU - Williams, Korwyn
AU - Wilfong, Angus
AU - Burrows, Brian
AU - Anderson, Anne
AU - Lai, Yi Chen
AU - Nayak, Anuranjita
AU - Goodkin, Howard P.
AU - Sacco, Melissa
AU - Zhu, Hong
AU - Nicholas Brenton, J.
N1 - Funding Information:
This study and consortium are funded by the Epilepsy Research Fund and the Pediatric Epilepsy Research Foundation. They were funded in the past by grant EF-213583, Targeted Initiative for Health Outcomes, from the Epilepsy Foundation of America and by a grant from the American Epilepsy Society/Epilepsy Foundation of America Infrastructure Awards.
Funding Information:
funded by the Epilepsy Research Fund and the Pediatric Epilepsy Research Foundation. They were funded in the past by grant EF-213583, Targeted Initiative for Health Outcomes, from the Epilepsy Foundation of America and by a grant from the American Epilepsy Society/Epilepsy Foundation of America Infrastructure Awards.
Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - IMPORTANCE Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown. OBJECTIVE To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes. DESIGN, SETTING, AND PARTICIPANTS This multicenter, observational, prospective cohort study included 218 pediatric patients admitted between June 1, 2011, and July 7, 2016, into the 11 tertiary hospitals in the United States within the Pediatric Status Epilepticus Research Group. Patients, ranging in age from 1 month to 21 years, with refractory convulsive status epilepticus (RCSE) that did not stop after the administration of at least 2 antiseizure medications were included. Patients were divided into 2 cohorts: those who received the first-line benzodiazepine treatment in less than 10 minutes and those who received it 10 or more minutes after seizure onset (untimely). Data were collected and analyzed from June 1, 2011, to July 7, 2016. MAIN OUTCOMES AND MEASURES The primary outcome was death during the related hospital admission. The secondary outcome was the need for continuous infusion for seizure termination. Multivariate analysis of mortality controlled for structural cause, febrile RCSE, age, and previous neurological history (including previous RCSE events). Use of continuous infusions was additionally adjusted for generalized RCSE, continuous RCSE, and 5 or more administrations of antiseizure medication. RESULTS A total of 218 patients were included, among whom 116 (53.2%) were male and the median (interquartile range) age was 4.0 (1.2-9.6) years. The RCSE started in the prehospital setting for 139 patients (63.8%). Seventy-four patients (33.9%) received their first-line benzodiazepine treatment in less than 10 minutes, and 144 (66.1%) received untimely first-line benzodiazepine treatment. Multivariate analysis showed that patients who received untimely first-line benzodiazepine treatment had higher odds of death (adjusted odds ratio [AOR], 11.0; 95% CI, 1.43 to ; P = .02), had greater odds of receiving continuous infusion (AOR, 1.8; 95% CI, 1.01-3.36; P = .047), had longer convulsive seizure duration (AOR, 2.6; 95% CI, 1.38-4.88; P = .003), and had more frequent hypotension (AOR 2.3; 95% CI, 1.16-4.63; P = .02). In addition, the timing of the first-line benzodiazepine treatment was correlated with the timing of the second-line (95% CI, 0.64-0.95; P < .001) and third-line antiseizure medications (95% CI, 0.25-0.78; P < .001). CONCLUSIONS AND RELEVANCE Among pediatric patients with RCSE, an untimely first-line benzodiazepine treatment is independently associated with a higher frequency of death, use of continuous infusions, longer convulsion duration, and more frequent hypotension. Results of this study raise the question as to whether poor outcomes could, in part, be prevented by earlier administration of treatment.
AB - IMPORTANCE Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown. OBJECTIVE To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes. DESIGN, SETTING, AND PARTICIPANTS This multicenter, observational, prospective cohort study included 218 pediatric patients admitted between June 1, 2011, and July 7, 2016, into the 11 tertiary hospitals in the United States within the Pediatric Status Epilepticus Research Group. Patients, ranging in age from 1 month to 21 years, with refractory convulsive status epilepticus (RCSE) that did not stop after the administration of at least 2 antiseizure medications were included. Patients were divided into 2 cohorts: those who received the first-line benzodiazepine treatment in less than 10 minutes and those who received it 10 or more minutes after seizure onset (untimely). Data were collected and analyzed from June 1, 2011, to July 7, 2016. MAIN OUTCOMES AND MEASURES The primary outcome was death during the related hospital admission. The secondary outcome was the need for continuous infusion for seizure termination. Multivariate analysis of mortality controlled for structural cause, febrile RCSE, age, and previous neurological history (including previous RCSE events). Use of continuous infusions was additionally adjusted for generalized RCSE, continuous RCSE, and 5 or more administrations of antiseizure medication. RESULTS A total of 218 patients were included, among whom 116 (53.2%) were male and the median (interquartile range) age was 4.0 (1.2-9.6) years. The RCSE started in the prehospital setting for 139 patients (63.8%). Seventy-four patients (33.9%) received their first-line benzodiazepine treatment in less than 10 minutes, and 144 (66.1%) received untimely first-line benzodiazepine treatment. Multivariate analysis showed that patients who received untimely first-line benzodiazepine treatment had higher odds of death (adjusted odds ratio [AOR], 11.0; 95% CI, 1.43 to ; P = .02), had greater odds of receiving continuous infusion (AOR, 1.8; 95% CI, 1.01-3.36; P = .047), had longer convulsive seizure duration (AOR, 2.6; 95% CI, 1.38-4.88; P = .003), and had more frequent hypotension (AOR 2.3; 95% CI, 1.16-4.63; P = .02). In addition, the timing of the first-line benzodiazepine treatment was correlated with the timing of the second-line (95% CI, 0.64-0.95; P < .001) and third-line antiseizure medications (95% CI, 0.25-0.78; P < .001). CONCLUSIONS AND RELEVANCE Among pediatric patients with RCSE, an untimely first-line benzodiazepine treatment is independently associated with a higher frequency of death, use of continuous infusions, longer convulsion duration, and more frequent hypotension. Results of this study raise the question as to whether poor outcomes could, in part, be prevented by earlier administration of treatment.
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U2 - 10.1001/jamaneurol.2017.4382
DO - 10.1001/jamaneurol.2017.4382
M3 - Article
C2 - 29356811
AN - SCOPUS:85045133006
SN - 2168-6149
VL - 75
SP - 410
EP - 418
JO - JAMA Neurology
JF - JAMA Neurology
IS - 4
ER -