First-line medication dosing in pediatric refractory status epilepticus

Alejandra Vasquez; Marina Gaínza-Lein; Nicholas S. Abend; Marta Amengual-Gual; Anne Anderson; Ravindra Arya; J. Nicholas Brenton; Jessica L. Carpenter; Kevin Chapman; Justice Clark; Raquel Farias-Moeller; William D. Gaillard; Tracy Glauser; Joshua L. Goldstein; Howard P. Goodkin; Rejean M. Guerriero; Kush Kapur; Yi Chen Lai; Tiffani L. McDonough; Mohamad A. Mikati; Lindsey A. Morgan; Edward J. Novotny; Adam P. Ostendorf; Eric T. Payne; Katrina Peariso; Juan Piantino; James J. Riviello; Kumar Sannagowdara; Robert C. Tasker; Dmitry Tchapyjnikov; Alexis Topjian; Mark S. Wainwright; Angus Wilfong; Korwyn Williams; Tobias Loddenkemper; Seema Bansal; Sarah Kelley; Carl Stafstrom; Eric Kossoff; Christa Habela; Dalila Lewis; Tony Stanfield; Claudine Sculier; Cristina Barcia Aguilar; Arnold Sansevere; Melissa Sacco; Abby Duncan; Jordan McCoy; Kathryn Dasilva-Chiodo; Robert Faist; Daniel Santel; Victor Lafay; Peggy Clark; Sarah Borror; Andrea Debs; Caitlin Clohessy; Amanda Weber; Asri Yuliati; Aimee Luat; Azara Singh; Ashley Helseth; David Turner; Cecilia Fernandes; Linh Tran; Melissa McLean; Anuranjita Nayak; Kurt Hecox; Rupa Nallamothu; Rebecca Rehborg; David Goldstein; Erin Heinzen Cox; Colin Malone; Olivia Thornburg; Zachary Grinspan; Natasha Basma; Brian Appavu; Brian Burrows; Beata Dyar; Laura Mishler; Jacqueline Lee-Eng; Madison Streb; Cecil Hahn; Saptharishi Lalgudi Ganesan; Linda Huh; Nela Martic

doi:10.1212/WNL.0000000000010828

First-line medication dosing in pediatric refractory status epilepticus

Alejandra Vasquez, Marina Gaínza-Lein, Nicholas S. Abend, Marta Amengual-Gual, Anne Anderson, Ravindra Arya, J. Nicholas Brenton, Jessica L. Carpenter, Kevin Chapman, Justice Clark, Raquel Farias-Moeller, William D. Gaillard, Tracy Glauser, Joshua L. Goldstein, Howard P. Goodkin, Rejean M. Guerriero, Kush Kapur, Yi Chen Lai, Tiffani L. McDonough, Mohamad A. MikatiLindsey A. Morgan, Edward J. Novotny, Adam P. Ostendorf, Eric T. Payne, Katrina Peariso, Juan Piantino, James J. Riviello, Kumar Sannagowdara, Robert C. Tasker, Dmitry Tchapyjnikov, Alexis Topjian, Mark S. Wainwright, Angus Wilfong, Korwyn Williams, Tobias Loddenkemper, Seema Bansal, Sarah Kelley, Carl Stafstrom, Eric Kossoff, Christa Habela, Dalila Lewis, Tony Stanfield, Claudine Sculier, Cristina Barcia Aguilar, Arnold Sansevere, Melissa Sacco, Abby Duncan, Jordan McCoy, Kathryn Dasilva-Chiodo, Robert Faist, Daniel Santel, Victor Lafay, Peggy Clark, Sarah Borror, Andrea Debs, Caitlin Clohessy, Amanda Weber, Asri Yuliati, Aimee Luat, Azara Singh, Ashley Helseth, David Turner, Cecilia Fernandes, Linh Tran, Melissa McLean, Anuranjita Nayak, Kurt Hecox, Rupa Nallamothu, Rebecca Rehborg, David Goldstein, Erin Heinzen Cox, Colin Malone, Olivia Thornburg, Zachary Grinspan, Natasha Basma, Brian Appavu, Brian Burrows, Beata Dyar, Laura Mishler, Jacqueline Lee-Eng, Madison Streb, Cecil Hahn, Saptharishi Lalgudi Ganesan, Linda Huh, Nela Martic

Pediatrics

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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	https://doi.org/10.1212/WNL.0000000000010828
State	Published - Nov 10 2020

ASJC Scopus subject areas

Clinical Neurology

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Vasquez, A., Gaínza-Lein, M., Abend, N. S., Amengual-Gual, M., Anderson, A., Arya, R., Brenton, J. N., Carpenter, J. L., Chapman, K., Clark, J., Farias-Moeller, R., Gaillard, W. D., Glauser, T., Goldstein, J. L., Goodkin, H. P., Guerriero, R. M., Kapur, K., Lai, Y. C., McDonough, T. L., ... Martic, N. (2020). First-line medication dosing in pediatric refractory status epilepticus. Neurology, 95(19), E2683-E2696. https://doi.org/10.1212/WNL.0000000000010828

Vasquez, A, Gaínza-Lein, M, Abend, NS, Amengual-Gual, M, Anderson, A, Arya, R, Brenton, JN, Carpenter, JL, Chapman, K, Clark, J, Farias-Moeller, R, Gaillard, WD, Glauser, T, Goldstein, JL, Goodkin, HP, Guerriero, RM, Kapur, K, Lai, YC, McDonough, TL, Mikati, MA, Morgan, LA, Novotny, EJ, Ostendorf, AP, Payne, ET, Peariso, K, Piantino, J, Riviello, JJ, Sannagowdara, K, Tasker, RC, Tchapyjnikov, D, Topjian, A, Wainwright, MS, Wilfong, A, Williams, K, Loddenkemper, T, Bansal, S, Kelley, S, Stafstrom, C, Kossoff, E, Habela, C, Lewis, D, Stanfield, T, Sculier, C, Aguilar, CB, Sansevere, A, Sacco, M, Duncan, A, McCoy, J, Dasilva-Chiodo, K, Faist, R, Santel, D, Lafay, V, Clark, P, Borror, S, Debs, A, Clohessy, C, Weber, A, Yuliati, A, Luat, A, Singh, A, Helseth, A, Turner, D, Fernandes, C, Tran, L, McLean, M, Nayak, A, Hecox, K, Nallamothu, R, Rehborg, R, Goldstein, D, Heinzen Cox, E, Malone, C, Thornburg, O, Grinspan, Z, Basma, N, Appavu, B, Burrows, B, Dyar, B, Mishler, L, Lee-Eng, J, Streb, M, Hahn, C, Lalgudi Ganesan, S, Huh, L & Martic, N 2020, 'First-line medication dosing in pediatric refractory status epilepticus', Neurology, vol. 95, no. 19, pp. E2683-E2696. https://doi.org/10.1212/WNL.0000000000010828

@article{86d5bc7613314abda14f5fb21bc3e576,

title = "First-line medication dosing in pediatric refractory status epilepticus",

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.",

author = "Alejandra Vasquez and Marina Ga{\'i}nza-Lein and Abend, {Nicholas S.} and Marta Amengual-Gual and Anne Anderson and Ravindra Arya and Brenton, {J. Nicholas} and Carpenter, {Jessica L.} and Kevin Chapman and Justice Clark and Raquel Farias-Moeller and Gaillard, {William D.} and Tracy Glauser and Goldstein, {Joshua L.} and Goodkin, {Howard P.} and Guerriero, {Rejean M.} and Kush Kapur and Lai, {Yi Chen} and McDonough, {Tiffani L.} and Mikati, {Mohamad A.} and Morgan, {Lindsey A.} and Novotny, {Edward J.} and Ostendorf, {Adam P.} and Payne, {Eric T.} and Katrina Peariso and Juan Piantino and Riviello, {James J.} and Kumar Sannagowdara and Tasker, {Robert C.} and Dmitry Tchapyjnikov and Alexis Topjian and Wainwright, {Mark S.} and Angus Wilfong and Korwyn Williams and Tobias Loddenkemper and Seema Bansal and Sarah Kelley and Carl Stafstrom and Eric Kossoff and Christa Habela and Dalila Lewis and Tony Stanfield and Claudine Sculier and Aguilar, {Cristina Barcia} and Arnold Sansevere and Melissa Sacco and Abby Duncan and Jordan McCoy and Kathryn Dasilva-Chiodo and Robert Faist and Daniel Santel and Victor Lafay and Peggy Clark and Sarah Borror and Andrea Debs and Caitlin Clohessy and Amanda Weber and Asri Yuliati and Aimee Luat and Azara Singh and Ashley Helseth and David Turner and Cecilia Fernandes and Linh Tran and Melissa McLean and Anuranjita Nayak and Kurt Hecox and Rupa Nallamothu and Rebecca Rehborg and David Goldstein and {Heinzen Cox}, Erin and Colin Malone and Olivia Thornburg and Zachary Grinspan and Natasha Basma and Brian Appavu and Brian Burrows and Beata Dyar and Laura Mishler and Jacqueline Lee-Eng and Madison Streb and Cecil Hahn and {Lalgudi Ganesan}, Saptharishi and Linda Huh and Nela Martic",

note = "Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2020",

month = nov,

day = "10",

doi = "10.1212/WNL.0000000000010828",

language = "English (US)",

volume = "95",

pages = "E2683--E2696",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "19",

}

TY - JOUR

T1 - First-line medication dosing in pediatric refractory status epilepticus

AU - Vasquez, Alejandra

AU - Gaínza-Lein, Marina

AU - Abend, Nicholas S.

AU - Amengual-Gual, Marta

AU - Anderson, Anne

AU - Arya, Ravindra

AU - Brenton, J. Nicholas

AU - Carpenter, Jessica L.

AU - Chapman, Kevin

AU - Clark, Justice

AU - Farias-Moeller, Raquel

AU - Gaillard, William D.

AU - Glauser, Tracy

AU - Goldstein, Joshua L.

AU - Goodkin, Howard P.

AU - Guerriero, Rejean M.

AU - Kapur, Kush

AU - Lai, Yi Chen

AU - McDonough, Tiffani L.

AU - Mikati, Mohamad A.

AU - Morgan, Lindsey A.

AU - Novotny, Edward J.

AU - Ostendorf, Adam P.

AU - Payne, Eric T.

AU - Peariso, Katrina

AU - Piantino, Juan

AU - Riviello, James J.

AU - Sannagowdara, Kumar

AU - Tasker, Robert C.

AU - Tchapyjnikov, Dmitry

AU - Topjian, Alexis

AU - Wainwright, Mark S.

AU - Wilfong, Angus

AU - Williams, Korwyn

AU - Loddenkemper, Tobias

AU - Bansal, Seema

AU - Kelley, Sarah

AU - Stafstrom, Carl

AU - Kossoff, Eric

AU - Habela, Christa

AU - Lewis, Dalila

AU - Stanfield, Tony

AU - Sculier, Claudine

AU - Aguilar, Cristina Barcia

AU - Sansevere, Arnold

AU - Sacco, Melissa

AU - Duncan, Abby

AU - McCoy, Jordan

AU - Dasilva-Chiodo, Kathryn

AU - Faist, Robert

AU - Santel, Daniel

AU - Lafay, Victor

AU - Clark, Peggy

AU - Borror, Sarah

AU - Debs, Andrea

AU - Clohessy, Caitlin

AU - Weber, Amanda

AU - Yuliati, Asri

AU - Luat, Aimee

AU - Singh, Azara

AU - Helseth, Ashley

AU - Turner, David

AU - Fernandes, Cecilia

AU - Tran, Linh

AU - McLean, Melissa

AU - Nayak, Anuranjita

AU - Hecox, Kurt

AU - Nallamothu, Rupa

AU - Rehborg, Rebecca

AU - Goldstein, David

AU - Heinzen Cox, Erin

AU - Malone, Colin

AU - Thornburg, Olivia

AU - Grinspan, Zachary

AU - Basma, Natasha

AU - Appavu, Brian

AU - Burrows, Brian

AU - Dyar, Beata

AU - Mishler, Laura

AU - Lee-Eng, Jacqueline

AU - Streb, Madison

AU - Hahn, Cecil

AU - Lalgudi Ganesan, Saptharishi

AU - Huh, Linda

AU - Martic, Nela

PY - 2020/11/10

Y1 - 2020/11/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85095967709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85095967709&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000010828

DO - 10.1212/WNL.0000000000010828

M3 - Article

C2 - 32913024

AN - SCOPUS:85095967709

SN - 0028-3878

VL - 95

SP - E2683-E2696

JO - Neurology

JF - Neurology

IS - 19

ER -

First-line medication dosing in pediatric refractory status epilepticus

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