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Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs : a multi‐center randomized parallel group clinical study

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Abstract
Background: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. Objectives: To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. Animals Client-owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus. Methods: Randomized parallel group clinical trial. Patients were randomly allocated to the IN-MDZ (n = 21) or IV-MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for >= 10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at alpha < .05. Results: IN-MDZ and IV-MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P = .34). The median seizure cessation time was 33 and 64 seconds for IN-MDZ and IV-MDZ, respectively (P = .63). When the time to place an IV catheter was taken into account, IN-MDZ (100 seconds) was superior (P = .04) to IV-MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN-MDZ and IV-MDZ, respectively. Conclusions and Clinical Importance: Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account.
Keywords
benzodiazepines, canine, emergency, epilepsy, nasal, NASAL DRUG-DELIVERY, BLOOD-BRAIN-BARRIER, RECTAL DIAZEPAM, ACUTE SEIZURES, PEDIATRIC-PATIENTS, PHARMACOKINETICS, TRANSPORT, CHILDREN, KETAMINE, EPILEPSY

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MLA
Charalambous, Marios, et al. “Comparison of Intranasal versus Intravenous Midazolam for Management of Status Epilepticus in Dogs : A Multi‐center Randomized Parallel Group Clinical Study.” JOURNAL OF VETERINARY INTERNAL MEDICINE, vol. 33, no. 6, 2019, pp. 2709–17.
APA
Charalambous, M., Volk, H. A., Tipold, A., Erath, J., Huenerfauth, E., Gallucci, A., … Bhatti, S. (2019). Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs : a multi‐center randomized parallel group clinical study. JOURNAL OF VETERINARY INTERNAL MEDICINE, 33(6), 2709–2717.
Chicago author-date
Charalambous, Marios, Holger A Volk, Andrea Tipold, Johannes Erath, Enrice Huenerfauth, Antonella Gallucci, Gualtiero Gandini, et al. 2019. “Comparison of Intranasal versus Intravenous Midazolam for Management of Status Epilepticus in Dogs : A Multi‐center Randomized Parallel Group Clinical Study.” JOURNAL OF VETERINARY INTERNAL MEDICINE 33 (6): 2709–17.
Chicago author-date (all authors)
Charalambous, Marios, Holger A Volk, Andrea Tipold, Johannes Erath, Enrice Huenerfauth, Antonella Gallucci, Gualtiero Gandini, Daisuke Hasegawa, Theresa Pancotto, John H Rossmeisl, Simon Platt, Luisa De Risio, Joan R Coates, Mihai Musteata, Federica Tirrito, Francesca Cozzi, Laura Porcarelli, Daniele Corlazzoli, Rodolfo Cappello, An Vanhaesebrouck, Bart Broeckx, Luc Van Ham, and Sofie Bhatti. 2019. “Comparison of Intranasal versus Intravenous Midazolam for Management of Status Epilepticus in Dogs : A Multi‐center Randomized Parallel Group Clinical Study.” JOURNAL OF VETERINARY INTERNAL MEDICINE 33 (6): 2709–2717.
Vancouver
1.
Charalambous M, Volk HA, Tipold A, Erath J, Huenerfauth E, Gallucci A, et al. Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs : a multi‐center randomized parallel group clinical study. JOURNAL OF VETERINARY INTERNAL MEDICINE. 2019;33(6):2709–17.
IEEE
[1]
M. Charalambous et al., “Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs : a multi‐center randomized parallel group clinical study,” JOURNAL OF VETERINARY INTERNAL MEDICINE, vol. 33, no. 6, pp. 2709–2717, 2019.
@article{8633909,
  abstract     = {Background: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail.
Objectives: To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. Animals Client-owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus.
Methods: Randomized parallel group clinical trial. Patients were randomly allocated to the IN-MDZ (n = 21) or IV-MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for >= 10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at alpha < .05.
Results: IN-MDZ and IV-MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P = .34). The median seizure cessation time was 33 and 64 seconds for IN-MDZ and IV-MDZ, respectively (P = .63). When the time to place an IV catheter was taken into account, IN-MDZ (100 seconds) was superior (P = .04) to IV-MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN-MDZ and IV-MDZ, respectively.
Conclusions and Clinical Importance: Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account.},
  author       = {Charalambous, Marios and Volk, Holger A and Tipold, Andrea and Erath, Johannes and Huenerfauth, Enrice and Gallucci, Antonella and Gandini, Gualtiero and Hasegawa, Daisuke and Pancotto, Theresa and Rossmeisl, John H and Platt, Simon and De Risio, Luisa and Coates, Joan R and Musteata, Mihai and Tirrito, Federica and Cozzi, Francesca and Porcarelli, Laura and Corlazzoli, Daniele and Cappello, Rodolfo and Vanhaesebrouck, An and Broeckx, Bart and Van Ham, Luc and Bhatti, Sofie},
  issn         = {0891-6640},
  journal      = {JOURNAL OF VETERINARY INTERNAL MEDICINE},
  keywords     = {benzodiazepines,canine,emergency,epilepsy,nasal,NASAL DRUG-DELIVERY,BLOOD-BRAIN-BARRIER,RECTAL DIAZEPAM,ACUTE SEIZURES,PEDIATRIC-PATIENTS,PHARMACOKINETICS,TRANSPORT,CHILDREN,KETAMINE,EPILEPSY},
  language     = {eng},
  number       = {6},
  pages        = {2709--2717},
  title        = {Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs : a multi‐center randomized parallel group clinical study},
  url          = {http://dx.doi.org/10.1111/jvim.15627},
  volume       = {33},
  year         = {2019},
}

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