DOI
https://doi.org/10.18849/ve.v9i4.689Abstract
Question
In canine patients in status epilepticus, is intranasal midazolam as effective as rectal diazepam for controlling seizures?
Clinical bottom line
The category of research question was:
Treatment.
The number and type of study designs that were critically appraised were:
One study was found—a multicentre randomised open-label clinical trial comparing intranasal midazolam and rectal diazepam in canine patients.
Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:
Weak.
The outcomes reported are summarised as follows…
The study critically appraised in this summary indicated that intranasal midazolam is effective in achieving seizure control in canine patients, with tolerable safety margins. Mild adverse effects associated with benzodiazepine administration such as sedation and drowsiness were noted, but there were no reports of serious adverse events related to the use of intranasal midazolam.
In view of the strength of evidence and the outcomes from the studies the following conclusion is made…
Intranasal midazolam appears to be safe and effective for achieving seizure control in canine patients, both in terms of efficacy and speed of onset, and is a suitable first-line treatment option for status epilepticus, especially when intravenous access is not rapidly available. Patients should be monitored after drug administration for development of adverse effects, including sedation, sneezing, and nasal irritation. A nasal mucosal atomisation device may be used to enhance bioavailability of the drug, improving efficacy.
References
Akman, C.I., Montenegro, M.A., Jacob, S., Eck, K., Chiriboga, C. & Gilliam, F. (2009). Seizure frequency in children with epilepsy: Factors influencing accuracy and parental awareness. Seizure. 18(7), 524–529. DOI: https://doi.org/10.1016/j.seizure.2009.05.009
Burmeister, E. & Aitken, L.M. (2012). Sample size: How many is enough? Australian Critical Care. 25(4), 271–274. DOI: https://doi.org/10.1016/j.aucc.2012.07.002
Charalambous, M., Bhatti, S.F.M., Van Ham, L., Platt, S., Jeffery, N.D., Tipold, A., Siedenburg, J., Volk, H.A., Hasegawa, D., Gallucci, A., Gandini, G., Musteata, M., Ives, E. & Vanhaesebrouck, A.E. (2017). Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial. Journal of Veterinary Internal Medicine. 31(4), 1149–1158. DOI: https://doi.org/10.1111/jvim.14734
Charalambous, M. (2018). Controlling epileptic seizures at home with intranasal midazolam. Vet Times. 48(1), 4–5. [Accessed 07 February 2023].
Charalambous, M., Volk, H.A., Tipold, A., Erath, J., Huenerfauth, E., Gallucci, A., Gandini, G., Hasegawa, D., Pancotto, T., Rossmeisl, J.H., Platt, S., De Risio, L., Coates, J.R., Musteata, M., Tirrito, F., Cozzi, F., Porcarelli, L., Corlazzoli, D., Cappello, R., Vanhaesebrouck, A., Broeckx, B.J.G., Van Ham, L. & Bhatti, S.F.M. (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. DOI: https://doi.org/10.1111/jvim.15627
Charalambous, M., Volk, H.A., Van Ham, L. & Bhatti, S.F.M. (2021). First-line management of canine status epilepticus at home and in hospital-opportunities and limitations of the various administration routes of benzodiazepines. BMC Veterinary Research. 17(1), 103. DOI: https://doi.org/10.1186/s12917-021-02805-0
Charalambous, M., Bhatti, S.F.M., Volk, H.A. & Platt, S. (2022). Defining and overcoming the therapeutic obstacles in canine refractory status epilepticus. The Veterinary Journal. 283–284 . DOI: https://doi.org/10.1016/j.tvjl.2022.105828
Cushner-Weinstein, S., Dassoulas, K., Salpekar, J.A., Henderson, S.E., Pearl, P.L., Gaillard, W.D. & Weinstein, S.L. (2008). Parenting stress and childhood epilepsy: The impact of depression, learning, and seizure-related factors. Epilepsy & Behavior. 13(1), 109–114. DOI: https://doi.org/10.1016/j.yebeh.2008.03.010
Davis, E.M., Feinsmith, S., Amick, A.E., Sell, J., McDonald, V., Trinquero, P., Moore, A., Gappmaier, V., Colton, K., Cunningham, A., Ford, W., Feinglass, J. & Barsuk, J.H. (2021). Difficult intravenous access in the emergency department: Performance and impact of ultrasound-guided IV insertion performed by nurses. The American Journal of Emergency Medicine. 46, 539–544. DOI: https://doi.org/10.1016/j.ajem.2020.11.013
De Haan, G.-J., Van Der Geest, P., Doelman, G., Bertram, E. & Edelbroek, P. (2010). A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations. Epilepsia. 51(3), 478–482. DOI: https://doi.org/10.1111/j.1528-1167.2009.02333.x
Detyniecki, K., Van Ess, P.J., Sequeira, D.J., Wheless, J.W., Meng, T.C. & Pullman, W.E. (2019). Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters—a randomized, double-blind, placebo-controlled trial. Epilepsia. 60(9), 1797–1808. DOI: https://doi.org/10.1111/epi.15159
Eagleson, J.S., Platt, S.R., Strong, D.L.E., Kent, M., Freeman, A.C., Nghiem, P.P., Zheng, B. & White, C.A. (2012). Bioavailability of a novel midazolam gel after intranasal administration in dogs. American Journal of Veterinary Research. 73(4), 539–545. DOI: https://doi.org/10.2460/ajvr.73.4.539
Edwards, J.E., McQuay, H.J., Moore, R.A. & Collins, S.L. (1999). Reporting of Adverse Effects in Clinical Trials Should Be Improved: Lessons from Acute Postoperative Pain. Journal of Pain and Symptom Management. 18(6), 427–437. DOI: https://doi.org/10.1016/S0885-3924(99)00093-7
Hróbjartsson, A., Thomsen, A.S.S., Emanuelsson, F., Jeppesen, B.T, Hilden, J., Boutron, I., Ravaud, P. & Brorson, S. (2013). Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors. Canadian Medical Association Journal. 185(4), E201–E211. DOI: https://doi.org/10.1503/cmaj.120744
Javadzadeh, M., Sheibani, K., Hashemieh, M. & Saneifard, H. (2012). Intranasal midazolam compared with intravenous diazepam in patients suffering from acute seizure: a randomized clinical trial. Iranian Journal of Paediatrics. 22(1), 1–8.
Kähn, C., Bhatti, S.F.M., Meller, S., Meyerhoff, N., Volk, H.A. & Charalambous, M. (2023). Out-of-hospital rescue medication in dogs with emergency seizure disorders: an owner perspective. Frontiers in Veterinary Science. 10, 1278618. DOI: https://doi.org/10.3389/fvets.2023.1278618
Mahmoudian, T. & Mohammadi Zadeh, M. (2004). Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy & Behavior. 5(2), 253–255. DOI: https://doi.org/10.1016/j.yebeh.2004.01.003
McMullan, J., Sasson, C., Pancioli, A. & Silbergleit, R. (2010). Midazolam Versus Diazepam for the Treatment of Status Epilepticus in Children and Young Adults: A Meta-analysis. Academic Emergency Medicine. 17(6), 575–582. DOI: https://doi.org/10.1111/j.1553-2712.2010.00751.x
Messahel, S., Bracken, L. & Appleton, R. (2022). Optimal Management of Status Epilepticus in Children in the Emergency Setting: A Review of Recent Advances. Open Access Emergency Medicine. 14, pp. 491–506. DOI: https://doi.org/10.2147/oaem.S293258
Mula, M. (2017). New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective. CNS Drugs. 31(1), 11–17. DOI: https://doi.org/10.1007/s40263-016-0398-4
Packer, R.M., Berendt, M., Bhatti, S., Charalambous, M., Cizinauskas, S., De Risio, L., Farquhar, R., Hampel, R., Hill, M., Mandigers, P.J., Pakozdy, A., Preston, S.M., Rusbridge, C., Stein, V.M., Taylor-Brown, F., Tipold, A. & Volk, H.A. (2015). Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists. BMC Veterinary Research. 11(1), 39. DOI: https://doi.org/10.1186/s12917-015-0356-2
Platt, S. (2014a). Benzodiazepines. In: L. De Risio & S. Platt (eds). Canine and feline epilepsy: diagnosis and management. Wallingford: CABI International Publishing. 476–495.
Platt, S. (2014b). Pathophysiology and management of status epilepticus. In: L. De Risio & S. Platt (eds). Canine and feline epilepsy: diagnosis and management. Wallingford: CABI International Publishing. 519–536.
Potschka, H., Fischer, A., von Rüden, E.-L., Hülsmeyer, V. & Baumgärtner, W. (2013). Canine epilepsy as a translational model? Epilepsia. 54(4) 571-579. DOI: https://doi.org/10.1111/epi.12138
Schwartz, M., Muñana, K.R., Nettifee-Osborne, J.A., Messenger, K.M. & Papich, M.G. (2013). The pharmacokinetics of midazolam after intravenous, intramuscular, and rectal administration in healthy dogs. Journal of Veterinary Pharmacology and Therapeutics. 36(5), 471–477. DOI: https://doi.org/10.1111/jvp.12032
Uriarte, A. & Maestro Saiz, I. (2016). Canine versus human epilepsy: are we up to date? Journal of Small Animal Practice. 57(3), 115–121. DOI: https://doi.org/10.1111/jsap.12437
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