Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel‐Group Clinical Trial

Abstract

BackgroundIntranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs.ObjectiveTo evaluate the clinical efficacy of intranasal midazolam (IN‐MDZ), via a mucosal atomization device, as a first‐line management option for canine status epilepticus and compare it to rectal administration of diazepam (R‐DZP) for controlling status epilepticus before intravenous access is available.AnimalsClient‐owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN‐MDZ (n = 20) or R‐DZP (n = 15).MethodsRandomized parallel‐group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2‐tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05.ResultsIN‐MDZ and R‐DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia.Conclusions and Clinical ImportanceIN‐MDZ is a quick, safe and effective first‐line medication for controlling status epilepticus in dogs and appears superior to R‐DZP. IN‐MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home.

Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs

“…The most frequently observed adverse event in this study was a short sneezing and snorting reaction, which was present in 4 out of 7 dogs. A brief episode of sneezing during or after intranasal administration was also reported in dogs receiving intranasal midazolam [57]. In another study, examining nasal administration of diazepam in dogs, several dogs developed salivation and reverse sneezing following intranasal administration [58].…”

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

“…The methodology we used was similar to that of a previous trial of IN‐MDZ, which has been described previously . The current study was an open‐label randomized parallel group clinical trial including client‐owned dogs and approved by the enrolling universities' ethical committees.…”

“…Benzodiazepines (eg, midazolam [MDZ]), are used commonly as a first‐line management option for status epilepticus in humans and dogs . Midazolam, a water‐soluble benzodiazepine, is considered an effective and safe anti‐seizure drug when administered by the IN, IV, or IM routes . Intranasal MDZ can be useful or even life‐saving, especially when IV access is not available .…”

“…Midazolam, a water‐soluble benzodiazepine, is considered an effective and safe anti‐seizure drug when administered by the IN, IV, or IM routes . Intranasal MDZ can be useful or even life‐saving, especially when IV access is not available . Intranasal MDZ has been reported to be an effective and safe choice as a sedative drug in children undergoing diagnostic and minor surgical procedures .…”

“…It was recently demonstrated that IN‐MDZ was effective and safe as well as superior to rectally administered diazepam for the management of status epilepticus in dogs with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin . In the present study, we compared MDZ given at the same dose but by different routes (IN or IV) for the treatment of status epilepticus in dogs.…”