VSPN AOW : Intranasal Midazolam vers... |
Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial.J Vet Intern Med. 2017 Jul-Aug;31(4):1149-1158.1 Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.; 2 Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.; 3 Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.; 4 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.; 5 Small Animal Department, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX.; 6 Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany.; 7 Clinical Department for Small Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria.; 8 Department of Clinical Science and Services, Royal Veterinary College, London, UK.; 9 Department of Clinical Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan.; 10 Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.; 11 Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.; 12 Department of Clinical Veterinary Medicine, Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine Iasi, Iasi, Romania.; 13 Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.; 14 Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
AbstractBACKGROUND:Intranasal 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.
OBJECTIVE:To 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.
ANIMALS:Client-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).
METHODS:Randomized 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.
RESULTS:IN-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 IMPORTANCE:IN-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.
Companion NotesMulticenter, randomized, parallel-group clinical trial comparing intranasal midazolam and rectal diazepam for status epilepticus in 35 dogs
Introduction on status epilepticus - occur in dogs either at home or during hospitalization - status epilepticus - can be caused by the following: - toxic causes - metabolic causes - structural brain disease - also occurs as manifestation of idiopathic epilepsy - estimated 20-60% of affected dogs have at least 1 episode in their lifetime - estimated case fatality rate: 25.3-38.5% - benzodiazepines - diazepam (DZP) and midazolam (MDZ) are common first-line options - for status epilepticus in humans and dogs - less common administration routes may be helpful (especially when IV access is not available) - rectal (R) - intranasal (IN) - intramuscular (IM) - buccal or sublingual - DZP commonly used as a first- or second-line medication - R-DZP is relatively easy and quick for owners or veterinarians to use - evidence on efficacy is contradictory - in 1 study, therapeutic plasma levels not attained quickly enough (to effect emergency seizures) - in 1 clinical trial, it was effective for generalized cluster seizures - in human medicine: - in several clinical trials on IN-MDZ in people with emergency seizures - with or without comparison to R-DZP - IN-MDZ effective and safe in the hospital and home settings - in human trials on emergency epileptic seizures - IN benzodiazepines superior to R for terminating those seizures
Study design - study population: - dogs with idiopathic or structural epilepsy manifesting status epilepticus - within a hospital environment - procedure: - dogs with status epilepticus were treated immediately - they were assumed to have been already seizuring for > 5 minutes - dogs randomly allocated to 1 of 2 treatment groups - IN-MDZ, 20 dogs - MDZ injectable solution (5 mg/mL), 0.2 mg/kg intranasally - using mucosal atomization device (MAD) - syringe (1 mL or 3 mL) attached to atomizer - turns medication into a fine mist (30-100 µm) - if present, excessive nasal secretions quickly removed with gauze - if administered dose > 1 ml, drug given via both nostrils - MAD device's dead space taken into account - history & signalment - median age: 5.1 years of age with a range of 0.5-7 - breeds accounting for 10% or more of population - German shepherd dog, 15% - golden retriever, 11% - R-DZP, 15 dogs - DZP injectable solution (5 mg/mL), 1 mg/kg per rectum - needleless syringe as deep as possible into rectum - history & signalment - median age: 4.8 years of age with a range of 0.9-6.8 - breeds accounting for 10% or more of population - German shepherd dog, 13% - Labrador retriever, 12% - golden retriever, 10% - dogs were first included in the trial and then treated - if testing indicated reactive seizures, dogs were excluded - 3 dogs initially enrolled were subsequently excluded - presumed intoxication, 2 dogs - seizures due to hypoglycemia, 1 dog - seizure cessation time and adverse effects recorded (time between drug administration and seizure cessation) - successful treatment defined as seizures that ceased within 5 minutes - and did not recur within 10 minutes after administration
Results - status epilepticus terminated - IN-MDZ: 70% (14/20) - median "seizure cessation" time: 47 seconds with a range of 6-280 - relapse, 11 successful cases - median "seizure relapse" time: 904 seconds - no relapse, 3 successful cases - R-DZP: 20% (3/15) (P = .0059) - median "seizure cessation" time: 214 seconds with a range of 204-290 - relapse, all successful cases - median "seizure relapse" time: 645 seconds - adverse effects - sedation and ataxia, all dogs - brief episode of sneezing, 7 IN-MDZ dogs - diagnosis - idiopathic epilepsy, 21 of the 35 (60%) - structural epilepsy, 12 (34%) - neoplasia, 7 - meningoencephalitis of unknown origin (MUO), 5 - epilepsy of unknown origin, 2
“In this study, IN-MDZ was significantly more effective than R-DZP for terminating status epilepticus in a hospital environment. It is likely that this finding could be extrapolated to at-home treatment of emergency seizures before hospital admittance and, as such, IN-MDZ might be a more appropriate and effective prehospital seizure management method than R-DZP.”
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