1. Introduction
Emergency seizure disorders, including status epilepticus (SE) and cluster seizures (CS), are commonly presented in both primary and specialty practices. SE is defined as a seizure lasting ≥5 min or ≥ 2 seizures with incomplete recovery in between seizures. SE can occur in dogs with reactive seizures, idiopathic epilepsy, or structural epilepsy (1, 2). CS are defined as two or more self-limiting seizures occurring within a 24-h period (1, 3). Approximately, 0.5-2.6% of the dogs presented to hospital manifest SE. Of the dogs admitted to hospital for seizures, 16.5% have SE; 58% of these dogs show SE as the first clinical manifestation of a seizure disorder. Overall, 20-60% of dogs with idiopathic epilepsy experience at least one SE. The overall mortality for SE has been reported to be 25.3-38.5%. (2, 4).
SE can be life-threatening and requires immediate care to avoid permanent brain damage (e.g., excitotoxicity, neuronal cell necrosis) or systemic dysfunction (e.g., shock, cardiorespiratory collapse, electrolyte disturbances, acidosis). The complications arising from SE are proportionally related to the duration of seizure activity (2, 5, 6). SE and CS often occur at home (7). Clinicians and especially owners should adopt a rapid and effective action plan for ceasing seizure emergencies before reaching refractory stages or occurrence of permanent brain damage; ideally seizures should terminate before reaching 30 min of continuous seizure activity (2, 5, 6, 8). The most common and first-line rescue medications used to manage seizure emergencies at home are benzodiazepines (BZDs), mainly diazepam (DZP) and midazolam (MDZ). These are potent and effective medications which can be administered in non-intravenous (IV) routes (2). Pharmacokinetic studies have demonstrated that intranasal administration of DZP, MDZ, triazolam, and flurazepam rapidly reaches maximal serum concentrations in dogs (8-11). Various studies have shown that intranasal MDZ has a high efficacy. In a meta-analysis in human medicine, which compared sublingual lorazepam, intranasal lorazepam, buccal MDZ, intranasal MDZ, and rectal DZP, showed that intranasal MDZ has the highest efficacy, followed by buccal MDZ and rectal DZP (12). Another study in 1991 has shown that the time between administration of intranasal MDZ to reach the highest plasma concentration is two times shorter and the plasma concentration is 2.9 times higher than oral administration (9). The therapeutic serum concentration of MDZ has not yet been determined in dogs, but in humans is 0.04 μg/mL. In dogs, DZP therapeutic concentration has been reported, which ranges from 0.15 to 0.5 μg/mL serum in dogs. In addition, MDZ is likely 5-6 times more potent than DZP (2, 13).
A study in humans showed that the first-line treatment is commonly delayed in both out-of-hospital and in-hospital settings. Rescue medications were administered only in 37.5% of patients at home (14) and even with prior diagnosis of epilepsy, rescue medication was administered only to a low number of patients from their family members (14). In another study, patients who received a delayed first benzodiazepine, i.e., > 10 min, had a higher mortality rate and a higher probability for receiving further multiple antiseizure medications (ASMs) than only BZDs (15). Therefore, it is by far vital to administer BZDs early in the course of the emergency seizures, i.e., at home, to prevent high rates of complications and mortality as well as refractory stages. In veterinary medicine, there are two clinical studies investigating the clinical efficacy of BZDs in dogs, in particular intranasal MDZ, as a rescue medication for SE within hospital settings (16, 17), however, no data exists regarding the evaluation of the emergency seizure treatment options at home by the owners. The aim of this online survey was to assess the use of rescue medication used at home from an owner perspective and identify any gaps that may lead to inadequate or delayed treatment of seizure emergencies.