Quantitative electroencephalographic comparison of intranasal midazolam, intranasal saline, and intrarectal diazepam...

Benzodiazepines are the recommended first-line treatment for canine seizure emergencies, and non-parenteral routes are essential when intravenous access is unavailable. Clinical trials show that intranasal midazolam controls emergency seizures more reliably than rectal diazepam, yet the cortical electrophysiological correlates of these routes remain uncharacterised in dogs. In a two-session, fixed-order (non-randomised) study, the quantitative electroencephalographic (qEEG) profiles of intranasal midazolam (IN-MDZ; 0.2 mg/kg), volume-matched intranasal saline (IN-SAL) and intrarectal diazepam (IR-DZP; 0.5 mg/kg) were compared in six healthy adult dogs. Propofol (1%, 0.5 mL/kg IV) was given in both sessions for electrode placement, and recording followed clinical recovery. Metrics were computed at baseline and 1, 3 and 5 min and analysed with the dog as the unit of replication (n = 6), using Friedman and exact Wilcoxon tests with false-discovery-rate (FDR) control. IN-MDZ was associated with a coherent, rapidly emerging cortical-slowing signature: at 1-3 min it separated from both controls across relative delta, beta, delta/beta, theta/alpha, alpha and entropy, unanimously and drug-specifically, the correlated indices reflecting a single coherent spectral shift reproduced at two time points. This slowing, in contrast to the beta activation reported in seizing human patients, is consistent with a genuine, rapidly acting GABAergic effect, and is concordant with the established clinical efficacy of intranasal midazolam. No contrast survived false-discovery-rate correction; the core indices nonetheless persisted on baseline-corrected change scores (r = 0.7-0.9). The study defines the qEEG endpoints, effect sizes and sample size required for an adequately powered confirmatory trial.