The efficacy and safety of the combination of tiletamine-zolazepam (Vezotil®) with dexmedetomidine for controlled sedation of dogs and cats during invasive mechanical ventilation: a pilot prospective randomized controlled trial

Background. Invasive mechanical ventilation (MV) has become an accessible intensive care option in small animal veterinary practice; however, sedation protocols for ventilated patients remain unregulated. There is a lack of standardized protocols, no validated tools for assessing sedation depth in intubated dogs and cats have been developed, and the most well-studied regimens rely on controlled substances, which limits their clinical application. Objective. To compare the efficacy and safety of tiletamine–zolazepam (Vezotil®) combined with dexmedetomidine versus ketamine combined with dexmedetomidine for controlled sedation in dogs and cats receiving invasive mechanical ventilation. Materials and Methods. This pilot prospective randomized controlled trial included 40 patients (23 dogs and 17 cats) receiving invasive mechanical ventilation in an intensive care unit. The patients were randomized to the tiletamine-zolazepam plus dexmedetomidine group (TZ+D; n = 20) or the ketamine plus dexmedetomidine group (K+D; n = 20). The primary endpoint was sedation depth assessed using the Medication-Controlled Sedation during Mechanical Ventilation scale developed by the authors (MCS-MV; range, 0–15 points; target range, 8–10 points). The secondary endpoints were the need for rescue boluses, the incidence of complications associated with their administration, and the rate of an unfavorable outcome. The exact Mann–Whitney U test and Fisher’s exact test were used. Effect estimates were reported with 95% confidence intervals (CIs). Results. No statistically significant between-group differences were observed in the MCS-MV score (median, 9.5 vs 9.0; U = 192.0; p = 0.841; Hodges–Lehmann shift estimate, 0.0 points; 95% CI, −1.0 to +1.0), the number of rescue boluses (median, 0.5 vs 2.0; U = 167.5; p = 0.398), the incidence of complications (15.0% vs 10.0%; p = 1.000; risk difference, +5.0 percentage points; 95% CI, −17.3 to +27.2), or the rate of an unfavorable outcome (40.0% vs 30.0%; p = 0.741; risk difference, +10.0 percentage points; 95% CI, −18.4 to +36.3). The target sedation range was achieved in both groups. Similar results were obtained in a post hoc subgroup analysis of patients with cardiogenic pulmonary edema. Conclusion. In this pilot study, the tiletamine-zolazepam plus dexmedetomidine combination provided a depth of controlled sedation comparable to the ketamine-dexmedetomidine regimen, with a similar safety profile. While the width of the confidence intervals precludes a formal claim of equivalence, the findings justify a full-scale non-inferiority trial and highlight the practical significance of this regimen for clinics lacking licenses for the handling of controlled substances.