The cardiopulmonary effects of romifidine in dogs with and without prior or concurrent administration of glycopyrrolate.

Objective: To determine the electrocardiographic and cardiopulmonary effects of romifidine with and without prior or concurrent administration of glycopyrrolate.

Study Design: Randomized crossover experimental study.

Animals: Six (three male, three female) cross-bred dogs weighing 23 ± 2.4 kg.

Methods: Baseline cardiopulmonary measurements were obtained in conscious dogs and one of five treatments was administered. Glycopyrrolate (G) 0.01 mg kg, or saline (S) 0.5 mL, were administered IM as premedication (Gp or Sp), or G was administered concurrently (Gc) with romifidine (RO). Treatments were as follows T1, Sp + RO 40 μg kg; T2, Gp + RO (40 μg kg); T3, Sp + RO 120 μg kg; T4, Gp + RO (120 μg kg); T5, Sp + Gc + RO (120 μg kg). Romifidine or RO + Gc was administered subcutaneously 20 minutes after premedication (time 0), and further measurements were taken 10, 20, 30, 60 and 90 minutes after RO. The main treatment effect was evaluated using two-way anova for repeated measures, followed by one-way anova and a post-hoc least squares difference test with a modified Bonferroni correction (p < 0.02). A Student's t-test was used to compare the effect of romifidine at 20 and 60 minutes versus baseline values (p < 0.05).

Results: Both low- and high-dose RO (T1, T3) significantly decreased heart rate (HR), respiratory rate (RR), cardiac index (CI) and stroke volume index, and increased arterial blood pressure (SAP), systemic vascular resistance (SVR), pulmonary arterial occlusion pressure (PAOP) and central venous pressure. High-dose RO produced greater increases in SVR and SAP measurements. Neither dose of RO produced an alteration in blood gas values or the alveolar to arterial oxygen gradient. Glycopyrrolate significantly increased HR and CI from 10 to 90 minutes between T1/T2 and T3/T4. Increases in SAP were dose related with significant differences between T1/T3 and T2/T4 at 90 and 10 minutes, respectively, and were highest in animals receiving Gp or Gc. High-dose RO groups (T3, T4) had higher values for SVR than low-dose RO groups (T1, T2), unrelated to G administration. There was an increase in PAOP in all treatments. The oxygen extraction ratio was increased with all treatments: larger increases were observed in T1, T3 and T4 compared with only minimal changes in T2. Concurrent G administration was associated with an increased frequency of high-grade second-degree atrioventricular heart block with variable conduction at 10 and 20 minutes.

Conclusions: Romifidine produced effects consistent with other selective α-adrenoreceptor agonists. Glycopyrrolate offset the decrease in HR and partially offset the decrease in CI associated with RO administration. Glycopyrrolate premedication produced an initial tachycardia and added to the increase in SAP associated with RO. Concurrent G administration was associated with a higher frequency of dysrhythmias and is not recommended. Despite the decrease in RR, RO sedation did not alter blood gas values.

Clinical Relevance: It appears likely that G administration prior to or concurrent with RO produces an increase in myocardial workload and oxygen demand suggesting that this combination should not be used in dogs with cardiomyopathy or heart failure. The improvement in oxygen extraction ratio with T2 suggests that G may be beneficial with lower doses of RO, nevertheless, the use of G and RO in cardiovascularly compromised patients is not advised.