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ANESTHETIC PHARMACOLOGY

A Comparison of the Effects on Respiratory Carbon Dioxide Response, Arterial Blood Pressure, and Heart Rate of Dexmedetomidine, Propofol, and Midazolam in Sevoflurane-Anesthetized Rabbits

From the Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Japan.

Address correspondence and reprint requests to Akinori Uchiyama, MD, PhD, Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan. Address e-mail to auchiyama{at}hp-icu.med.osaka-u.ac.jp.

BACKGROUND: Dexmedetomidine, propofol, and midazolam are commonly used sedative-hypnotic drugs. Using a steady-state method, we examined the CO₂ ventilatory response, mean arterial blood pressure (MAP) and heart rate (HR) effects of these three drugs in sevoflurane-anesthetized rabbits.

METHODS: New Zealand white rabbits weighing 2.9 ± 0.2 kg (mean ± sd) were used. After anesthetic induction and tracheostomy, the animals inhaled 2% sevoflurane to ensure a stable level of sedation throughout the experiment. After preparation, the rabbits were randomly assigned to four groups (n = 10 x 4) and received the following drugs: Group C, control; Group D, dexmedetomidine infused at 2 µg · kg^–1 · h^–1; Group P, propofol with the plasma concentration maintained at 15 µg/mL; Group M, midazolam initial IV 0.3 mg/kg bolus dose, followed by infusion at 1.86 mg · kg^–1 · h^–1. At 15 minutes after the start of infusion, for 20 min periods, in random sequences, gas including 0%, 1%, 2%, 3%, 4%, or 5% of CO₂ was delivered to each animal. Fraction of inspired oxygen was maintained at 0.9. We did intergroup comparisons of minute ventilation (MV), respiratory rate, MAP, and HR during the final minute of each inspiratory carbon dioxide concentration (FiCO₂) period.

RESULTS: For Groups P and M, the rightward shift of plots for MV against FiCO₂ indicated significant respiratory depression compared with Group C. There was also significantly more depression than in Group D. We found no significant differences between Groups P and M or between Groups C and D in the plots of MV against FiCO₂. No significant differences among the four groups were apparent for respiratory rate. Paco₂-MV response plots were derived from linear regression analysis of data for mean MV and mean Paco₂ at each FiCO₂ to compute apneic CO₂ thresholds and CO₂ sensitivities. The apneic CO₂ thresholds of Groups P and M were larger than those of Groups C and D. The CO₂ sensitivities of Group D were slightly lower than in Group C. No similar significant difference between the CO₂ sensitivities of other group pairs was apparent. MAP in Group D was lower than in Groups C and M. In Group D, HR was lower than in Groups C, P, and M.

CONCLUSIONS: The major finding is that, during sevoflurane anesthesia in rabbits, dexmedetomidine slightly altered the ventilatory response to CO₂. It decreased MAP more than propofol and midazolam, which both significantly depressed the ventilatory response to CO₂.