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.
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 microg x kg(-1) x h(-1); Group P, propofol with the plasma concentration maintained at 15 microg/mL; Group M, midazolam initial IV 0.3 mg/kg bolus dose, followed by infusion at 1.86 mg x kg(-1) x 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.
Chang
Cheng
C
Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan.
Uchiyama
Akinori
A
Ma
Ling
L
Mashimo
Takashi
T
Fujino
Yuji
Y
D000769:Anesthesia, Inhalation / Q000379:methods; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000502:physiology*; D020927:Dexmedetomidine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008738:Methyl Ethers / Q000494:pharmacology*; D008874:Midazolam / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D011817:Rabbits; D012119:Respiration / Q000187:drug effects*; D000077149:Sevoflurane
D008738:Methyl Ethers; D002245:Carbon Dioxide; D000077149:Sevoflurane; D020927:Dexmedetomidine; D008874:Midazolam; D015742:Propofol