Anesthetic Pharmacology

Preclilnical Pharmacology section Editor:Marcel E.Durieux Clinical Pharmacology Section Editor:Tony Gin

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

Cheng Chang,MD Akinori Uchiyama,MD,PhD

Ling Ma,MD Takashi Mashimo,MD,PhD

Yuji Fujino,MD,PhD BACKGROUND:Dexmedetomidine,propofol,and midazolam are commonly used sedative-hypnotic http://www.doczj.com/doc/d82f861da300a6c30c229f4c.htmling 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 weighing2.9?0.2kg(mean?sd)were used. After anesthetic induction and tracheostomy,the animals inhaled2%sevoflurane to ensure a stable level of sedation throughout the experiment.After preparation, the rabbits were randomly assigned to four groups(n?10?4)and received the following drugs:Group C,control;Group D,dexmedetomidine infused at2?g?kg?1?h?1;Group P,propofol with the plasma concentration maintained at15?g/mL;Group M,midazolam initial IV0.3mg/kg bolus dose,followed by infusion at1.86mg?kg?1?h?1.At15minutes after the start of infusion,for20min periods,in random sequences,gas including0%,1%,2%,3%,4%,or5%of CO2was delivered to each animal.Fraction of inspired oxygen was maintained at0.9.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 FiCO

2 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.Pa co2-MV response plots were derived from linear regression analysis of data for mean MV and mean Pa co2at each FiCO2to compute apneic CO2thresholds and CO2sensitivities.The apneic CO2thresholds of Groups P and M were larger than those of Groups C and D.The CO2sensitivities of Group D were slightly lower than in Group C.No similar significant difference between the CO2sensitivities 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.

(Anesth Analg2009;109:84–9)

P ropofol,midazolam,and dexmedetomidine are of-

ten used to achieve satisfactory sedation for critically ill intensive care unit patients.1Although several human and animal studies have presented evidence that each of the three commonly used sedatives cause respiratory depression,2–8no direct comparison of the respiratory depression associated with dexmedetomidine,propofol, and midazolam had previously been performed.

Knowing that CO2ventilatory response is affected by many factors,such as hypoxia,exercise,state of wakefulness,sleep,or anesthesia,9in the groups un-der comparison,we aimed to maintain a uniform level of anesthesia,which has varied in previous reports for dexmedetomidine.7,8,10To clarify the depressive ef-fects on respiration,we designed a steady-state proto-col using a sevoflurane-anesthetized rabbit model to examine and the different effects of dexmedetomidine,

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

Accepted for publication January7,2009.

Address correspondence and reprint requests to Akinori Uch-iyama,MD,PhD,Department of Anesthesiology and Intensive Care Medicine,Osaka University Graduate School of Medicine,2-15 Yamadaoka,Suita,Osaka565-0871,Japan.Address e-mail to auchiyama@hp-icu.med.osaka-u.ac.jp.

Copyright?2009International Anesthesia Research Society DOI:10.1213/ane.0b013e3181a2ad5f