Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers.
BACKGROUND
Dexmedetomidine, a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients, has minimal effect on ventilation.


METHODS
This study compared the respiratory effect of dexmedetomidine to that of remifentanil. The authors measured and compared respiratory responses of six healthy male volunteers during (1) a stepwise target-controlled infusion of remifentanil, (2) a stepwise target-controlled infusion of dexmedetomidine, and (3) a pseudonatural sleep session.


RESULTS
Compared with baseline, remifentanil infusions resulted in respiratory depression as evidenced by a decrease in respiratory rate and minute ventilation, respiratory acidosis, and apnea episodes resulting in desaturations. Remifentanil disturbed the natural pattern of breathing and flattened the distribution of ventilatory timing (inspiratory time/ventilatory cycle time). The respiratory effects of dexmedetomidine markedly contrasted with those of remifentanil. When compared with baseline, during dexmedetomidine infusions, the respiratory rate significantly increased, and the overall apnea/hypopnea index significantly decreased. The distribution of inspiratory time/ventilatory cycle time showed an increased peak. In addition, dexmedetomidine seemed to mimic some aspect of natural sleep. While the subjects were breathing a 5% CO2 mixture, hypercapnic arousal phenomena (documented by the Bispectral Index, the electroencephalogram, and sudden increase in the minute ventilation) were observed during dexmedetomidine infusions. Similar phenomena during natural sleep have been reported in the literature.


CONCLUSIONS
In comparison with remifentanil, dexmedetomidine infusions (1) did not result in clinically significant respiratory depression, (2) decreased rather than increased the apnea/hypopnea index, and (3) exhibited some similarity with natural sleep.
Hsu
Yung-Wei
YW
Human Pharmacology Laboratory, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cortinez
Luis I
LI
Robertson
Kerri M
KM
Keifer
John C
JC
Sum-Ping
Sam T
ST
Moretti
Eugene W
EW
Young
Christopher C
CC
Wright
David R
DR
Macleod
David B
DB
Somma
Jacques
J
D000328:Adult; D000465:Algorithms; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000493:pharmacokinetics; D002138:Calibration; D002245:Carbon Dioxide / Q000097:blood; D018592:Cross-Over Studies; D020927:Dexmedetomidine / Q000009:adverse effects* / Q000493:pharmacokinetics; D004569:Electroencephalography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006935:Hypercapnia / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008297:Male; D010100:Oxygen / Q000097:blood; D010880:Piperidines / Q000009:adverse effects* / Q000493:pharmacokinetics; D000077208:Remifentanil; D015656:Respiratory Mechanics / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects
D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D010880:Piperidines; D002245:Carbon Dioxide; D020927:Dexmedetomidine; D000077208:Remifentanil; D010100:Oxygen