Dexmedetomidine pharmacodynamics: Part I. Crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers

Dexmedetomidine, a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients, has minimal effect on ventilation. This study compared the respiratory effect of dexmedetomidine to that of remifentanil. The authors measured and compared respiratory re...

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Bibliographic Details
Published in:Anesthesiology (Philadelphia) 2004-11, Vol.101 (5), p.1066-1076
Main Authors: HSU, Yung-Wei, CORTINEZ, Luis I, ROBERTSON, Kerri M, KEIFER, John C, SUM-PING, Sam T, MORETTI, Eugene W, YOUNG, Christopher C, WRIGHT, David R, MACLEOD, David B, SOMMA, Jacques
Format: Article
Language:English
Subjects:
Adult
Algorithms
Analgesics, Opioid - adverse effects
Analgesics, Opioid - pharmacokinetics
Anesthesia
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Biological and medical sciences
Calibration
Carbon Dioxide - blood
Cross-Over Studies
Dexmedetomidine - adverse effects
Dexmedetomidine - pharmacokinetics
Electroencephalography - drug effects
Hemodynamics - drug effects
Humans
Hypercapnia - metabolism
Hypnotics and Sedatives - adverse effects
Hypnotics and Sedatives - pharmacokinetics
Infusions, Intravenous
Male
Medical sciences
Oxygen - blood
Piperidines - adverse effects
Piperidines - pharmacokinetics
Remifentanil
Respiratory Mechanics - drug effects
Sleep - drug effects
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Summary:Dexmedetomidine, a highly selective alpha2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients, has minimal effect on ventilation. 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. 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. 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.
ISSN:0003-3022
1528-1175
DOI:10.1097/00000542-200411000-00005