Dexmedetomidine pharmacodynamics

Part I - Crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers

Yung Wei Hsu, Luis I. Cortinez, Kerri M. Robertson, John C. Keifer, Sam T. Sum-Ping, Eugene W. Moretti, Christopher C. Young, David R. Wright, David B. MacLeod, Jacques Somma

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

Background: Dexmedetomidine, a highly selective α 2- 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% CO 2 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.

Original languageEnglish (US)
Pages (from-to)1066-1076
Number of pages11
JournalAnesthesiology
Volume101
Issue number5
DOIs
StatePublished - Nov 2004

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Dexmedetomidine
Healthy Volunteers
Sleep
Apnea
Ventilation
Respiratory Rate
Respiratory Insufficiency
Respiration
Respiratory Acidosis
remifentanil
Carbon Monoxide
Arousal
Adrenergic Receptors
Electroencephalography

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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

In: Anesthesiology, Vol. 101, No. 5, 11.2004, p. 1066-1076.

Research output: Contribution to journalArticle

Hsu, YW, Cortinez, LI, Robertson, KM, Keifer, JC, Sum-Ping, ST, Moretti, EW, Young, CC, Wright, DR, MacLeod, DB & Somma, J 2004, 'Dexmedetomidine pharmacodynamics: Part I - Crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers', Anesthesiology, vol. 101, no. 5, pp. 1066-1076. https://doi.org/10.1097/00000542-200411000-00005
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. / Dexmedetomidine pharmacodynamics : Part I - Crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. In: Anesthesiology. 2004 ; Vol. 101, No. 5. pp. 1066-1076.
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abstract = "Background: Dexmedetomidine, a highly selective α 2- 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{\%} CO 2 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.",
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AU - Cortinez, Luis I.

AU - Robertson, Kerri M.

AU - Keifer, John C.

AU - Sum-Ping, Sam T.

AU - Moretti, Eugene W.

AU - Young, Christopher C.

AU - Wright, David R.

AU - MacLeod, David B.

AU - Somma, Jacques

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