Sedation with Dexmedetomidine or Propofol Impairs Hypoxic Control of Breathing in Healthy Male Volunteers: A Nonblinded, Randomized Crossover Study. (October 2016)

• Record Type: Journal Article
• Authors: Lodenius, Åse; Ebberyd, Anette; Hårdemark Cedborg, Anna; Hagel, Eva; Mkrtchian, Souren; Christensson, Eva; Ullman, Johan; Scheinin, Mika; Eriksson, Lars I.; Jonsson Fagerlund, Malin
• Is Part Of: Anesthesiology. Volume 125:Number 4(2016)
• Publication Date: 2016-10
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000001236
• Languages: English
• ISSNs: 0003-3022

Abstract

Abstract : Background: In contrast to general anesthetics such as propofol, dexmedetomidine when used for sedation has been put forward as a drug with minimal effects on respiration. To obtain a more comprehensive understanding of the regulation of breathing during sedation with dexmedetomidine, the authors compared ventilatory responses to hypoxia and hypercapnia during sedation with dexmedetomidine and propofol. Methods: Eleven healthy male volunteers entered this randomized crossover study. Sedation was administered as an intravenous bolus followed by an infusion and monitored by Observer's Assessment of Alertness/Sedation (OAA/S) scale, Richmond Agitation Sedation Scale, and Bispectral Index Score. Hypoxic and hypercapnic ventilatory responses were measured at rest, during sedation (OAA/S 2 to 4), and after recovery. Drug exposure was verified with concentration analysis in plasma. Results: Ten subjects completed the study. The OAA/S at the sedation goal was 3 (3 to 4) (median [minimum to maximum]) for both drugs. Bispectral Index Score was 82 ± 8 and 75 ± 3, and the drug concentrations in plasma at the sedation target were 0.66 ± 0.14 and 1.26 ± 0.36 μg/ml for dexmedetomidine and propofol, respectively. Compared with baseline, sedation reduced hypoxic ventilation to 59 and 53% and the hypercapnic ventilation to 82 and 86% for dexmedetomidine and propofol, respectively. In addition, some volunteers displayed upper airway obstruction and episodes of apnea during sedation. Conclusions: Dexmedetomidine-induced sedation reduces ventilatory responses to hypoxia and hypercapnia to a similar extent as sedation with propofol. This finding implies that sedation with dexmedetomidine interacts with both peripheral and central control of breathing. Abstract : In this randomized crossover healthy volunteer study, sedation with dexmedetomidine and propofol significantly reduced hypoxic ventilation to 59 and 53% and the hypercapnic ventilation to 82 and 86%, respectively. Clinicians should recognize respiratory-depressant effects of dexmedetomidine.