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

Anesthesiology 2016 10;125(4):700-15

From the Department of Anesthesiology, Surgical Services and Intensive Care, Karolinska University Hospital, Stockholm, Sweden (Å.L., E.C., J.U., L.I.E., M.J.F.); Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology (Å.L., A.E., A.H.C., S.M., E.C., J.U., L.I.E., M.J.F.) and Medical Statistics Unit, Department of Learning, Informatics, Managements and Ethics (E.H.), Karolinska Institutet, Stockholm, Sweden; Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland (M.S.); and Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland (M.S.).

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.

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http://dx.doi.org/10.1097/ALN.0000000000001236DOI Listing
October 2016
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