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

• Published in: Anesthesiology (Philadelphia) Vol. 125; no. 4; pp. 700 - 715
• Main Authors: Lodenius, Åse, Ebberyd, Anette, Hårdemark Cedborg, Anna, Hagel, Eva, Mkrtchian, Souren, Christensson, Eva, Ullman, Johan, Scheinin, Mika, Eriksson, Lars I, Jonsson Fagerlund, Malin
• Format: Journal Article
• Language: English
• Published: United States Copyright by , the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc 01.10.2016
• Subjects: Adolescent; Adult; Cross-Over Studies; Dexmedetomidine - pharmacology; Humans; Hypercapnia - physiopathology; Hypnotics and Sedatives - pharmacology; Hypoxia - physiopathology; Male; Medicin och hälsovetenskap; Propofol - pharmacology; Reference Values; Respiration - drug effects; Young Adult
• ISSN: 0003-3022; 1528-1175; 1528-1175
• DOI: 10.1097/ALN.0000000000001236

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.