The effects of increasing plasma concentrations of dexmedetomidine in humans

Background: This study determined the responses to increasing plasma concen trations of dexmedetomidine in humans. Methods: Ten healthy men (20-27 yr) provided informed consent and were moni tored (underwent electrocardiography, measured arterial, central venous [CV P] and pulmonary artery [PAP] pressures, cardiac output, oxygen saturation, end-tidal carbon dioxide [ETCO2] respiration, blood gas, and catecholamine s). Hemodynamic measurements, blood sampling, and psychometric, cold presse r, and baroreflex tests were performed at rest and during sequential 40-min intravenous target infusions of dexmedetomidine (0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml; baroreflex testing only at 0.5 and 0.8 ng/ml). Results: The initial dose of dexmedetomidine decreased catecholamines 45-76 % and eliminated the norepinephrine increase that was seen during the cold presser test. Catecholamine suppression persisted in subsequent infusions. The first two doses of dexmedetomidine increased sedation 38 and 65%, and l owered mean arterial pressure by 13%, but did not change central venous pre ssure or pulmonary artery pressure. Subsequent higher doses increased sedat ion, all pressures, and calculated vascular resistance, and resulted in sig nificant decreases in heart rate, cardiac output, and stroke volume. Recall and recognition decreased at a dose of more than 0.7 ng/ml. The pain ratin g and mean arterial pressure increase to cold presser test progressively di minished as the dexmedetomidine dose increased. The baroreflex heart rate s lowing as a result of phenylephrine challenge was potentiated at both doses of dexmedetomidine. Respiratory variables were minimally changed during in fusions, whereas acid-base was unchanged. Conclusions: Increasing concentrations of dexmedetomidine in humans resulte d in progressive increases in sedation and analgesia, decreases in heart ra te, cardiac output, and memory. A biphasic (low, then high) dose-response r elation for mean arterial pressure, pulmonary arterial pressure, and vascul ar resistances, and an attenuation of the cold presser response also were o bserved.