Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes.
Dexmedetomidine (DMED) is a novel clonidine-like compound known to have sedative, analgesic, and cardiovascular stabilizing qualities. DMED is a more highly selective alpha 2-adrenergic agonist than clonidine. This investigation examined the hemodynamic effects of four selected iv doses in consenting healthy male volunteers. In a randomized, double-blind, placebo-controlled trial subjects received 0 (n = 9), 0.25 (n = 6) 0.5 (n = 6), 1.0 (n = 6), or 2.0 (n = 10) micrograms/kg of DMED by infusion (2 min). ECG, heart rate (HR), arterial blood pressure (MABP), bioimpedance cardiac output (CO), and plasma catecholamines concentrations (CA) were monitored from 90 min before to 360 min after infusion. Plasma DMED concentrations were measured. DMED produced a maximum decrease in MABP at 60 min of 14%, 16%, 23%, and 27% for the 0.25, 0.5, 1.0, and 2.0 micrograms/kg groups, respectively (P < .05). At 330 min MABP remained below baseline by 8% and 17% at the two largest doses (P < .05). Both HR and CO decreased maximally by both 17% at 105 min. The two largest doses produced a transient (peak at 3 min lasting < 11 min) increased in MABP (16 +/- 2.5 and 24 +/- 10 mmHg, respectively; P < .05) with a concomitantly reduced CO (41%, 2 micrograms/kg; P < .05) and HR (22%, 2 micrograms/kg; P < .05), whereas systemic vascular resistance doubled. Even the lowest dose decreased CA immediately to values close to 20 pg/ml for 5 h. A 2-min iv infusion of DMED produced a transient increase in MABP and a longer lasting decrease in MABP and CA. These DMED doses were well tolerated in the healthy volunteers.
Department of Anesthesiology, University of California, Los Angeles.
B C
BC
Bloor
D S
DS
Ward
J P
JP
Belleville
M
M
Maze
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D020926:Medetomidine; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D020926:Medetomidine; D009638:Norepinephrine; D004837:Epinephrine