Monitored anesthesia care with dexmedetomidine: a prospective, randomized, double-blind, multicenter trial.
BACKGROUND
Dexmedetomidine (DEX) is increasingly being used as a sedative for monitored anesthesia care (MAC) because of its analgesic properties, "cooperative sedation," and lack of respiratory depression. In this randomized, multicenter, double-blind, Phase III Food and Drug Administration study, we evaluated the safety and efficacy of two doses of DEX for sedation of patients undergoing a broad range of surgical or diagnostic procedures requiring MAC.


METHODS
Three hundred twenty-six patients were randomized 2:2:1 to DEX 0.5 microg/kg, DEX 1 microg/kg, or saline placebo initial loading dose, followed by a maintenance infusion of 0.2-1.0 microg x kg(-1) x h(-1) of DEX (or equivalent volume of saline) titrated to a targeted level of sedation (< or = 4 on the Observer's Assessment of Alertness/Sedation Scale [OAA/S]). Study drug was started at least 15 min before placement of regional or local anesthetic block. Midazolam was given for OAA/S > 4 and fentanyl for pain. The primary end-point was the percentage of patients not requiring rescue midazolam.


RESULTS
Significantly fewer patients in the 0.5- and 1-microg/kg DEX groups required supplemental midazolam compared with placebo (59.7% [80/134], 45.7% [59/129] vs 96.8% [61/63], respectively; P < 0.001) and at lower doses to achieve an OAA/S < or = 4 before and during surgery compared with the saline group (1.4 and 0.9 mg vs 4.1 mg, respectively; P < 0.001, each group compared with placebo). Both DEX groups required significantly less fentanyl (84.8 and 83.6 microg vs 144.4 microg, respectively; P < 0.001, for both DEX groups versus placebo) for all surgical subtypes. Anesthesiologists indicated significantly increased ease of achieving and maintaining targeted sedation in both DEX groups compared with placebo with midazolam (P < 0.001). Patient satisfaction was significantly higher with DEX (P < or = 0.009, both groups versus placebo). Common adverse events with DEX were protocol-defined bradycardia and hypotension that were predominately mild to moderate in severity. The incidence of clinically significant respiratory depression (defined as a respiratory rate of < 8 or an oxygen saturation of < 90%) was lower in DEX-treated patients (P = 0.018, for both groups versus placebo).


CONCLUSIONS
DEX is an effective baseline sedative for patients undergoing MAC for a broad range of surgical procedures providing better patient satisfaction, less opioid requirements, and less respiratory depression than placebo rescued with midazolam and fentanyl.
Candiotti
Keith A
KA
Division of Perioperative Medicine, University of Miami, Miami, Florida 33101, USA. kcandiot@med.miami.edu
Bergese
Sergio D
SD
Bokesch
Paula M
PM
Feldman
Marc A
MA
Wisemandle
Wayne
W
Bekker
Alex Y
AY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000758:Anesthesia; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D017060:Patient Satisfaction; D011446:Prospective Studies; D055815:Young Adult
D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D005283:Fentanyl