Critical Illness: SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazola) 2009m)

Question 1

SEDCOM Clincial Q

Answer 1

In mechanically ventilated ICU patients, what is the efficacy and safety of prolonged sedation with dexmedetomidine compared to midazolam?

Question 2

SEDCOM Bottom Line

Answer 2

Among mechanically ventilated ICU patients, there was no difference between dexmedetomidine and midazolam in achieving the time within the targeted sedation level, but dexmedetomidine resulted in less time on the ventilator, less delirium, and less tachycardia and hypertension, at the cost of more bradycardia.

Question 3

SEDCOM Primary outcome

Answer 3

Percentage of time within target Richmond Agitation-Sedation Scale (RASS) range

Question 4

SEDCOM Inclusion criteria

Answer 4

Age ≥18 years Intubated and mechanically ventilated for <96 hours prior with anticipated ventilation/sedation duration of ≥3 more days

Question 5

SEDCOM intervention

Answer 5

• Randomized in 2:1 fashion within 96 hours after intubation to receive:
  
  • Dexmedetomidine 0.2-1.4 µg/kg/h IV; optional 1 µg/kg loading dose, then maintenance infusion starting at 0.8 µg/kg/h
  • Midazolam 0.02-0.1 mg/kg/h IV; optional 0.05 mg/kg loading dose, then maintenance infusion starting at 0.06 mg/kg/h
• Sedation assessed according to Richmond Agitation-Sedation Scale (RASS); dosing titrated to achieve light sedation (scores between -2 and +1); f still not adequately sedated, open-label midazolam bolus doses of 0.01-0.05 mg/kg at 10- to 15-minute intervals could be administered (maximum dose of 4 mg over 8 h)
• Delirium assessed according to Confusion Assessment Method for ICU (CAM-ICU) Fentanyl 0.5-1.0 µg/kg bolus q15 mins prn pain Haldol 1-5 mg IV q 10-20 mins prn agitation or delirium
• No other sedatives or analgesics allowed Infusions stopped at extubation, after maximum of 30 days, or if deemed in the best interest of the patient

Question 6

SEDCOM Criticism

Answer 6

• Internal
  
  • High starting dose of midazolam (approximately 5 mg/h)
  • Lack of daily interruption of sedative infusions (“sedation vacations” which are now considered standard-of-care)
  • High dexmedetomidine dose (up to twice the currently FDA-approved dose, 0.7 mcg/kg/h)
• External
  
  • Many centers in this study enrolled few (<5) patients, raising concern for variability and unbalanced center effect.
  • Common alternatives to midazolam such as lorazepam or propofol were not tested.