Synergistic sedation with propofol and midazolam in intensive care patients after coronary artery bypass grafting.
OBJECTIVE
To evaluate and compare the clinical efficacy, impact on hemodynamics, safety profiles, and cost of combined administration of propofol and midazolam (synergistic sedation) vs. midazolam and propofol administered as sole agents, for sedation of mechanically ventilated patients after coronary artery bypass grafting.


METHODS
Prospective, controlled, randomized, double-blind clinical trial.


METHODS
Intensive care unit of SCIAS-Hospital de Barcelona.


METHODS
Seventy-five mechanically ventilated patients who underwent coronary artery bypass graft surgery under low-dose opioid anesthesia.


METHODS
According to the double-blind method, patients were randomly assigned to receive propofol (n = 25), midazolam (n = 25), or propofol combined with midazolam (n = 25). Infusion rates were adjusted to stay between 8 and 11 points on Glasgow Coma Score modified by Cook and Palma.


RESULTS
Mean +/- SD duration of sedation was 14.4 +/- 1.5 hrs, 14.1 +/- 1.1 hrs, and 14.7 +/- 1.9 hrs for the propofol, midazolam, and synergistic groups, respectively. The induction dose was 0.55 +/- 0.05 mg/kg for propofol as sole agent, 0.05 +/- 0.01 mg/kg for midazolam as sole agent, and 0.22 +/- 0.03 mg/kg for propofol administered in combination with 0.02 +/- 0.00 mg/kg of midazolam (p = .001). The maintenance dose was 1.20 +/- 0.03 mg/kg/hr for propofol as sole agent, 0.08 +/- 0.01 mg/kg/hr for midazolam as sole agent, and 0.50 +/- 0.09 mg/kg/hr for propofol administered in combination with 0.03 +/- 0.01 mg/kg/hr of midazolam (p < .001). All sedative regimens achieved similar efficacy in percentage of hours of adequate sedation (93% for propofol, 88% for midazolam, and 90% for the synergistic group, respectively). After induction, both propofol and midazolam groups had significant decreases in systolic blood pressure, diastolic blood pressure, left atrial pressure, and heart rate. Patients in the synergistic group had significant bradycardia throughout the study, without impairment in other hemodynamic parameters. Patients sedated with propofol or synergistic regimen awoke sooner and could be extubated before those patients sedated with midazolam (0.9 +/- 0.3 hrs and 1.2 +/- 0.6 hrs vs. 2.3 +/- 0.8 hrs, respectively, p = .01). Synergistic sedation produced cost savings of 28% with respect to midazolam and 68% with respect to propofol.


CONCLUSIONS
In the study conditions, the new synergistic treatment with propofol and midazolam administered together is an effective and safe alternative for sedation, with some advantages over the conventional regimen with propofol or midazolam administered as sole agents, such as absence of hemodynamic impairment, >68% reduction in maintenance dose, and lower pharmaceutical cost.
Carrasco
G
G
Intensive Care Service, SCIAS-Hospital de Barcelona, Spain.
Cabré
L
L
Sobrepere
G
G
Costa
J
J
Molina
R
R
Cruspinera
A
A
Lacasa
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D016292:Procedural Sedation; D001026:Coronary Artery Bypass; D003422:Critical Care; D004311:Double-Blind Method; D004338:Drug Combinations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D017850:Economics, Pharmaceutical; D005260:Female; D015600:Glasgow Coma Scale; D006439:Hemodynamics; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D008874:Midazolam / Q000008:administration & dosage*; D008875:Middle Aged; D011184:Postoperative Period; D015742:Propofol / Q000008:administration & dosage*; D012121:Respiration, Artificial
D014151:Anti-Anxiety Agents; D004338:Drug Combinations; D006993:Hypnotics and Sedatives; D008874:Midazolam; D015742:Propofol