Tl. Higgins et al., PROPOFOL VERSUS MIDAZOLAM FOR INTENSIVE-CARE UNIT SEDATION AFTER CORONARY-ARTERY BYPASS-GRAFTING, Critical care medicine, 22(9), 1994, pp. 1415-1423
Objective: To compare the safety and effectiveness of propofol (2,6-di
isopropylphenol) to midazolam for sedation of mechanically ventilated
patients after coronary artery bypass grafting. Design: Open, randomiz
ed, prospective trial. Setting: Cardiothoracic intensive care unit (IC
U), Cleveland Clinic Foundation. Patients: Eighty-four patients with n
ormal or; moderately impaired left ventricular function who underwent
elective coronary artery bypass graft surgery under high-dose opioid a
nesthesia. Interventions: Patients were randomly selected to receive e
ither propofol (mean loading dose 0.24 mg/kg; mean maintenance dose 0.
76 mg/kg/hr) or midazolam (mean loading dose 0.012 mg/kg; mean mainten
ance dose 0.018 mg/kg/hr). Infusion rates were titrated to keep patien
ts comfortable, drowsy, and responsive to verbal stimulation. Study du
ration, 8 to 12 hrs; infusions were started in the ICU when patients w
ere awake and hemodynamically stable. Measurements and Main Results: D
uring therapy, both groups had lower mean arterial pressures and heart
rates compared with baseline measurements; however, the propofol grou
p had significantly lower heart rates than the midazolam group during
the first 2 hrs of infusion. The propofol group also had significantly
lower blood pressure measurements 5 and 10 mins after the initial dos
e, although there was no difference during infusion. Baseline cardiac
output was measured before starting the infusion, and measurements wer
e repeated during continuous infusion at 4, 8, and 12 hrs. Cardiac out
put values were similar. Propofol maintenance infusions ranged from 3
to 30 mu g/kg/min and midazolam infusions ranged from 0.1 to 0.7 mu g/
kg/min. At these infusion rates. both groups had adequate sedation, ba
sed on nurse and patient evaluations; however, the propofol group used
significantly lower total doses of sodium nitroprusside and supplemen
tal opioids. Conclusions: Both propofol and midazolam provided safe an
d effective sedation of coronary artery bypass graft patients recoveri
ng from high-dose opioid anesthesia. The reduced need for both antihyp
ertensive medication and opioids seen in the propofol group may be adv
antageous. However, the hypotension seen after the initial bolus dose
of propofol may be a concern. No difference between the two drugs coul
d be demonstrated in time to extubation or ICU discharge, although it
is probable that time to extubation was governed more by residual oper
ative opioids than the study agents.