Effect of remifentanil and midazolam on ED95 of propofol for loss of consciousness in elderly patients: A randomized, clinical trial

BACKGROUND: Older people are more vulnerable to hemodynamic instability caused by propofol due to their decreased initial distribution volume and increased sensitivity to propofol. Midazolam or remifentanil can often be coadministered because of their synergistic or additive effects with propofol as well as amnesic properties and the blockade of sympathetic stimulation. However, no study has confirmed the appropriate dose of propofol for loss of consciousness in aged patients when administered with other drugs, including opioids or benzodiazepines. METHODS: Patients >65 years scheduled for general anesthesia were enrolled. The patients were randomized into 3 groups using a computer-generated randomization table. Patients in group P (propofol) received only propofol for loss of consciousness, those in group PR (propofol-remifentanil) received remifentanil before propofol, and those in group PMR (propofol-midazolam-remifentanil) received remifentanil and midazolam before propofol. After propofol administration, loss of both eyelash reflex and verbal response represented success. The 95% effective dose of propofol for loss of consciousness in each group, which was the primary outcome, was determined using a modified biased coin up-and-down method. RESULTS: In total, 120 patients were randomized into the 3 groups (n = 40). The 95% effective dose of propofol for loss of consciousness was 1.13, 0.87, and 0.72 mg/kg in groups P, PR, and PMR, respectively. The mean blood pressure (MBP) in group PMR was more significantly decreased before propofol injection (P = .041) as well as 2 minutes (P = .005) and 3 minutes after propofol administration (P<.001), compared with group P, but there were no intergroup differences at other time points. CONCLUSIONS: The effective dose of propofol for loss of consciousness in elderly patients could be decreased by 23% and 36% when remifentanil pretreatment was used without and with midazolam, respectively. However, the decrease in MBP was greater with remifentanil and midazolam pretreatment than with propofol alone. These findings suggest that pretreatment with midazolam for propofol infusions with remifentanil in elderly patients should be cautiously used, due to hemodynamic instability during induction.ope