Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction

Abstract

Background:Propofol is a rapid, efficient hypnotic agent with antiemetic effects. However, a high dosage is related to hemodynamic abnormalities such as hypotension and bradycardia. Pretreatment with remifentanil can decrease injection pain and stabilize hemodynamics during the induction period. Remifentanil or midazolam in combination with propofol can provide synergistic or additive effects during anesthesia induction. However, the hypnotic doses of propofol required in patients who receive pretreatment with remifentanil or midazolam remain unclear.Methods:Patients aged 20 to 50 years who were scheduled to undergo surgery under general anesthesia were enrolled in this study. 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 prior to propofol, and those in Group PMR (Propofol-Midazolam-Remifentanil) received remifentanil and midazolam prior to propofol. After propofol administration, loss of both the 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:A total of 124 patients were initially enrolled. Of these, 4 were excluded, and the remaining 120 patients were randomized to each (n = 40) of the 3 groups. The 95% effective dose of propofol for loss of consciousness was 1.74 , 1.38, and 0.92 mg/kg in Groups P, PR, and PMR, respectively. Blood pressure decreased at 2 minutes after propofol administration in all the groups. However, compared with Group P, Groups PR and PMR exhibited a significant decrease in blood pressure.Conclusions:The effective dose of propofol for loss of consciousness could be decreased by 21% and 47% when remifentanil pretreatment was used without and with midazolam, respectively. However, the decrease in blood pressure was greater with pretreatment than sole propofol use. These findings suggest that the combination of remifentanil with or without midazolam may have no benefit on hemodynamic stability during induction using propofol.Trial registration:NCT02536690 (clinicaltrials.gov).

Effect of remifentanil and midazolam on ED95 of propofol for loss of consciousness in elderly patients

“…[9] In our result, the ED 95 of propofol for loss of consciousness in elderly patients (>65 years) was 1.13 mg/kg, which is 35% lower than that reported for 20- to 50-year-old patients (1.74 mg/kg) in a previous study. [7] Our findings are similar to those of Olmos et al, showing a 37% reduction in the effect-site concentration of propofol for hypnosis in patients >60 years compared with those <40 years. [10] Our results confirm the guideline for minimal administration of propofol, as higher doses can be unnecessarily excessive in elderly patients.…”

“…The reduction of the dose of propofol after pretreatment with remifentanil in elderly patients is comparable to that reported for young patients (21% dose reduction of propofol). [7] We cannot estimate the exact drug interaction of propofol and remifentanil because an isobolographic analysis was not conducted in our study. However, our results suggest that propofol doses ≥1.0 mg/kg are more than necessary for loss of consciousness in the elderly (>65 years) when remifentanil pretreatment is coadministered during the induction period.…”

“…Due to concerns about increased brain sensitivity and decreased drug clearance in elderly patients, the initial propofol dose was determined to be 0.5 mg/kg, and the doses of remifentanil and midazolam were half of the doses reported in a prior study by Koh et al that was performed in healthy young patients. [6,7] After the predetermined dose of propofol was administered, the loss of the eyelash reflex and verbal response was assessed for 3 minutes. Induction success was represented by loss of both the eyelash reflex and verbal response.…”

“…A minimum of 40 subjects were required, according to the methods of Durham et al [7] We therefore enrolled 40 patients in each group. Statistical analyses were performed using the Statistical Package for Social Sciences (ver.…”

Terminal Withdrawal of Mechanical Ventilation: A Hospice Perspective for the Intensivist

“…Essentially, the greater the stimulus and dose of propofol, the more pronounced the interaction. [59][60][61][62][63][64][65] In the realm of general anesthesia, very appreciable effects can be obtained with relatively small concentrations of remifentanil (3-6 ng/mL) when the initial propofol dose is 150 to 200 mg/kg/min or more. 60,61 When added to propofol rates below 100 mg/kg/min, the interaction begins to approach quickly the point of diminishing return.…”