Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial

Jae Chul Koh, Juyeon Park, Na Young Kim, Ann Hee You, Seo Hee Ko, Dong Woo Han, Jae Chul Koh, Juyeon Park, Na Young Kim, Ann Hee You, Seo Hee Ko, Dong Woo Han

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).

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Assessment of success or failure of anesthesia induction by a predetermined bolus dose of propofol determined for consecutive patients using a modified biased coin design in each group. Induction success (loss of consciousness) is indicated by solid circles, and induction failure (no loss of consciousness) is indicated by open circles. Group P: patients who received only propofol for loss of consciousness. Group PR: patients who received remifentanil (0.25 μg/kg/min) prior to propofol. Group PMR: patients who received both midazolam (0.05 μg/kg) and remifentanil prior to propofol.
Figure 2
Figure 2
The pooled adjacent violators algorithm response rate for each group. For the higher success rate for loss of consciousness, Group P required higher dose of propofol, followed by Group PR and Group PMR. Group P: patients who received only propofol for loss of consciousness. Group PR: patients who received remifentanil (0.25 μg/kg/min) prior to propofol. Group PMR: patients who received both midazolam (0.05 μg/kg) and remifentanil prior to propofol.
Figure 3
Figure 3
Mean blood pressure and heart rate values at baseline, before propofol administration, and 1 and 2 minutes after propofol administration in each group. Values are presented as mean ± standard deviation. MBP was more significantly decreased at Group PR and PMR compared with Group P at 2 minutes after propofol administration (P = .02 and P = .01, respectively). There were no intergroup differences in HR at each time point.∗, †, ‡: Significantly decreased compared with baseline values in Group P, Group PR, and Group PMR, respectively (P < .05). §: Significantly decreased compared with Group P. MBP = mean blood pressure, HR = heart rate, 0 min, 1 min, 2 min = before and 1 and 2 minutes after propofol administration, respectively. Group P: patients who received only propofol for loss of consciousness. Group PR: patients who received remifentanil (0.25 g/kg/min) prior to propofol. Group PMR: patients who received both midazolam (0.05 g/kg) and remifentanil prior to propofol.

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