Anesthesia
Conditions
Keywords
propofol, midazolam, remifentanil, combination, synergic, pharmacodynamics, Loss of consciousness
Brief summary
Propofol in combination with remifentanil or midazolam can result in synergistic or additive effect. The patients who are scheduled to undergo general anesthesia are enrolled in this study. 120 patients will be randomly allocated to 3 groups(P, PR, PMR). The patients in group P will receive general anesthesia only with propofol and group PR and PMR will receive 0.25 mcg/kg/min remifentanil infusion prior to propofol. The patients in group PMR will receive 0.03 mg/kg bolus dose of midazolam 1 min after start of the remifentanil infusion. 'Success' is defined as loss of both verbal response and eyelash reflex in 2 min after propofol administration. When 'success', the next patient will receive the same dose(in 18/19 probability) or 0.25 mg/kg lower dose(in 1/19 probability) of propofol. When 'failure', the next patient will receive 0.25 mg/kg higher dose of propofol at induction period.
Detailed description
Propofol is a well-known induction agent which can provide sound and quick hypnosis with anti-emetic effects. However, dose dependent hypotension or bradycardia have reported while using this agent. Propofol in combination with remifentanil or midazolam can result in synergistic or additive effect. There are not many studies which provide minimum dose of propofol to induce hypnosis in combination with these agents and advantage of the combination. The patients who are scheduled to undergo general anesthesia are enrolled in this study. 120 patients will be randomly allocated to 3 groups(P, PR, PMR). Sample size have been decided due to the previous studies which have mentioned 40 participants as a adequate sample size for this biased coin design - up and down study. After receiving informed consent, patients will be participated in this study. No premedication will be given to the patients before induction. The patients in group P will receive general anesthesia only with propofol and group PR and PMR will receive 0.25 mcg/kg/min remifentanil infusion for 5 min prior to propofol administration. The patients in group PMR will receive 0.03 mg/kg bolus dose of midazolam 1 min after the start of the remifentanil infusion. Initial propofol dose will be 1 mg/kg in each group and the dose will be changed by the result of prior study participant. 'Success' of this study will be defined as loss of both verbal response and eyelash reflex in 2 min after propofol administration. When 'success', the next patient will receive the same dose(in 18/19 probability) or 0.25 mg/kg lower dose(in 1/19 probability) of propofol. When 'failure', the next patient will receive 0.25 mg/kg higher dose of propofol at induction period.
Interventions
DRUGPropofol
Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.
DRUGRemifentanil
Remifentanil 0.25 mcg/kg/min infusion for 5 min before propofol administration.
DRUGMidazolam
Remifentanil 0.25 mcg/kg/min infusion for 5 min before propofol administration followed by midazolam 0.03 mg/kg administration 1 min after remifentanil infusion start.
Sponsors
Severance Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* The patients who are scheduled to undergo general anesthesia for a surgery.
Exclusion criteria
1. ASA class (American Society of Anesthesiologist physical status classification) II or higher 2. Patients with history of allergy or side effects on propofol, remifentanil, midazolam 3. BMI (body mass index) less than 20 or higher than 30 4. Pregnancy 5. Patients taking sedatives or hypnotic agents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Loss of verbal response and eyelash reflex | 2 minutes after propofol administration | Checking verbal response by verbal stimulation (yes or no) and reflex by palpation of the levator palpebrae (yes or no). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean blood pressure | baseline, propofol administration time (Just after finishing monitoring on the patient in P group, 5 minutes after remifentanil infusion start in PR and PMR group), 1 minute and 2 minutes after propofol administration | To compare differences among groups in mean blood pressure change (mmHg). |
| Heart rate | baseline, propofol administration time (Just after finishing monitoring on the patient in P group, 5 minutes after remifentanil infusion start in PR and PMR group), 1 minute and 2 minutes after propofol administration | To compare differences among groups in heart rate change (mmHg). |
Countries
South Korea
Outcome results
None listed