Clincosm LogoSign in Get a demo

Remifentanil and Midazolam on Propofol for Loss of Consciousness

Sponsor
Severance Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT02536690
Collaborator
(none)
120
Enrollment
1
Location
3
Arms
9
Duration (Months)
13.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Official Title:
The Effect of Remifentanil and Midazolam on Propofol for Loss of Consciousness During Induction of Anesthesia
Study Start Date :
Aug 1, 2015
Actual Primary Completion Date :
May 1, 2016
Actual Study Completion Date :
May 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Group P

Induction with propofol bolus. Dose will be started at 1 mg/kg and will be adjusted as described in summary.

Drug: Propofol
Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.
Other Names:
  • Fresofol

    		•
    Active Comparator: Group PR

    Induction with propofol and remifentanil. Remifentanil infusion 0.25 mcg/kg/min for 5 min followed by propofol bolus Propofol dose will be started at 1 mg/kg and will be adjusted as described in summary.

    Drug: Propofol
    Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.
    Other Names:
  • Fresofol

    • Drug: Remifentanil
    Remifentanil 0.25 mcg/kg/min infusion for 5 min before propofol administration.
    Other Names:
  • Ultiva

    		•
    Active Comparator: Group PMR

    Induction with propofol, midazolam and remifentanil. Remifentanil infusion 0.25 mcg/kg/min for 5 min followed by midazolam 0.03 mg/kg bolus 1 min after remifentanil infusion start and propofol bolus administration. Propofol dose will be started at 1 mg/kg and will be adjusted as described in summary.

    Drug: Propofol
    Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.
    Other Names:
  • Fresofol

    • Drug: Remifentanil
    Remifentanil 0.25 mcg/kg/min infusion for 5 min before propofol administration.
    Other Names:
  • Ultiva

    • Drug: Midazolam
    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.
    Other Names:
  • Vascam

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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).

    2. 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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 50 Years
    Sexes Eligible for Study:
    Female
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Gangnam Severance hospital Seoul Gangnam-gu Korea, Republic of 135-720

    Sponsors and Collaborators

    • Severance Hospital

    Investigators

    • Study Chair: Dong Woo Han, MD, PhD, Department of Anesthesiology and Pain medicine, Gangnam Severance Hospital, Seoul, Korea

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Dr. Koh, Jae Chul, MD, Clinical fellow in department of anesthesiology and pain medicine, Severance Hospital
    ClinicalTrials.gov Identifier:
    NCT02536690
    Other Study ID Numbers:
    • 2015-0183-004
    First Posted:
    Sep 1, 2015
    Last Update Posted:
    Jun 2, 2016
    Last Verified:
    May 1, 2016
    Keywords provided by Dr. Koh, Jae Chul, MD, Clinical fellow in department of anesthesiology and pain medicine, Severance Hospital
    propofol
    midazolam
    remifentanil
    combination
    synergic
    pharmacodynamics
    Loss of consciousness
    Additional relevant MeSH terms:
    Unconsciousness
    Midazolam
    Remifentanil
    Propofol

    Study Results

    No Results Posted as of Jun 2, 2016