Remifentanil and Midazolam on Propofol for Loss of Consciousness in Elderly Patients

Sponsor

Gangnam Severance Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02818387

Collaborator

(none)

120

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 in elderly patients. 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 elderly patients (over 65 years old) 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 0.125 mcg/kg/min remifentanil infusion for 5 min prior to propofol administration. The patients in group PMR will receive 0.015 mg/kg bolus dose of midazolam 1 min after the start of the remifentanil infusion. Initial propofol dose will be 0.5 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 3 min after propofol administration. When 'success', the next patient will receive the same dose(in 18/19 probability) or 0.125 mg/kg lower dose(in 1/19 probability) of propofol. When 'failure', the next patient will receive 0.125 mg/kg higher dose of propofol at induction period.

Condition or Disease	Intervention/Treatment	Phase
Anesthesia	Drug: Propofol Drug: Remifentanil Drug: Midazolam	N/A

Detailed Description

Study Design

Study Type:

Interventional

Anticipated 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 in Elderly Patients

Study Start Date :

Oct 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2016

Anticipated Study Completion Date :

Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group P Induction with propofol bolus. Dose will be started at 0.5 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 0.125 mcg/kg/min for 5 min followed by propofol bolus Propofol dose will be started at 0.5 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 0.125 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 0.125 mcg/kg/min for 5 min followed by midazolam 0.015 mg/kg bolus 1 min after remifentanil infusion start and propofol bolus administration. Propofol dose will be started at 0.5 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 0.125 mcg/kg/min infusion for 5 min before propofol administration. Other Names: Ultiva Drug: Midazolam Remifentanil 0.125 mcg/kg/min infusion for 5 min before propofol administration followed by midazolam 0.015 mg/kg administration 1 min after remifentanil infusion start.

Arm

Intervention/Treatment

Active Comparator: Group P

Induction with propofol bolus. Dose will be started at 0.5 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 0.125 mcg/kg/min for 5 min followed by propofol bolus Propofol dose will be started at 0.5 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 0.125 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 0.125 mcg/kg/min for 5 min followed by midazolam 0.015 mg/kg bolus 1 min after remifentanil infusion start and propofol bolus administration. Propofol dose will be started at 0.5 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 0.125 mcg/kg/min infusion for 5 min before propofol administration.

Other Names:

Ultiva

Drug: Midazolam

Remifentanil 0.125 mcg/kg/min infusion for 5 min before propofol administration followed by midazolam 0.015 mg/kg administration 1 min after remifentanil infusion start.

Outcome Measures

Primary Outcome Measures

Loss of verbal response and eyelash reflex [3 minutes after propofol administration]
Checking verbal response by verbal stimulation (response or no response).
Loss of eyelash reflex [3 minutes after propofol administration]
Checking reflex by palpation of the levator palpebrae (reflex or no reflex).

Secondary Outcome Measures

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, 2 minutes and 3 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, 2 minutes and 3 minutes after propofol administration]
To compare differences among groups in heart rate change (mmHg)

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The elderly patients (over 65 years old) who are scheduled to undergo general anesthesia.

Exclusion Criteria:

ASA class (American Society of Anesthesiologist physical status classification) IV or higher
Patients with history of allergy or side effects on propofol, remifentanil, midazolam
BMI (body mass index) less than 20 or higher than 30
Patients taking sedatives or hypnotic agents.