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

NCT ID: NCT02818387

Last Updated: 2016-06-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2016-10-31

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.

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 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.

Conditions

Anesthesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: DOUBLE

Study Groups

Group P

Induction with propofol bolus. Dose will be started at 0.5 mg/kg and will be adjusted as described in summary.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.

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.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.

Remifentanil

Intervention Type: DRUG

Remifentanil 0.125 mcg/kg/min infusion for 5 min before propofol administration.

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.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.

Remifentanil

Intervention Type: DRUG

Remifentanil 0.125 mcg/kg/min infusion for 5 min before propofol administration.

Midazolam

Intervention Type: DRUG

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.

Interventions

Propofol

Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.

Intervention Type: DRUG

Remifentanil

Remifentanil 0.125 mcg/kg/min infusion for 5 min before propofol administration.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Fresofol; Ultiva

Eligibility Criteria

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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gangnam Severance Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jiwon An

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dong Woo Han, MD,PhD

Role: STUDY_CHAIR

Gangnam Severance Hospital

Locations

Gangnam Severance Hospital, Yonsei University College of Medicine

Seoul, Korea, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Jiwon An, MD

Role: CONTACT

82-2-2019-3520

Facility Contacts

Dong Woo Han, MD, PhD

Role: primary

82-2-2019-3520

References

Conway DH, Hasan SK, Simpson ME. Target-controlled propofol requirements at induction of anaesthesia: effect of remifentanil and midazolam. Eur J Anaesthesiol. 2002 Aug;19(8):580-4. doi: 10.1017/s0265021502000935.

Reference Type: BACKGROUND

PMID: 12200947 (View on PubMed)

Other Identifiers

3-2015-0222

Identifier Type: -

Identifier Source: org_study_id