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

Anesthesia Clinical Trial

Official title:

The Effect of Remifentanil and Midazolam on Propofol for Loss of Consciousness During Induction of Anesthesia in Elderly Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02818387
• Other study ID #: 3-2015-0222
• Status: Recruiting
• Phase: N/A
• First received: June 22, 2016
• Last updated: June 28, 2016
• Start date: October 2015
• Est. completion date: October 2016

Study information

• Verified date: June 2016
• Source: Gangnam Severance Hospital
• Contact: Jiwon An, MD
• Phone: 82-2-2019-3520
• Is FDA regulated: No
• Health authority: Korea: Ministry for Health and Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver)

Related Conditions & MeSH terms

• Anesthesia
• Unconsciousness

Intervention

Drug:
• Propofol
Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.
• Remifentanil
Remifentanil 0.125 mcg/kg/min infusion for 5 min before propofol administration.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Gangnam Severance Hospital, Yonsei University College of Medicine	Seoul	Korea

Sponsors (1)

Lead Sponsor	Collaborator
Gangnam Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Loss of verbal response and eyelash reflex	Checking verbal response by verbal stimulation (response or no response).	3 minutes after propofol administration	No
Primary	Loss of eyelash reflex	Checking reflex by palpation of the levator palpebrae (reflex or no reflex).	3 minutes after propofol administration	No
Secondary	Mean blood pressure	To compare differences among groups in mean blood pressure change (mmHg)	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	No
Secondary	Heart rate	To compare differences among groups in heart rate change (mmHg)	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	No