Clinical trial NCT02536690: Remifentanil and Midazolam on Propofol for Loss of Consciousness
Official title: The Effect of Remifentanil and Midazolam on Propofol for Loss of Consciousness During Induction of Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anesthesia
Keywords: propofol
midazolam
remifentanil
combination
synergic
pharmacodynamics
Loss of consciousness
Lead sponsor: Severance Hospital
Sponsor class: OTHER
First posted: 2015-09-01
Enrollment: 120
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Loss of verbal response and eyelash reflex
timeFrame: 2 minutes after propofol administration
Secondary outcomes:
measure: Mean blood pressure
timeFrame: 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
measure: Heart rate
timeFrame: 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
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance hospital
state: Gangnam-gu
Study officials:
affiliation: Department of Anesthesiology and Pain medicine, Gangnam Severance Hospital, Seoul, Korea
name: Dong Woo Han, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: Choi SH, Min KT, Lee JR, Choi KW, Han KH, Kim EH, Oh HJ, Lee JH. Determination of EC95 of remifentanil for smooth emergence from propofol anesthesia in patients undergoing transsphenoidal surgery. J Neurosurg Anesthesiol. 2015 Apr;27(2):160-6. doi: 10.1097/ANA.0000000000000094.
citation: Koh JC, Park J, Kim NY, You AH, Ko SH, Han DW. Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial. Medicine (Baltimore). 2017 Dec;96(49):e9164. doi: 10.1097/MD.0000000000009164.