Remifentanil and Midazolam on Propofol for Loss of Consciousness
Condition: Anesthesia
MeSH terms: Unconsciousness
Study type: Interventional

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.
    

Intervention name(s): Propofol; Remifentanil; Midazolam
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Propofol bolus dose administration according to the predetermined dose by biased coined design up-and-down study.; Remifentanil 0.25 mcg/kg/min infusion for 5 min before propofol administration.; 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 intervention name(s): Fresofol; Ultiva; Vascam
Intervention MeSH terms: Midazolam; Remifentanil; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Keywords: propofol; midazolam; remifentanil; combination; synergic; pharmacodynamics; Loss of consciousness