Optimal Sevoflurane Concentration for Intubation in Combination of Clincal Remifentanil Doses
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional

Summary: 
      Intubation is a procedure that requires well relaxed muscles while general anesthesia is
      performed. In order to get adequate muscle relaxation, remifentanil, sevoflurane or both
      agents in combination have been reported as they can provide adequate conditions for
      laryngoscopy and tracheal intubation without using muscle relaxants.

      However, there were no previous studies to find the effective dose of sevoflurane in
      combination with different bolus doses of remifentanil to obtain adequate endotracheal
      intubation conditions without using muscle relaxants. The aim of this study is to investigate
      the change in the minimum sevoflurane alveolar concentration which produces an adequate
      endotracheal intubation condition when sevoflurane is combined with different bolus doses of
      remifentanil used in clinical practice.
    

Detailed description: 
      After Institutional Review Board approval and written informed consent, patients aged 18~30
      years with American Society of Anesthesiologists physical status I or II who are scheduled to
      undergo elective otolaryngological surgery are enrolled in the study. Exclusion criterias are
      a history of reactive airway disease, smoking, a predictive signs of difficult intubation,
      and a body mass index ≥ 30 kg•m-2 or ≤ 15 kg•m-2. The patients will be assigned in 3 groups
      (group 1.0, 1.5, and 2.0) according to a computer-generated randomization table, to receive
      remifentanil bolus dose 1.0, 1.5 or 2.0 µg•kg-1, respectively.

      Two anesthesiologists will participate in induction procedure in this study. One who is not
      blinded on patient's group or target sevoflurane concentration recorded the data, will adjust
      the dose of the sevoflurane and remifentanil and the other who is blinded will perform the
      mask ventilation and endotracheal intubation. Patients will be premedicated with
      glycopyrrolate 0.2 mg intravenously. An 18-gauge intravenous catheter will be established and
      0.9% normal saline will be infused. In the operating room, all patients will be monitored
      with electrocardiogram, pulse oximetry, non-invasive blood pressure measurement, and
      measurement of both inspired and end-tidal concentration of oxygen, carbon dioxide and
      sevoflurane. After preoxygenation for 3 min, anesthesia is induced using a face mask with a
      semi-closed anesthetic circuit (Primus®, Dräger) prefilled with 8% sevoflurane for 10 min.
      The fresh gas flow will be set at 6 l•min-1. At first, patients will be left to breath
      spontaneously. However, when the tidal volume is too small to provide adequate end-tidal
      sampling for expiratory gas concentration measurement or end-tidal carbon dioxide level is
      above 40 mmHg, ventilation will be assisted. If the patient's spontaneous ventilation is
      disappeared, mechanical ventilation will be started with a tidal volume of 10 ml•kg-1, and
      respiratory rate will be adjusted to maintain end tidal carbon dioxide level between 35 mmHg
      and 40 mmHg. When the patient lost consciousness and the end-tidal sevoflurane level is
      higher than the preselected target concentration, the inspired concentration will be set 0
      until the end-tidal concentration changed similar to the preselected target end-tidal
      sevoflurane concentration. Then the inspired concentration will be adjusted in a range of 1.0
      to 1.4 times of the preselected sevoflurane level to find a concentration that can maintain
      preselected target end-tidal sevoflurane concentration steady for at least 3 min. The steady
      state end-tidal sevoflurane concentration will be maintained for 1 min. Even if the steady
      state concentration is found in less than 3 min, the remaining time will be added to this 1
      min of steady state maintenance. After confirmation of the steady state, bolus dose of
      remifentanil will be administerd via intravenous line over 60 seconds to prevent chest wall
      rigidity according to the preselected group. 90 seconds after the end of remifentanil bolus
      administration, endotracheal intubation will be performed using a 7.5 mm (internal diameter)
      reinforced endotracheal tube. If the intubation condition is not good enough to perform an
      successful intubation, anesthesia will be deepened by increasing inspired sevoflurane
      concentration, and rocuronium 0.3 mg•kg-1 will be used to facilitate intubation.

      The concentration of sevoflurane used for each patient will be determined by the response of
      the previously tested patient using the modified Dixon's up-and-down method[8]. The first
      patient will be tested at end-tidal sevoflurane concentration of 2.5%, which has been
      determined as a concentration for acceptable intubating condition in a previous study.
      According to a scoring system described by Helbo-Hansen S. et al., intubation condition will
      be scored. Successful intubation is defined as intubation under acceptable intubating
      condition by this scoring system. If intubation fails, the target concentration of
      sevoflurane will be increased by 0.5%. If intubation is successful, it will be decreased by
      0.5%.

      Statistical analyses will be performed using the statistical package SPSS 20.0 for windows
      (SPSS Inc., Chicago, IL). The sample size was determined to achieve seven response crossovers
      in each group to provide adequate minimum alveolar sevoflurane concentration defined as an
      average of response crossover midpoints. A response crossover is defined as an independent
      pair failure to success of intubation. To calculate the regression models allowing the
      prediction of the effective concentration of sevoflurane for successful intubation in
      50%(ED50) and 95%(ED95) of the patients, a logistic regression analysis will be performed in
      each group. A repeated measures of ANOVA will be performed to compare hemodynamic data
      changes in each group. A p-value less than 0.05 is considered statistically significant.
    

Intervention name(s): Intubation; Remifentanil; Sevoflurane
Intervention type(s): Procedure; Drug; Drug
Intervention description(s): After setting the end-tidal sevoflurane concentration in a predetermined concentration, remifentanil will be injected according to their group and intubation will be performed 90 seconds after.; After setting the end-tidal sevoflurane concentration in a predetermined concentration, remifentanil will be administered according to their group in 1 minute to prevent remifentanil induced rigidity or complications.; The end-tidal sevoflurane concentration will be set as predetermined, which starts from 2.5 vol% and adjusted by the up-and-down study model which have been described by Dixon JW et al.
Other intervention name(s): Ultiva; Sevoran
Intervention MeSH terms: Remifentanil; Sevoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: sevoflurane; remifentanil; intubation without using muscle relaxants