Clinical Drug Experience Knowledgebase

Optimal Sevoflurane Concentration for Intubation Without Using Muscle Relaxants in Combination of Different Clinical Bolus Doses of Remifentanil

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.