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Optimal Sevoflurane Concentration for Intubation in Combination of Clincal Remifentanil Doses

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02440204
Enrollment
68
Registered
2015-05-12
Start date
2015-05-31
Completion date
2016-04-30
Last updated
2019-01-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Postoperative Pain

Keywords

sevoflurane, remifentanil, intubation without using muscle relaxants

Brief 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.

Interventions

PROCEDUREIntubation

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.

DRUGRemifentanil

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.

DRUGSevoflurane

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.

Sponsors

Armed Forces Capital Hospital, Republic of Korea
CollaboratorOTHER_GOV
Severance Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)

Eligibility

Sex/Gender
MALE
Age
19 Years to 30 Years
Healthy volunteers
Yes

Inclusion criteria

* American Society of Anesthesiologists physical status I or II who were scheduled to undergo elective otolaryngological surgery

Exclusion criteria

* history of reactive airway disease * smoking hx. * a predictive signs of difficult intubation * body mass index ≥ 30 kg•m-2 or ≤ 15 kg•m-2

Design outcomes

Primary

MeasureTime frameDescription
EC50 for Successful Intubation in Each GroupsDuring the induction of anesthesiaSevoflurane concentration used to perform intubation (For ED50 finding)

Secondary

MeasureTime frameDescription
EC95 for Successful IntubationDuring the induction of anesthesiaSevoflurane concentration used to perform intubation (For ED95 finding)

Countries

South Korea

Participant flow

Participants by arm

ArmCount
Remifentanil 1.0 mcg/kg
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. Intubation: 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. Remifentanil: 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. Sevoflurane: 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.
22
Remifentanil 1.5 mcg/kg
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. Intubation: 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. Remifentanil: 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. Sevoflurane: 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.
24
Remifentanil 2.0 mcg/kg
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. Intubation: 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. Remifentanil: 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. Sevoflurane: 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.
22
Total68

Baseline characteristics

CharacteristicRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kgRemifentanil 1.0 mcg/kgTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
24 Participants22 Participants22 Participants68 Participants
Age, Continuous21.3 years
STANDARD_DEVIATION 1.6
21.5 years
STANDARD_DEVIATION 2.2
21.3 years
STANDARD_DEVIATION 1.7
21.3 years
STANDARD_DEVIATION 1.7
Race and Ethnicity Not Collected0 Participants
Region of Enrollment
South Korea
24 participants22 participants22 participants68 participants
Sex: Female, Male
Female
0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Male
24 Participants22 Participants22 Participants68 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
1 / 222 / 246 / 22
serious
Total, serious adverse events
0 / 220 / 240 / 22

Outcome results

Primary

EC50 for Successful Intubation in Each Groups

Sevoflurane concentration used to perform intubation (For ED50 finding)

Time frame: During the induction of anesthesia

ArmMeasureValue (MEAN)
Remifentanil 1.0 mcg/kgEC50 for Successful Intubation in Each Groups3.00 vol%
Remifentanil 1.5 mcg/kgEC50 for Successful Intubation in Each Groups2.00 vol%
Remifentanil 2.0 mcg/kgEC50 for Successful Intubation in Each Groups1.29 vol%
Secondary

EC95 for Successful Intubation

Sevoflurane concentration used to perform intubation (For ED95 finding)

Time frame: During the induction of anesthesia

ArmMeasureValue (MEAN)
Remifentanil 1.0 mcg/kgEC95 for Successful Intubation3.45 vol%
Remifentanil 1.5 mcg/kgEC95 for Successful Intubation2.91 vol%
Remifentanil 2.0 mcg/kgEC95 for Successful Intubation1.89 vol%

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026