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CompletedNCT02440204Updated Jan 17, 2019Results posted

Optimal Sevoflurane Concentration for Intubation in Combination of Clincal Remifentanil Doses

An interventional study of Intubation and Remifentanil in Postoperative Pain, sponsored by Severance Hospital. Completed at 1 site in Korea, Republic of. Open to male participants aged 19 Years to 30 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-01-17.

Sponsored by Severance Hospital · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
68
Allocation
Randomized
Ages
19 Years to 30 Years
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Postoperative Pain

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Keywords

  • sevoflurane
  • remifentanil
  • intubation without using muscle relaxants
03

In context

Pain, Postoperative

5,089 studies on the registry are indexed under Pain, Postoperative; 1,137 are open to participants now.

This study's enrollment of 68 is close to the median of 75 across 4,341 interventional studies indexed under Pain, Postoperative.

Browse Pain, Postoperative studies →

Lead sponsor

Severance Hospital is the lead sponsor of 50 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
19 Years to 30 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

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

Exclusion criteria

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
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Care provider)
Enrollment
68 participants (actual)

Study arms

  • Active comparator
    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.

    Procedure: Intubation · Drug: Remifentanil · Drug: Sevoflurane

  • Active comparator
    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.

    Procedure: Intubation · Drug: Remifentanil · Drug: Sevoflurane

  • Active comparator
    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.

    Procedure: Intubation · Drug: Remifentanil · Drug: Sevoflurane

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.

    Also known as: Ultiva

  • 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.

    Also known as: Sevoran

06

What researchers measure

Primary outcomes

  1. EC50 for Successful Intubation in Each Groups

    Sevoflurane concentration used to perform intubation (For ED50 finding)

    Time frame: During the induction of anesthesia

Secondary outcomes

  1. EC95 for Successful Intubation

    Sevoflurane concentration used to perform intubation (For ED95 finding)

    Time frame: During the induction of anesthesia

07

Results

Posted Jan 17, 2019

Participant flow

Participant flow — Overall Study
MilestoneRemifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kg
Started222422
Completed222422
Not completed000

Outcome measures

PrimaryEC50 for Successful Intubation in Each Groups

Sevoflurane concentration used to perform intubation (For ED50 finding)

Time frame:
During the induction of anesthesia
Reported as:
Mean · vol%
EC50 for Successful Intubation in Each Groups
vol%Remifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kg
EC50 for Successful Intubation in Each Groups3.00 (2.36 to 3.18)2.00 (1.38 to 2.54)1.29 (1.14 to 1.50)
SecondaryEC95 for Successful Intubation

Sevoflurane concentration used to perform intubation (For ED95 finding)

Time frame:
During the induction of anesthesia
Reported as:
Mean · vol%
EC95 for Successful Intubation
vol%Remifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kg
EC95 for Successful Intubation3.45 (3.00 to 3.47)2.91 (2.35 to 2.95)1.89 (1.47 to 1.95)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Remifentanil 1.0 mcg/kg—0/22 (0%)1/22 (4.5%)
Remifentanil 1.5 mcg/kg—0/24 (0%)2/24 (8.3%)
Remifentanil 2.0 mcg/kg—0/22 (0%)6/22 (27.3%)
Most frequent other events
Most frequent other events
EventRemifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kg
BradycardiaCardiac disorders0/221/243/22
Closed vocal cordsRespiratory, thoracic and mediastinal disorders1/221/243/22

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Remifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kgTotal
<=18 years0000
Between 18 and 65 years22242268
>=65 years0000
Age, Continuous
Age, Continuous(years)Remifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kgTotal
Mean21.3 ± 1.721.3 ± 1.621.5 ± 2.221.3 ± 1.7
Sex: Female, Male
Sex: Female, Male(Participants)Remifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kgTotal
Female0000
Male22242268
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Remifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kgTotal
Count of participants———0
Region of Enrollment
Region of Enrollment(participants)Remifentanil 1.0 mcg/kgRemifentanil 1.5 mcg/kgRemifentanil 2.0 mcg/kgTotal
South Korea22242268
08

Study locations

1 site
  • Armed Forces Capital Hospital, Republic of Korea
    Seongnam-si, Kyung-ki Do, Korea, Republic of
09

References and documents

Publications

  • Cros AM, Lopez C, Kandel T, Sztark F. Determination of sevoflurane alveolar concentration for tracheal intubation with remifentanil, and no muscle relaxant. Anaesthesia. 2000 Oct;55(10):965-9. doi: 10.1046/j.1365-2044.2000.01538.x. PubMed 11012491 ↗
  • Min SK, Kwak YL, Park SY, Kim JS, Kim JY. The optimal dose of remifentanil for intubation during sevoflurane induction without neuromuscular blockade in children. Anaesthesia. 2007 May;62(5):446-50. doi: 10.1111/j.1365-2044.2007.05037.x. PubMed 17448054 ↗
  • Dixon WJ. Staircase bioassay: the up-and-down method. Neurosci Biobehav Rev. 1991 Spring;15(1):47-50. doi: 10.1016/s0149-7634(05)80090-9. PubMed 2052197 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 17, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02440204
Lead sponsor
Severance Hospital
Collaborators
Armed Forces Capital Hospital, Republic of Korea
Responsible party
Dr. Koh, Jae Chul, MD (Fellow, Department of anesthesiology and pain medicine, Severance Hospital) — Principal investigator
First posted
May 12, 2015
Start date
May 2015
Primary completion
Apr 2016
Completion
Apr 2016
Results posted
Jan 17, 2019
Last update
Jan 17, 2019

Study contacts

Eui-Kyoung Goo, MD
study director · Armed forces capital hospital

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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