Postoperative PainNCT02440204
Optimal Sevoflurane Concentration for Intubation in Combination of Clincal Remifentanil Doses
A study testing Intubation, Remifentanil and Sevoflurane in people with Postoperative Pain, run by Severance Hospital at 1 site in South Korea.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 to 30 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Postoperative Pain
- What is being tested?
- Intubation, Remifentanil and Sevoflurane
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2015to Apr 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 30 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- American Society of Anesthesiologists physical status I or II who were scheduled to undergo elective otolaryngological surgery
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Armed Forces Capital Hospital, Republic of Korea
Seongnam-si, Kyung-ki Do
About this study
Official title: Optimal Sevoflurane Concentration for Intubation Without Using Muscle Relaxants in Combination of Different Clinical Bolus Doses of Remifentanil
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.
- Conditions
- Postoperative Pain
- Being tested
- Intubation, Remifentanil, Sevoflurane
- Keywords
- sevoflurane, remifentanil, intubation without using muscle relaxants
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IntubationProcedure or surgery
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.
RemifentanilDrug
Also called Ultiva
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.
SevofluraneDrug
Also called Sevoran
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.
| Study group | Role | What they receive |
|---|---|---|
| Remifentanil 1.0 mcg/kg | Active comparator | 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. Receives: Procedure: Intubation; Drug: Remifentanil; Drug: Sevoflurane |
| Remifentanil 1.5 mcg/kg | Active comparator | 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. Receives: Procedure: Intubation; Drug: Remifentanil; Drug: Sevoflurane |
| Remifentanil 2.0 mcg/kg | Active comparator | 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. Receives: Procedure: Intubation; Drug: Remifentanil; Drug: Sevoflurane |
What is being measured
The primary outcome is the main question the study is designed to answer.
EC50 for Successful Intubation in Each Groups
Sevoflurane concentration used to perform intubation (For ED50 finding)
Measured: During the induction of anesthesia
Secondary outcomes (1)
EC95 for Successful Intubation
Sevoflurane concentration used to perform intubation (For ED95 finding)
Measured: During the induction of anesthesia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study startMay 2015
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Postoperative PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Severance Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Armed Forces Capital Hospital, Republic of Korea
- Responsible party
- Principal investigator, Dr. Koh, Jae Chul, MD, Severance Hospital
- Investigators
- Eui-Kyoung Goo, MD, Study director, Armed forces capital hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02440204
- Sponsor's protocol ID
- AFMC-15036
- Status last verified
- Jul 2018
- First submitted
- 5 May 2015
- Last updated
- 17 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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 11012491Min 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 17448054Dixon 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
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Sevoflurane Concentration for Intubation Without Using Muscle Relaxants in Combination of Different Clinical Bolus Doses of Remifentanil
- ClinicalTrials.gov ID
- NCT02440204
- Acronym / sponsor ID
- AFMC-15036
- Conditions
- Postoperative Pain
- Keywords
- sevoflurane, remifentanil, intubation without using muscle relaxants
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Severance HospitalUniversity, hospital or other
- Collaborators
- Armed Forces Capital Hospital, Republic of Korea
- Study start
- May 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 12 May 2015 (estimated)
- Results
- Posted 17 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Remifentanil 1.0 mcg/kg | Active comparator | Procedure: Intubation, Drug: Remifentanil, Drug: SevofluraneAfter 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 1.5 mcg/kg | Active comparator | Procedure: Intubation, Drug: Remifentanil, Drug: SevofluraneAfter 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 2.0 mcg/kg | Active comparator | Procedure: Intubation, Drug: Remifentanil, Drug: SevofluraneAfter 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. |
Who may qualify
- Ages
- 19 to 30 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- American Society of Anesthesiologists physical status I or II who were scheduled to undergo elective otolaryngological surgery
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IntubationAfter 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 or surgery | Remifentanil 1.0 mcg/kg, Remifentanil 1.5 mcg/kg, Remifentanil 2.0 mcg/kg |
| RemifentanilAlso: UltivaAfter 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. | Drug | Remifentanil 1.0 mcg/kg, Remifentanil 1.5 mcg/kg, Remifentanil 2.0 mcg/kg |
| SevofluraneAlso: SevoranThe 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. | Drug | Remifentanil 1.0 mcg/kg, Remifentanil 1.5 mcg/kg, Remifentanil 2.0 mcg/kg |
Primary outcome
EC50 for Successful Intubation in Each Groups
Time frame: During the induction of anesthesia
Sevoflurane concentration used to perform intubation (For ED50 finding)
1 secondary outcome
EC95 for Successful Intubation
Time frame: During the induction of anesthesia
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11012491Cros 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.
- Background: PubMed 17448054Min 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.
- Results publication: PubMed 2052197Dixon 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.
Related trials for Postoperative Pain
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
Recruiting
Effect of Cryotherapeutic and Nanotherapeutic Sodium Hypochlorite on Post-Operative Endodontic Pain.
Symptomatic Irreversible Pulpitis, Symptomatic Apical Periodontitis
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative Pain
Active, not recruitingPhase 4
Effect of Dexmedetomidine on Postoperative Pain in Spinal Anesthesia for Cesarean Section at Assuit University Hospital
Cesarean Section
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eui-Kyoung Goo, MD study director
Armed forces capital hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intubation, Remifentanil and Sevoflurane in people with Postoperative Pain, run by Severance Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EC50 for Successful Intubation in Each Groups (time frame: During the induction of anesthesia). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02440204, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2019.