Trial Outcomes & Findings for The Effects of General Anesthetics on Upper Airway Collapsibility in Healthy Subjects (NCT NCT01557920)
NCT ID: NCT01557920
Last Updated: 2016-09-13
Results Overview
Upper airway closing pressure will be measured during steady state anesthesia as well as during carbon dioxide reversal.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
18 participants
Primary outcome timeframe
participants will be followed for the duration of anesthesia, an expected average of 6 hours
Results posted on
2016-09-13
Participant Flow
Participant milestones
| Measure |
Propofol First, Then Sevoflurane
The healthy subject will be anesthetized first with Propofol, and secondarily with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
Sevoflurane First, Then Propofol
The healthy subject will be anesthetized first with Sevoflurane, and secondarily with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
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|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
Propofol First, Then Sevoflurane
The healthy subject will be anesthetized first with Propofol, and secondarily with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
Sevoflurane First, Then Propofol
The healthy subject will be anesthetized first with Sevoflurane, and secondarily with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
3
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
Baseline Characteristics
The Effects of General Anesthetics on Upper Airway Collapsibility in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Crossover Randomized Propofol and Sevoflurane
n=18 Participants
The healthy subject will be anesthetized with Propofol and Sevoflurane in a randomized crossover fashion. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Spontaneous swallows were identified, and categorized as physiological or pathological. Physiological swallows were followed by expiratory flow (E or I-E). Pathological swallows were followed by inspiration (I and E-I).
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
|---|---|
|
Age, Continuous
|
24.3 years
STANDARD_DEVIATION 3.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: participants will be followed for the duration of anesthesia, an expected average of 6 hoursPopulation: Ten out of 12 subjects were analyzed. In two subjects we could not record high quality biologically plausible recordings of upper airway closing pressure. Data from multiple measurements per participant were combined to calculate an average upper airway closing pressure per subject.
Upper airway closing pressure will be measured during steady state anesthesia as well as during carbon dioxide reversal.
Outcome measures
| Measure |
Propofol
n=10 Participants
The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
|
Sevoflurane
n=10 Participants
The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
Anesthesia With Propofol and Sevoflurane (Baseline CO2)
Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (during baseline CO2).
|
Anesthesia With Propofol and Sevoflurane (CO2 Insufflation)
Proportion of pathological (inspiratory) swallows during anesthesia (with CO2+4 and +8 insufflation).
|
Wakefulness (During Baseline CO2)
Proportion of pathological (inspiratory) swallows during anesthesia (during baseline CO2).
|
Wakefulness (With CO2 Insufflation)
Proportion of pathological (inspiratory) swallows during wakefulness (with CO2+4 and +8 insufflation).
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|---|---|---|---|---|---|---|
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Upper Airway Closing Pressure
|
-9.83 cm H20
Standard Deviation 3.92
|
-10.77 cm H20
Standard Deviation 4.69
|
—
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—
|
—
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—
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PRIMARY outcome
Timeframe: swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)Population: 224 swallows in 11 out of 12 subjects were analyzed (1 excluded due to faulty recording of swallows).
A pathological swallow was defined as a swallow that was followed by inspiratory flow. A physiological swallow was defined as a swallow that was followed by expiratory flow. The number of pathological and physiological swallows were measured during wakefulness and anesthesia. The pathological swallows are presented as percentage of path. swallows calculated as path.sw/\[path.sw+phys.sw\]\*100 (%).
Outcome measures
| Measure |
Propofol
n=11 Participants
The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
|
Sevoflurane
n=11 Participants
The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
Anesthesia With Propofol and Sevoflurane (Baseline CO2)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (during baseline CO2).
|
Anesthesia With Propofol and Sevoflurane (CO2 Insufflation)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia (with CO2+4 and +8 insufflation).
|
Wakefulness (During Baseline CO2)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia (during baseline CO2).
|
Wakefulness (With CO2 Insufflation)
n=11 Participants
Proportion of pathological (inspiratory) swallows during wakefulness (with CO2+4 and +8 insufflation).
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|---|---|---|---|---|---|---|
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Proportion of Pathological Swallows
|
25.9 percentage of pathological swallows
|
4.9 percentage of pathological swallows
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15.8 percentage of pathological swallows
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34.9 percentage of pathological swallows
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1.0 percentage of pathological swallows
|
13.2 percentage of pathological swallows
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SECONDARY outcome
Timeframe: participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hoursPopulation: No data were obtained.
Using acoustic pharyngometry, we intend to measure the cross-sectional area of the airway at several points during recovery from anesthesia.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hoursPopulation: The number of participants in this group are only 9 since the genioglossus EMG signals were poor in 2 participants and these were excluded from the analysis.
will be measured during steady state anesthesia as well as during carbon dioxide reversal, and during recovery from anesthesia.
Outcome measures
| Measure |
Propofol
n=9 Participants
The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
|
Sevoflurane
n=9 Participants
The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
Anesthesia With Propofol and Sevoflurane (Baseline CO2)
n=9 Participants
Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (during baseline CO2).
|
Anesthesia With Propofol and Sevoflurane (CO2 Insufflation)
n=9 Participants
Proportion of pathological (inspiratory) swallows during anesthesia (with CO2+4 and +8 insufflation).
|
Wakefulness (During Baseline CO2)
Proportion of pathological (inspiratory) swallows during anesthesia (during baseline CO2).
|
Wakefulness (With CO2 Insufflation)
Proportion of pathological (inspiratory) swallows during wakefulness (with CO2+4 and +8 insufflation).
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|---|---|---|---|---|---|---|
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Genioglossus Muscle Electromyogram
|
32.8 percentage of maximum recorded activity
Standard Error 2.1
|
24.2 percentage of maximum recorded activity
Standard Error 1.8
|
26.0 percentage of maximum recorded activity
Standard Error 1.8
|
22.3 percentage of maximum recorded activity
Standard Error 2.0
|
—
|
—
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SECONDARY outcome
Timeframe: Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hoursPopulation: In one subject we could not record high quality biologically plausible recordings of minute ventilation.
Measured by spirometry. Subjects wear a full-face mask. Reported in L/min
Outcome measures
| Measure |
Propofol
n=11 Participants
The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
|
Sevoflurane
n=11 Participants
The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
Anesthesia With Propofol and Sevoflurane (Baseline CO2)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (during baseline CO2).
|
Anesthesia With Propofol and Sevoflurane (CO2 Insufflation)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia (with CO2+4 and +8 insufflation).
|
Wakefulness (During Baseline CO2)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia (during baseline CO2).
|
Wakefulness (With CO2 Insufflation)
Proportion of pathological (inspiratory) swallows during wakefulness (with CO2+4 and +8 insufflation).
|
|---|---|---|---|---|---|---|
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Minute Ventilation (Tidal Volume and Respiratory Rate)
|
7.9 L/min
Standard Deviation 1.7
|
6.7 L/min
Standard Deviation 1.3
|
5.6 L/min
Standard Deviation 1.5
|
7.2 L/min
Standard Deviation 1.7
|
5.7 L/min
Standard Deviation 1.3
|
—
|
SECONDARY outcome
Timeframe: Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hoursPopulation: In one subject we could not record high quality biologically plausible recordings of Duty cycle.
(T(ins)/T(total))\*100
Outcome measures
| Measure |
Propofol
n=11 Participants
The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
|
Sevoflurane
n=11 Participants
The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
Anesthesia With Propofol and Sevoflurane (Baseline CO2)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (during baseline CO2).
|
Anesthesia With Propofol and Sevoflurane (CO2 Insufflation)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia (with CO2+4 and +8 insufflation).
|
Wakefulness (During Baseline CO2)
n=11 Participants
Proportion of pathological (inspiratory) swallows during anesthesia (during baseline CO2).
|
Wakefulness (With CO2 Insufflation)
Proportion of pathological (inspiratory) swallows during wakefulness (with CO2+4 and +8 insufflation).
|
|---|---|---|---|---|---|---|
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Duty Cycle
|
42 percentage of Ttotal
Standard Deviation 3
|
42 percentage of Ttotal
Standard Deviation 5
|
43 percentage of Ttotal
Standard Deviation 4
|
40 percentage of Ttotal
Standard Deviation 3
|
41 percentage of Ttotal
Standard Deviation 3
|
—
|
POST_HOC outcome
Timeframe: swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)Population: 224 swallows in 11 out of 12 subjects were analyzed (1 excluded due to faulty recording of swallows). If the pathological swallow incidence between sevoflurane and propofol anesthesia had a p-value \>0.05, subsequent analyses were conducted to evaluate depth of anesthesia related differences rather than compound specific ones.
The number of swallows were counted during wakefulness and anesthesia. The frequency of swallowing was calculated per hour
Outcome measures
| Measure |
Propofol
n=11 Participants
The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Propofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
|
Sevoflurane
n=11 Participants
The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.
Sevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
Anesthesia With Propofol and Sevoflurane (Baseline CO2)
Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (during baseline CO2).
|
Anesthesia With Propofol and Sevoflurane (CO2 Insufflation)
Proportion of pathological (inspiratory) swallows during anesthesia (with CO2+4 and +8 insufflation).
|
Wakefulness (During Baseline CO2)
Proportion of pathological (inspiratory) swallows during anesthesia (during baseline CO2).
|
Wakefulness (With CO2 Insufflation)
Proportion of pathological (inspiratory) swallows during wakefulness (with CO2+4 and +8 insufflation).
|
|---|---|---|---|---|---|---|
|
Frequency of Spontaneous Swallows During Anesthesia vs Wakefulness
|
1.7 number of swallows/hr
Standard Deviation 3.3
|
28 number of swallows/hr
Standard Deviation 22.3
|
—
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—
|
—
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—
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Adverse Events
Propofol
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Sevoflurane
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place