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Trial record 10 of 579 for:    CARBON DIOXIDE AND anesthesia

The Effects of General Anesthetics on Upper Airway Collapsibility in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT01557920
Recruitment Status : Completed
First Posted : March 20, 2012
Results First Posted : April 21, 2016
Last Update Posted : September 13, 2016
Sponsor:
Information provided by (Responsible Party):
Matthias Eikermann, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Single (Participant);   Primary Purpose: Prevention
Conditions Airway Complication of Anaesthesia
Healthy
Interventions Drug: Propofol
Drug: Sevoflurane
Enrollment 18
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Propofol First, Then Sevoflurane Sevoflurane First, Then Propofol
Hide Arm/Group Description

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.

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.

Period Title: Overall Study
Started 9 9
Completed 6 6
Not Completed 3 3
Reason Not Completed
Withdrawal by Subject             2             3
Lack of Efficacy             1             0
Arm/Group Title Crossover Randomized Propofol and Sevoflurane
Hide Arm/Group Description

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.

Overall Number of Baseline Participants 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants
24.3  (3.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Female
7
  38.9%
Male
11
  61.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants
18
1.Primary Outcome
Title Upper Airway Closing Pressure
Hide Description Upper airway closing pressure will be measured during steady state anesthesia as well as during carbon dioxide reversal.
Time Frame participants will be followed for the duration of anesthesia, an expected average of 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Propofol Sevoflurane
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: cm H20
-9.83  (3.92) -10.77  (4.69)
2.Primary Outcome
Title Proportion of Pathological Swallows
Hide Description 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 (%).
Time Frame swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)
Hide Outcome Measure Data
Hide Analysis Population Description
224 swallows in 11 out of 12 subjects were analyzed (1 excluded due to faulty recording of swallows).
Arm/Group Title Anesthesia With Propofol and Sevoflurane (All Cases) Wakefulness (All Cases) Anesthesia With Propofol and Sevoflurane (Baseline CO2) Anesthesia With Propofol and Sevoflurane (CO2 Insufflation) Wakefulness (During Baseline CO2) Wakefulness (With CO2 Insufflation)
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Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (across carbon-dioxide (CO2) levels).
Proportion of pathological (inspiratory) swallows during wakefulness (across CO2 levels)
Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (during baseline CO2).
Proportion of pathological (inspiratory) swallows during anesthesia (with CO2+4 and +8 insufflation).
Proportion of pathological (inspiratory) swallows during anesthesia (during baseline CO2).
Proportion of pathological (inspiratory) swallows during wakefulness (with CO2+4 and +8 insufflation).
Overall Number of Participants Analyzed 11 11 11 11 11 11
Measure Type: Number
Unit of Measure: percentage of pathological swallows
25.9 4.9 15.8 34.9 1.0 13.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anesthesia With Propofol and Sevoflurane (All Cases), Wakefulness (All Cases)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments pathological swallows under anesthesia vs. wakefulness: 25.9% vs. 4.9%
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Anesthesia With Propofol and Sevoflurane (Baseline CO2), Anesthesia With Propofol and Sevoflurane (CO2 Insufflation), Wakefulness (During Baseline CO2), Wakefulness (With CO2 Insufflation)
Comments Comparison of pathological swallow-rate increase by carbon-dioxide during anesthesia and wakefulness
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
3.Secondary Outcome
Title Airway Diameter
Hide Description Using acoustic pharyngometry, we intend to measure the cross-sectional area of the airway at several points during recovery from anesthesia.
Time Frame participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours
Hide Outcome Measure Data
Hide Analysis Population Description
No data were obtained.
Arm/Group Title Wakefulness Anesthesia With Low Dose Sevoflurane (Baseline CO2) Anesthesia With High Dose Sevoflurane (Baseline CO2) Anesthesia With Low Dose Propofol (CO2 Baseline) Anesthesia With High Dose Propofol (CO2 Baseline)
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Genioglossus Muscle Electromyogram
Hide Description will be measured during steady state anesthesia as well as during carbon dioxide reversal, and during recovery from anesthesia.
Time Frame participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phasic Genioglossus Activity (Light Anesthesia) Tonic Genioglossus Activity (Light Anesthesia) Phasic Genioglossus Activity (Deep Anesthesia) Tonic Genioglossus Activity (Deep Anesthesia)
Hide Arm/Group Description:
Phasic activity (Peak activity - Tonic activity)
Tonic Genioglossus activity (light anesthesia)
Phasic activity (Peak activity - Tonic activity)
Tonic Genioglossus activity (deep anesthesia)
Overall Number of Participants Analyzed 9 9 9 9
Mean (Standard Error)
Unit of Measure: percentage of maximum recorded activity
32.8  (2.1) 24.2  (1.8) 26.0  (1.8) 22.3  (2.0)
5.Secondary Outcome
Title Minute Ventilation (Tidal Volume and Respiratory Rate)
Hide Description Measured by spirometry. Subjects wear a full-face mask. Reported in L/min
Time Frame Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
In one subject we could not record high quality biologically plausible recordings of minute ventilation.
Arm/Group Title Wakefulness Anesthesia With Low Dose Sevoflurane (Baseline CO2) Anesthesia With High Dose Sevoflurane (Baseline CO2) Anesthesia With Low Dose Propofol (CO2 Baseline) Anesthesia With High Dose Propofol (CO2 Baseline)
Hide Arm/Group Description:
Minute Ventilation (CO2 baseline)
Minute ventilation during anesthesia with sevoflurane (during baseline CO2).
Minute ventilation during anesthesia with sevoflurane (baseline CO2)
Minute Ventilation during anesthesia with propofol (CO2 baseline).
Minute Ventilation during anesthesia with propofol (during baseline CO2).
Overall Number of Participants Analyzed 11 11 11 11 11
Mean (Standard Deviation)
Unit of Measure: L/min
7.9  (1.7) 6.7  (1.3) 5.6  (1.5) 7.2  (1.7) 5.7  (1.3)
6.Secondary Outcome
Title Duty Cycle
Hide Description (T(ins)/T(total))*100
Time Frame Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
In one subject we could not record high quality biologically plausible recordings of Duty cycle.
Arm/Group Title Wakefulness Anesthesia With Low Dose Sevoflurane (Baseline CO2) Anesthesia With High Dose Sevoflurane (Baseline CO2) Anesthesia With Low Dose Propofol (CO2 Baseline) Anesthesia With High Dose Propofol (CO2 Baseline)
Hide Arm/Group Description:
Duty cycle (CO2 baseline)
Duty cycle during anesthesia with sevoflurane (during baseline CO2).
Duty cycle during anesthesia with sevoflurane (baseline CO2)
Duty cycle during anesthesia with propofol (CO2 baseline).
Duty cycle during anesthesia with propofol (during baseline CO2).
Overall Number of Participants Analyzed 11 11 11 11 11
Mean (Standard Deviation)
Unit of Measure: percentage of Ttotal
42  (3) 42  (5) 43  (4) 40  (3) 41  (3)
7.Post-Hoc Outcome
Title Frequency of Spontaneous Swallows During Anesthesia vs Wakefulness
Hide Description The number of swallows were counted during wakefulness and anesthesia. The frequency of swallowing was calculated per hour
Time Frame swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Anesthesia With Propofol and Sevoflurane Wakefulness
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 11 11
Mean (Standard Deviation)
Unit of Measure: number of swallows/hr
1.7  (3.3) 28  (22.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anesthesia With Propofol and Sevoflurane, Wakefulness
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The number of swallows per hour: 1.7±3.3 during anesthesia vs. 28.0±22.3 during wakefulness
Method Mixed Models Analysis
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Propofol Sevoflurane
Hide Arm/Group Description

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.

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.

All-Cause Mortality
Propofol Sevoflurane
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Propofol Sevoflurane
Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/12 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Propofol Sevoflurane
Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/12 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Matthias Eikermann
Organization: Massachusetts General Hospital
Phone: 6176434408
EMail: meikermann@partners.org
Layout table for additonal information
Responsible Party: Matthias Eikermann, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01557920     History of Changes
Other Study ID Numbers: 2011P002472
First Submitted: March 15, 2012
First Posted: March 20, 2012
Results First Submitted: April 12, 2015
Results First Posted: April 21, 2016
Last Update Posted: September 13, 2016