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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01557920
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 13.9
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The investigators hypothesize that propofol, when compared to sevoflurane, causes the upper airway to collapse more easily and causes less activity in the tongue muscle. Additionally, the investigators hypothesize that, under increased carbon dioxide concentrations of the air inhaled, the upper airway will be less likely to collapse under anesthesia and there will be increased activity in the tongue muscle under both propofol and sevoflurane, when compared to breathing normal concentrations of carbon dioxide, as in room air. Furthermore the investigators hypothesize that anesthesia disrupt the breathing swallow coordination, an effect additionally altered by increased carbon dioxide through increased respiratory drive.

Condition or Disease	Intervention/Treatment	Phase
Airway Complication of Anaesthesia; Healthy	Drug: Propofol; Drug: Sevoflurane	Phase 4

Detailed Description

Upper airway patency depends on an appropriate balance between the dilating force of pharyngeal muscles and the collapsing force of negative intraluminal pressure, which is generated by respiratory "pump" muscles. The genioglossus (GG) protects pharyngeal patency in humans. This muscle receives various types of neural drive, distributed differentially across the hypoglossal motoneuron pool, including phasic (inspiratory) and tonic (non-respiratory) drives. In addition, reflex GG activation in response to negative pharyngeal pressure stabilizes upper airway patency both in humans and in rats. General anesthetic agents, including propofol and sevoflurane, predispose the upper airway to collapse, at least in part by decreasing upper airway muscle activity.

Theoretically anesthetics could affect upper airway dilator activity by several mechanisms, including an anesthetic-induced, dose-dependent decrease in hypercapnic and hypoxic ventilatory drive, hypoglossal motoneuron depression, decreased skeletal muscle contractility, an increase in phasic GG activity as a result of decreased arterial blood pressure, and an increase in phasic hypoglossal nerve discharge.

Previous studies have shown that certain anesthetics, including pentobarbital and isoflurane, can increase genioglossus phasic activity in rats and in humans. The effects of propofol on airway collapsibility have been studied in humans however, to our knowledge, they have not been measured under conditions of hypercapnia. Studies of airway collapsibility under sevoflurane anesthesia have been performed in children, but no data exists for airway collapsibility in sevoflurane-anesthetized adults. Similarly no data exists on the effects of sevoflurane on GG activity

In a previous trial of pentobarbital-anesthetized volunteers, the investigators observed that mild hypercapnia (5 - 10 mmHg above baseline) produced a significant increase in flow rate and GG phasic activity, as well as a smaller increase in GG tonic activity. If our proposed study shows a beneficial effect, then the investigators plan a follow-up study addressing the possibility that hypercapnia may be used therapeutically for airway protection. A similar concept has already been considered for critically ill ICU patients.

However, previous studies have shown that a hypercapnia-induced increase in ventilatory drive can inhibit airway protective reflexes by disrupting the breathing swallowing coordination. In order to assess the safety of induced mild hypercapnia as an intervention for airway protection, we evaluated whether variable levels of hypercapnia occurring during anesthesia with sevoflurane and propofol impair the coordination of breathing and swallowing compared with the effects of anesthesia alone.

With this pharmaco-physiological interaction study on healthy adults we aim to:

1. Compare the effects of sevoflurane and propofol on upper airway closing pressure, upper airway muscle control and breathing.

2. Assess the effects of evoked hypercapnia (carbon dioxide reversal) on propofol-induced upper airway collapsibility

3. Evaluate the effects of sevoflurane, propofol, and induced hypercapnia on coordination of breathing and swallowing.

Comparative drug studies on airway effects of anesthetics in humans are important for defining an optimal anesthetic regimen for patients at risk of airway collapse, such as patients with obstructive sleep apnea. Our studies are also particularly relevant for patients undergoing procedural sedation, which is typically being conducted under spontaneous ventilation with the upper airway being unprotected. In addition, our results may increase our understanding of postoperative airway obstruction, a common complication in the post-anesthesia recovery room.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: The Effects of Sevoflurane, Propofol, and Carbon Dioxide 'Reversal' on Upper Airway Collapsibility in Healthy, Adult Subjects
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Propofol 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. Assessment of swallow patterns during anesthesia and wakefulness, as well as under differential CO2 levels will be assessed offline after recovery from anesthesia.	Drug: Propofol; Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.
Active Comparator: Sevoflurane 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. Assessment of swallow patterns during anesthesia and wakefulness, as well as under differential CO2 levels will be assessed offline after recovery from anesthesia.	Drug: Sevoflurane; Sevoflurane will be administered via mask inhalation to achieve anesthesia.

Outcome Measures

Primary Outcome Measures

1. Upper Airway Closing Pressure [participants will be followed for the duration of anesthesia, an expected average of 6 hours]

   Upper airway closing pressure will be measured during steady state anesthesia as well as during carbon dioxide reversal.

2. Proportion of Pathological Swallows [swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)]

   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 (%).

Secondary Outcome Measures

1. Airway Diameter [participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours]

   Using acoustic pharyngometry, we intend to measure the cross-sectional area of the airway at several points during recovery from anesthesia.

2. Genioglossus Muscle Electromyogram [participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours]

   will be measured during steady state anesthesia as well as during carbon dioxide reversal, and during recovery from anesthesia.

3. Minute Ventilation (Tidal Volume and Respiratory Rate) [Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours]

   Measured by spirometry. Subjects wear a full-face mask. Reported in L/min

4. Duty Cycle [Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours]

   (T(ins)/T(total))*100

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) class I

• Age between 18 and 45

• BMI 18-28 kg/m^2

Exclusion Criteria:

• Concurrent significant medical illness (heart disease including untreated hypertension, Clinically significant kidney disease, liver disease, or lung disease, History of myasthenia gravis or other muscle and nerve disease)

• Anxiety disorder requiring treatment

• Concurrent medications known to affect anesthesia, upper airway muscles or respiratory function (e.g., gabaergic anxiolytics, antipsychotics)

• Individuals with a history of allergy or adverse reaction to lidocaine, propofol, or sevoflurane

• For women: pregnancy

• Suggestion of obstructive sleep apnea (OSA) or any other sleep disorder (e.g. witnessed apneas, gasping or choking during sleep, unexplained excessive daytime sleepiness)

• History of drug or alcohol abuse

• Acute intermittent porphyria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Matthias Eikermann, MD, PhD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Eikermann M, Eckert DJ, Chamberlin NL, Jordan AS, Zaremba S, Smith S, Rosow C, Malhotra A. Effects of pentobarbital on upper airway patency during sleep. Eur Respir J. 2010 Sep;36(3):569-76. doi: 10.1183/09031936.00153809. Epub 2009 Dec 23.
• Eikermann M, Grosse-Sundrup M, Zaremba S, Henry ME, Bittner EA, Hoffmann U, Chamberlin NL. Ketamine activates breathing and abolishes the coupling between loss of consciousness and upper airway dilator muscle dysfunction. Anesthesiology. 2012 Jan;116(1):35-46. doi: 10.1097/ALN.0b013e31823d010a.
• Eikermann M, Malhotra A, Fassbender P, Zaremba S, Jordan AS, Gautam S, White DP, Chamberlin NL. Differential effects of isoflurane and propofol on upper airway dilator muscle activity and breathing. Anesthesiology. 2008 May;108(5):897-906. doi: 10.1097/ALN.0b013e31816c8a60.

• Responsible Party: Matthias Eikermann, Director of Research, Surgical Intensive Care Unit, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01557920
• Other Study ID Numbers: 2011P002472
• First Posted: Mar 20, 2012
• Last Update Posted: Sep 13, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Matthias Eikermann, Director of Research, Surgical Intensive Care Unit, Massachusetts General Hospital: apnea; airway collapsibility; healthy; hypercapnia; general anesthesia; breathing-swallow coordination; aspiration
• Additional relevant MeSH terms: Propofol; Sevoflurane

Study Results

Participant Flow

Arm/Group Title	Propofol First, Then Sevoflurane	Sevoflurane First, Then Propofol
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

Baseline Characteristics

Arm/Group Title	Crossover Randomized Propofol and Sevoflurane
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 Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.3 (3.3)
Sex: Female, Male (Count of Participants)
Female	7 38.9%
Male	11 61.1%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Upper Airway Closing Pressure
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

Outcome Measure Data

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
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.
Measure Participants	10	10
Mean (Standard Deviation) [cm H20]	-9.83 (3.92)	-10.77 (4.69)

2. Primary Outcome

Title	Proportion of Pathological Swallows
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)

Outcome Measure Data

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)
Arm/Group Description	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).
Measure Participants	11	11	11	11	11	11
Number [percentage of pathological swallows]	25.9	4.9	15.8	34.9	1.0	13.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propofol, Sevoflurane
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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

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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Airway Diameter
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

Outcome Measure Data

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)
Arm/Group Description
Measure Participants	0	0	0	0	0

4. Secondary Outcome

Title	Genioglossus Muscle Electromyogram
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

Outcome Measure Data

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)
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)
Measure Participants	9	9	9	9
Mean (Standard Error) [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)
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

Outcome Measure Data

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)
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).
Measure Participants	11	11	11	11	11
Mean (Standard Deviation) [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
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

Outcome Measure Data

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)
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).
Measure Participants	11	11	11	11	11
Mean (Standard Deviation) [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
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)

Outcome Measure Data

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
Arm/Group Description
Measure Participants	11	11
Mean (Standard Deviation) [number of swallows/hr]	1.7 (3.3)	28 (22.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propofol, Sevoflurane
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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

Adverse Events

Arm/Group Title	Propofol		Sevoflurane
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Propofol		Sevoflurane
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Propofol		Sevoflurane
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.