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

Healthy Clinical Trial

Official title:

The Effects of Sevoflurane, Propofol, and Carbon Dioxide 'Reversal' on Upper Airway Collapsibility in Healthy, Adult Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01557920
• Other study ID #: 2011P002472
• Status: Recruiting
• Phase: Phase 4
• First received: March 15, 2012
• Last updated: August 27, 2013
• Start date: January 2013
• Est. completion date: March 2014

Study information

• Verified date: August 2013
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: March 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Airway Complication of Anaesthesia
• Healthy

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Upper airway closing pressure	Upper airway closing pressure will be measured during steady state anesthesia as well as during carbon dioxide reversal.	participants will be followed for the duration of anesthesia, an expected average of 6 hours	No
Secondary	Duty Cycle	Duty cycle (inspiratory time/total time of respiration) will be assessed before and during anesthesia, and after recovery from anesthesia. Multiple measurements will be taken as the subject continues his/her recovery.	participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours	No
Secondary	Airway Diameter	Using acoustic pharyngometry, we intend to measure the cross-sectional area of the airway at several points during recovery from anesthesia.	participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours	No
Secondary	Genioglossus muscle electromyogram	will be measured during steady state anesthesia as well as during carbon dioxide reversal, and during recovery from anesthesia.	participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours	No
Secondary	Minute ventilation (tidal volume and respiratory rate)	Measured by spirometry. Subjects wear a full-face mask.	Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours	Yes