The Effects of General Anesthetics on Upper Airway Collapsibility in Healthy Subjects
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Airway Complication of Anaesthesia Healthy |
Drug: Propofol Drug: Sevoflurane |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Prevention |
| Official Title: | The Effects of Sevoflurane, Propofol, and Carbon Dioxide 'Reversal' on Upper Airway Collapsibility in Healthy, Adult Subjects |
- Upper airway closing pressure [ Time Frame: participants will be followed for the duration of anesthesia, an expected average of 6 hours ] [ Designated as safety issue: No ]Upper airway closing pressure will be measured during steady state anesthesia as well as during carbon dioxide reversal.
- Duty Cycle [ Time Frame: participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours ] [ Designated as safety issue: No ]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.
- Airway Diameter [ Time Frame: participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours ] [ Designated as safety issue: No ]Using acoustic pharyngometry, we intend to measure the cross-sectional area of the airway at several points during recovery from anesthesia.
- Genioglossus muscle electromyogram [ Time Frame: participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours ] [ Designated as safety issue: No ]will be measured during steady state anesthesia as well as during carbon dioxide reversal, and during recovery from anesthesia.
- Minute ventilation (tidal volume and respiratory rate) [ Time Frame: Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours ] [ Designated as safety issue: Yes ]Measured by spirometry. Subjects wear a full-face mask.
| Estimated Enrollment: | 16 |
| Study Start Date: | January 2013 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | October 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
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.
|
Drug: Sevoflurane
Sevoflurane will be administered via mask inhalation to achieve anesthesia.
|
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.
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.
Eligibility| Ages Eligible for Study: | 18 Years to 45 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- American Society of Anesthesiologists (ASA) class I
- Age between 18 and 45
- BMI 22-28 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
Contacts and Locations| United States, Massachusetts | |
| Massachusetts General Hospital | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Matthew J Meyer, MD mjmeyer@partners.org | |
| Principal Investigator: Matthias Eikermann, MD, PhD | |
| Principal Investigator: | Matthias Eikermann, MD, PhD | Massachusetts General Hospital |
More Information
Publications:
| Responsible Party: | Matthias Eikermann, Director of Research, Surgical Intensive Care Unit, Massachusetts General Hospital |
| ClinicalTrials.gov Identifier: | NCT01557920 History of Changes |
| Other Study ID Numbers: | 2011P002472 |
| Study First Received: | March 15, 2012 |
| Last Updated: | January 15, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Massachusetts General Hospital:
|
apnea airway collapsibility healthy hypercapnia general anesthesia |
Additional relevant MeSH terms:
|
Anesthetics Propofol Sevoflurane Anesthetics, General Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions |
Central Nervous System Agents Therapeutic Uses Anesthetics, Intravenous Hypnotics and Sedatives Platelet Aggregation Inhibitors Hematologic Agents Anesthetics, Inhalation |
ClinicalTrials.gov processed this record on May 16, 2013