The Effects of General Anesthetics on Upper Airway Collapsibility in Healthy Subjects
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 4/2/2016 |
| Start Date: | January 2013 |
| End Date: | March 2014 |
The Effects of Sevoflurane, Propofol, and Carbon Dioxide 'Reversal' on Upper Airway Collapsibility in Healthy, Adult Subjects
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.
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.
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.
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.
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
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