The Effects of General Anesthetics on Upper Airway Collapsibility in Healthy Subjects
Condition: Airway Complication of Anaesthesia; Healthy
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Propofol; Sevoflurane
Intervention type(s): Drug; Drug
Intervention description(s): Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.; Sevoflurane will be administered via mask inhalation to achieve anesthesia.
Intervention MeSH terms: Propofol; Sevoflurane
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: apnea; airway collapsibility; healthy; hypercapnia; general anesthesia; breathing-swallow coordination; aspiration