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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Matthias Eikermann, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01557920
First received: March 15, 2012
Last updated: August 27, 2013
Last verified: August 2013
  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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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: March 2014
Estimated Primary Completion Date: November 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
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01557920

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         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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: August 27, 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
Anesthetics, Inhalation
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Hematologic Agents
Hypnotics and Sedatives
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014