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

NCT01557920 | Completed Phase 4 Results

• 1 other identifier: 2011P002472
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Airway Complication of Anaesthesia; Healthy

Keywords

apnea; airway collapsibility; healthy; hypercapnia; general anesthesia; breathing-swallow coordination; aspiration

Outcome Measures

Primary Outcomes (2)

• 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

• Proportion of Pathological Swallows

  A pathological swallow was defined as a swallow that was followed by inspiratory flow. A physiological swallow was defined as a swallow that was followed by expiratory flow. The number of pathological and physiological swallows were measured during wakefulness and anesthesia. The pathological swallows are presented as percentage of path. swallows calculated as path.sw/\[path.sw+phys.sw\]\*100 (%).

  swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)

Secondary Outcomes (4)

• Airway Diameter

  participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours

• Genioglossus Muscle Electromyogram

  participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours

• Minute Ventilation (Tidal Volume and Respiratory Rate)

  Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours

• Duty Cycle

  Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours

Study Arms (2)

Propofol

ACTIVE COMPARATOR

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. Assessment of swallow patterns during anesthesia and wakefulness, as well as under differential CO2 levels will be assessed offline after recovery from anesthesia.

Drug: Propofol

Sevoflurane

ACTIVE COMPARATOR

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. Assessment of swallow patterns during anesthesia and wakefulness, as well as under differential CO2 levels will be assessed offline after recovery from anesthesia.

Drug: Sevoflurane

Interventions

Propofol DRUG

Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.

Propofol

Sevoflurane DRUG

Sevoflurane will be administered via mask inhalation to achieve anesthesia.

Sevoflurane

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• American Society of Anesthesiologists (ASA) class I
• Age between 18 and 45
• BMI 18-28 kg/m\^2

You may not qualify if:

• 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 obstructive sleep apnea (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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

• 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.

  PMID: 18431126 BACKGROUND

• 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.

  PMID: 22108392 BACKGROUND

• 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.

  PMID: 20032012 BACKGROUND

MeSH Terms

Conditions

Apnea; Hypercapnia

Interventions

Propofol; Sevoflurane

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Methyl Ethers; Ethers; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated

Results Point of Contact

• Title: Dr. Matthias Eikermann
• Organization: Massachusetts General Hospital

meikermann@partners.org

6176434408

Study Officials

• Matthias Eikermann, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research, Surgical Intensive Care Unit

Study Record Dates

• First Submitted: March 15, 2012
• First Posted: March 20, 2012
• Study Start: January 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: March 1, 2014
• Last Updated: September 13, 2016
• Results First Posted: April 21, 2016

Record last verified: 2016-08

Locations

US (1)