Sedation in Patients at Risk for Upper Airway Collapse

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01045122
Recruitment Status : Completed
First Posted : January 8, 2010
Results First Posted : April 27, 2015
Last Update Posted : April 27, 2015
Information provided by (Responsible Party):
Suzanne Karan, University of Rochester

Brief Summary:

Overview of Protocol:

Between Subject - Repeated Measures design will be used to assess the airway response of two groups of subjects under two different sedated conditions. Each group will be comprised of six subjects and will be categorized according to their baseline profile for risk for SDB (< 10 RDI or > 25 RDI). Some subjects will have been prescribed continuous positive airway pressure (CPAP) therapy by their treating physician as a result of their overnight sleep study. CPAP treatment is effective in splinting the airway open and thus decreasing the incident of airway collapse during sleep. Thus, CPAP utilization will also be tracked as an independent and continuous variable as regular CPAP use has been found to be associated with increased resistance to UAC (upper airway collapse).

The experimental conditions will evaluate upper airway patency and instability in response to two forms of intravenous sedation: propofol and dexmedetomidine.

Subjects will be continuously monitored during each experimental condition for respiratory effort and flow, and for EEG, EMG, and ECG.

Respiratory instability will first be assessed while subjects are under sedation without any airway provocation. The degree of respiratory instability will be quantified in terms of the following measurements: a modified Respiratory Disturbance Index (RDIsedated), respiratory arousals, and minute ventilation. The apneic periods will be classified by their mixture of central and obstructive components.All outcome measurements are assessed over the period of sedation which last for approximately one hour.

Upper airway patency will be quantified in terms of the critical pharyngeal pressure (Pcrit) (the pressure beyond which complete upper airway collapse occurs, see background).

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Drug: Propofol Drug: Dexmedetomidine Not Applicable

Detailed Description:

The propensity to experience sleep disordered-breathing (SDB) is controlled by the interplay of anatomic factors (i.e. BMI, neck circumference, retrognathia) and neurological drive (sleep stage, arousal). The interaction of baseline anatomic factors and drug-induced altered neurologic drive may also convey a risk for upper airway collapse (UAC) in patients receiving analgesics, or sedation/anesthesia.1;2 While there is mainly only anecdotal evidence to support the proposition that SDB is a strong predictor of sedation-related adverse events,3;4 there is such a remarkable consensus of opinion regarding this association that, for example, the American Society of Anesthesiologists is developing guidelines to specifically address the issue of managing this group of "at risk" patients who are to undergo sedation or anesthesia. SDB is a term that is used to describe a spectrum of sleep-related breathing disturbances. Obstructive Sleep Apnea (OSA) is a condition that incorporates SDB with daytime symptoms (i.e. hypersomnolence). These terms are commonly used interchangeably.

At this juncture, what is needed are clear demonstrations: 1) that SDB confers risk for sedation-related adverse events (epidemiologically and/or experimentally), 2) of the patient and drug factors that moderate/mediate the risk, and 3) of the mechanisms responsible for the patient by drug interactions.

This proposed project will, in a preliminary way, address the first and second of these issues. Specifically, the upper airway characteristics of patients with different severity classifications of SDB will be assessed while under the influence of two, neuropharmacologically distinct, intravenous sedatives.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Official Title: Sedation in Patients at Risk for Sleep-induced Upper Airway Collapse
Study Start Date : December 2006
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Is an alkylphenol, is primarily indicated for use as a general anesthetic and has minimal analgesic properties.
Drug: Propofol
For propofol, the current study will employ the Marsh parameters, with an initial effect site target concentration of 1.0 mcg/ml, a level likely to produce only mild sedation. Though our patient population is expected to be predominantly obese, a previous pharmacokinetic study has validated that constant infusions utilizing the dosing scheme of mcg-1•kg-1•min will yield similar effect site concentrations.25 The effect site target will be increased in increments approximately every five minutes until the pharmacodynamic targets defined in the study are attained.
Other Name: Diprivan

Dexmedetomidine is an alpha-2 adrenoreceptor agonist that has sedative, hypnotic, and analgesic effects.
Drug: Dexmedetomidine
For dexmedetomidine, an intravenous loading dose of 0.5 mcg/kg will be infused over 10 minutes and followed by an infusion starting at 0.5 mcg/kg/hr. This infusion will be titrated up to a maximum of 1.2 mcg/kg/hr.
Other Name: Precedex

Primary Outcome Measures :
  1. Respiratory Disturbance Index [ Time Frame: during infusion of study drugs ]
    respiratory events (apneas, hypopneas) per hour

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with mild or no Sleep disorder breathing
  • Patients with moderate to severe Sleep disorder breathing

Exclusion Criteria:

  • No unstable medical conditions
  • Anatomic pathology of airway
  • Pregnancy or nursing
  • Inability to fit an anesthesia facemask
  • Excessive alcohol or drug abuse
  • Bleeding abnormalities
  • Claustrophobia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01045122

United States, New York
University of Rochester
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Principal Investigator: Suzanne B Karan, Medical University of Rochester
Principal Investigator: Denham Ward, Medical University of Rochester

Responsible Party: Suzanne Karan, Principal investigator, University of Rochester Identifier: NCT01045122     History of Changes
Other Study ID Numbers: Sleep Study CReFF award
5M01RR000044 ( U.S. NIH Grant/Contract )
First Posted: January 8, 2010    Key Record Dates
Results First Posted: April 27, 2015
Last Update Posted: April 27, 2015
Last Verified: April 2015

Keywords provided by Suzanne Karan, University of Rochester:
Obstructive Sleep Apnea

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action