Sedation in Patients at Risk for Upper Airway Collapse

Sedation in Patients at Risk for Sleep-induced Upper Airway Collapse

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).

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Propofol; Drug: Dexmedetomidine

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
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Propofol; 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 Names: Diprivan
Other: Dexmedetomidine; 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 Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Disturbance Index	respiratory events (apneas, hypopneas) per hour	during infusion of study drugs

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Suzanne B Karan, Medical, University of Rochester; Principal Investigator: Denham Ward, Medical, University of Rochester

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: December 11, 2009
• First Submitted That Met QC Criteria: January 7, 2010
• First Posted (Estimate): January 8, 2010

Study Record Updates

• Last Update Posted (Estimate): April 27, 2015
• Last Update Submitted That Met QC Criteria: April 24, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Obstructive Sleep Apnea
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: Sleep Study CReFF award; 5M01RR000044 (U.S. NIH Grant/Contract)