Sedation in Patients at Risk for Upper Airway Collapse
Condition: Obstructive Sleep Apnea
MeSH terms: Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

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).
    

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.
    

Intervention name(s): Propofol; Dexmedetomidine
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 intervention name(s): Diprivan; Precedex
Intervention MeSH terms: Dexmedetomidine; Propofol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Keywords: Obstructive Sleep Apnea