Sedation in Patients at Risk for Upper Airway Collapse

NCT ID: NCT01045122

Last Updated: 2015-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2008-10-31

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).

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.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: DOUBLE

Study Groups

Propofol

Is an alkylphenol, is primarily indicated for use as a general anesthetic and has minimal analgesic properties.

Group Type: OTHER

Propofol

Intervention Type: DRUG

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.

Dexmedetomidine

Dexmedetomidine is an alpha-2 adrenoreceptor agonist that has sedative, hypnotic, and analgesic effects.

Group Type: OTHER

Dexmedetomidine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Diprivan; Precedex

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Suzanne Karan

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Suzanne B Karan, Medical

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Denham Ward, Medical

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of Rochester

Rochester, New York, United States

Countries

United States

Other Identifiers

5M01RR000044

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Sleep Study CReFF award

Identifier Type: -

Identifier Source: org_study_id