Sedation in Patients at Risk for Upper Airway Collapse

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT01045122
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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	N/A

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 Design

• Study Type: Interventional
• 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: Dec 1, 2006
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Respiratory Disturbance Index [during infusion of study drugs]

   respiratory events (apneas, hypopneas) per hour

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Rochester	Rochester	New York	United States	14642

Sponsors and Collaborators

• University of Rochester

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Suzanne Karan, Principal investigator, University of Rochester
• ClinicalTrials.gov Identifier: NCT01045122
• Other Study ID Numbers: Sleep Study CReFF award; 5M01RR000044
• First Posted: Jan 8, 2010
• Last Update Posted: Apr 27, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Suzanne Karan, Principal investigator, University of Rochester: Obstructive Sleep Apnea
• Additional relevant MeSH terms: Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Dexmedetomidine; Propofol

Study Results

Participant Flow

Recruitment Details	Dates of recruitment April 2006 to November 2008. Subjects were recruited from advertisements, patient letters sent out through the strong sleep center.
Pre-assignment Detail	Subjects excluded from trial before assignment to group because Prior airway surgery, unstable medical conditions.

Arm/Group Title	Propofol First	Dexmedetomidine First
Arm/Group Description	Propofol was administered first in 5/11 subjects with a one week washout at least between the next run with dexmedetomidine	Dexmedetomidine was administered on the first day in 6/11 subjects with at least a one week washout between runs before the subjects underwent the experiment with propofol.
Period Title: Dexmedetomidine Then Propofol
STARTED	5	6
COMPLETED	5	6
NOT COMPLETED	0	0
Period Title: Dexmedetomidine Then Propofol
STARTED	5	6
COMPLETED	5	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Propofol vs Dexmedetomidine
Arm/Group Description	We aim to study two commonly used sedatives (propofol vs dexmedetomidine) in subjects with OSA for their propensity to produce sedation related respiratory events
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (13.7)
Sex: Female, Male (Count of Participants)
Female	6 54.5%
Male	5 45.5%
Region of Enrollment (participants) [Number]
United States	11 100%
Respiratory Disturbance Index (events per hour) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [events per hour]	39.99 (40.1)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Propofol	Dexmedetomidine
Arm/Group Description	The respiratory disturbance index and airway closing pressures (Pcrit) were quantified for both arms	The respiratory disturbance index and airway closing pressures (Pcrit) were quantified for both arms
Measure Participants	11	11
Mean (Standard Deviation) [events per hour]	57.52 (165.6)	21.32 (39.2)

Adverse Events

Arm/Group Title	Propofol		Dexmedetomidine
Arm/Group Description	Is an alkylphenol, is primarily indicated for use as a general anesthetic and has minimal analgesic properties. 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.		Dexmedetomidine is an alpha-2 adrenoreceptor agonist that has sedative, hypnotic, and analgesic effects. 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.
All Cause Mortality
	Propofol		Dexmedetomidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Propofol		Dexmedetomidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Propofol		Dexmedetomidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.