Sleep Apnea Syndromes
Conditions
Keywords
chronic pain, sleep disordered breathing, Opioids
Brief summary
The purpose of this study is to evaluate positive pressure in patients with chronic pain taking opioid medications who have sleep disordered breathing.
Detailed description
Purpose: Opioid treatment of non-malignant chronic pain can result in hypoxemia, hypercarbia, and central sleep apnea. The aim of this study was to determine the initial efficacy of auto servo-ventilation (ASV) and after 3 months of home use. Methods: This prospective multicenter interventional study recruited chronic pain patients prescribed ≥100 morphine equivalents for at least 4 months. Participants: Following full-night polysomnography (PSG) to confirm the presence of sleep-disordered breathing, patients were randomized to three additional full-night-attended PSGs with continuous positive airway pressure (CPAP), ASV, and servo-ventilation with an initial mandatory pressure support of 6 cm water (H2O) ASV manual Minimum Pressure Support (PSmin). Following the PSGs, patients were sent home with EncoreAnywhere and ASV with or without mandatory pressure support.
Interventions
DEVICEservo ventilation auto
Expiratory pressure automatically adjusted to stabilize the upper airway. Inspiratory pressure automatically adjusted to deliver consistent peak flow.
DEVICEContinuous positive airway pressure
continuous positive airway pressure
DEVICEservo ventilation manual
servo ventilation titrated in manual mode
Sponsors
Philips Respironics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females, ages 21-70. 2. Able to provide written informed consent. 3. Diagnosis of chronic non-malignant pain (pain present for ≥ 6 months). 4. Stable regimen of opioids (oral, transdermal, and/or intravenous) for chronic pain for at least 4 weeks prior to study participation with a prescribed opioid dose equal to at least 100 milliequivalents of morphine per 24 hours (Appendix 1). 5. Agreement to undergo an in-lab Diagnostic polysomnography (PSG) demonstrating an Apnea-Hypopnea Index (AHI) of at least 20 and Central Apnea Index (CAI) ≥ 10 events per hour of sleep OR at least 25% of Total Sleep Time (TST) below 90% Oxygen Saturation (SAO2) saturation and AHI ≥ 10 6. Agreement to undergo 3 full-night, in-lab PSG's on positive airway pressure therapy. 7. Agreement to undergo breathalyzer testing prior to each PSG visit 8. Ability to provide reliable documentation of opioid medications (ex. Pharmacy records) as treatment for chronic pain for the previous 30 days. 9. Willingness to undergo urine drug screening.
Exclusion criteria
1. Participation in other interventional, sleep or pharmaceutical related research studies within 30 days prior to giving consent. 2. Workers with variable shift schedules. 3. Previous treatment with positive airway pressure therapy within 90 days of providing consent. 4. Participants with any conditions in which positive airway pressure is medically contraindicated (e.g. recent pneumothorax, systolic BP \< 80 mmHg). 5. BMI \> 40 6. Unwilling to wear PAP. 7. Any surgery involving the upper airway, eye, nose, sinuses or middle ear within the last 90 days. 8. Major or poorly managed medical or psychiatric condition that would interfere with the demands of the study, to the use of positive airway pressure, or the ability to complete the study. 9. Previous diagnosis of severe chronic obstructive pulmonary disease (COPD) with an forced expiratory volume at one second (FEV1) \< 1 liter or less than 50% predicted 10. Presence of elevated arterial carbon dioxide levels while awake (PaCO2 ≥ 50mmHg) due to intrinsic lung disease, neuromuscular or musculoskeletal disorders. 11. Participants currently prescribed 24 hour oxygen therapy (nocturnal O2 therapy for obstructive sleep apnea (OSA) treatment is allowed) 12. Females who are pregnant or, if of child bearing potential, not currently using medically reliable birth control methods. 13. Participants prescribed opioids for reasons other than the management of chronic, non-malignant pain. 14. Failure of two consecutive breathalyzer tests from study PSG nights 15. Periodic Limb Movements (PLM's) with arousals \> 15
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Sleep Related Events Per Hour | four full night Polysomnography (PSG's) | The number of Apnea-Hypopnea Events, Central Apneas, Obstructive Apneas and Hypopneas were compared among no treatment, CPAP, Auto SV and Manual SV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Oxygen Saturation | four full night Polysomnography (PSG's) | Oxygen Saturation were compared among using no treatment, CPAP, Auto SV and Manual SV. |
| Number of Arterial Oxygen Saturation Per Hour | four full night Polysomnography (PSG's) | Arterial Oxygen Saturation was compared among using no treatment, CPAP, Auto SV and Manual SV. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from pain treatment centers and clinics by either Pain Center/Clinic staff or staff from a Sleep Testing facility.
Pre-assignment details
74 participants were screened; 40 were excluded after completing the diagnostic PSG (did not meet the inclusion/exclusion criteria).
Participants by arm
| Arm | Count |
|---|---|
| Total Group 34 subjects completed part 1 of the study which consisted of diagnostic PSG screening and met all inclusion/exclusion criteria | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First Night | Didn't meet inclusion/exclusion criteria | 37 | 0 | 0 | 0 |
| First Night | Withdrawal by Subject | 3 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total Group |
|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 11.6 |
| Morphine equivalents | 390.1 mEq STANDARD_DEVIATION 338.1 |
| Race/Ethnicity, Customized African American | 3 participants |
| Race/Ethnicity, Customized Caucasian | 31 participants |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 34 |
| serious Total, serious adverse events | 0 / 34 |
Outcome results
Primary
Number of Sleep Related Events Per Hour
The number of Apnea-Hypopnea Events, Central Apneas, Obstructive Apneas and Hypopneas were compared among no treatment, CPAP, Auto SV and Manual SV.
Time frame: four full night Polysomnography (PSG's)
Population: After the Diagnostic Polysomnography (PSG) each participant completed a night in each arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diagnostic Polysomnography (PSG) | Number of Sleep Related Events Per Hour | Apnea-hyopnea index | 38.8 events/hour | Standard Deviation 31.1 |
| Diagnostic Polysomnography (PSG) | Number of Sleep Related Events Per Hour | Central Apnea Index | 16.1 events/hour | Standard Deviation 18.8 |
| Diagnostic Polysomnography (PSG) | Number of Sleep Related Events Per Hour | Obstructive Apnea Index | 9.7 events/hour | Standard Deviation 6.3 |
| Diagnostic Polysomnography (PSG) | Number of Sleep Related Events Per Hour | Hypopnea Index | 14.8 events/hour | Standard Deviation 12.6 |
| CPAP | Number of Sleep Related Events Per Hour | Central Apnea Index | 8.4 events/hour | Standard Deviation 12.4 |
| CPAP | Number of Sleep Related Events Per Hour | Obstructive Apnea Index | 4.5 events/hour | Standard Deviation 6.3 |
| CPAP | Number of Sleep Related Events Per Hour | Hypopnea Index | 4.5 events/hour | Standard Deviation 5.1 |
| CPAP | Number of Sleep Related Events Per Hour | Apnea-hyopnea index | 17.4 events/hour | Standard Deviation 20.1 |
| Servo Ventilation Auto Mode | Number of Sleep Related Events Per Hour | Obstructive Apnea Index | 0.3 events/hour | Standard Deviation 0.5 |
| Servo Ventilation Auto Mode | Number of Sleep Related Events Per Hour | Central Apnea Index | 0.2 events/hour | Standard Deviation 0.8 |
| Servo Ventilation Auto Mode | Number of Sleep Related Events Per Hour | Hypopnea Index | 4.6 events/hour | Standard Deviation 7.4 |
| Servo Ventilation Auto Mode | Number of Sleep Related Events Per Hour | Apnea-hyopnea index | 4.5 events/hour | Standard Deviation 7.3 |
| Servo Ventilation Manual | Number of Sleep Related Events Per Hour | Hypopnea Index | 7.9 events/hour | Standard Deviation 16.2 |
| Servo Ventilation Manual | Number of Sleep Related Events Per Hour | Central Apnea Index | 0.2 events/hour | Standard Deviation 0.9 |
| Servo Ventilation Manual | Number of Sleep Related Events Per Hour | Apnea-hyopnea index | 7.6 events/hour | Standard Deviation 16.7 |
| Servo Ventilation Manual | Number of Sleep Related Events Per Hour | Obstructive Apnea Index | 0.5 events/hour | Standard Deviation 1.1 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Number of Arterial Oxygen Saturation Per Hour
Arterial Oxygen Saturation was compared among using no treatment, CPAP, Auto SV and Manual SV.
Time frame: four full night Polysomnography (PSG's)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diagnostic Polysomnography (PSG) | Number of Arterial Oxygen Saturation Per Hour | 32.8 times per hour | Standard Deviation 29.2 |
| CPAP | Number of Arterial Oxygen Saturation Per Hour | 15.1 times per hour | Standard Deviation 20.2 |
| Servo Ventilation Auto Mode | Number of Arterial Oxygen Saturation Per Hour | 5.9 times per hour | Standard Deviation 8.6 |
| Servo Ventilation Manual | Number of Arterial Oxygen Saturation Per Hour | 9.5 times per hour | Standard Deviation 19.2 |
p-value: 0.161Wilcoxon (Mann-Whitney)
Secondary
Percent Oxygen Saturation
Oxygen Saturation were compared among using no treatment, CPAP, Auto SV and Manual SV.
Time frame: four full night Polysomnography (PSG's)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diagnostic Polysomnography (PSG) | Percent Oxygen Saturation | Av. O2 saturation | 92.9 percentage of oxygen saturation | Standard Deviation 3.4 |
| Diagnostic Polysomnography (PSG) | Percent Oxygen Saturation | Min. O2 saturation | 79.9 percentage of oxygen saturation | Standard Deviation 7.8 |
| CPAP | Percent Oxygen Saturation | Min. O2 saturation | 85.5 percentage of oxygen saturation | Standard Deviation 6 |
| CPAP | Percent Oxygen Saturation | Av. O2 saturation | 94.6 percentage of oxygen saturation | Standard Deviation 2.3 |
| Servo Ventilation Auto Mode | Percent Oxygen Saturation | Av. O2 saturation | 94.6 percentage of oxygen saturation | Standard Deviation 2.6 |
| Servo Ventilation Auto Mode | Percent Oxygen Saturation | Min. O2 saturation | 82.9 percentage of oxygen saturation | Standard Deviation 16.2 |
| Servo Ventilation Manual | Percent Oxygen Saturation | Av. O2 saturation | 94.5 percentage of oxygen saturation | Standard Deviation 3.2 |
| Servo Ventilation Manual | Percent Oxygen Saturation | Min. O2 saturation | 79.7 percentage of oxygen saturation | Standard Deviation 22.8 |
p-value: 0.627Wilcoxon (Mann-Whitney)