Sleep Disordered Breathing and Chronic Pain

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.

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