Targeting Chemoreceptor Control of Breathing During Sleep to Mitigate Opioid-Associated Sleep Disordered Breathing
VA Office of Research and Development
Summary
There is an increased risk for sleep disordered breathing (SDB), sleep-related hypoventilation and irregular breathing in individuals on chronic prescription opioid medications. Almost 30% of a veteran sleep clinic population had opioid-associated central sleep apnea (CSA). The proposal aims to identity whether oxygen and acetazolamide can be effective in reducing unstable breathing and eliminating sleep apnea in chronic opioid use via different mechanisms. We will study additional clinical parameters like quality of life, sleep and pain in patients with and without opioid use. This proposal will enhance the investigators' understanding of the pathways that contribute to the development of sleep apnea with opioid use. The investigators expect that the results obtained from this study will positively impact the health of Veterans by identifying new treatment modalities for sleep apnea.
Description
In a national sample of Veterans, SDB was a significant risk factor for opioid-related toxicity and overdose; and the presence of CSA combined with chronic prescription opioid use compounded the mortality risk. There are only limited and partially effective therapies for this sleep disorder and the exact mechanisms by which opioids produce SDB in adults remain unclear, and varied and conflicting ventilatory control mechanisms have been suggested. This proposal will investigate whether alternative therapies can be developed by modulating specific physiologic mechanisms of ventilatory control. S…
Eligibility
- Age range
- 18–89 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Veterans, age 18-89 years * Veterans with prescription opioids Exclusion Criteria: * Patients with BMI\>40kg/m2 will be excluded to avoid the effects of morbid obesity on pulmonary mechanics and ventilatory control * Patients with history of unresolved/untreated cardiac disease, including recent myocardial infarction, recent bypass surgery, untreated atrial and ventricular tachy-bradycardias * Congestive heart failure with Cheyne-Stokes respiration (CSR) * Current unstable angina * Recent stroke * Untreated schizophrenia * Untreated hypothyroidism * Unresolved seizure…
Interventions
- OtherHyperoxia
The ventilatory effects of brief hyperoxia will be assessed by analyzing control breaths on room air immediately preceding the hyperoxic exposure, and comparing with the primary end-point, nadir minute ventilation breath, immediately following the brief hyperoxic exposure.
- DrugAcetazolamide
Participants with sleep apnea will ingest capsules containing either placebo or acetazolamide 500 mg twice a day for 6 days. On the final 4 consecutive nights while still on ACZ, the investigators will perform i) physiology tests and ii) in-lab follow-up PSG.
Location
- John D. Dingell VA Medical Center, Detroit, MIDetroit, Michigan