Remifentanil in Adults With OSA
| Status: | Completed |
|---|---|
| Conditions: | Insomnia Sleep Studies |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 10/6/2018 |
| Start Date: | September 16, 2016 |
| End Date: | May 2, 2018 |
Opioid Sensitivity in Adults With Treated and Untreated Obstructive Sleep Apnea
Obstructive Sleep Apnea (OSA) is the most common problem that affects sleep. People with this
problem have their airway blocked or minimized, causing snoring or gasping while sleeping. It
can also reduce the amount of oxygen that circulates in the blood of people affected by it.
Millions of Americans have OSA; 10% of adults have diagnosed OSA, an estimated 25% have
undiagnosed OSA. There is concern in the medical community about how to manage pain in
patients with OSA because of the risk of decreased or slower breathing associated with
certain pain medications called opioids. Giving OSA patients opioids could cause them to have
even lower oxygen amounts in their blood stream. It is conceivable that patients with OSA may
require lower doses of opioids to cause decreased breathing as compared to patients without
OSA, however this has not been proven. In this study, we are using a very short acting and
easily reversible opioid pain medication called remifentanil in patients with OSA in order to
find out if treated and untreated OSA patients respond to opioid differently than patients
without OSA.
problem have their airway blocked or minimized, causing snoring or gasping while sleeping. It
can also reduce the amount of oxygen that circulates in the blood of people affected by it.
Millions of Americans have OSA; 10% of adults have diagnosed OSA, an estimated 25% have
undiagnosed OSA. There is concern in the medical community about how to manage pain in
patients with OSA because of the risk of decreased or slower breathing associated with
certain pain medications called opioids. Giving OSA patients opioids could cause them to have
even lower oxygen amounts in their blood stream. It is conceivable that patients with OSA may
require lower doses of opioids to cause decreased breathing as compared to patients without
OSA, however this has not been proven. In this study, we are using a very short acting and
easily reversible opioid pain medication called remifentanil in patients with OSA in order to
find out if treated and untreated OSA patients respond to opioid differently than patients
without OSA.
Open-label, parallel group study. Twenty adults each with untreated OSA, CPAP-treated OSA,
and no OSA will undergo a stepped-dose target-controlled opioid (remifentanil) infusion,
measurement of opioid effects (miosis, respiratory rate, end-expired CO2, thermal analgesia)
and plasma drug concentrations. Remifentanil clinical effects, pharmacodynamics
(concentration-effect relationships), and pharmacokinetics will be compared between the three
groups, as will relationships between effects and nighttime hypoxemia (assessed by home PSG).
The ultimate long-term goal for this research is to improve the perioperative care and pain
management of patients with obstructive sleep apnea (OSA). While patients with OSA are
believed to be more sensitive to the analgesic and adverse effects of opioids, there are no
studies that assess the effects of the OSA gold-standard treatment, namely CPAP, on this
purported sensitivity. Furthermore, OSA is a heterogeneous disease and not all patients who
carry an OSA diagnosis are likely to have the same opioid sensitivity. At present no easily
administered test is able to determine the degree of opioid sensitivity of an individual
patient.
The specific goal of this research is to validate or refute, the untested yet "conventional
wisdom" that adults with untreated OSA have increased sensitivity to the clinical effects of
opioids, especially ventilatory depression. We will test the presumptive hypotheses that a)
untreated OSA increases ventilatory, miotic, and analgesic effects of opioids, b) the
magnitude of increase is proportional to the degree of nighttime hypoxia, and c) CPAP
treatment of OSA normalizes altered opioid responses.
These hypotheses will be tested by evaluating the pharmacodynamics (concentration-effect
relationship) of the prototype opioid remifentanil in patients with and without OSA using
objective opioid sensitivity markers to determine if patients with OSA have increased
sensitivity to opioids and to determine if treatment with CPAP alters this purported
sensitivity. Our study drug, remifentanil, is an ultra-short acting μ-selective opioid
agonist, which is the same receptor at which longer acting opioids such as morphine act.
Since the site of action of remifentanil is the same as other opioids, the results of this
study will be able to be generalized to other opioids, improving our clinical understanding
and practice in this patient population. Opioid effects will be determined by the decrease in
pupil diameter, which is the most sensitive measure of opioid effects at the drug
concentrations and subanesthetic doses to be used. The degree to which changes in pupil
diameter correlate with changes in respiratory rate will be compared.
and no OSA will undergo a stepped-dose target-controlled opioid (remifentanil) infusion,
measurement of opioid effects (miosis, respiratory rate, end-expired CO2, thermal analgesia)
and plasma drug concentrations. Remifentanil clinical effects, pharmacodynamics
(concentration-effect relationships), and pharmacokinetics will be compared between the three
groups, as will relationships between effects and nighttime hypoxemia (assessed by home PSG).
The ultimate long-term goal for this research is to improve the perioperative care and pain
management of patients with obstructive sleep apnea (OSA). While patients with OSA are
believed to be more sensitive to the analgesic and adverse effects of opioids, there are no
studies that assess the effects of the OSA gold-standard treatment, namely CPAP, on this
purported sensitivity. Furthermore, OSA is a heterogeneous disease and not all patients who
carry an OSA diagnosis are likely to have the same opioid sensitivity. At present no easily
administered test is able to determine the degree of opioid sensitivity of an individual
patient.
The specific goal of this research is to validate or refute, the untested yet "conventional
wisdom" that adults with untreated OSA have increased sensitivity to the clinical effects of
opioids, especially ventilatory depression. We will test the presumptive hypotheses that a)
untreated OSA increases ventilatory, miotic, and analgesic effects of opioids, b) the
magnitude of increase is proportional to the degree of nighttime hypoxia, and c) CPAP
treatment of OSA normalizes altered opioid responses.
These hypotheses will be tested by evaluating the pharmacodynamics (concentration-effect
relationship) of the prototype opioid remifentanil in patients with and without OSA using
objective opioid sensitivity markers to determine if patients with OSA have increased
sensitivity to opioids and to determine if treatment with CPAP alters this purported
sensitivity. Our study drug, remifentanil, is an ultra-short acting μ-selective opioid
agonist, which is the same receptor at which longer acting opioids such as morphine act.
Since the site of action of remifentanil is the same as other opioids, the results of this
study will be able to be generalized to other opioids, improving our clinical understanding
and practice in this patient population. Opioid effects will be determined by the decrease in
pupil diameter, which is the most sensitive measure of opioid effects at the drug
concentrations and subanesthetic doses to be used. The degree to which changes in pupil
diameter correlate with changes in respiratory rate will be compared.
Inclusion Criteria
1. 18 to 70 year-old males or non-pregnant females
2. Provide informed consent
Exclusion Criteria
1. History of liver disease
2. pregnant or nursing females
3. known history of addiction to drugs or alcohol
4. craniofacial anomalies that preclude proper fit of pupillometry goggles
5. eye abnormalities that preclude the measurement of pupil diameter
6. use of home oxygen
We found this trial at
1
site
Saint Louis, Missouri 63110
Phone: 314-747-5531
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