Remifentanil in Adults With OSA
Condition: Apnea, Sleep
MeSH terms: Sleep Apnea Syndromes
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Targeted infusion of remifentanil
Intervention type(s): Drug
Intervention description(s): Remifentanil dosing will be calculated using ideal body weight and infused to achieve brain concentrations of 0.5, 1, 2, 3, and 4 ng/ml; approximately 10 minutes at each concentration.
Other intervention name(s): Ultiva
Intervention MeSH terms: Remifentanil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: sensitivity, opioid