A chronic condition, obstructive sleep apnea (OSA) has a high prevalence in adults,[1] and the propensity for developing it depends on the complex interaction between anatomical and physiologic factors.[2] Continuous positive airway pressure (CPAP) stabilizes the upper airway, targeting some, but not all, of the traits that cause the disease. The limitations of CPAP and the identification of specific physiologic contributors to OSA have led to experimentation with different therapies.[2]
What Is the RAT?
A review published online in the American Journal of Respiratory and Critical Care Medicine (AJRCCM) describes one such physiologic contributor: a low respiratory arousal threshold (RAT).[3] The respiratory centers in the brainstem track mechanical constraints (low lung volumes, resistance to airflow) and gas-exchange abnormalities (oxygen, pH, and carbon dioxide changes) during sleep. A specific threshold of increased respiratory effort, in response to derangements in mechanics or gas exchange, triggers an arousal from sleep. This is the RAT.
In one sense, arousals are protective: They stabilize the airway by harnessing the muscle tone inherent to the "wake" state. However, if triggered too early, they can be disruptive. Persons with a high arousal threshold can make adjustments to breathing and to the airway without awakening, thus avoiding the fragmentation and ventilatory overshoot associated with the sleep/wake transition.
The level of respiratory effort required to initiate arousal from sleep differs by many factors, including age, weight, and severity of OSA.[4] Sedative medications can also alter the arousal threshold. In theory, then, these medications could be administered to patients with OSA and a low RAT to improve sleep continuity.[3]
The Challenges of Targeted Treatment for OSA
The authors of the AJRCCM review thoroughly outline the challenges to providing targeted treatment for OSA. To start, identifying the RAT has traditionally required an esophageal or epiglottic catheter, but neither is used in routine clinical practice. Although polysomnographic (PSG) surrogates have been identified,[5] they have yet to be validated and cannot be used if testing is done using level 3 portable monitors (the percentage of hypopneas will be underestimated).
Even if patients with a low RAT can be identified, it is not clear who will benefit or which sedative should be used. For some, a given medication may not be potent enough to effect change, whereas for others, the sedative will prolong the respiratory limitation and allow gas-exchange abnormalities to worsen before arousal and correction.[3]
The science behind sleep-related breathing disorders has advanced. Rather than assuming that all OSA is related to an abnormal critical closing pressure (Pcrit), we now know that muscle tone, loop gain, and the RAT contribute to sleep-related breathing disorders.[2] Investigators have developed PSG surrogates for defining Pcrit,[6] loop gain,[7] and the RAT,[5] so identifying phenotypes no longer requires sophisticated, invasive testing. These advances are very exciting, but challenges remain.
Lessons learned while targeting the low RAT are instructive. Simply identifying an abnormal trait does not translate to successful treatment. Each trait interacts with the others in complex ways, and results from modifying one will depend on the others.[8] In addition, sedative medications and loop-gain modifiers (acetazolamide) have varying effects on their targeted traits at the individual level.[3] Finally, the push toward portable testing limits our ability to use PSG surrogates to identify OSA phenotypes.
In summary, we have some work to do before we can turn research into practice. As it stands, the only way to know whether targeting a given trait will improve your patient's OSA is to repeat PSG when the patient is on treatment.
Medscape Pulmonary Medicine © 2017 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Obstructive Sleep Apnea: Targeting the Low Arousal Threshold - Medscape - Jun 30, 2017.
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