Respiratory Drive on Obstructive Apnea

This study is being conducted to determine whether inhaling exhaled carbon dioxide is effective for the treatment of sleep apnea. A mild increase in this gas can stimulate the respiratory drive by 2-3 fold, which in turn can stimulate the upper airway dilator muscles and decrease the severity of obstructive sleep apnea by at least 50% in selected patients.

During wakefulness pharyngeal dilator muscles (dilators) provide the necessary force to permit an adequate flow in all subjects regardless of how collapsible their passive pharynx is. This dilator activity is substantially lost at sleep onset. Subjects in whom the passive pharynx cannot permit adequate ventilation must recruit dilators through reflex mechanisms if they are to remain asleep. Dilators can be recruited reflexly via changes in blood gas tensions and in afferent activity of pharyngeal mechanoreceptors.

Patients with obstructive sleep apnea (OSA) develop repetitive obstructive events during which air flow decreases substantially (hypopneas) or ceases altogether (apneas). These last from 10 to \>60 seconds following which there is a substantial increase in ventilation (hyperventilatory phase) that lasts for several breaths. The cycle then repeats. Arousal from sleep occurs at some point during the hyperventilatory phase in the vast majority of obstructive respiratory events. However it has been shown that in the majority of OSA patients, the reflex mechanisms are competent and can deal with the obstruction without arousal. The respiratory drive must increase a finite amount before the upper airway muscles begin responding to increasing respiratory drive, and often the patient wakes up first. Thus, when a subject with a narrowed or more compliant pharynx falls asleep and obstructs his/her airway, blood gas tensions must deteriorate a threshold amount before the pharyngeal dilators begin responding. Once this threshold is reached, the dilators respond briskly to further changes in blood gas tensions and open the airway. This threshold was termed the Effective Recruitment Threshold (TER).

The basis for this research project is that if respiratory drive can be maintained at or near the threshold, the dilators would respond promptly to any obstruction and there would be little further increase in respiratory drive during obstruction.We estimate that the required increase in drive can be attained by simply raising carbon dioxide pressure (PCO2) 2-3 mmHg, a highly tolerable increase. We intend to increase respiratory drive on a continuous basis, beginning before sleep by asking the participants to breath through a regular continuous positive airway pressure (CPAP) mask with added dead space.

To increase dead-space we will modify commercial rebreathing bags used for oxygen therapy so that the amount of rebreathing can be adjustable. This should raise arterial carbon dioxide pressure (PaCO2) a few millimetres of mercury (mmHg) in the steady state. Upon sleep, the respiratory drive would be at or above TER in nearly half the patients. Should the airway obstruct, the dilator muscles would be in a position to respond promptly, preventing an acute further rise in respiratory drive. This will reduce the frequency of obstructive respiratory events by \>50% in at least half the patients, and improve sleep quality and nocturnal oxygen saturation.

Eligibility Criteria:
Inclusion Criteria:

* Moderate to severe OSA Apnea Hypopnea Index \> 20/hr.
* Minimum oxygen saturation by pulse oximetry (SpO2) during events \>70% throughout sleep during the clinical sleep study

Exclusion Criteria:

* Neuromuscular disease.
* Obesity-hypoventilation syndrome.
* Chronic obstructive pulmonary disease.
* Pregnancy.
* Significant comorbidities:

  1. Dialysis-dependant renal failure
  2. Severe asthma
  3. Congestive
  4. Heart failure
  5. Previous stroke
* Recent (within 3 months) myocardial infarction or Active coronary ischemia event.