Effects of stabilizing or increasing respiratory motor outputs on obstructive sleep apnea

Abstract

To determine how the obstructive sleep apnea (OSA) patient's pathophysiological traits predict the success of the treatment aimed at stabilization or increase in respiratory motor outputs, we studied 26 newly diagnosed OSA patients [apnea-hypopnea index (AHI) 42 ± 5 events/h with 92% of apneas obstructive] who were treated with O2 supplementation, an isocapnic rebreathing system in which CO2 was added only during hyperpnea to prevent transient hypocapnia, and a continuous rebreathing system. We also measured each patient's controller gain below eupnea [change in minute volume/change in end-tidal Pco2 (ΔVe/ΔPetCO2)], CO2 reserve (eupnea-apnea threshold PetCO2), and plant gain (ΔPetCO2/ΔVe), as well as passive upper airway closing pressure (Pcrit). With isocapnic rebreathing, 14/26 reduced their AHI to 31 ± 6% of control (P < 0.01) (responder); 12/26 did not show significant change (nonresponder). The responders vs. nonresponders had a greater controller gain (6.5 ± 1.7 vs. 2.1 ± 0.2 l·min(-1)·mmHg(-1), P < 0.01) and a smaller CO2 reserve (1.9 ± 0.3 vs. 4.3 ± 0.4 mmHg, P < 0.01) with no differences in Pcrit (-0.1 ± 1.2 vs. 0.2 ± 0.9 cmH2O, P > 0.05). Hypercapnic rebreathing (+4.2 ± 1 mmHg PetCO2) reduced AHI to 15 ± 4% of control (P < 0.001) in 17/21 subjects with a wide range of CO2 reserve. Hyperoxia (SaO2 ∼95-98%) reduced AHI to 36 ± 11% of control in 7/19 OSA patients tested. We concluded that stabilizing central respiratory motor output via prevention of transient hypocapnia prevents most OSA in selected patients with a high chemosensitivity and a collapsible upper airway, whereas increasing respiratory motor output via moderate hypercapnia eliminates OSA in most patients with a wider range of chemosensitivity and CO2 reserve. Reducing chemosensitivity via hyperoxia had a limited and unpredictable effect on OSA.

The Combination of Supplemental Oxygen and a Hypnotic Markedly Improves Obstructive Sleep Apnea in Patients with a Mild to Moderate Upper Airway Collapsibility

“…In contrast to the findings of the current study and others, 30 Xie et al 31 reported that hyperoxia had no effect on mean AHI (room air vs. hyperoxia: 39 ± 6 vs. 34 ± 6 events/h, P = 0.25) and found there was no relationship between anatomy/collapsibility and the changes in AHI across participants. Apparent discrepancies are possibly explained by their greater average age (+10 y), more severe average collapsibility (Pcrit in the current study [ …”

Defining Phenotypic Causes of Obstructive Sleep Apnea. Identification of Novel Therapeutic Targets

“…In the category 2b patients, a primarily nonanatomic intervention may be beneficial. For example, oxygen therapy reduces loop gain and OSA severity by approximately 50% in patients with OSA with high loop gain (22), acetazolamide reduces loop gain and OSA severity by about 50% (21), and stabilizing or increasing CO 2 reduces OSA severity by more than 30% in patients with high loop gain (by controller gain) (47). A roughly doubling of genioglossus EMG activity reduces Pcrit by 1.6 cm H 2 O (48), whereas a standard dose of eszopiclone increases the arousal threshold and reduces OSA severity by approximately 45% in patients with OSA with a low arousal threshold (9).…”

Clinical Predictors of the Respiratory Arousal Threshold in Patients with Obstructive Sleep Apnea

“…These respiratory stimuli can activate the upper airway dilator muscles to restore pharyngeal patency during sleep, which can protect against OSA (5)(6)(7)(8)(9). However, restoration of sufficient airflow can only occur if ventilatory drive can build up during sleep without an arousal (5,10,11). Instead, in approximately one-third of patients with OSA (8), respiratory events are terminated early because of a low respiratory arousal threshold (ArTH), preventing the opportunity for ventilatory drive to build up and restore pharyngeal patency during sleep.…”