Obesity in anaesthesia and intensive care

The role of chemical control instability in the pathogenesis of obstructive sleep apnea (OSA) is not clear. We studied 32 patients with OSA during sleep while their upper airway was stabilized with continuous positive airway pressure. Twelve patients had repetitive OSA whenever they were asleep, regardless of body position or sleep stage, and were classified as having severe OSA (apnea–hypopnea index [AHI] = 88 ± 19). The remaining 20 patients had sporadic OSA or repetitive OSA for only part of the time (mild/moderate OSA; AHI = 27 ± 16). Susceptibility to periodic breathing (PB) was assessed by gradually increasing controller gain, using proportional assist ventilation. The increase in loop gain (LG) at each assist level was quantified from the ratio of assisted tidal volume (Vt) to the Vt obtained during single-breath reloading tests (Vt amplification factor [VtAF]). Nine of 12 patients with severe OSA developed PB, with recurrent central apneas, whereas only six of 20 patients in the mild/moderate grou...

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.163.5.2007013

Chemical Control Stability in Patients with Obstructive Sleep Apnea

Arousal is believed to be needed for upper airway opening in obstructive hypopneas-apneas, without compelling evidence to support this notion. The association may be incidental. I studied the temporal relation between arousal and opening and impact of arousal on flow response at opening in 82 patients (apnea-hypopnea index, 46 +/- 35/hour). Obstructive apneas-hypopneas were induced by dial-down of continuous positive airway pressure. Obstructions and hypopneas occurred in 44 and 56% of dial-downs, respectively. When arousal occurred (83% of dial-downs), the temporal relation between arousal and opening was inconsistent between and within patients. Frequency of opening without or before arousal increased with milder obstructions (p < 10(-9)) and with delta power of EEG (p < 10(-6)). Time of opening was unaffected by whether arousal occurred before or after opening (18.0 +/- 9.8 vs. 18.1 +/- 10.5 seconds). Flow response was already excessive when opening occurred without or before arousal (180 +/- 148% of initial flow decline) and was considerably higher when arousal occurred (267 +/- 154%, p < 10(-10)). Flow undershoot after first ventilatory response was greater if arousal occurred (p < 0.01). It is concluded that arousals are incidental events that occur when thresholds for arousal and for arousal-independent opening are close. They are not needed to initiate opening or to obtain adequate flow and they likely increase the severity of the disorder by promoting greater ventilatory instability.

https://www.atsjournals.org/doi/pdf/10.1164/rccm.200307-1023OC

Role of arousals in the pathogenesis of obstructive sleep apnea

The pathophysiology of obstructive sleep apnoea (OSA) is complex and incompletely understood. A narrowed upper airway is very common among OSA patients, and is usually in adults due to nonspecific factors such as fat deposition in the neck, or abnormal bony morphology of the upper airway. Functional impairment of the upper airway dilating muscles is particularly important in the development of OSA, and patients have a reduction both in tonic and phasic contraction of these muscles during sleep when compared to normals. A variety of defective respiratory control mechanisms are found in OSA, including impaired chemical drive, defective inspiratory load responses, and abnormal upper airway protective reflexes. These defects may play an important role in the abnormal upper airway muscle responses found among patients with OSA. Local upper airway reflexes mediated by surface receptors sensitive to intrapharyngeal pressure changes appear to be important in this respect. Arousal plays an important role in the termination of each apnoea, but may also contribute to the development of further apnoea, because of reduction in respiratory drive related to the hypocapnia which results from postapnoeic hyperventilation. A cyclical pattern of repetitive obstructive apnoeas may result. A better understanding of the integrated pathophysiology of OSA should help in the development of new therapeutic techniques.

https://erj.ersjournals.com/content/erj/8/7/1161.full.pdf

Pathophysiology of obstructive sleep apnoea

The contributions of pharyngeal mechanical abnormalities, flow demand, and compensatory effectiveness to obstructive sleep apnea severity were determined in 82 patients. Flow demand was estimated from mean inspiratory flow on continuous positive airway pressure. Mechanical load on upper airway muscles was estimated from minimal effective continuous positive airway pressure, flow demand, and minimum flow observed during brief pressure dial downs. Compensatory effectiveness was estimated by relating polysomnographic severity and mechanical load. Mechanical load was more severe in men, in supine position, and in older and heavier patients. Higher flow demand contributed significantly to mechanical load in men and in those who are obese. At the same mechanical load, severity was independent of age, sex, or body mass index but was greater in the supine position and in REM sleep. Mechanical load accounted for only 34% of variability in severity. Eighty-two percent of patients experienced periods of stable breathing despite mechanical loads that would produce continuous cycling without compensation. I conclude that most patients can adequately compensate for the abnormal mechanics, at least part of the time. Higher flow demand contributes to severity in men and in obesity. Severity is largely due to factors other than mechanical load. Compensatory effectiveness is impaired in the supine position and in REM sleep, but not by age, sex, or body mass index.

Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea

Previous work from our laboratory has indicated that mechanoreceptor feedback from the respiratory muscles may play an important role in arousal and apnea termination in obstructive sleep apnea (OSA). Other studies have pointed to a prominent role for chemoreceptor stimuli. We postulated that mechanoreceptor stimuli from the respiratory system are the primary determinant of apnea termination, and that chemoreceptor stimuli exert their effect indirectly through stimulation of ventilation and thus proprioceptive feedback. To test this, we measured the diaphragmatic tension-time index (TTdi) during obstructive sleep apneas in seven male subjects with severe untreated OSA. We compared the maximal TTdi values at end-apnea during administration of air, O2, and CO2. We reasoned that if mechanoreceptor stimuli mediate apnea termination, changing the degree of chemoreceptor stimulation during apneas should not alter the level of respiratory effort at end-apnea. O2 administration produced a significant increase in end-apneic arterial oxygen saturation (SaO2) and increased apnea duration. CO2 administration led to an increase in pre- and postapneic end-tidal carbon dioxide pressure (PETCO2), and tended to shorten apneas. However, the mean value for maximal end-apneic TTdi was 0.12 +/- 0.01 (SEM) during room air breathing and was unaltered by O2 (0.12 +/- 0.01) or CO2 (0.11 +/- 0.01) administration. The consistency of end-apneic TTdi values despite the varying chemical drive supports the hypothesis that apnea termination in OSA is mediated by mechanoreceptor feedback from the respiratory system, most likely from the respiratory muscles. The influence of chemoreceptor information may be mediated indirectly through an effect on ventilatory effort.

A. E. Olha

Papers

Mechanisms of Apnea Termination in Obstructive Sleep Apnea Role of Chemoreceptor and Mechanoreceptor Stimuli