The prevalence of OSA has increased in epidemiological studies over time. Differences and the increase in prevalence of sleep apnea are probably due to different diagnostic equipment, definitions, study design, and characteristics of included subjects including effects of the obesity epidemic [2]. The estimated prevalence of OSA syndrome (AHI ≥5 and excessive daytime sleepiness) has been reported between 6 and 22% in men and 4 and 17% in women. This disease is often asymptomatic, and the prevalence of patients with OSA, who do not present clinical syndrome, has increased in the last studies. It was reported in 37% of men and in 50% of women in the middle-aged population [1, 2, 7].

OSA is characterized by recurrent periods of upper airway occlusion during sleep. When the pharynx collapses, airflow obstruction elicits neuromuscular responses that can mitigate the obstruction and restore airway patency and ventilation [7]. If these neuromuscular mechanisms are inadequate, additional factors contribute to the development of recurrent periods of airway obstruction and arousals from sleep.

We consider that the upper airway collapses dynamically during sleep and reopens during wakefulness. Investigators have previously modeled dynamic alterations in patency as a function of transmural pressure across collapsible segments in biologic conduits in the cardiovascular, gastrointestinal, and genitourinary systems. The human pharynx is considered as a collapsible tube whose purposes are speech, swallowing, and respiration. There is not provided with a rigid structure as a skeletal support and during inhalation collapse [1, 7].

In the upper airway, the collapsible segment is bordered by two rigid segments: upstream, the nasal passages, and downstream, like the trachea. The segments upstream and downstream to the collapsible site have fixed diameters and resistances, R_US and R_DS, respectively, and the pressures upstream and downstream are P_US and P_DS, respectively. When P_US and P_DS are less than the critical pressure surrounding the collapsible segment (P_CRIT), the transmural pressure is negative, the airway closes, and the airflow ceases. Flow can be reestablished by raising P_US above P_CRIT. Taking into account this model, flow through the upper airway is proportional to the pressure gradient across the entire airway. Moreover, when P_US is greater than P_CRIT and P_DS is less than P_CRIT, however, the airway enters a flow-limited condition, and flow would cease transiently. As the upper airway occludes, the pressure immediately upstream of the occlusion would equilibrate with P_US and rise above P_CRIT. This increase in pressure would inevitably lead to reopening of the airway (Fig. 8.2).

Current evidence suggests that disturbances in P_CRIT play a primary role in OSA pathogenesis. Elevations in P_CRIT have been demonstrated in OSA patients compared to age, sex, and body mass index (BMI)-matched controls under general anesthesia and neuromuscular blockade as well as during sleep. Additional evidence for the primacy of upper airway collapse in OSA pathogenesis is provided by studies demonstrating a dose-response relationship between pharyngeal collapsibility and severity of OSA. As P_CRIT rises progressively, increases in severity of upper airway obstruction during sleep have also been observed clinically [3, 7].

In addition, evidence shows that treatments that decrease P_CRIT (e.g., weight loss or uvulopalatopharyngoplasty) lead to improvements in OSA and to resolution of disease. Similarly, a positive transmural pressure can be induced by increasing P_US, leading to resolution of upper airway obstruction. With application of progressively increasing nasal pressure during CPAP titration, upper airway obstruction and recurrent obstructive apneas and hypopneas are reversed [3, 7, 10].

Many conditions such as negative pressure, soft tissues, and bony structures predispose the pharynx to collapse. However, the tonic and phasic contractile activity of the dilator muscles produces the opposite effect. When an imbalance between these forces is developed, the upper airway obstruction is produced and recurs in patients with sleep-disordered breathing [1].

In fact, both anatomic and neuromuscular factors are involved and the development of OSA. The findings suggest that elevations in pressure in the collapsible segment of the pharynx of OSA patients are due to defects in both upper airway structural and neuromuscular controls, and both play a pivotal role in OSA pathogenesis. OSA can only develop when neuromuscular responses do not adequately mitigate the obstruction caused [2, 7].

Anatomic alterations have been identified such as a variety of factors that contribute to increased collapsibility. In a narrow upper airway, according to the Venturi effect, while airflow velocity increases, pressure on the lateral wall of the pharynx decreases, and the collapsibility does it as well. Excessive fat deposits, particularly parapharyngeal ones, also contribute to OSA development. In addition, lung volumes are decreased in obese persons, leading to decreased caudal traction on the upper airway and an increased critical closing pressure. Another anatomic factor associated with OSA is the presence of tonsillar and tongue hypertrophy, retrognathia, or inferior displacement of the hyoid bone [2, 7].

An impairment in neuromuscular control responses account for much of the balance of the OSA variability. This kind of patients depends on neuromuscular activity to maintain airway patency and ventilation during sleep. Reductions in neuromuscular tone, especially with reduction in pharyngeal dilator tone at sleep onset, are suspected to contribute to increased OSA severity during REM compared to NREM sleep in selected patients and particularly in women and children. Current studies also suggest that endogenous neurohumoral agents can contribute to modulation of neuromuscular responses. Neurohormonal modulation of pharyngeal neuromuscular activation may take part in prevalence and severity of OSA and differences between men and women. It could be explained because of elevations in circulating leptin levels in women compared to men [1, 7].

Neuromuscular responses are also influenced by pharmacologic modulators of sleep-wake state. Alcohol, sedative medications, and hypnotics could decrease responses to upper airway occlusion and promote upper airway obstruction during sleep. Benzodiazepines are known to prolong obstructive apneas and hypopneas. Opiates have not been well studied in association with upper airway collapsibility. Nevertheless, blockade of opioid receptors has been demonstrated to decrease pressure in the airway, which suggests that it may increase susceptibility to pharyngeal occlusion [5, 7].

Pharyngeal neuromuscular activity is also controlled by chemical and mechanical reflexes. Hypercapnia is also a potent stimulator of upper airway neuromuscular activity.

Hypocapnia, on the other hand, produces a relatively passive state and is associated with elevations in pressure. Pharyngeal sensory inhibition has been demonstrated to decrease neuromuscular responses to upper airway obstruction [7].

OSA manifestations develop in a variety of ways from unrecognized symptoms to classic findings. However, the most common presentation is not the recognizable one, and usually OSA progresses over years, delaying diagnosis and producing adverse effects.

As epidemiologic studies are observed, OSA is underdiagnosed, and it is necessary that clinicians are familiar with both the subtle and overt clinical manifestations of OSA to accurately identify patients at risk for the disease and order appropriate testing, to decrease the risk of postoperative mortality in patients with a known diagnosis of sleep apnea [2, 4]. Perioperatively identification of patients is mandatory in order to optimal management [5].

Many classic symptom and exam findings are shown in OSA patients (Table 8.1). The association between OSA and different disorders has been shown in several studies, especially cardiovascular and neurocognitive impairments but also metabolic and endocrine disturbances [4, 11].

From the cardiovascular point of view, the consequences of OSA, hypoxemia, and intrathoracic pressure changes produce intermediate mechanisms as sympathetic activation, endothelial dysfunction, hypercoagulability, inflammation, oxidative stress, and metabolic dysregulation, which finally develop into cardiovascular diseases, systemic hypertension, heart failure, arrhythmia, stroke, myocardial ischemia, and even sudden death (Fig. 8.3).

OSA is associated with variable degrees of neurocognitive impairment. Traffic accidents and work performance deficits are surrogate markers of these neurocognitive impairments in the OSA population that may be reported in clinic. OSA produces negative effects on inductive and deductive reasoning, attention, vigilance, learning, and memory. OSA usually is manifested by impaired judgment, slowed reaction time, impaired learning, and poor working memory, compromised driving, and poor performance at work. Patients with OSA often complain of difficulty staying on task at work, falling asleep inappropriately at their work space, and memory trouble causing professional difficulties [12].

There also seems to be an association between sleep health and mood disorders. Studies relate risk for the development of depression in patients with OSA and also found a dose-response association. However, other studies have not found a relationship between depression and OSA, particularly in men [1, 11].

OSA also affects the metabolic profile, particularly in moderate-to-severe disease. The adverse impact of the OSA on glucose homeostasis, lipid metabolism, and fatty liver disease suggests that OSA should be considered as a potential component of metabolic syndrome [1, 11, 12].

Among the causes of metabolic syndrome in OSA patients, alterations in the hypothalamic-pituitary-adrenal axis, aberrant sympathetic activation, induction of certain adipokines, an increased inflammation/oxidative stress and altered glucose metabolism has been described. Investigators found a significant reduction in insulin sensitivity in patients with OSA, and this reduction in insulin sensitivity correlated with severity of the disease, and the correct treatment of apneic events improves glycemic control [7, 11].