Obstructive sleep apnea

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is typically associated with obesity. It is characterized by obstruction of the upper airways due to the collapse of the pharyngeal muscles during sleep, which causes multiple episodes of interrupted breathing (apnea and hypopnea events), leading to alveolar hypoventilation. Severe daytime sleepiness due to sleep disruption is a common symptom. Partners of affected individuals commonly describe observing restless sleep and irregular snoring, gasping, or choking episodes. The diagnosis is based on polysomnography or home sleep apnea testing. Many patients develop hypertension secondary to OSA, the cardiovascular consequences of which can reduce life expectancy. First-line treatment consists of nightly continuous positive airway pressure (CPAP); alternatives include oral appliances and surgical interventions. Lifestyle changes such as weight loss, avoidance of precipitating factors (e.g., alcohol), and improvement of sleep hygiene are recommended.

• Obstructive sleep apnea: (OSA): a sleep-related breathing disorder in which airflow significantly decreases or ceases due to upper airway obstruction (typically in the oropharynx) ^[1][2]
• Abnormal breathing events
  • Apnea: complete or nearly complete (≥ 90%) cessation of inspiratory airflow for ≥ 10 seconds ^[1][3]
  • Hypopnea: airflow reduction by ≥ 30% of the pre-event baseline for ≥ 10 seconds in combination with either desaturation by ≥ 3% or arousal from sleep ^[3][4][5]
  • Respiratory effort-related arousal (RERA): arousal from sleep due to increased respiratory effort or reduced airflow for ≥ 10 seconds without significant hypopnea or apnea ^[3]

• Sex: ♂ > ♀ (2:1)
• Prevalence: ∼ 20–30% in men and 10–15% in women

References:^[6][7]

Epidemiological data refers to the US, unless otherwise specified.

• Obstruction of the upper airways due to the collapse of the pharyngeal muscles during sleep
• Risk factors for obstructive sleep apnea
  • Obesity, especially around the neck (short, wide “bull neck”)
  • Structural abnormalities that impair respiratory flow, including:
    • Adenotonsillar hyperplasia (especially in children)
    • Nasal septum deviation
    • Previous upper airway surgery
    • Enlarged uvula, tongue, or soft palate (especially in adults)
    • Overbite with a small chin
    • Hypertrophied pharyngeal muscles
    • Nasal polyps
  • Alcohol consumption before sleep
  • Intake of sedatives and/or beta blockers before sleep
  • Smoking
  • Family history
  • Acromegaly
  • Hypothyroidism

An increased neck circumference (> 40 cm) is the most important risk factor for OSA.

• Obstruction of the upper airways → apnea → ↓ partial pressure of oxygen in arterial blood (PaO₂), ↑ partial pressure of carbon dioxide in arterial blood (PaCO₂, also known as hypercapnia), which leads to:
  • ↑ Hypoxic pulmonary vasoconstriction → ↑ pulmonary hypertension → cor pulmonale
  • ↑ Sympathetic activity → secondary hypertension
  • Respiratory acidosis → renal compensation → increased HCO₃ retention and decreased chloride reabsorption

• Typical symptoms ^[5]
  • Restless sleep with waking, gasping, or choking
  • Loud, irregular snoring with apneic episodes (third-party reports)
  • Excessive daytime sleepiness (e.g., patient falls asleep, microsleep while seated)
  • Morning headaches
• Signs of complications, including:
  • Impaired cognitive function (e.g., impaired concentration, memory loss) ^[4]
  • Depression ^[10]
  • Decreased libido ^[11]
  • Hypertension with increased pulse pressure ^[12]

Obstructive sleep apnea is one of the most common causes of secondary hypertension. ^[13]

General principles ^[4][5]

• A detailed evaluation should include:
  • Sleep history, including third-party reports (e.g., interviewing the sleep partner about snoring and witnessed apneas)
  • Evaluation for comorbidities (including complications of OSA) and risk factors for OSA
• Screening for OSA
  • Standardized screening questionnaires may be used to assess risk for OSA in certain clinical settings (e.g., STOP-BANG questionnaire for preoperative evaluation).
  • Screening asymptomatic patients is not routinely recommended. ^[14]
• Sleep studies are required to confirm the diagnosis and determine the severity of OSA (e.g., using the apnea-hypopnea index).

The diagnosis of obstructive sleep apnea requires sleep studies and should not be made based on clinical tools or questionnaires alone. ^[4]

STOP-BANG questionnaire: S – Snoring loudly, T – feeling Tired or fatigued, O – Observed apneas during sleep, P – high blood Pressure, B – BMI > 35, A – Age > 50 years, N – Neck circumference > 40 cm, G – male Gender. ^[15]

Laboratory tests

Laboratory tests are not usually considered useful in the diagnosis of OSA but can help identify physiological consequences of OSA and detect associated conditions.

• CBC may show polycythemia (↑ Hct, ↑ Hb): Hypoxia induces erythropoietin secretion by the kidneys, which stimulates the blood marrow, leading to increased RBC production. ^[16]
• Arterial blood gas
  • PaO₂ is usually normal during the day.
  • ↑ Serum bicarbonate ^[17]

Sleep studies ^[4][5]

• Indicated in all patients with excessive daytime sleepiness and at least two of the following:
  • Loud snoring
  • Witnessed choking, gasping, or apnea during sleep
  • Diagnosis of hypertension
• Consider in patients with comorbidities (including complications of OSA) and risk factors for OSA.

In-laboratory polysomnography (PSG)

• Description: Physiologic variables are recorded during sleep to diagnose sleep-related disorders.
  • Variables include oxygen saturation, respiratory pauses and flow, sleep stages, and arousal events.
  • Recordings include EEG, EMG, EOG, and ECG.
• Indications
  • Patients with significant cardiovascular or respiratory disease
  • Suspicion of other types of sleep-related disorders
  • Circumstances precluding a home assessment ^[4]
  • Home sleep apnea testing is inconclusive or negative.
• Findings
  • Apnea and hypopnea events
  • Oxygen desaturation
  • Respiratory effort-related arousal events, possibly causing sleep fragmentation
  • In some cases, signs of associated comorbidities (e.g., hypertension, cardiac arrhythmias) ^[5][18]
• Important considerations
  • Consider repeated testing if the initial test is negative and clinical suspicion remains (first night effect). ^[4][5]
  • Consider split-night testing. ^[4]

In-laboratory polysomnography is the gold standard for the diagnosis of sleep-related breathing disorders and can also help identify other sleep-related conditions (e.g., seizures).

Home sleep apnea testing (HSAT)

• Description: an ambulatory screening method for sleep-related breathing disorders that assesses ventilation and oxygenation parameters but not sleep stages or arousal events
• Indications
  • Patients with a high pretest probability for OSA and no significant comorbidities
  • In-laboratory testing is not feasible.
• Findings: cardiorespiratory findings similar to those in PSG

Due to its lower sensitivity, HSAT cannot be used to rule out the diagnosis of OSA. ^[4]

Interpretation of sleep study findings ^[1][4]

Scores

Scores are calculated based on sleep study findings and are then used to diagnose OSA and determine its severity.

• Apnea-hypopnea index (AHI): number of apneas plus hypopneas per hour of sleep
• Respiratory disturbance index (RDI): number of apneas plus hypopneas plus RERAs per hour of sleep ^[19]
• Respiratory event index (REI): number of apneas plus hypopneas with desaturation of ≥ 4% per hour of recorded time

Diagnostic criteria for OSA ^[4][20]

Depending on the type of sleep study used, different scores can be calculated. Any of them can be used to diagnose OSA.

• AHI/RDI/REI ≥ 5 in patients with symptoms of OSA and/or associated comorbidities
• OR AHI/RDI/REI ≥ 15 in patients without symptoms

Classification of OSA by severity ^[21]

Severity is graded by the number of sleep-related obstructive breathing events, most commonly using the AHI.

• AHI 5–15: mild OSA
• AHI 16–30: moderate OSA
• AHI > 30: severe OSA

Central sleep apnea (CSA) syndromes ^[22][23]

• Description
  • A sleep-related breathing disorder in which the drive to breathe periodically decreases or ceases due to impaired function of the respiratory center
  • Caused either by hyperventilation (nonhypercapnic CSA) or hypoventilation (hypercapnic CSA)

• Clinical features ^[22]
  • Similar to symptoms of OSA
    • Daytime sleepiness
    • Repeated waking at night
    • Morning headaches
    • Snoring
  • In some cases: Cheyne-Stokes breathing pattern ^[23]
• Diagnostics
  • Clinical history of underlying conditions (e.g., heart failure, stroke)
  • Polysomnography, ideally with esophageal pressure manometry (gold standard) ^[25]
• Treatment
  • Optimize treatment of the underlying condition.
  • Ventilation support
    • Recommended in certain forms of CSA, e.g., forms related to heart failure or idiopathic CSA
    • Options include CPAP, BPAP, and adaptive servoventilation (ASV). ^[23][26]
  • Further treatment may be considered based on the underlying cause. ^[23]
    • Pharmacological treatment, e.g., for idiopathic CSA
    • Nocturnal oxygen therapy, e.g., for CSA related to heart failure

The 3 C’s of Central sleep apnea are Congestive heart failure, CNS trauma or toxicity, and Cheyne-Stokes breathing.

Hypoventilation disorders

Alveolar hypoventilation is defined as an elevation of PaCO₂ > 45 mmHg.

Obesity hypoventilation syndrome (Pickwickian syndrome) ^[27][28]

• Definition: a type of sleep-related hypoventilation disorder defined by a BMI of ≥ 30 kg/m², diurnal hypercapnia, and disordered breathing during sleep ^[20]
• Risk factors: same as those for obesity ^[29]
• Pathophysiology: Multiple mechanisms caused by obesity contribute to the development of OHS.
  • Structural component: reduction in inspiratory muscle strength and restriction of respiratory excursions → reduction; in lung volume → alveolar hypoventilation
  • Central component: increased work of breathing → increased respiratory drive → inability to maintain during REM sleep → hypoventilation (↓ PaO_2,↑ PaCO₂) during sleep → repetitive hypoventilation causes depression of central respiratory centers → diurnal hypercapnia
  • Obstructive component: ∼ 90% of OHS patients have concurrent OSA. ^[27]
• Clinical features
  • Symptoms similar to clinical features of OSA; , including headaches and severe sleepiness ^[30]
  • Possibly dyspnea during the day
  • Often diagnosed in acute state of respiratory failure ^[29]
• Diagnostics
  • Routine laboratory studies: serum bicarbonate ≥ 27 mEq/L
  • Arterial blood gas
    • PaCO₂ > 45 mm Hg that cannot be explained by another condition
    • Hypoxemia
    • Respiratory acidosis
  • Polysomnography: hypoventilation during sleep with or without obstructive apnea events
• Treatment
  • Weight loss
  • Ventilation support
    • CPAP: preferred in patients with concomitant OSA
    • Noninvasive ventilation (NIV), e.g., BPAP: may be considered in patients without OSA

Patients presenting with respiratory failure due to OHS are frequently misdiagnosed with COPD. ^[28]

Other sleep-related hypoventilation disorders

Sleep-related hypoventilation disorders are defined as sustained desaturation (SpO₂ ≤ 88% for > 5 minutes) with a rise in pCO₂ during sleep. ^[20]

• Sleep-related hypoventilation due to a medical condition ^[30]
  • Disease of the respiratory tract (e.g., COPD)
  • Musculoskeletal disorders (e.g., kyphoscoliosis)
  • Neuromuscular disorders (e.g., myasthenia gravis)
• Sleep-related hypoventilation due to medication ^[30]
  • Opioids
  • Benzodiazepines
  • Propofol
• Congenital central hypoventilation syndrome (Ondine's curse): a dysfunction of automatic central breathing control that is typically seen in newborns and is characterized by shallow breathing or complete lack of spontaneous breathing during sleep ^[31]
• Late-onset central hypoventilation with hypothalamic dysfunction
  • Central hypoventilation with onset after newborn period
  • Often related to hypothalamic dysfunction ^[32]
• Idiopathic central alveolar hypoventilation: Diagnosis requires exclusion of lung parenchyma disease, airway or pulmonary vessel disease, neuromuscular disease, drug-induced hypoventilation, or congenital hypoventilation. ^[30]

The differential diagnoses listed here are not exhaustive.

Approach ^[21][33][34]

• Treat all patients with diagnosed OSA.
• First-line treatment: positive airway pressure (PAP)
• Consider alternative treatment in patients who are unable to tolerate or decline PAP: ^[1][35][36]
  • Oral appliances
  • Upper airway modifications
  • Positional therapy
• Supportive care should include management of risk factors, e.g., weight loss and sleep hygiene.

Nocturnal positive pressure therapy is the therapy of choice in OSA. The success of therapy is highly dependent on patient adherence.

Positive airway pressure (PAP)

• Description: Pressure is used to pneumatically splint collapsible airways open to reduce the frequency of respiratory events. ^[18]
• Types
  • Preferred modalities: Continuous PAP (CPAP) or auto-adjusting PAP (APAP)
  • Bilevel PAP (BPAP)
• Procedure
  • Should be used over the entire sleep period ^[33]
  • Initial titration can be done using in-laboratory or APAP devices. ^[33]
  • Minimum starting pressures
    • CPAP: 4 cm H₂O
    • BPAP: 8 cm H₂O IPAP; 4 cm H₂O EPAP ^[18]

Encourage inpatients to continue using PAP during their admission, if possible, as sudden discontinuation is associated with recurrence of OSA symptoms. ^[37][38]

Alternative treatment options ^[1][21]

Conservative treatment

Conservative treatment options are usually only appropriate for mild to moderate disease.

• Oral appliances ^[35][39]
  • Devices are worn during sleep to maintain mandibular advancement and prevent airway collapse.
  • Custom-fitted titratable devices are preferred.
• Positional therapy: : devices to keep patients in a lateral as opposed to supine sleeping position ^[40]

Upper airway modification ^[36]

• Description: surgical dilatation of the upper airway or neurostimulation of upper airway muscles
• Approach: single-stage, multilevel, or stepwise surgery
• Procedures
  • Maxillomandibular advancement: advancement and fixation of the maxillary and mandibular bones, increasing the retrolingual and retropalatal airway space
  • Uvulopalatopharyngoplasty: resection of the uvula and redundant retrolingual, soft palate, and tonsillar tissue
  • Tracheostomy: may be considered in the case of clinical urgency or as a last resort after failure of other treatment options
  • Other procedures include hypoglossal nerve stimulation, radiofrequency ablation of tongue and/or soft palate tissue, and palatal implants. ^[36][41][42]

Supportive treatment ^[1]

• Lifestyle interventions
  • Reduce and/or avoid risk factors for OSA.
    • Avoid alcohol, nicotine, and sedatives (e.g., benzodiazepines).
    • Overweight patients: weight loss ^[21]
  • Sleep hygiene ^[43][44]
• Supportive measures
  • Treatment of associated conditions and complications of OSA, e.g., blood pressure control ^[45]
  • Patient counseling regarding risks of drowsy driving

• Systemic hypertension
• Hypoxia-induced cardiac arrhythmia (e.g., (atrial fibrillation, atrial flutter) ^[1]
• Pulmonary hypertension and cor pulmonale
• Global respiratory insufficiency
• Cardiac infarction, stroke, and sudden cardiac death (the risk of sudden death is high in infants and the elderly)
• Polycythemia
• Risk of accidents (e.g., car crashes, occupational accidents) due to microsleep
• Increased risk of developing vascular dementia
• Poor sleep leads to increased appetite and obesity.

References:^{[46][47][48][49][50]}

We list the most important complications. The selection is not exhaustive.

• The mortality rate is higher in patients with severe OSA who do not receive adequate treatment.
• CPAP ventilation can significantly lower the risk of mortality in OSA.

• One-Minute Telegram 65-2022-1/3: 2022 U.S. Preventive Services Task Force: summary of recommendations

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