Sleep-Disordered Breathing
GENERAL PRINCIPLES
Sleep-disordered breathing (SDB) is comprised of multiple different entities:
• Obstructive sleep apnea (OSA)
• Central sleep apnea (CSA)
• Sleep-related hypoventilation
Definitions
• An apnea is defined as ≥90% decrease in airflow as measured by thermistor, lasting at least 10 seconds in duration.
• An hypopnea is a ≥30% decrease in airflow as measured by pressure transducer lasting at least 10 seconds in duration and associated with a ≥4% desaturation.
• A respiratory effort-related arousal (RERA) is a sequence of breaths lasting at least 10 seconds with increased respiratory effort or change in airflow which is associated with an arousal.
• The apnea–hypopnea index (AHI) is the number of apneas and hypopneas per hour of sleep.
• The respiratory disturbance index (RDI) is the number of apneas, hypopneas, and RERAs per hour of sleep.
• Sleep-related hypoventilation is defined as an increase in PaCO2 during sleep by at least ≥10 mm Hg when compared to an awake supine value.
• Morbid obesity is defined by a body mass index (BMI) ≥40.
Classification
• Apneas can be obstructive, central, or mixed in nature.1
Apneas are classified as obstructive when there is no airflow, but continued respiratory effort.
Central apneas have no airflow and no respiratory effort.
Mixed apneas have no airflow associated with a lack of respiratory effort during the first part of the event but resumption of respiratory effort during the latter part of the event.
• Severity of sleep apnea based on AHI1
An AHI <5 is normal.
Mild sleep apnea has an AHI of 5–15.
Moderate sleep apnea has an AHI of >15 and <30.
Severe sleep apnea has an AHI ≥30.
• Severity of sleepiness1
Mild sleepiness is when sleepiness occurs in sedentary situations such as watching TV or reading.
Moderate sleepiness is when sleepiness occurs in settings such as meetings or the theater.
Severe sleepiness is when sleepiness occurs with activities such as talking, eating, or driving.
Epidemiology
• OSA is the most common form of SDB.
OSA associated with daytime sleepiness (OSA-hypopnea syndrome) occurs in 2–4% of the general population.2
This percentage likely underestimates current prevalence due to the increasing prevalence of obesity in the United States and the strong association between obesity and OSA.
• Prevalence of SDB increases with age.3,4
The prevalence of OSA increases with age but CSA also becomes more prevalent.
The prevalence of SDB in postmenopausal women is higher than in premenopausal women.
• As BMI increases, obesity hypoventilation (OHV) is more likely to occur.4 In patients with a BMI >50, ∼50% of patients have evidence of hypoventilation.5,6
Etiology
• OSA occurs due to narrowing of the upper airway either due to excessive soft tissue or structural abnormalities.
• CSA can have a variety of causes
Stroke
Brain tumor
Congestive heart failure
Use of positive airway pressure devices can result in treatment-emergent central apneas.
• Sleep-related hypoventilation can be due to a variety of causes
Morbid obesity-OHV
Severe OSA
Neuromuscular disease with respiratory muscle weakness
Severe kyphoscoliosis or thoracic cage deformity
Diaphragmatic paralysis
Severe obstructive lung disease
Pathophysiology
• OSA: Narrowing of the upper airway leads to recurrent arousals.
• CSA
Central apneas can occur due to direct effects on the medullary respiratory centers (stroke or brain tumor).
In addition, central apneas may be due to increased sensitivity to small changes in carbon dioxide levels (congestive heart failure).
Central apneas can occur in the setting of using positive airway pressure to treat OSA.
• OHV
OHV may be due to frequent obstructive apneas or hypopneas that lead to a decrease in minute ventilation.6
Impairment of respiratory mechanics due to morbid obesity can also contribute to OHV.6
Leptin resistance in morbidly obese patients may impair their ability to increase their minute ventilation appropriately.6–8
Risk Factors
• Risk factors for OSA include the following: obesity, macroglossia, micrognathia, retrognathia, neck circumference >17 in in men and >16 in in women, enlarged tonsils, increasing age, male gender, family history, use of alcohol or sedatives, and concomitant medical conditions such as hypothyroidism.1–4,9
• Risk factors for CSA include the following: use of positive airway pressure, severe congestive heart failure, and stroke or brain injury.1
• Risk factors for sleep-related hypoventilation include the following: very severe OSA, respiratory muscle weakness, morbid obesity, severe obstructive lung disease, and thoracic cage abnormalities.1
Prevention
• The following factors help in the prevention of OSA:
Weight loss can be beneficial. However, weight loss alone may not prevent OSA if there are craniopharyngeal structural abnormalities.
Avoidance of alcohol and sedatives may help prevent OSA as these substances contribute to muscle relaxation and impaired arousal threshold.
Treatment of underlying conditions such as hypothyroidism may help prevent OSA. Hypothyroidism can result in weight gain and decreased upper airway muscle tone.
• The following factors help in the prevention of CSA:
Medical treatment of severe congestive heart failure may improve CSA.
Avoiding over titration of continuous positive airway pressure (CPAP) may help prevent CSA, as treatment-emergent CSA is more likely to occur at higher pressure settings.
• The following factors may help in the prevention of sleep-related hypoventilation: weight loss in the morbidly obese may improve underlying OSA, respiratory muscle dysfunction, and leptin resistance which can all contribute to OHV.
Associated Conditions
• Conditions associated with OSA include the following: hypertension, coronary artery disease, stroke, diabetes mellitus, metabolic syndrome, mild pulmonary hypertension, and increased risk of motor vehicle collisions due to sleepiness.10–18
• Conditions associated with CSA include congestive heart failure and stroke.1,17,19
• Conditions associated with OHV include the following: congestive heart failure, hypertension, coronary artery disease, stroke, diabetes mellitus, metabolic syndrome, pulmonary hypertension, right heart failure, and increased risk of motor vehicle collisions due to sleepiness.1,6
DIAGNOSIS
Clinical Presentation
History
During the history, the presence of the following symptoms should be queried9:
• Daytime sleepiness
• Unrefreshing sleep
• Witnessed apneas
• Awakening, snorting, or gasping
• Loud snoring (OSA and OHV)
• Morning headaches
• Nocturia
• Poorly controlled hypertension (OSA)
• Decreased concentration/memory, irritability
• Decreased libido
Physical Examination
• The physical examination to evaluate for OSA mainly focuses on the upper airway. The presence or absence of the following features should be ascertained:
Obesity
Macroglossia
Micrognathia
Retrognathia
Neck circumference >17 in in men and >16 in in women
Enlarged tonsils
Crowded posterior oropharynx
• Physical examination findings for CSA are examination findings that would be associated with underlying medical conditions that predispose to CSA.
Findings consistent with severe heart failure
Findings consistent with stroke or previous brain injury
• The physical examination for OHV should focus on many of the same areas as for OSA. In addition, examination findings related to complications from OHV, such as right heart failure, should be elucidated.
Morbid obesity, BMI >40
Upper airway examination findings may be similar to OSA
Findings consistent with right heart failure
Cyanosis
Diagnostic Criteria
• OSA as defined by the International Classification of Sleep Disorders1:
RDI >5 with events being associated with ongoing respiratory effort with reported complaint of daytime sleepiness, awakening gasping, loud snoring, or witnessed apneas, OR
RDI >15 with events being associated with ongoing respiratory effort.
• CSA as defined by the International Classification of Sleep Disorders1:
Primary CSA
Five or more central apneas per hour.
Must experience one of the following: excessive daytime sleepiness, frequent arousals or insomnia, or awakening short of breath.
Cheyne–Stokes respirations
Ten or more central apneas/hypopneas per hour with an alternating pattern of apnea/hypopnea followed by hyperpnea in a crescendo–decrescendo pattern.
Occurring in the setting of other serious medical conditions such as heart failure or stroke.
• Sleep-related hypoventilation/hypoxemia as defined by the International Classification of Sleep Disorders1:
Underlying disorder that can contribute to hypoventilation such as neuromuscular weakness, chest wall deformity, morbid obesity, or severe obstructive lung disease.
One of the following features on sleep study:
Oxygen saturation <90% for >5 continuous minutes while asleep with a nadir of at least 85%.
Oxygen saturation <90% for at least 30% of total sleep time.
Elevation of PaCO2 that is abnormally elevated compared to waking levels.
Differential Diagnosis
• Any of the SDB entities can be in the differential diagnoses for any of the other disorders.1
• Consider other causes of nocturnal dyspnea: congestive heart failure and laryngospasm.
• Consider other causes of daytime sleepiness: periodic limb movement disorder, narcolepsy, and idiopathic hypersomnia.
Diagnostic Testing
Laboratories
Thyroid-stimulating hormone should be measured when hypothyroidism suspected.
Diagnostic Procedures
• Split-night polysomnogram
First 2 hours of sleep recorded to determine severity of underlying SDB.
Positive airway pressure initiated if AHI >40 during baseline.
• All-night polysomnogram: performed if SDB is mild to moderate during baseline. Allows determination of severity of SDB in different stages of sleep and sleeping positions.
• Positive airway pressure titration: performed if diagnosis of SDB already known.
• The use of non–sleep-laboratory (mostly at-home) portable diagnostic testing is evolving.9
Multiple different types of devices are available which record a variable number of physiologic parameters, but less than standard overnight polysomnography.
Sensitivity is less with these devices.
Treatment for a diagnosis of OSA made with just a few parameters (e.g., only arterial oxygen saturation and airflow) may not be reimbursed by insurers.
These portable monitors are best used in those with a high clinical pretest probability of moderate to severe OSA after a comprehensive sleep evaluation. Sensors should either be placed by an appropriately trained healthcare provider or that provider should directly educate the patient about the proper way to do so. They should not be used in patients with comorbid conditions (e.g., heart failure) or when there is suspicion of other causes of SBD. The results of such testing should be evaluated by sleep medicine specialist.
TREATMENT
Medications
• Multiple medications (e.g., certain antidepressants, theophylline, and respiratory stimulants) have been studied as primary therapy (i.e., without other forms of treatment) for OSA with largely inconclusive results. None are recommended.9,20
• Stimulants are approved for patients with OSA and residual sleepiness despite adequate use of CPAP. These include modafinil or armodafinil.9,21
First, proper adherence to and functioning of mechanical treatments should be ascertained.
Which patients will most benefit from the addition of pharmacotherapy is currently uncertain.
Both modafinil and armodafinil have been reasonably well tolerated in clinical trials. More common side effects include headache, nervousness/anxiety, dizziness, and nausea. Rare severe dermatologic and systemic hypersensitivity reactions have been reported. There are many potential drug interactions.
Caution is advised when used in patients with cardiovascular, hepatic, and psychiatric conditions. Lower doses should be used in the elderly.
• Nasal steroids may be useful in OSA for nasal congestion/inflammation due to allergic rhinitis.9,22,23
• In patients with CSA medical therapy for underlying congestive heart failure should be undertaken if present.
Other Nonpharmacologic Therapies
CPAP is the most effective therapy if patient is compliant, especially in severe OSA.
Autotitrating positive airway pressure in patients without significant comorbid conditions.
Positional therapy if events occur mainly in supine position—sleep belt or sleep shirt to maintain lateral position.
An oral appliance is less effective in severe OSA. Typically, the patient should be evaluated by a dentist specializing in sleep medicine. This is not a good choice for patients who are edentulous.
A nasal expiratory resistance device, which uses the patient’s own breathing to produce expiratory positive airway pressure (EPAP) may be helpful but is less effective for severe OSA.26–28
• CSA29
Bilevel positive airway pressure (BiPAP) with a backup rate may be used for central apneas.
Adaptive/autoservo ventilation (ASV) may also be used in the setting of CSA. The device is equipped with an algorithm for titrating inspiratory positive airway pressure (IPAP) to help stabilize significant respiratory variations that can occur in CSA.
• OHV6
BiPAP can be used to improve hypoventilation. As patients may have concomitant OSA, the EPAP will need to be titrated to alleviate obstructive events.
Average volume-assured pressure support (AVAPS) allows for a targeted tidal volume. The machine allows the IPAP to be titrated to meet the goal tidal volume.
Nocturnal ventilation via tracheostomy may be necessary if no optimal setting can be found for noninvasive ventilation or if a patient cannot tolerate noninvasive ventilation.
Surgical Management
• OSA30
Laser-assisted uvulopalatoplasty (LAUP) is a treatment for snoring, not OSA.
Uvulopalatopharyngoplasty (UPPP) is less effective in severe OSA.
Radiofrequency ablation should only be an option for patients with mild–moderate OSA who cannot tolerate CPAP.
Palatal implants should only be an option for patients with mild OSA who cannot tolerate CPAP.
Maxillomandibular advancement is only performed at highly specialized centers.
Tracheostomy is essentially a cure for OSA as the site of upper airway obstruction resulting in apnea is bypassed.
Bariatric surgery for weight loss may be beneficial.31
• CSA: heart transplant in patients with severe heart failure.
• OHV6
Tracheostomy with use of nocturnal ventilator is very effective for OHV.
Bariatric surgery for weight loss may be beneficial.
Lifestyle/Risk Modification
The following modifications may benefit patients with OSA/OHV:
• Diet for weight loss.
• Exercise for weight loss.
• Avoidance of alcohol and other sedatives.
Special Considerations
In the elderly, the following items must be considered:
• The risk of OSA increases with age.
• Central apneas become more common.
• SDB may be associated with atypical symptoms such as nocturnal falls, enuresis, and decreased cognition.
Complications
• OSA is associated with the following medical complications:
Hypertension.
Cardiovascular disease.
Insulin resistance.
Daytime sleepiness—increased risk of motor vehicle collisions.
• CSA can also be associated with daytime sleepiness.
• OHV is associated with the following medical complications:
Pulmonary hypertension.
Right heart failure.
Daytime sleepiness—increased risk of motor vehicle collisions.10,16
Referrals
If SDB is suspected, the patient should be referred to a sleep physician for further evaluation and testing.
Patient Education
• The patient should be educated about the potential health consequences of untreated SDB and the importance of compliance with positive airway pressure.
• Counsel on weight loss if needed.
• Counsel on avoiding sedatives and alcohol.
• Counsel on driving precautions.
Follow-Up
• After initiation of positive airway pressure, the patient should be seen back within 2–3 months to assure proper use and compliance with positive airway pressure. Arrangements should be made to see the patient sooner if there is difficulty in tolerating the device.
• Newer machines have download cards so that use can be monitored.
• If the patient is stable, routine follow-up can occur every 6–12 months.
Outcome/Prognosis
Prognosis depends upon severity of underlying disorder and patient’s ability to comply with therapy.32
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