A. Definitions

1. Sleep disordered breathing - general term for abnormal sleep with oxygen desaturation
2. Subsets of Sleep Disordered Breathing
   1. Apnea = repetitive prolonged (>10 seconds) cessation of airflow associated with an arousal from sleep
   2. Hypopnea is >50% reduction in air flow with either an oxygen desaturation >3% or an arousal from sleep (defined electroencephalographically)
   3. Apnea-hypopnea index (episodes per hour of sleep) >4 makes SA likely
3. Types of Apnea
   1. Central: no airflow with no respiratory effort (CNS lesions, trauma)
   2. Obstructive (OSA): no airflow despite respiratory effort
   3. Mixed: combination of above
4. OSA [4]
   1. Usual obstruction of hypopharynx at base of tongue WITH
   2. Hypotonia of neck strap muscles
5. Sleep Apnea Syndrome
   1. Repeated episodes of apnea or hypopnea (index >4 episodes per hour) during sleep AND
   2. Daytime sleepiness OR
   3. Altered cardiopulmonary function
6. Occurs during non-REM (rapid eye movement) sleep
7. Sleep disruption - due to increased ventilatory effort in response to upper arway closure

B. Epidemiology

1. Middle aged men (North America): 4%
2. Middle aged women (North America): 2%
3. Associated with reduced-caliber upper airway (vulnterable ot further narrowing, collapse)
4. Risk Factors [16]
   1. Obesity - central body fat distribution strongest link
   2. Male Sex (2-4:1 men to women)
   3. Increasing age
   4. Craniofacial and other upper airway abnormalities
   5. Congestive heart failure (CHF) may be a risk
   6. Previous tonsillectomy may be a risk
5. Sleep apnea occurs in >50% of patients with chronic renal failure (CRF; see below)
6. OSA increases risk for cardiac, vascular, and other diseases [4,16,17,18]

C. Symptoms

1. Snoring: due to flow limitation
2. Withnessed Apneas
   1. Arousals from sleep leads to hypersomnolence
   2. Abnormal motor activity during sleep
3. Excessive daytime sleepiness
4. Overall neurocognitive impairment occurs (see below)
   1. Personality change
   2. Intellectual impairment
   3. Automobile accidents
5. Increased risk of systemic hypertension (HTN) and congestive heart failure (CHF)
6. Hypoxemia leads to pulmonary HTN (Cor Pulmonale), arrhythmias
7. Consider other symptoms / signs of hypothyroidism
8. Episodes of Apnea/Hypopnea
   1. Blood oxygen desaturation to 70% saturation level
   2. Electroencephalogram (EEG) shows brain wave anomalies on desaturation
   3. Sympathetic neuronal activity increases during hypopnea and climaxes at apnic episodes
   4. Sympathetic neuronal increases lead to elevated blood pressures and heart rates
   5. Result is disturbed sleeping, lack of REM sleep, elevated cardiac risk factors

D. Screening for Sleep Apnea (Berlin Questionnaire) [5]

1. Positive predictive value of 89%, Specificity 77%, Sensitivity 86%
2. Has your weight changed ? (increased weight is a risk factor for SA)
3. Do you snore ? (snoring is found in SA)
4. Snoring loudness (compare with talking, breathing)
5. Snoring frequency (1-2 or 3-4 times per week is found in SA)
6. Does your snoring ever bother another person ("yes" consistent with SA)
7. How often have your breathing pauses been noted ? (>2 times per week in SA)
8. Are you tired after sleeping ? ("almost every day" is common in SA)
9. Are you tired during waketime ? ("almost every day" is common in SA)
10. Have you ever fallen asleep while driving ? (not very sensitive; "yes" in SA)
11. Do you have high blood pressure ? (increased prevalence in SA)

E. Diagnosis of Mechanical Obstruction

1. Polysomnography (PSG)
   1. PSG for two nights is the gold standard for diagnosis of SA
   2. Confirm PaO2 desaturaton during episodes
   3. Also used for titration of effective CPAP (see below)
   4. In patients at high risk for OSA, autotitrating CPAP machines without PSG evaluation are equally effective [22]
2. Progression During an Episode
   1. After obstruction, pleural pressure changes to -40 to -60 cm H2O
   2. Paradoxical chest motion in (due to vacuum) and abdomen out
   3. Fall in PaO2 and rise in PaCO2 lead to arousal from sleep
3. Patients usually have large tonsils or micrognathia (may be exacerbated during REM sleep)
4. At sea level, 95% of patients show obstructive apnea (compared with central)

F. Pulmonary Function Tests (PFTs)

1. Little alteration in waking PFTs
2. Arterial Blood Gases show mild hypoxemia (70-80 mm Hg), mild hypercapnea
3. Flow volume curve may show blunted inspiratory flow typical of upper airway obstruction
4. Ventilatory response to CO2 is abnormal in central hypoventilation syndromes

G. Complications of Sleep Apnea [1,3,4,16]

1. Related to Activation of Sympathetic Nervous System
   1. Increased catecholamines
   2. Vasoconstriction
   3. Tachycardia and other arrhythmias
   4. Increased coagulation
   5. Insulin resistance - may drive metabolic anomalies seen in OSA
   6. Inflammation - increased interleukin 6 and C-reactive protein (CRP) levels
2. Systemic Hypertension (HTN) [6,7,8]
   1. Increased risk 1.4-6.6X
   2. This risk is present even with correction for body-mass index, smoking, other variables
   3. Risk increases with increasing apnea-hypopnea index
   4. Snoring alone does not carry an increased risk of systemic HTN
3. Pulmonary HTN
4. Cardiac Events
   1. Significantly increased risk of fatal (~2.8X) and non-fatal (~3.2X) cardiac events [17]
   2. Myocardial Infarction ~5.5X increased risk
   3. CHF: Right > Left Ventricular Failure
   4. Nocturnal arrhythmias most common
   5. Ventricular arrhythmias and sudden cardiac death ~4X increased risk
   6. Sudden death from cardiac causes in patients with OSA peak during sleep [18]
5. Stroke ~3X increased risk
6. Neurocognitive Impairment
   1. Increased risk of motor vehicle accidents ~7X [9]
   2. Occupational accidents increased ~2X [1]
7. Overall ~2X increased risk of stroke or death associated with OSA [20]

H. Therapy

1. Overview of Options
   1. Behavioral modification
   2. Continuous positive airway pressure (CPAP)
   3. Mechanical devices
   4. Injection of botulinum toxin into soft palate
   5. ENT outpatient surgical procedures
   6. Palatal implants - Pillar® procedure
2. Behavioral (Conservative) Therapy
   1. Reduction in body weight
   2. Avoidance of alcohol, benzodiazepines, other sedatives
   3. Smoking should be stopped (increases pulmonary hypertension, risk of MI, others)
3. CPAP [2,10]
   1. Nasal CPAP is standard treatment for AHI >15
   2. AHI 5-15 may also be an indication for CPAP, especially with daytime symptoms
   3. CPAP prevents upper airway collapse
   4. CPAP improves neurocognitive function and reduces blood pressure [1,2]
   5. May be used at home, usually only required at night
   6. Pressures of 2.5 to 10cm are usually tried
   7. Use for ~5.4 hours each night is leads to clear improvement in symptoms
   8. Improves blood pressure and left ventricular function in CHF patients with sleep apnea [15]
   9. CPAP is not effective in sleep apnea without daytime sleepiness [11]
   10. CPAP treatment reduces risk of fatal and non-fatal cardiac events in men with severe sleep apnea [17]
   11. CPAP improved symptoms and six-minute walk distance but did not affect survival in patients with central sleep apnea and CHF [19]
   12. Relatively contraindicated with bullous lung disease and recurrent sinus or ear infections
4. Medical Treatment
   1. Thyroid replacement therapy for hypothyroidism
   2. Tricyclic andipressants (decreased REM sleep)
   3. Progesterones
   4. Theophylline - particularly with apnea related to CHF
   5. Nocturnal oxygen therapy
   6. Fluoxetine and other SSRI's of limited benefit
   7. Stimulants such as modafinil (Provigil®) appear to be quite effective [12]
5. Surgeries [23]
   1. Uvulopalatopharyngoplasty (with tonsillectomy) - curative in <50% of patients, controversial
   2. Laser-assisted uvulopalatoplasty
   3. Radiofrequency treatment of soft palate
   4. Injection snoreplasty
6. Palatal (Pillar®) Implants [23]
   1. Polyethylene terephthalate palatal implants
   2. Measure 18mm x 1.8 mm
   3. Usually inserted under local anesthesia in office
   4. Three iimplants inserted transmucosally in upper soft palate (central portion)
   5. Serve to stiffen tissues of soft palate and reduce dynamic flutter
   6. Four to 5 implants can also be used
   7. Good tolerability and moderate efficacy
7. Tracheostomy (open during sleep) - CPAP is usually preferred
8. Pacemakers
   1. Atrial overdrive pacing reduces episodes of central or obstructive sleep apnea [13]
   2. Atrial overdrive pacing had no benefit in OSA patients with implanted dual chamber pacemakers [21]
9. Sleep Apnea in CRF
   1. Nocturnal (7 nights per week) but not standard hemodialysis improves sleep apnea in CRF patients [14]
   2. Renal transplantation also improves sleep apnea in CRF patients

I. Indications for Uvulopalatopharyngoplasty

1. O2 saturation <80 mm
2. Apnea index >20: 20 apneas and hypopneas per hour of sleep
3. Significant daytime hypersomnolence
4. Snoring, substantial (disruptive)
5. Cardiac arrhythmias during sleep (except for tachycardia and bradycardia)

References

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