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Obstructive Sleep Apnea-Hypopnea Syndrome

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					          Obstructive Sleep Apnea-Hypopnea Syndrome

Obstructive sleep apnea-hypopnea (OSAH) is characterized by
recurrent episodes of upper airway collapse and obstruction during
sleep. These episodes of obstruction are associated with recurrent
oxyhemoglobin desaturations and arousals from sleep. OSAH
associated with excessive daytime sleepiness (EDS) is commonly
called obstructive sleep apnea-hypopnea syndrome (OSAHS).
Despite being a common disease, OSAHS is underrecognized by
most primary care physicians in the United States; an estimated 80%
of Americans with OSAHS are not diagnosed.

Pathophysiology

Conceptually, the upper airway is a compliant tube and, therefore, is
subject to collapse. Most patients with OSAHS demonstrate upper
airway obstruction at either the level of the soft palate (ie,
nasopharynx) or the level of the tongue (ie, oropharynx). Recent
research indicates that both anatomic and neuromuscular factors are
important. Anatomic factors, such as enlarged tonsils, macroglossia,
or abnormal positioning of the maxilla and mandible, decrease the
cross-sectional area of the upper airway and/or increase the pressure
surrounding the airway, both of which predispose the airway to
collapse. Upper airway neuromuscular activity, including reflex
activity, decreases with sleep, and this decrease may be more
pronounced in patients with OSAHS. Reduced ventilatory motor
output to upper airway muscles is believed to be the critical initiating
event leading to upper airway obstruction; this effect is most
pronounced in patients with an upper airway predisposed to collapse
for anatomical reasons.

Central breathing instability is a well-established factor contributing to
the development of central sleep apnea, particularly in patients with
severe congestive heart failure. Evidence also indicates that central
breathing instability contributes to the development of OSAHS. First,
evidence of upper airway obstruction in the absence of ventilatory
motor output (central sleep apnea) has been observed. Second,
reduction in pharyngeal dilator activity has been associated with
periodic breathing and hypocapnia in subjects with evidence of
inspiratory flow limitation. Third, men have been shown to be more
susceptible to the development of central sleep apnea and have a
decreased responsiveness to carbon dioxide compared with woman,
a result consistent with the increased prevalence of OSAHS in men
over women.

Race

      The prevalence of sleep apnea in young African Americans
       (<25 y) appears to be greater than in white Americans.
      Recent evidence indicates that the prevalence in older age
       groups is similar between African Americans and white
       Americans, but the OSAHS is more severe in African
       Americans (ie, African Americans have higher AHIs).

Sex

      The male-to-female ratio in community-based studies is 2-3:1.
      Premenopausal women with OSAHS tend to be more obese
       than men with the same severity of disease. Thin women with
       symptoms of OSAHS appear to have an increased frequency of
       craniofacial abnormalities.
      Evidence indicates that women underreport the symptoms of
       loud snoring and witnessed apneas, leading to underreferral to
       sleep centers. This may explain the marked male
       predominance (male-to-female ratio of approximately 8:1) in
       sleep center–based studies.
      Women have lower AHIs than men, even after correcting for
       other demographic factors such as body mass index and neck
       circumference.

Age: The prevalence of OSAHS increases with age, with an estimated rate as
high as 65% in a community sample of people older than 65 years. However,
the significance of the incidental finding of OSAHS in elderly persons has been
debated .

CLINICAL:

History

Symptoms generally begin insidiously and are often present for years
before the patient is referred for evaluation.
   Nocturnal symptoms
      o Snoring, usually loud, habitual, and bothersome to others
      o Witnessed apneas, which often interrupt the snoring and
         end with a snort
      o Gasping and choking sensations that arouse the patient
         from sleep
      o Restless sleep, with patients often experiencing frequent
         arousals and tossing or turning during the night
   Daytime symptoms
      o Not feeling refreshed upon awakening
      o Morning headache, dry or sore throat
      o EDS that usually begins during quiet activities (eg,
         reading, watching television): As the severity worsens,
         patients begin to feel sleepy during activities that
         generally require alertness (eg, school, work, driving).
             EDS is most frequently assessed by a sleep
               physician using the Epworth Sleepiness Scale
               (ESS). This questionnaire is used to help determine
               how frequently the patient is likely to doze off in 8
               frequently encountered situations.
             An ESS score greater than 10 is generally
               considered sleepy. However, a recent study showed
               that an ESS score of 12 is associated with a greater
               propensity to fall asleep on the Multiple Sleep
               Latency Test (MSLT), suggesting that 12 would be
               a better cutoff.
             The ESS score does not correlate well with the
               primary objective measurement of sleepiness, the
               MSLT in that a higher ESS score does not mean
               shorter latencies on the MSLT. However, a higher
               ESS score does mean a greater likelihood of falling
               asleep on the MSLT.
             The ESS is useful for evaluating responses to
               treatment; the ESS score should decrease with
               effective treatment.
      o Daytime fatigue/tiredness: Most patients who do not
         complain of excessive daytime sleepiness complain of
         being fatigued, having a lack of energy, or being tired
         during the day.
         o   Personality changes,     problems    with   memory     or
             concentration

Physical

The general physical examination is frequently normal in OSAHS,
other than the presence of obesity (defined as a body mass index
>30 kg/m2), an enlarged neck circumference, and hypertension.
Perform an evaluation of the upper airway in all patients, but
particularly in nonobese adults with symptoms consistent with
OSAHS. The following features have been associated with the
presence of OSAHS:

     Neck circumference: A neck circumference greater than 43 cm
      (17 in) in men and 37 cm (15 in) in women has been associated
      with an increased risk of OSAHS.
     Narrowing of the lateral airway walls, which is an independent
      predictor of the presence of OSAHS in men but not women
     Enlarged tonsils
     Retrognathia or micrognathia
     Large degree of overjet
     High-arched hard palate

Causes

     Risk factors for sleep apnea
         o Obesity
         o Male sex
         o Age
         o Adenotonsillar hypertrophy, particularly in children and
            young adults
         o Alcohol use
         o Craniofacial     skeletal abnormalities, particularly in
            nonobese adults and children.
     Other diseases associated with the development of OSAHS
         o Hypothyroidism: This has been associated with the
            development of OSAHS; however, recent evidence
            indicates that the prevalence of hypothyroidism in patients
            with OSAHS is no higher than in the general population,
            and patients with OSAHS should not be routinely
            screened for hypothyroidism, except possibly elderly
            women.
        o   Neurologic syndromes such as postpolio syndrome,
            muscular dystrophies, and autonomic failure syndromes
            such as Shy-Drager syndrome
        o   Stroke: The relationship of OSAHS to cerebrovascular
            disease is still being determined. Growing evidence
            indicates that the prevalence of OSAHS is increased in
            patients who have had a stroke. However, whether
            OSAHS is a risk factor for stroke or stroke is a risk factor
            for developing OSAHS remains unclear.
        o   Acromegaly

Lab Studies

     A thyroid-stimulating hormone test should be performed on any
      patient with possible OSAHS who has other signs or symptoms
      of hypothyroidism.
     An arterial blood gas determination should be performed in
      patients presenting with cor pulmonale to rule out daytime
      hypoxemia or hypercapnia.

Other Tests

     Pulmonary function tests should be performed if the patient has
      evidence of cor pulmonale or if nocturnal symptoms are
      suggestive of nocturnal asthma (ie, patient wakes up with
      shortness of breath that does not immediately resolve or is
      associated with wheezing).
     An overnight sleep study, or polysomnography, is required to
      diagnose OSAHS. Preferably, polysomnography is performed
      in a sleep center in the presence of specially trained
      technicians. During polysomnography, multiple body functions
      are monitored.
         o Sleep stages are recorded via an electroencephalogram,
            electrooculogram, and chin electromyogram.
         o Heart rhythm is monitored with a single-lead ECG.
         o Leg movements are recorded via an anterior tibialis
            electromyogram.
      o   Breathing is monitored, including airflow at nose and
          mouth, effort, and oxygen saturation.
   The breathing pattern is analyzed for the presence of apneas
    and hypopneas. Standard definitions have been proposed but
    are still not used consistently by personnel at sleep centers.
       o Obstructive apnea is the cessation of airflow with
          persistent respiratory effort.
       o Central apnea is the cessation of airflow with no
          respiratory effort.
       o Mixed apnea is an apnea that begins as a central apnea
          and ends as an obstructive apnea .
       o The definition of a hypopnea varies significantly between
          sleep centers. However, a recent consensus statement
          defined a hypopnea as a 30% or more reduction in flow
          associated with a 4% drop in oxygen saturation. Many
          centers also score a hypopnea if flow decreases in
          association with an arousal.
       o Respiratory event–related arousal is a recently defined
          event in which patients have a series of breaths with
          increasingly negative pleural pressure that terminates
          with an arousal. As defined, there is no clear decrease in
          flow that would cause the event to be labeled apnea or
          hypopnea. This event cannot be scored if the esophageal
          pressure is not monitored; therefore, it is not used by
          many sleep centers.
   The AHI is derived from the total number of apneas and
    hypopneas divided by the total sleep time.
       o A normal cutoff for AHI has never been defined in an
          epidemiological study of healthy people. Most sleep
          centers use a cutoff of 5-10 episodes per hour.
       o The severity of OSAHS is arbitrarily defined and differs
          widely between centers. Recent recommendations for
          cutoff levels on AHIs are as follows:
                Mild - 5-15 episodes per hour
                Moderate - 15-30 episodes per hour
                Severe - More than 30 episodes per hour
   Polysomnography is often followed by an MSLT. The MSLT is
    considered an objective measurement of EDS.
       o The MSLT consists of 4-5 naps of 20-minute duration
          every 2 hours during the day. The latency to sleep onset
            for each nap is averaged to determine the daytime sleep
            latency.
        o   Normal daytime sleep latency is greater than 10-15
            minutes. OSAHS is generally associated with latencies of
            less than 10 minutes.
        o   The routine use of the MSLT in the evaluation of OSAHS
            is decreasing because sleep physicians generally treat
            OSAHS based on the subjective symptoms reported by
            the patient.
        o   The MSLT is helpful to rule out narcolepsy in those
            patients in whom narcolepsy is a consideration. As
            opposed to people without narcolepsy, narcoleptic
            patients have rapid eye movement sleep on at least 2 of
            the 4-5 naps during the day.

Medical Care

The treatment of OSAHS in part depends on the severity of the sleep-
disordered breathing. People with mild apnea have a wider variety of
options, while people with moderate-to-severe apnea should be
treated with nasal CPAP.

Conservative measures include weight loss, avoidance of alcohol for
4-6 hours prior to bedtime, and sleeping on one's side rather than on
the stomach or back. Include these measures in the treatment of all
patients with OSAHS, but use them only in patients with very mild
apnea whose main symptom is snoring. In a recent practice
parameter, both weight loss and positional therapy were rated as
"guidelines," indicating a patient care strategy with a moderate
degree of evidence.

     Nasal CPAP: CPAP is the most effective treatment for OSAHS,
      and it has become the standard of care. CPAP works by
      splinting the upper airway, preventing the soft tissues from
      collapsing. By this mechanism, it effectively eliminates the
      apneas and/or hypopneas, decreases the arousals, and
      normalizes the oxygen saturation.
         o Most sleep center physicians still titrate the CPAP level
             during a sleep study. This can be conducted as a second
             night of study or during the second half of the diagnostic
    study (this type of study is called split-night
    polysomnography). Currently, CPAP devices are
    available that automatically change pressures based on
    the presence and/or absence of OSAHS. The exact
    indications for these devices are still being determined.
o   Recent Medicare guidelines specify criteria for ordering
    CPAP for patients with OSAHS. All patients with an AHI
    greater than 15 are considered eligible for CPAP,
    regardless of symptomatology. For patients with an AHI of
    5-14.9, CPAP is indicated only if the patient has one of
    the     following:    excessive     daytime       sleepiness,
    hypertension, or cardiovascular disease.
o   CPAP has been shown to improve daytime sleepiness,
    mood, and cognitive function in people with both mild and
    moderate apnea. CPAP has also been shown to increase
    quality of life and decrease health care costs. Data
    indicate that CPAP decreases blood pressure, primarily in
    patients with severe OSAHS. Evidence also indicates that
    it may improve the left ventricular ejection fraction in
    patients with congestive heart failure and OSAHS.
o   The most common adverse effects of CPAP are dry
    mouth, rhinitis, and sinus congestion. These can be
    treated effectively with humidification and antihistamines
    and/or nasal steroids.
o   Unfortunately, compliance is a major problem, with only
    approximately 50% of patients using CPAP on a regular
    basis in short-term studies. Predictors of compliance
    include severe daytime sleepiness, baseline AHI, and a
    higher level of education.
o   Some patients require the use of bilevel positive airway
    pressure (BPAP). In BPAP, a higher inspiratory pressure
    and a lower expiratory pressure are used. In patients with
    sleep apnea, the levels are set such that the expiratory
    pressure eliminates apneas and the inspiratory pressure
    eliminates hypopneas. BPAP is generally used in patients
    who cannot tolerate high CPAP pressures (ie, patients
    who experience difficult exhalations) or who have
    barotrauma complications (eg, ear infections, bloating).
    Many laboratories automatically place a patient on BPAP
    if the CPAP level needs to be increased above 15 cm
            water. Compliance with BPAP has not been
            demonstrated to be better than compliance with CPAP.
     Oral appliances
        o These devices act by moving the tongue or mandible
            forward, enlarging the posterior airspace. Multiple
            different devices are available on the market. The
            American Academy of Sleep Medicine (AASM) has
            recently published practice parameters and a review of
            the use of oral appliances in OSAHS.
        o Oral appliances should not be considered effective
            therapy for patients with severe OSAHS.

Surgical Care

Surgical correction of the upper airway is still performed but is not
considered primary therapy for OSAHS. The theoretic advantage of
surgery is that if the patient is cured, compliance with CPAP or an
oral appliance is no longer an issue. However, a primary reason that
surgery has not become a standard therapy is the lack of long-term
outcome studies that show that the surgical correction continues to
be effective 5 or more years after it is performed.

Factors that increase the likelihood of successful surgery include (1)
lower AHI, (2) lower BMI, (3) the location of collapse (Surgeries
targeted specifically to collapse at either the nasopharynx or
oropharynx improve outcome.), (4) the degree of mandibular
protrusion (Better outcomes are achieved in patients with clear
deficiencies.), and (5) the presence of fewer comorbidities.

     Surgeries include the following:
        o Uvulopalatopharyngoplasty (UPPP) is resection of the
          uvula and soft palate. It is effective in approximately 40%
          of patients, but predicting which patients will benefit from
          the procedure is problematic. Long-term, patients with
          treatment success often present with a recurrence of
          symptoms, especially if they continue to gain weight.
        o Craniofacial reconstruction involves advancement of the
          tongue (ie, geniohyoid advancement with hyoid myotomy
          [GAHM])        or      maxillomandibular      bones       (ie,
          maxillomandibular osteotomy [MMO]). These surgeries
            should be performed only at centers with expert
            personnel. Short-term success rates are approximately
            70% for GAHM and 95% for MMO. No good long-term
            studies have been performed to evaluate the success for
            either GAHM or MMO.
         o Tracheostomy provides definitive correction because it
            bypasses the obstruction. It is recommended for patients
            with very severe OSAHS, especially if the patient does
            not tolerate CPAP or has cor pulmonale.
     Patients should be considered for surgery primarily if multiple
      attempts at therapy with CPAP have failed and if an oral
      appliance is not an option. If the patient opts for surgery, ensure
      the following:
         o Surgery should be performed by a qualified ear, nose,
            and throat surgeon.
         o Surgery should be based on the location of collapse.
         o Patient should be willing to undergo combination or
            multiple surgeries.

MEDICATION:

The American Academy of Sleep Medicine recently published a
practice parameter and review of the medical therapies of OSAHS.
Use of protriptyline for OSAHS was listed as a guideline.

The use of modafinil is recommended for the treatment of residual
sleepiness in persons with OSAHS and was considered a standard
treatment (generally accepted patient-care strategy with level 1 or
excellent level 2 evidence).

The parameters state as standards that selective serotonin reuptake
inhibitors, methylxanthines, and estrogen replacement therapy should
not be considered for the treatment of OSAHS.

Drug Category: Tricyclic Antidepressants

Protriptyline in low doses has been used in people with mild apnea
and snoring with mild success. Increases upper airway
neuromuscular activity and decreases REM sleep. Not considered
primary therapy for OSAHS. Consider use in a person with mild
apnea who does not want CPAP or an oral appliance.
Drug  Category:        Central     nervous      system      stimulants,
nonamphetamine

Used for treatment of fatigue without interfering with normal sleep
architecture. They promote wakefulness.

FOLLOW-UP

Further Outpatient Care

     Once diagnosed with OSAHS and started on nasal CPAP,
      patients require regular follow-up with a sleep specialist. Most
      patients are seen within 2 months of initiating CPAP to
      determine if it has been effective in alleviating symptoms, to
      troubleshoot problems preventing regular use of the CPAP, and
      to reinforce the importance of daily use. Further follow-up
      depends on whether the CPAP has been effective.
          o If effective, the patient is generally seen at 6- to 12-month
             intervals to troubleshoot new problems, to reinforce daily
             use, and to be certain the CPAP remains effective.
          o If CPAP has not been effective, problems preventing use
             are identified, steps are taken to eliminate problems, and
             the patient is seen at 2- to 3-month intervals until use is
             regular and the CPAP is alleviating symptoms. Repeat
             titration may be necessary.
          o Routine     repeat polysomnography is generally not
             indicated for patients who report improved symptoms.
             Repeat CPAP titrations are usually performed in patients
             without effective relief of their symptoms despite
             intervention or in patients who had relief of symptoms but
             present months to years later reporting the return of
             symptoms, generally in association with weight gain.
     If a patient chooses upper airway surgery or a dental device, he
      or she requires repeat polysomnography after surgery or with
      the device in place to be sure the OSAHS has been effectively
      treated.
     Management of residual EDS is as follows:
          o Residual EDS after treatment with CPAP is a commonly
             encountered problem for the physician.
        o   Residual EDS is generally considered present if the ESS
            score remains higher than 10 after treatment.

Prognosis

     The short-term prognosis, in relation to symptoms such as
      daytime sleepiness and snoring, ranges from good to excellent
      with regular use of CPAP.
     The long-term prognosis is unknown because no randomized
      treatment studies investigating the effect of CPAP on
      preventing the development of cardiovascular sequelae have
      been conducted.

Patient Education

     All patients with OSAHS should receive education about sleep
      and proper sleep hygiene, OSAHS, and the risks of driving
      while sleepy. They also should receive education regarding the
      role of nasal CPAP and the importance of daily use.

     Driving and sleep apnea
         o Patients with OSAHS have an increased frequency of
            motor vehicle accidents, particularly those with severe
            OSAHS. For instance, in the Wisconsin Cohort Study,
            persons with AHIs greater than 15 were 7 times more
            likely to have had multiple vehicle accidents.
         o One approach to this problem is the concept of shared
            responsibilities. Educating the patient about the risks of
            driving while sleepy or inattentive is the physician's
            responsibility. One suggestion is that the patient
            acknowledges this education by signing a statement to
            that effect. After receiving proper education, the patient's
            responsibilities are avoiding driving while sleepy and,
            preferably, refraining from driving until starting treatment
            for OSAHS.