1. Sleep Disorders
Dr.Samet.M Yazd University Harrison's PRINCIPLES OF INTERNAL MEDICINE-7th Edition

2. Obstructive Sleep Apnea
Obstructive sleep apnea/hypopnea syndrome (OSAHS)
It is a major cause of morbidity, a significant cause of mortality throughout the world, and the most common medical cause of daytime sleepiness
Central sleep apnea is a less common clinical problem

3. Definition
may be defined as the coexistence of unexplained excessive daytime sleepiness with at least five obstructed breathing events (apnea or hypopnea) per hour of sleep
This event threshold may need to be refined upward in the elderly
Apneas are defined in adults as breathing pauses lasting 10s
hypopneas are defined as 10s events where there is continued breathing but the ventilation is reduced by at least 50% from the previous baseline during sleep
As a syndrome, OSAHS is association of a clinical picture with specific abnormalities on testing
asymptomatic individuals with abnormal breathing during sleep should not be labeled as having OSAHS

4. Clinical Indicators in the Sleepy Patient
OSAHS
Narcolepsy
IHS
Age of onset (years)
35–60
10–30
Cataplexy No
Yes
Night sleep
Duration
Normal
Long
 Awakenings
Occasional
Frequent
Rare
 Snoring
Yes, loud
 Morning drunkenness
Common
Daytime naps
 Frequency
Usually few
Many
Few
 Time of day
Afternoon/evening
Morning
 Duration
<1 h
>1 h

5. Mechanism of Obstruction
Apneas/hypopneas are caused by the airway being sucked closed on inspiration during sleep
occurs as upper-airway dilating muscles (like all striated muscles) normally relax during sleep
In patients with OSAHS, the dilating muscles can no longer successfully oppose negative pressure within the airway during inspiration
primary defect is not in upper-airway muscles, which function normally in OSAHS when awake
These patients have narrow upper airways already during wakefulness, but when they are awake their airway dilating muscles have higher than normal activity, which ensures airway patency
snoring may commence before the airway occludes, and apnea results
Apneas/hypopneas terminate when the subject arouses, i.e., wakens briefly, from sleep
This arousal is sometimes too subtle to be seen on EEG but may be detected by:
cardiac acceleration, blood pressure elevation, sympathetic tone increase
arousal results in return of upper-airway dilating muscle tone

6. factors predisposing to OSAHS by narrowing pharynx include:
Obesity  around 50% have a BMI >30 kg/m2 in western populations
shortening of the mandible and/or maxilla  this change in jaw shape may be subtle and can be familial
Hypothyroidism
Acromegaly predispose to OSAHS by narrowing the upper airway with tissue infiltration
male gender
middle age (40–65 years)
myotonic dystrophy
Ehlers Danlos syndrome
smoking

7. Epidemiology
frequency of OSAHS is in the range of 1–4% of the middle-aged male population
it is around half as common in women
also occurs in childhood (usually associated with tonsil or adenoid enlargement)
syndrome also occurs in elderly, although frequency is slightly lower in old age
Irregular breathing during sleep without daytime sleepiness is much more common
occurring in perhaps 1/4 of the middle-aged male population
However, as these individuals are asymptomatic, they do not have OSAHS and there is no evidence at present that these events are harmful

8. Clinical Features
daytime sleepiness
impaired vigilance
cognitive performance
Driving
Depression
disturbed sleep
Hypertension
difficulty concentrating
Unrefreshing nocturnal sleep
nocturnal choking
Nocturia
decreased libido
Daytime sleepiness may range from mild to irresistible
sleep attacks can be indistinguishable from those in narcolepsy
sleepiness may result in inability to work effectively and may damage interpersonal relationships
3 to 6 risk in accidents on the road or when operating machinery

9. Cardiovascular and Cerebrovascular Events
OSAHS raises 24-h mean blood pressure
increase is greater in those with recurrent nocturnal hypoxemia
is at least 4–5 mmHg, and may be as great as 10 mmHg in those with >20% arterial O2 desaturations / h
This rise probably results from a combination of surges in blood pressure accompanying each arousal from sleep that end each apnea or hypopnea and from the associated 24-h increases in sympathetic tone
that this rise in blood pressure would increase risk of MI by around 20% and stroke by about 40%
observational studies suggest an increase in risk of MI and stroke in untreated OSAHS
studies suggest, but dont prove, increased vascular risk in normal subjects with raised apneas/hypopneas
Patients with recent stroke have a high frequency of apneas and hypopneas
seem largely to be a consequence, not a cause, of stroke and to decline over weeks after vascular event
There is no evidence that treating apneas/hypopneas improves stroke outcome
There has been debate for decades whether OSAHS is an adult form of sudden infant death syndrome
reported excess nocturnal deaths in subjects previously shown to have apneas/hypopneas

10. Diabetes Mellitus
association of OSAHS with DM is not just due to obesity being common in both conditions
Recent data suggest that increased apneas and hypopneas during sleep are associated with insulin resistance independent of obesity
uncontrolled trials suggest that OSAHS can aggravate diabetes and that treatment of OSAHS in patients who also have diabetes decreases their insulin requirements

11. Liver
Hepatic dysfunction has also been associated with irregular breathing during sleep
Non-alcohol drinking subjects with apneas/hypopneas during sleep were found to have raised liver enzymes and more steatosis and fibrosis on liver biopsy, independent of body weight

12. Anesthestic Risk
Patients with OSAHS are at increased risk perioperatively as their upper airway may obstruct during recovery period or as a consequence of sedation
Patients whose anesthesiologists have difficulty intubating are much more likely to have irregular breathing during sleep
referring patients suspected of having OSAHS for investigation
some elective operations may need to be postponed until the OSAHS is treated

13. Differential Diagnosis
Insufficient sleep
this can usually be diagnosed by history
Shift work
this is a major cause of sleepiness, especially in those over 40 years old on either rotating shift or night shift work patterns
Psychological/psychiatric causes
depression is a major cause of sleepiness
Drugs
both stimulant and sedative drugs can produce sleepiness
Narcolepsy
around 50 times less common than OSAHS
narcolepsy is usually evident from childhood or teens and is associated with cataplexy
Idiopathic hypersomnolence
this is an ill-defined condition typified by long sleep duration and sleepiness
Phase alteration syndromes
both the phase delay and the less-common phase advancement syndromes are characterized by sleepiness at the characteristic time of day

14. ] WHO to Refer for Diagnosis
guideline I use for patients with troublesome sleepiness includes:
those with an Epworth Sleepiness Score >11
sleepiness during work
sleepiness during driving poses problems
ESS is not a perfect measure for detecting troublesome sleepiness, as many whose life is troubled by frequently fighting sleepiness but who never doze will correctly score themselves as having a low ESS
patient and his/her partner often give divergent scores for patient's sleepiness, and in such cases higher of two scores should be used

15. Epworth Sleepiness Score
How often are you likely to doze off or fall asleep in the following situations, in contrast to feeling just tired? This refers to your usual way of life in recent times. Even if you have not done some of these things recently, try to work out how they would have affected you. Use the following scale to choose the most appropriate number for each situation:
0 = would never doze
1 = slight chance of dozing
2 = moderate chance of dozing 
3 = high chance of dozing
Sitting and reading
Watching TV
Sitting, inactive in a public place (e.g., a theater or a meeting)
As a passenger in a car for an hour without a break
Lying down to rest in the afternoon when circumstances permit
Sitting and talking to someone
Sitting quietly after lunch without alcohol
In a car, while stopped for a few minutes in traffic
TOTAL

16. Diagnosis obtaining a good sleep history from the patient and partner
asking both to complete sleep questionnaires
Physical examination must include assessment of:
obesity, jaw structure, upper airway, blood pressure, predisposing causes (hypothyroidism and acromegaly)
Full polysomnographic or limited studies
the diagnostic test must demonstrate recurrent breathing pauses during sleep
a reasonable approach at present is for patients with troublesome sleepiness but negative limited studies to then have polysomnography to exclude or confirm

17. Obstructive Sleep Apnea Treatment
Whom to Treat ??????
treatment improves symptoms, sleepiness, driving, cognition, mood, QOL, blood pressure in patients who have:
Epworth score of >11
troublesome sleepiness while driving or working
AHI >15
for those with similar degrees of sleepiness and AHI 5–15, RCTs indicate improvements in:
symptoms, including subjective sleepiness
with less strong evidence indicating gains in cognition and quality of life
There is no evidence of blood pressure improvements in this group
treatment cannot be advocated for this large group:
there is not evidence that treating nonsleepy subjects improves their symptoms, function, blood pressure

18. Obstructive Sleep Apnea Treatment
How to Treat 
should have condition and its significance explained to them and to their partner
discussion of the implications of the local regulations for driving
weight loss
reduction of alcohol consumption
to reduce caloric intake
alcohol acutely decreases upper-airway dilating muscle tone
Sedative drugs

19. Continuous Positive Airway Pressure (CPAP)
CPAP therapy works by blowing the airway open during sleep
usually with pressures of 5–20 cmHg
CPAP has been shown to improve:
breathing during sleep, sleep quality, sleepiness, blood pressure, vigilance, cognition, driving ability, mood and quality of life in patients with OSAHS
finding the most comfortable mask from the ranges of several manufacturers
trying system for at least 30 min during the daytime to prepare for the overnight trial
An overnight monitored trial of CPAP is used to identify pressure required to keep patient's airway patent
main side effect of CPAP is airway drying, which can be countered using an integral heated humidifier
CPAP use, like that of all therapies, is imperfect, but around 94% of patients with severe OSAHS are still using their therapy after 5 years on objective monitoring

20. Mandibular Repositioning Splint (MRS)
Also called oral devices
work by holding lower jaw & tongue forward, thereby widening pharyngeal airway
MRSs have been shown to improve OSAHS patients' breathing during sleep, daytime somnolence, blood pressure

21. Surgery Four forms of surgery have a role in OSAHS
1) Bariatric surgery can be curative in the morbidly obese
2) Tonsillectomy can be highly effective in children but rarely in adults
3) Tracheostomy is curative but rarely used because of associated morbidity; nevertheless, it should not be overlooked in extremely advanced cases
4) Jaw advancement surgery—particularly maxillo-mandibular osteotomy—is effective in those with retrognathia (posterior displacement of the mandible) and should be particularly considered in young and thin patients
There is no robust evidence that pharyngeal surgery, including uvulopalatopharyngoplasty (whether by scalpel, laser, or thermal techniques) helps OSAHS

22. Drugs
no drugs are clinically useful in the prevention or reduction of apneas and hypopneas
A marginal improvement in sleepiness in patients who remain sleepy despite CPAP can be produced by modafinil

23. Choice of Treatment CPAP is the current treatment of choice
CPAP and MRS are the two most widely used and best evidence-based therapies
better outcomes with CPAP in terms of apneas and hypopneas, nocturnal oxygenation, symptoms, quality of life, mood, and vigilance
Adherence to CPAP is generally better than to an MRS
there is evidence that CPAP improves driving, but there are no such data on MRS
CPAP is the current treatment of choice
MRSs are evidence-based second-line therapy in those who fail CPAP
In younger, thinner patients, maxillo-mandibular advancement should be considered

24. Health Resources
Untreated OSAHS patients are heavy users of health care and dangerous drivers
they also work beneath their potential
Treatment of OSAHS with CPAP is cost-effective

25. Central Sleep Apnea
are respiratory pauses caused by lack of respiratory effort
These occur occasionally in normal subjects, particularly at sleep onset and in REM sleep, and are transiently increased following ascent to altitude
Recurrent CSA is most commonly found in the presence of cardiac failure or neurologic disease, especially stroke
Spontaneous central sleep syndrome is rare and can be classified on the basis of the arterial PCO2
Hypercapnic CSA occurs in conjunction with diminished ventilatory drive in Ondine's curse (central alveolar hypoventilation)
Normocapnic CSA have a normal or low arterial PCO2 when awake, with brisk ventilatory responses to hypercapnia
This combination results in unstable ventilatory control, with subjects breathing close to or below their apneic threshold for PCO2 during sleep; this apneic tendency is compounded by cycles of arousal-induced hyperventilation, inducing further hypocapnia

26. Clinical Features
Patients may present with sleep maintenance insomnia 
is relatively unusual in OSAHS
Daytime sleepiness may occur

27. Investigation
Identification of movement being particularly difficult in the very obese  Many apneas previously labeled central because of absent thoracoabdominal movement are actually obstructive
CSA can only be identified with certainty if:
1) esophageal pressure or
2) respiratory muscle electromyography
is recorded and shown to be absent during the events

28. Central Sleep Apnea Treatment
Patients with underlying CHF should have their failure treated appropriately
CPAP may improve outcome but is difficult to initiate and has not been shown to improve survival
Patients with spontaneous normocapnic CSA may be successfully treated with acetazolamide
In a minority of patients, CPAP is effective, perhaps because in some patients with OSAHS, pharyngeal collapse initiates reflex inhibition of respiration, and these episodes are prevented by CPAP
Oxygen and nocturnal nasal positive/pressure ventilation may also be tried

29. Max Hirshkowitz - - Flatland Logic Group - -
Positive Airway Pressure Therapy

30. Max Hirshkowitz - - Flatland Logic Group - -
Retrognathia in OSA
Max Hirshkowitz - - Flatland Logic Group - -
Schellenberg, J ARRCCM 2000;162: