sleep Obstructive apnea : recent
advances and future trends
Ajay Handa
Dept of Pulmonary Medicine
Sleep physiology
Historical aspects
Clinical profile
Polysomnography
Management
Recent advances
Future directions
Sleep physiology
Sleep is a period of bodily rest with reduced
awareness of the environment
Two phases of sleep REM, NREM
NREM and REM sleep bouts alternate with
each other throughout night (average cycle
length is 90 mins)
REM sleep
Rapid eye movements
Generalized hypotonia of muscles
Irregular rate and depth of respiration
Marked suppression of hypothalamic
regulation of homeostasis
NREM sleep
Normal muscle tone
Regular respiration
Four stages of NREM sleep based on EEG
Stage 1- small amplitude high frequency
waves resembling awake state
Stage 4- large amplitude and lowest
frequency waves approaching REM
EEG record
Functions of sleep
Restoration of body as metabolic and
energy demands are reduced. But what is
restored ?
NREM - replenishes cerebral glycogen
stores
REM restoration of depleted
noradrenergic neurons
Consolidation of memory and improved
learning !!
Resp effects of NREM sleep
depresses activity of respiratory pump muscles
markedly depresses activity of airway dilator
muscles
upper airway obstruction
resultant decreased ventilation causes PaCO2 to
rise by 5-6 mmHg
fall in PaO2 in sleep does not affect healthy
individuals.
causes significant hypoxemia in COPD patients
who may require supplemental oxygen during
sleep not during waking hours.
CO2 Apnea threshold increased during
NREM sleep .
Awake AT is 20 mmHg ,increases to 40
mmHg in NREM.
In hypoxic patients who may be hypocapnic
during NREM there are increased chances
of having central sleep apneas(CSA)
upper airway obstruction due to reduced
tone of dilator muscles may cause OSA
usually stage 1,2 of NREM
Reduced CO2 responsiveness
Due to reduced CO2 sensitivity of central
chemo receptors ( change in membrane
properties of neurons )
Reduced activity of respiratory motor
neurons due to withdrawal of excitatory
effects of wakefulness on these neurons.
Contribute to the hypoventilation that
occurs during sleep
Resp effects of REM sleep
Profound atonia all muscles
Thoracic muscles are more depressed than
abdominal muscles
Irregular respirations result but average
ventilation changes little compared to
wakefulness
Resp effects of REM sleep
Increased upper airway obstruction due to
hypotonia of dilator pharyngeal muscles
Considerable suppression and disorganized
activity of diaphragm
OSA episodes and oxygen desaturation are
longer and more severe than NREM
Cardiovascular effects of REM
Marked fluctuations in sympathetic outflow
Bidirectional changes in HR and BP
Sinus bradycardia, sinus arrest have been
reported
Adverse cardiac events such as arrhythmia,
Ac MI , sudden death may occur in pt with
CAD
Pharyngeal muscles
affecting hyoid: geniohyoid, sternohyoid(XII)
affecting tongue: genioglossus(XII)
affecting palate: tensor palatini levator palatini (V)
Nuclei receive inputs from respiratory centres
(ventral medulla) phasic vs tonic
Most impt stimulus is negative intrapharyngeal
pressure during inspiration
contraction
keeps pharynx open during inspiration
Pharyngeal airway
Patency depends on balance of forces that
tend to collapse(negative intraluminal
pressure and extraluminal pressure) and the
contraction of dilator muscles
Transmural press(Ptm)=Plumen Ptissue
Closing pressure is Ptm at which the pharynx
collapses
PCritical at which airflow ceases completely
OSA: > 0 cm H2O
Normal: 8 cm H2O
Other factors
Role of lung volume in airway size
OSAHS airways have greater dependence
on lung volumes
Decreased FRC with sleep may lead to
pharyngeal collapse and increased airflow
resistance
Instability of resp control - contribute to
compromised airway patency in some cases
Progression of OSA
Severity of apnea known to worsen over time
Roughly AHI doubles every decade
Wisconsin sleep study AHI increased 2.6 to 5.1 /h
over 8 years
Accelerated by obesity: 10% weight gain caused
32% increase in AHI
Vibration induced trauma and edema of soft
tissues of upper airways and pharyngeal muscle
dysfunction responsible for progression
Historical aspects
1918 - Sir William Osler first proposed the
relationship between obesity and Pickwickian
syndrome
1956 - Burwell et al first described alveolar
hypoventilation with extreme obesity caused
Pickwickian syndrome
1966 - Gastaut et al demonstrated the occurrence
of recurrent apneas in sleep by polysomnography
and suggested , sleep disruption was the cause of
daytime sleepiness
Sleep apnea
Apnea is cessation of airflow for at least 10
seconds
OSA- apnea with continued respiratory
efforts
CSA- airflow and resp efforts are absent
Mixed- starts as central but becomes
obstructive in the same episode
Hypopneas
Decrement of airflow of 50 % or more
accompanied by fall of 4% in oxygen
saturation or EEG evidence of arousal
Produces the same pathophysiological
changes as apnea
Oxyhemoglobin desaturation maybe less
severe than apnea episodes
OSAHS
Recurrent episodes of obstructive apnea or
hypopnea associated with both excessive daytime
sleepiness and night-time symptoms
Apnea hypopnea index(AHI) on
polysomnography > 5/h
Usually not hypercapnic when awake (PaCO2 <45
mmHg) when compared with Obesity
Hypoventilation Syndrome.
Recent study: 17% OSA were hypercapnic
Resta et alNeth Med J 2000
Underlying causes
Skeletal abnormalities
Soft tissue abnormalities -pharyngeal/nasal
Craniofacial disorders
Endocrine
Obesity
Genetic
Clinical profile
Snoring
Witnessed apneas
Nocturnal choking
Excessive daytime sleepiness(EDS)
Personality changes
Nocturia
Automobile accidents
Snoring
affects bed partner/family and neighbors !!
common in population : 35-45% men, 1528% women have habitual snoring
most freq symptom of OSA 70-95%
only 6% OSA pts do not report snoring
patients who deny snoring are found to
snore during objective assessment
EDS
Assessed by Epworth sleepiness scale (ESS)
subjective questionnaire
Has poor correlation with severity of OSA
Inputs from bed partner are useful
Exclude lethargy,exhaustion, shift work,
drug intake,sleep related movement
disorder,depression, narcolepsy and
idiopathic hypersomnolence
Apneas
Reported in 6% normal population
Females less likely to report apneas
Nocturnal panic or choking episodes
Cause considerable distress
Exclude PND, nocturnal asthma, Cheyne
Stokes respiration and acute stridor
( usually last longer)
Atypical
presentation
Classification of severity
Consequences
Recurrent apneas
Stimulation of resp centre
Arousal and sleep
disruption
EDS and cognitive
dysfunction
hypoxemia
Sympathetic
stimulation
Hypertension
Arrhythmias
Pulm HTN
Cardiac failure
Stroke
Clinical assessment
Diagnosis may be wrong in 50 % cases
Loud snoring + witnessed apneas identified
OSAHS with sensitivity 78% and
specificity 67%
Neck circumference <37cm , >48 cm are
associated with low and high risk of OSA
Obesity(BMI>30)independent risk factor
but ~ 50% cases are not obese
Polysomnography
EEG
EOG
EMG
ECG
Oronasal airflow
Pulse oximetry
Respiratory efforts
Snoring
Position
Leg movements
PSG
Full PSG is gold standard for diagnosis of
OSA
Time consuming ,expensive, req trained
technician and hosp admission
Criteria used by observers to define
hypopnea lead to wide differences in RDI
AHI correlated poorly with EDS and not
predict did long term morbidity /mortality
AASM Classification
Level
Parameters
1
min x7
EEG+
2
3
4
min x7
EEG+
min x 4
min x1
Body postn monitor possible
possible
no
Leg movts
EMG
optional
optional
no
Personnel
yes
no
no
no
Interventn
possible no
no
no
PGI sleep lab
Name: Compumedics, Australia
Type: Level III (except EEG &EMG)
No of cases studied ~55
CPAP : ~15 patients
Drawbacks - lack of EEG leads to error in
calculated AHI (bed time vs sleep time)
Normal Sleep Study
Obstructive apnea: Complete cessation of airflow despite efforts to
breathe
Desaturation
Obstructive apnea
Respiratory paradox
Snore
Central apnea: Complete cessation of respiratory effort and airflow
Central
apnea
Mixed apnea: Complete cessation of airflow with gradual increase
in respiratory effort after an initial absence
Desaturation
Mixed apnea
No effort
Effort +
Hypopnea: Reduction in airflow compared to baseline, associated
with desaturation
Desaturation
Hypopnea
Progressively increasing
respiratory effort
Role of monitoring sleep
Sleep assessed by EEG, EOG & EMG
Detects arousal ,micro-arousal with apneas
Various studies showed arousal index had no
relation with EDS
Drinnan et al AJRCCM 1998
Electrophysiological analysis did not alter the
diagnosis in 200 cases of OSAHS established
accurately with AHI.
Douglas et al Lancet 1992
Problems in hypopnea
Air flow detection by thermistors cannot reliably
detect hypopneas
Nasal pressure sensor connected via prongs are
more sensitive in detecting hypopneas
Nasal obstruction produces false elevations
Resp inductance plethysmography (RIP) semiquantitative assessment of ventilation and
hypopnea
Recommended by AASM task force Sleep 1999
Role of oximetry
Desaturations are common with apnea , but can be
absent in hypopneas , upper airway resistance
syndrome(UARS)
Oxygen desaturation index(ODI) 4%
desaturation is considered significant by most
authors ( 3% and 5% are also used)
CT 90 cumulative percentage of time SpO2 was
below 90% is a useful index of severity (CT90
>1% indicates SA)
Level 4 study : Dual parameter record
Oximetry
As a screening test for OSA sensitivity of 69%
and specificity of 97%
Lee CL Clin Chest Med 2003
To confirm OSA in cases with high clinical
suspicion
To exclude OSA in snorers with low clinical
suspicion
ODI 4- has been shown to be best variable
predicting benefit from CPAP
Schlosshan et al Thorax 2004
Problems with oximetry
Dyshemoglobinemia
Hypotension ,hypothermia
Poor attachment / disconnection
Recording artifacts in obese
Split night study
Ist part diagnosis of OSA
IInd part CPAP titration
Value in patients with EDS as therapy with CPAP
will be well accepted .
AHI > 40/h over first 2 hours proceed to CPAP
titration
Not recommended for mild to moderate OSA
without daytime sleepiness
Chesson AL et al ,Sleep1997
Home studies
Portable unattended sleep studies at home are yet
to be standardized against the full PSG
Most devices do not monitor sleep stage and
cannot distinguish OSA and CSA
Prone to tech failures
Data should be manually analyzed by physician
Not recommended at present
Christopher KL et al Clin Chest Med 2003
Diagnostic role of APAP device
Automatic positive airway pressure devices have
built in sensors to detect upper airway obstruction
and airflow.
Detects apnea, hypopnea, snoring and
appropriately delivers positive pressure to
overcome the obstruction
Does not detect sleep hence AHI may be
erroneous
Can be used for diagnosing cases with high
clinical suspicion
Requires to be validated against full PSG
Clinical decision algorithm
Adjusted neck circumference predict the clinical
probability OSA and guide evaluation &
management
Add
+4 for hypertension
+3 for snoring
+3 for Choking episodes
<43 cm low clinical probability
43-48cm intermediate
>48 cm high probability
Flemmons WW, N Engl J Med 2002
Management
Conservative measures
Continuous Positive airway pressure
Medications
Oral appliances
Surgery
Miscellaneous
Indications of treatment
Daytime sleepiness and its consequences
Cardiovascular morbidity and mortality
Snoring
Difficulty in deciding treatment occurs in
asymptomatic case with severe OSA and
symptomatic case with low AHI
Behavioral therapy
Weight reduction
Effective in short term
Recurrence may occur despite wt loss
Positional therapy
50-60% have positional apnea in supine postn
Sleep with head end elevated & lateral postn
Posture alarm , balls in backpack to train
Pharmacologic measures
Protriptiline
SSRI
Medroxyprogesterone
Thyroid hormones*
Acetazolamide
Modafinil*
Currently no drugs are recommended as
alternative to CPA P
Role of nocturnal oxygen
Unable to accept CPAP (esp increased risk
of vascular complications )
Elderly patients (>80 years)
Mentally retarded( Downs Syndrome)
Hospitalized patients (before stabilization)
Strollo PJ, Clin Chest Med 2003
CPAP
Treatment of choice
Acts as pneumatic splint to keep UA open
Improves the airway obstr in 70-80 %
Administered via nasal mask /pillow
Mouth leak chin strap or oronasal mask used
Effective pressure(P eff) which abolishes apnea
,hypopnea, snoring, airflow limitation and arousals
determined by titration study.
CPAP
Reduced nocturnal sleep disturbances
Improved nocturnal oxygenation
Improved sleep architecture
Improves EDS & cognitive function
Improves cardiovasccular endpoints
May be assoc with reduction in mortality
Roux FJ et al Clin Chest Med 2003
CPAP
Mask intolerance:claustrophobia
Nasal congestion ,dryness
Discomfort
Noise
Compliance depends on symptom relief
Vary from 50-80%
Median use 3-5 h /night
CPAP
Inadequate pressure - may rarely be fatal , may
allow patient to go into REM sleep where airway
muscles and resp muscles are severely depressed
Can cause cardiac arrhythmia and hypoventilation
in cases with cardiac diseases
Excessive pressure - discomfort can interfere with
sleep, and can precipitate episode of CSA
Attarian HP Postgraduate Medicine 2002
Role of BiPAP
Intolerance to CPAP
Coexisting OSA and COPD
Coexisting OSA and OHS
Persistent Right heart failure
Role of APAP
Overall results are similar to conventional CPAP
Mean pressure lower than CPAP
Compliance and preference slightly better
Cost 1.5-3 times the conventional device
Not recommended to be used in OSA
complicated by OHS or CSA
comorbid diseases
high level of CPAP >15 cm
Problems with APAP
Leaks are interpreted as apnea / hypopnea
Some cases may develop CSA after
changing to APAP (mechanism ?) hence
cases likely to have CSA are excluded
Stroke
COPD / Resp failure
Cardiac failure
Role of oral appliances
Two types of devices
Tongue advancing device
Mandibular repositioning device
Improve airway patency by enlarging the
airway and improving the muscle tone
Devices are not as effective as CPAP
Useful for patients with simple snoring
OSA cases who do not tolerate or fail
CPAP
Oral appliances
Tongue advancing device
Mandibular repositioning device
Role of surgery
Adenoidectomy/tonsillectomy/septoplasty
(for specific cases)
Uvulopalatopharyngoplasty
Genioglossus advancement with hyoid
myotomy
Maxillomandibular advancement
recommended in those intolerant of CPAP
Tracheostomy
Future directions
definition of hypopnea
Ideal cut off between normal and SA
Role of unattended sleep study
APAP devices in diagnosis of OSA
Role of Modafinil with CPAP
SSRI in mild OSA