CENTRAL SLEEP APNEA /Hypoventillation
Syndrome
BY
AHMAD YOUNES
PROFESSOR OF THORACIC MEDICINE
Mansoura faculty of medicine
CENTRAL SLEEP APNEA /Hypoventillation Syndrome
• The central sleep apnea (CSA) syndromes include a diverse
group of disorders associated with the presence of central
apnea during sleep.
• In some of the disorders the patients have primarily nocturnal
hypoventilation (increased PaCO2) due to decreased tidal
volume and/or respiratory rate with relatively few discrete
central apneas.
• Discussion of patients with central apnea and hypoventilation
syndromes together is useful clinically because they have many
similar aspects of pathophysiology and treatment.
Central sleep apnea
• Central sleep apnea (CSA) is characterized by
repetitive apneic episodes lasting at least 10 seconds
each occurring during sleep without associated
ventilatory efforts.
• Heterogeneous group of sleep-related breathing
disorders in which respiratory effort is absent in an
intermittent or cyclical fashion.
• Many patients with CSA also have some obstructive
respiratory events.
CSA is considered to be the primary
diagnosis when 50% of apneas are scored as central in origin
• CSA, like OSA, is associated with important complications,
1- frequent nighttime awakenings,
2- excessive daytime sleepiness
3- increased risk of adverse cardiovascular outcomes.
Manifestations of CSA.
1-Hgh altitude-induced periodic breathing
2-Cheyne-Stokes breathing (CSB).
3- Idiopathic CSA (ICSA),
4-Narcotic-induced central apnea
5- Obesity hypoventilation syndrome (OHS)
Prevalence of CSA
•CSA is estimated to represent about 5% to 10% of patients
with sleep-related breathing disorders.
•Most healthy individuals will have periodic breathing on highaltitude ascent, provided the magnitude of the ascent is
sufficient to cause substantial alveolar hypoxia.
•Given the global increase in obesity, the prevalence of OHS
is likely on the rise.
•ICSA is relatively uncommon and may constitute < 5% of
patients referred to a sleep
•patients with heart failure and left ventricular ejection fraction
< 45% revealed that 37% of patients had CSA. Interestingly,
OSA is not uncommon in this population at 12%
Risk Factors
• High CO2 ventilatory drive
• Sleep disturbance: Increased frequency of sleep-wake
transitions
• Gender: Men are more likely to have central apneas due to a
higher apneic threshold during NREM sleep. The lower apneic
threshold in women than in men could be mediated by both
female and male hormones
• Age: Central apneas are more common in older adults due to
the increased prevalence of underlying medical disorders (eg,
CHF,neurologic disorders), or greater sleep disturbance and
awakenings
• Altitude: Central apneas can develop acutely following ascent
to high altitudes
• Nasal obstruction
During the waking state, respiration is controlled by three processes,
namely the metabolic (automatic), the wake-related drive to breathe and
behavioral (voluntary) systems
• During NREM sleep, the wake-related drive to breathe and
behavioral control systems are abolished, and respiration is
controlled entirely by the metabolic control system, primarily
by the hypercapnic ventilatory drive and to a lesser degree
by the hypoxic ventilatory drive
• A PaCO2 above the apneic threshold stimulates ventilation,
whereas a PaCO2 below this threshold leads to a central
apnea that continues until PaCO2 increases and once again
exceeds the apneic threshold.
Mechanism of CSA
• Chemoreceptor inputs (medullary neurons and peripherally at the carotid
body) play a key role in modulating ventilation. The ventilatory output to a
given change in PaO2 or PaCO2 ("chemo-sensitivity") can vary greatly
between individuals and with disease status.
• Highly sensitive chemo-responses can place an individual at risk for
unstable breathing patterns because these individuals "over-respond" to
small changes in chemical stimuli.
• The inherent delays in the negative feedback loop controlling ventilation also
contribute to the risk for developing instability.
• individuals with high chemo-responsiveness will hyperventilate markedly to
a perturbation potentially, lowering PaCO2 below the eupnic level and
leading to hypoventilation and potential apnea.
• Similarly, an individual with a long delay in the loop, such as individuals with
reduced cardiac output, may have more prolonged hyperventilation, also
leading to greater hyperventilation and a subsequent unstable breathing
Mechanism of CSA
• Several respiratory control mechanisms are down
regulated at sleep onset.
• Upper airway (UA) dilator and respiratory pump
muscle tone is reduced, and there is an
accompanying increase in UA resistance leading to
a reduction in ventilation for a given level of drive.
• Chemosensitivity is also likely reduced at sleep
onset. Although of variable magnitude and rate,
these normal physiologic responses occur in all
individuals.
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Mechanism of CSA
• During sleep all individuals are susceptible to breathing
cessation should the PaCO2 fall below a critical threshold
known as the apnea threshold. The apnea threshold is
usually 2 to 6 mm Hg below the eucapnic sleeping PaCO2
level. This typically equates to the wakefulness eucapnic
PaCO2 level or marginally lower
• Regardless of the underlying cause of arousal from sleep
(ie, spontaneous arousal, periodic leg movements,
respiratory load induced arousal), an individual with a low
arousal threshold (ie, susceptible to waking up easily) will be
vulnerable to sleep state instability. That is, the combination
of a predisposition to sleep transition apnea and a low
arousal threshold may be sufficient to facilitate a repetitive
CSA cycle as the individual oscillates between wakefulness
and sleep.
The arousal threshold increase with progressively deeper sleep
stage, as does breathing stability provided slow wave sleep
can be achieved.
• The rapid switch from sleep to wakefulness that occurs with
arousal causes a sudden shift in the underlying homeostatic
control of the cardio-respiratory system. The eucapnic set
point rapidly shifts from the sleep set point (approximately 45
mm Hg) to the wakefulness level (approximately 40 mm Hg)
creating a state of relative hypocapnia. In addition, sleepinduced UA resistance is removed and the wakefulness
drive is reintroduced. The brisk ventilatory response
causes a rapid reduction in PaCO2, such that central apnea
may ensue during subsequent sleep if the hypocapnia is
sufficient to cross the apnea threshold
Central hypopneas
• The American Academy of Sleep Medicine (AASM) scoring
manual discourages identification of central hypopnea unless
an accurate method to quantify respiratory effort is being
used (esophageal pressure or respiratory inductance
plethysmography).
• In general, central hypopneas are characterized by a
proportionate decrease in both airflow and respiratory
effort .
• Usually, there is no snoring or chest-abdominal paradox and
the nasal pressure or PAP device flow signal is fairly
rounded (minimal or no signs of airflow limitation).
False Classification of Apneas as Central
• Even with RIP, an obstructive apnea may appear to
be a central apnea.
• The RIP rib cage and abdominal band tracings are
nearly flat but persistent respiratory effort is definitely
noted in the esophageal pressure tracing.
• Although misclassification of a few events is unlikely
to have major clinical consequences, proper
adjustment of chest and abdominal bands (position
and tightness) is crucial to avoid significant errors in
event classification.
PSG features of central apneas
• Pauses in respiration and absent ventilatory effort lasting 10 seconds or
longer
• Loss of chest and abdominal movement (strain gauge or respiratory
inductance plethysmography)
• No EMG activity of the respiratory muscles including diaphragm
• No change in intrathoracic pressures (esophageal balloon)
• Central hypopneas have a rounded profile on nasal pressure monitoring
• Associated with oxygen desaturation (generally mild) and, occasionally,
arousals
• In patients with obstructive, central and mixed apneas, at least 50% of the
respiratory events are central in nature
• At least five central apneas per hour of sleep
• Snoring may occur (less prominent than in obstructive sleep apnea)
• Increased NREM stages 1 and 2 sleep(N1,N2)
• Decreased NREM stages 3 and 4 sleep(N3).
Comparison between central and
obstructive apneas
Characteristics
1-Oxygen desaturation
2-Hemodynamic changes
2-Concurrent respiratory effort
OSA
Worse
Greater
Present
CSA
Mild
Less
Absent
Hypoventilation Rule (AASM Scoring
Manual
• Score hypoventilation during sleep if there is a ≥10 mm Hg
increase in PaCO2 during sleep in comparison with an
awake supine value
• Both end-tidal carbon dioxide pressure (PETCO2) and
transcutaneous carbon dioxide pressure (TcPCO2) may be
used as surrogate measures of PaCO2 if demonstrated to
be reliable and valid.
• Continuous arterial blood gas monitoring during PSG is not
practical (or well tolerated).
• It is observed that finding an increase in the PaCO2
obtained immediately upon awakening is suggestive of sleep
hypoventilation.
Sleep Hypoventilation
• The most common approaches to documenting
hypoventilation during sleep monitoring include
measurement of PETCO2 or TcPCO2.
• The PETCO2 tracing should show an alveolar
plateau to be accepted as an accurate estimate of
the PaCO2.
• It should also be noted that the PaCO2 typically
exceeds the PETCO2 by 4 to 6 mm Hg in normal
individuals. The difference can be increased in
patients with lung disease.
Clasification of CSA
There is a number of classifications of CSA and the
hypoventilation syndrome but none of these classifications is
entirely satisfactory
• Central sleep apnea can be classified based on:
1. Underlying level of ventilation—hypercapnic or nonhypercapnic; or
2. Etiology—idiopathic or secondary
• Hypercapnic CSA
patients with impaired ventilatory output during wakefulness
will have some degree of daytime hyper-capnia.
Undoubtedly with the removal of the wakefulness drive and
other behavioral influences, hyper-capnia will worsen during
sleep.
• Nonhyper-capnic CSA
patients who are eu-capnic or hypo-capnic
Hypercapnic CSA
• Impaired Central Drive ("Won’t Breathe"):
1-Tumors or trauma-induced lesions to brainstem
2-Congenital central hypoventilation syndrome
3-Opioid-induced CSA
4- OHS
5- Apnea of infancy
Impaired Respiratory Motor Control ("Can’t Breathe")
1-Myasthenia gravis
2-Amyotrophic lateral sclerosis
3-Post-polio syndrome
4-Myopathies
5-Chest wall syndromes such as kypho-scoliosis
Non-hypercapnic CSA
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•
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Sleep onset CSA
Cheyne-Stokes breathing (CSB).
High altitude-induced periodic breathing
Idiopathic CSA (ICSA )
Complex sleep apnea (treatment emergent or
persistent sleep apnea)
Sleep-Onset Central Apneas
• As sleep states oscillate between sleep and wakedrowsiness at sleep onset, repetitive episodes of
central apneas may occur if PaCO2 (higher during
sleep and lower during wakefulness) fluctuates
above or below the apneic threshold.
• Sleep-onset central apneas are generally transient,
disappearing once stable sleep is attained (ie, when
PaCO2 is maintained continuously at higher levels).
• Frequency of central apneas is normally less than
five episodes per hour of sleep. Repetitive sleep
onset central apneas can result in sleep-initiation
insomnia.
Types of sleep related breathing disorders
in patients with congestive heart failure
1- Central sleep apnea
2- Cheyne-Stokes respiration
3- Obstructive sleep apnea
• AASM score Cheyne-Stokes Respiration if there are at
least 3 consecutive cycleal crescendo-decrescendo
change in breathing amplitude and at least one of the
following:
–
–
Five or more central apneas or hypopneas / hour sleep.
The cyclic crescendo-decrescendo change in breathing amplitude
has duration of at least 10 cosequtive minutes.
Note that Cheyne-Stokes breathing has varible cycle length that is most
commonly in the range of 60 seconds.
Evaluation:
• Patients with CSA-CSB may complain of the typical
symptoms of sleep apnea including disturbed sleep or
daytime sleepiness.
• However, in most studies, the majority of patients do
not complain of subjective excessive daytime
sleepiness. Thus, a high index of suspicion is needed
to suspect the presence of CSB.
• Nocturnal sleep complaints are often assumed to be
secondary to CHF rather than to co-morbid sleep
apnea.
Therapy:
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Optimize medical management
Supplemental oxygen
CPAP (effective in ~40–50%)
BPAP with backup rate (BPAP-ST)
ASV
Transplant
Neurologic Disorders
• Several neurologic and neuromuscular disorders can decrease central
ventilatory drive and give rise to CSA. Patients are usually hypercapnic.
Periodic Breathing Secondary to High Altitude
• Periodic breathing, or cycles of central apneas and hyperpneas, can occur
on ascent to high altitude (usually > 4000 to 7600 meters).
• Severity of symptoms is influenced by elevation, speed of ascent, and
individual predisposition. Persons withse incread hypoxic ventilatory
chemoresponsiveness appear to have a greater risk for developing highaltitude–related periodic breathing
• Hyperventilation due to hypoxia on ascent to altitude gives rise to
hypocapnic (low PaCO2) alkalosis that, in turn, results in central apneas
during sleep, particularly NREM sleep, on the first few nights at altitude.
Ventilation resumes as PaCO2 rises and PaO2 falls during the apneic
episode.
• The pattern of periodic breathing at high altitude resembles Cheyne–Stokes
breathing in heart failure, with one exception. The cycle of periodic breathing
is short.
Therapy of Periodic Breathing Secondary
to High Altitude
• Therapy consists of either oxygen therapy or
administration of acetazolamide (250 mg /6h)
reduce central apnea over 1-2 weeks
• Acetazolamide causes metabolic acidosis and
decreases PaCO2. In spite of a lower (than normal)
PaCO2, central apneas decrease. This is because
the apneic threshold PCO2 decreases more than
that of PaCO2. This results in a widening of the two
PCO2 set points. which will decrease the likelihood
of developing central apnea.
Central Sleep Apnea Related to
Medication Use
• Central apneas can develop during administration
of opiate drugs.
• Other respiratory pattern abnormalities, such as
periodic breathing, Biot respiration, and obstructive
hypoventilation, can develop due to receptor-related
depression of the hypercapnic ventilatory drive and
increase in hypoxic ventilatory drive.
Central Apnea During Positive Airway
Pressure Titration
• Central sleep apnea may emerge during CPAP titration
in patients with OSA.
• This may be due to unmasking of a previously
concurrent central apnea that becomes apparent when
the more predominant obstructive events are controlled
by CPAP therapy.
• Alternatively, it may be due to recurrent arousals related
to the use of CPAP with central apnea occurring in the
post-arousal period.
Complex sleep apnea
• CompSA is defined as a form of CSA identified by the
persistence or emergence sleep of central apneas or
hypopneas upon exposure to CPAP or BPAP without a
backup rate when obstructive events have disappeared.
• These patients have predominantly obstructive or mixed
apneas during the diagnostic portion of the study
occurring 5/hr or more.
• With use of CPAP or BPAP without a backup rate, they
show a pattern of apneas and hypopneas that meets the
definition of CSA.
Treatment of Complex sleep apnea
• In the absence of CSB-CSA or opioids, it appears that a significant
portion will improve with chronic CPAP alone. The only problem
with watchful waiting is that if the AHI remains high, sleep quality
will be impaired and adherence may decrease. Therefore, it is
prudent to assess patients soon after starting CPAP.
• Many CPAP devices provide the ability to estimate residual events.
• It is also important to remember that the patient is being treated,
not the AHI. Therefore, if a patient reports good sleep and objective
adherence is good, intervention may not be necessary if the
residual AHI remains mildly elevated (5–10/hr). If patients do not
improve or if the residual AHI is high, most clinicians would order a
titration with ASV.
• Another option would be treatment with BPAP-ST (backup rate) if
ASV is not effective.
Obesity Hypoventilation Syndrome
• The two essential features of obesity hypoventilation
syndrome (OHS) are the presence of a body mass index
>30 kg/m2 and PaCO2 > 45 mmHg during wakefulness.
Hypoventilation is not due to another respiratory or
neuromuscular disorder.
• Many patients with OHS also have OSA (80-90 %)
• The American Academy of Sleep Medicine has
incorporated the definition of OHS into a broader term of
sleep hypoventilation syndrome
Pathophysiology:
• Patients with the OHS are a heterogeneous group.
• Up to 20% of OHS patients have an AHI of 5/hr or less but exhibit both
daytime hypercapnia and severe sleep sleep-related hypoventilation and
arterial oxygen desaturation.
Etiology of hypercapnia in obesity hypoventilation syndrome
1-Increased production of CO2 :
Greater work of breathing
Decreased chest wall compliance
2- Decreased ventilation:
Decreased expiratory reserve volume
Decreased tidal volume
Increased resistive load
Increased dead space
3-Decreased ventilatory response to hypercapnia and hypoxemia
4- coexistence of obstructive sleep apnea (OSA)
Clinical Features
• Clinical manifestations include excessive sleepiness,
sleep fragmentation with frequent arousals
(insomnia), decreased attention or concentration,
peripheral edema and cyanosis. Chronic hypoxemia
can result in polycythemia, pulmonary hypertension,
and cor pulmonale.
Prevalence
• The prevalence of OHS is from 5% to 31% of obese
adults, and it is uncommon but possible in obese
children
Treatment of OHS:
• Some OHS patients could be adequately treated with CPAP
alone.
• Others still had hypoventilation despite the absence of
apnea or hypopnea.
• Some with persistent airflow limitation responded to higher
levels of CPAP
• Some patients required the addition of supplemental oxygen
along with CPAP.
• Another group of patients required either nasal bilevel
positive airway pressure (BPAP) or mechanical ventilation
with or without oxygen.
• Tracheostomy can be life-saving in patients noncompliant
with PAP treatment who have repeated bouts of hypercapnic
respiratory failure.
Overlap Syndrome
• Patients with the OSA and COPD may have daytime
hypoventilation and severe nocturnal oxygen
desaturation.
• Patients with mild COPD have no higher incidence of
OSA than the general population.
• However, because both COPD and OSA are common,
the combination is common even if by chance.
Idiopathic Central Sleep Apnea
• The etiology of idiopathic CSA is unknown.
• In patients with idiopathic CSA, carbon dioxide
(CO2) ventilatory drive is increased. Thus, PaCO2
is low during wakefulness and sleep.
Etiology—idiopathic or secondary
• CSA can be
1- idiopathic (primary): Primary CSA is termed
idiopathic central sleep apnea (ICSA), in keeping
with much of the literature.
2- secondary to other medical disorders, such as
cardiac, renal, neurologic (eg, brainstem lesions)
conditions. chronic use of long-acting opioids,
including methadone, hydrocodone and morphine .
Secondary forms of CSA are more common than the
idiopathic form.
The ICSD-2 lists five categories of sleep hypoventilation
syndromes
1. Sleep-related non-obstructive alveolar hypoventilation,
• Idiopathic: Rare, usually case reports
2. Congenital central alveolar hypoventilation syndrome
• Example: Central congenital hypoventilation syndrome
3. Sleep-related hypoventilation due to medical condition
A. Sleep-related hypoventilaton/hypoxemia due to lower airways obstruction
• Examples: Hypercapnic COPD, bronchiectasis, or cystic fibrosis
B. Sleep-related hypoxemia due to pulmonary parenchymal or vascular
pathology
• Example: Sleep-related hypoventilation with interstitial lung diseases or pulmonary
vascular disease associated with end-stage lung disease
C. Sleep-related hypoventilation due to neuromuscular and chest wall disorders
• Examples: Obesity hypoventilation syndrome, neuromuscular disease,
kyphoscoliosis
Clinical Features
• Sleep disturbance with repeated nocturnal awakenings
• Nocturnal sensation of dyspnea
• Insomnia
• Morning headaches
• Excessive sleepiness
Note: Patients may be asymptomatic.
Associated features
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Cardiovascular disorders
Systemic hypertension
Pulmonary hypertension,Cor pulmonale
Cardiac arrhythmias
Respiratory insufficiency
Polycythemia
Depression
Cognitive impairment
Impotence
Physical features
• Peripheral edema
• Cyanosis
• Shallow breathing
Therapeutic Interventions
• improve cardiac status for patients with an underlying heart
condition may attenuate SDB
• Gradual dose reduction of opioid medication
• Weight loss is likely to lead to improvement of SDB in
patients with, morbidly obese patients with OHS.
• Acetazolamide and theophylline have been shown to
improve CSA in patients with heart failure. Acetazolamide
has also been shown to improve SDB in ICSA.
• Nasal CPAP has been shown to be effective in some
patients with ICSA.