Flashcards in Sixteen Deck (21):
Explain the various risk factors for OSAS.
The high male-to-female prevalence ratio for OSAS of
2:1 is attributed to the protective effect of female sex hormones
predominant in premenopausal women; the prevalence
of OSAS in women triples after menopause and is reduced
to premenopausal levels with hormone replacement therapy.
Meanwhile, increased body mass index (BMI) is the major
risk factor for OSAS in adults (Chap. 12). There appears to
be a linear relationship between BMI and OSAS severity:
Each 10% increase in body weight results in a 30% increase
in AHI. On the other hand, adenotonsillar hypertrophy is
the major cause of OSAS in children. For patients who are
not overweight or obese, certain craniofacial features (eg, retrognathia, long uvula) can predispose to OSAS. Increased
nasal resistance from rhinitis or a deviated nasal septum can
worsen airway collapse due to the greater inspiratory effort
required to breathe through such nasal passages. Asians may
be at a higher risk for OSAS due to crowding of the posterior
oropharynx and a steep thyromental plane. Smoking causes
nasal and oropharyngeal mucosal edema that can aggravate
upper airway obstruction. Hormonal abnormalities may alter
craniofacial skeletal and soft tissue structure, thereby promoting
oropharyngeal crowding, as seen in the macroglossia of
hypothyroidism and acromegaly. Up to 50% of patients with
Down syndrome suffer from OSAS due to multiple risk factors.
These can include midfacial and mandibular hypoplasia,
small upper airways with superfi cially positioned tonsils and
relative tonsillar and adenoidal encroachment, generalized
hypotonia, and an increased prevalence of obesity and hypothyroidism.
Describe the pathophys of OSAS.
OSAS occurs due to dynamic upper airway closure or narrowing.
These may be secondary to excessive pharyngeal tissue
volume from obesity, adenotonsillar hypertrophy, craniofacial
anatomy, and can accompany attenuated tone of the pharyngeal
dilating muscles during sleep (Fig. 25.1).
List the adverse effects of OSAS and explain how they come about.
Left untreated, OSAS is associated with neurocognitive
impairment, cardiovascular dysfunction, endocrine abnormalities,
and mortality (Table 25.2). In prospective cohort studies,
moderate-to-severe OSAS has been associated with an increased
incidence in systemic hypertension and diabetes mellitus, as well as an increased risk of overall mortality. The Sleep Heart
Health Study, based upon a large cross-sectional population,
showed a signifi cant increase in the prevalence of congestive
heart failure in middle-aged individuals with moderateto-
severe OSAS. Neurocognitive dysfunction in OSAS is a
consequence of poor sleep effi ciency and reduced slow wave
and rapid eye movement sleep that are caused by frequent
nocturnal awakenings from disordered-breathing events. Neurocognitive
dysfunction can manifest as hypersomnolence,
decreased vigilance, impaired short-term memory, depression,
and increased risk of motor vehicle accidents. Meanwhile,
the surges in hypoxemia, hypercapnia, and circulating
catecholamines associated with OSAS are now implicated
in development of both hypertension and increased insulin
Explain how OSAS is diagnosed.
The diagnosis of OSAS requires the presence of its clinical
features (snoring, witnessed apneas, excessive daytime sleepiness,
etc), and a polysomnogram showing a respiratory disturbance index (RDI) of ≥5 scoreable respiratory events
(obstructive apneas, hypopneas, and respiratory-related arousals)
per hour of sleep (Fig. 25.2 and Tables 25.3 and 25.4).
In the absence of clinical features or cardiovascular comorbidities,
an RDI ≥15 scoreable respiratory events per hour of
sleep is required to make the diagnosis.
Explain the differences between obstructive apneas, obstructive hypopneas, and RERAs and how they come about.
correspond to episodes of complete upper airway obstruction
(Fig. 25.2), while obstructive hypopneas are episodes
of partial upper airway obstruction (Fig. 25.3). Respiratory
effort-related arousals (RERAs) are “mini-awakenings,” or
shifts in electroencephalographic waveforms. These RERAs
result from progressively increasing inspiratory efforts (ie,
negative intrathoracic pressures) by the patient in an attempt
to overcome high upper airway resistance. These arousals
are preceded by blunting of the nasal pressure airfl ow waveform
normally associated with increasing respiratory efforts,
and are best detected by measuring intrathoracic pressures
using esophageal manometry (see Fig. 4.6). RERAs do not
meet the criteria for a decrease in Sao2% (of ≥3%-4%) nor
the airfl ow reduction criteria (≥50%) that signify obstructive
Explain various therapeutic approaches to OSAS, how they work, and what effects they have. What is the mainstay?
Weight loss for obese patients has been shown to decrease
the AHI and improve nocturnal Sao2% in patients with OSAS.
Compared to controls, OSA patients have been found to have
higher serum [leptin], a peptide hormone which regulates
appetite and metabolism. These higher [leptin] levels in OSA
patients may indicate resistance to its anorexigenic effect,
making weight loss more diffi cult to achieve.
Continuous positive airway pressure (CPAP) provides a
mechanical air stent to the upper airways and is the mainstay for
treating OSAS in adults. CPAP is demonstrated to have multisystemic
effects, notably ameliorating the neurocognitive deficits, cardiovascular dysfunction, and endocrinologic abnormalities
(Fig. 25.3, Table 25.5). The optimal CPAP level is that pressure
(in cm H2O) determined to be effective in abolishing apneas,
hypopneas, RERAs, and snoring during a therapeutic CPAP trial.
Positional obstructive sleep apnea is said to occur in
those patients whose supine AHI is twice their lateral decubitus
AHI, and in whom the lateral decubitus AHI < 10 events/h.
In such patients, relatively simple positional adjustments to
promote sleeping in the lateral decubitus position can decrease
their overall nightly AHI and respiratory-related arousal index,
and ameliorate their excessive daytime sleepiness.
Oral appliances are dental devices designed to advance
the mandible, thereby increasing the orohypopharyngeal space. Oral appliances have been demonstrated to moderately
decrease the AHI in patients with mild-to-moderate OSA and,
to a lesser extent, their systemic blood pressure if they are
Tonsillectomy and adenoidectomy is the treatment of
choice for children with OSAS and adenotonsillar hypertrophy
(Clinical Correlation 25.1).
(UPPP) is the most commonly performed surgical procedure
for adult patients with OSAS, and involves the surgical
removal of the tonsils and redundant soft palate and tonsillar
pillars. UPPP has been found to have an overall success rate of
40% when defi ned as reducing the severity of patients’ OSA
by at least 50%. Other surgical procedures for OSAS may
help correct specifi c anatomic abnormalities responsible for
causing upper airway obstruction (Table 25.6).
What is CSA and what causes it? What is CSR?
Central sleep apnea (CSA) is a condition characterized by
recurrent cessation of respiration during sleep, with the observed
apnea having no associated ventilatory effort (Fig. 25.4). A CSA
may be due to idiopathic/primary disorders, or be caused by
medical and neurological conditions, drugs, or ascent to high
altitude (Table 25.7).
Cheyne-Stokes respiration (CSR) is a subtype of CSA
in which a breathing pattern consists of hypopneas alternating
with hyperpneas. During such episodes, the patient’s VT
gradually waxes and wanes in a crescendo-decrescendo pattern
What is primary CSA? What is it associated with? What is CSR usually associated with? Why are high altitude periodic breathing and CSR more common in men? Which drugs are associated with CSA?
Primary CSA is a rare idiopathic subtype of CSA diagnosed
after ruling out other secondary causes of CSA or CSR, and
it typically affects middle-age to elderly individuals. CSA due
to Cheyne-Stokes respiration occurs in subjects 60 years and
older with congestive heart failure, cerebrovascular disease,
and renal insuffi ciency, with a male predominance. Highaltitude
periodic breathing occurs more commonly in men
who recently ascended to high altitude (≥4,000 m). The
increased prevalence of both CSR and high-altitude periodic
breathing in men compared to women is attributed not only to their higher prevalence of cardiovascular disease and outdoor
activity participation but also to greater ventilatory chemoresponsiveness
in men. Long-acting opioids (eg, methadone,
time-released morphine, and hydrocodone) taken for at least 2
months are the most common drugs associated with CSA.
Explain the pathophys of CSA and CSR, including the pathophys of CSR associated with CHF.
A high ventilatory chemoresponsiveness to Paco2 is believed
to be the underlying predisposing factor for the development
of CSA and CSR. In CSA patients with such increased ventilatory
chemoresponsiveness, sleep-related rises in Paco2 stimulate
an exaggerated ventilatory response, resulting in subsequent decrements
of the Paco2 to below the patient’s apneic threshold.
This exaggerated hyperpnea for a given disturbance (apnea or
hypopnea with resulting ↑Paco2 and/or ↓Pao2), or high loop
gain, is considered most likely to produce these sustained
oscillations in the system leading to periodic breathing or
CSR (Fig. 25.6).
In patients with CSR due to congestive heart failure, the
circulatory delay time, measured from the termination of the
central apnea to the nadir of Sao2%, is inversely related to Q˙ .
The prolonged circulatory delays in patients with heart failure
refl ect the longer time required for oxygenated blood to travel
from the pulmonary veins and left ventricle to a pulse oximeter
probe attached to the fi nger or ear because of their cardiac
pump failure. Heart transplantation has been demonstrated to
reduce circulatory delay time in patients with congestive heart
failure and CSA-CSR. However, their high ventilatory chemoresponsiveness
and dysregulated control of breathing seem to
persist post-transplantation in this cohort.
explain the diagnosis of CSA and CSR.
A diagnosis of CSAS requires clinical features (excessive daytime
sleepiness, frequent arousals and awakenings, insomnia
complaints, or awakenings due to dyspnea), plus a polysomnogram
showing a central apnea index of ≥5 scoreable events per
hour of sleep. A central apnea is a respiratory event characterized
by cessation of airfl ow lasting at least 10 seconds that
is unaccompanied by respiratory effort. The diagnosis of CSR
is confi rmed by a polysomnogram showing at least 10 central
apneas and hypopneas per hour of sleep, occurring in a crescendodecrescendo
pattern of VT accompanied by frequent arousals
from sleep and derangement of sleep structure.
Describe various therapeutic approaches to CSAS.
Most published clinical trials for CSAS focus on the treatment
of CSA-CSR that is due to congestive heart failure. Optimizing
treatment of such patients with congestive heart failure
(eg, antihypertensives/vasodilators, diuretics, and inotropes,
coronary revascularization, etc) is the fi rst step in treating
their CSA-CSR. Supplemental O2 therapy increases body
O2 reserves and blunts hypoxemic respiratory drive, thereby
reducing central apneas and periodic breathing pattern and
enhancing quality of life in patients with CSR due to CHF.
Acetazolamide, a carbonic anhydrase inhibitor, induces a
mild metabolic acidosis that stimulates respiration by increasing
the difference between the subject’s prevailing Paco2 and
their apneic Paco2 threshold. Acetazolamide improves central
sleep apnea, nocturnal oxygenation, and related daytime
symptoms. Theophylline, a phosphodiesterase inhibitor, has
excitatory effects on breathing, enhances ventilation, reduces
respiratory disturbances, and increases nocturnal oxygenation.
However, theophylline also nearly doubles circulating renin
levels in CHF patients. As for OSA patients, the use of CPAP
has been shown to improve left ventricular ejection fraction,
mitral regurgitant fraction, atrial natriuretic peptide level, and
ventilation effi ciency in patients with CSA-CSR due to CHF.
However, a large, randomized controlled trial conducted in
Canada found that CPAP did not affect overall survival in all
patients with CSA-CSR due to CHF, except in those whose
central apneas are suppressed soon after CPAP initiation.
Variable or bilevel positive airway pressure (BiPAP)
ventilation, in which the positive airway pressure applied is higher during inspiration than during expiration, appears to be
as effective as CPAP in improving respiratory disturbances,
nocturnal oxygenation, and sleep architecture in patients
with CSR due to CHF (Chap. 30). Adaptive support servoventilation
(ASV) suppresses CSA and/or CSR in CHF
patients and improves their sleep quality better than CPAP
or O2 supplementation. Use of ASV automatically adjusts the
positive inspiratory PAW according to the patient’s fl uctuating
VT pattern. In patients with symptomatic sinus bradycardia,
the use of atrial overdrive pacing signifi cantly reduced
central apneas in one study, presumably by increasing Q˙ via
an increase in heart rate. Low-fl ow supplemental CO2 raises
the patient’s Paco2 above their apnea threshold and has been
demonstrated to improve CSA and CSR in patients with CHF.
However, such CO2 supplementation is ineffective in reducing
arousals and is associated with sympathetic activation that
may be detrimental in CHF.
Descending just 500-1,000 m of elevation can ameliorate
most high altitude clinical syndromes, including acute mountain
sickness, high-altitude periodic breathing, and high-altitude pulmonary
edema (Chap. 13). At altitude, nocturnal O2 enrichment
of the ambient air to an effective FIo2 = 0.25 can ameliorate the
central apneas and periodic breathing and improve both sleep
quality and daytime function. As mentioned above, theophylline
and acetazolamide both normalize sleep disordered breathing
at high altitude. Temazepam, a benzodiazepine receptor
agonist, reduces periodic breathing at high altitude by consolidating
sleep. However, its use has been associated with a small
decrease in nocturnal Sao2%. Zolpidem, a non-benzodiazepine
receptor agonist, improves sleep quality without affecting respiration
at high altitude.
In patients with known or suspected drug-related CSA,
the discontinuation of long-acting opioid medications, their
substitution with non-narcotic medications, or reduction of the
narcotic dose may each help ameliorate periodic breathing.
What is compsas and how does it differ from Mixed apnea?
Complex sleep apnea syndrome (CompSAS) is a form of
sleep apnea specifi cally identifi ed by the persistence or emergence
of central apneas or hypopneas upon exposure of a patient
to CPAP when any obstructive events have disappeared.
C L I N I C A L CO R R E L AT I O N 2 5 . 2
CompSAS should be distinguished from the term mixed
apnea. While CompSAS is diagnosed by unmasking central
apneas when using CPAP in a patient with OSA, a mixed
apnea is a specifi c respiratory pattern that begins as a
central apnea but ends as an obstructive event (Fig. 25.7).
Mixed apneas are traditionally considered as “obstructive”
respiratory events, although mixed apneas can also be
present in CompSAS.
What is the pathophys of compsas
The pathophysiology of this disorder involves the combination
of an anatomically narrow and excessively collapsible airway
with a highly sensitive hypocapnia-induced apneic threshold. Baseline polysomnography in CompSAS patients typically
demonstrates OSAS, and features predominantly obstructive
respiratory events (apnea, hypopneas, and respiratory-effort
related arousals). With administration of CPAP to eliminate
upper airway obstruction, however, the dysregulated central
control of ventilation is unmasked, causing the emergence of
central apneas and a Cheyne-Stokes breathing pattern. The
lowering by CPAP of Paco2 below the patient’s apneic threshold
likely precipitates the central apneas in those CompSAS
patients with highly sensitive hypocapnia-induced ventilatory
control system. Meanwhile, excessive CPAP that increases
intrathoracic pressures and hyperinfl ation may also trigger
central apneas via the Hering-Breuer refl ex (Chap. 11).
How is compsas diagnosed?
In a patient presenting with clinical features of a sleep apnea
syndrome, the diagnosis of CompSAS is based upon an initial
baseline polysomnogram that demonstrates predominately
obstructive respiratory events occurring at least fi ve times per
hour. Then a subsequent therapeutic CPAP trial should demonstrate
the resolution of obstructive respiratory events and the emergence of prominent or disruptive central apneas (again
≥5/h) and/or a Cheyne-Stokes respiratory pattern.
How is compsas treated?
As mentioned above, the use of adaptive support servoventilation
(ASV) appears to be superior to other PAP therapies
in controlling the respiratory disturbances in CompSAS. Several
promising therapies, including positive airway pressure
with gas modulation using a low FIco2 (PAPGAM), artifi cially
enhanced dead space, and prescription of acetazolamide,
all aim to stabilize chemoreceptor control of respiration by
inducing metabolic acidosis or raising Paco2 above a patient’s
Define sleep-related hypoventilation/hypoxemic syndrome. How is it classified?
Sleep-related hypoventilation/hypoxemic syndrome (SRH)
is a group of breathing disorders characterized by decreased ˙VA
from various causes that exclude OSA, all of which decrease
Sao2% and increase Paco2 during sleep. Most authors divide
SRH into two categories based on their underlying etiologies.
Primary or idiopathic
Sleep related non-obstructive alveolar hypoventilation
Congenital central alveolar hypoventilation syndrome (Ondine’s curse)
Secondary sleep related hypoventilation/hypoxemia due to a medical condition
Pulmonary parenchymal abnormalities, eg, interstitial lung disease
Pulmonary vascular abnormalities, eg, pulmonary embolism, right-to-left shunt
Lower airways obstruction, eg, chronic obstructive pulmonary disease
Neuromuscular disorder, eg, amyotrophic lateral sclerosis
Chest wall disorders, eg, kyphoscoliosis, obesity-related hypoventilation
How common are the primary cases of SRH? What is CCAHS associated with? What is sleep related non-obstructive alveolar hypoventilation associated with?
The demographics of patients with secondary SRH parallel
those of the underlying causative medical conditions. The primary
SRH syndromes occur very rarely, with only 160-180
confi rmed cases of CCAHS having been reported worldwide.
CCAHS affects newborns and infants, and is associated with
other congenital abnormalities including Hirschsprung disease,
autonomic dysfunction, neural tumors, swallowing dysfunctions, and ocular abnormalities. CCAHS usually occurs sporadically
but some cases are related to de novo mutations of the
PHOX2B gene. In contrast, little is known about the epidemiology
of adult idiopathic sleep-related non-obstructive alveolar
hypoventilation syndrome, whose onset is during adolescence
and early adulthood.
What is the pathophys of the primary SRHs? What is the pathophys of the secondary ones?
Idiopathic and congenital forms of SRH are characterized
by decreased ventilatory responsiveness to hypercapnia or
hypoxia during both wakefulness and sleep. Such altered
responsiveness is due to a postulated lesion in the medullary
chemoreceptors (adult idiopathic type) or to an abnormality
in brainstem integration of chemoreceptor afferents (congenital
type). Mutations of PHOX2B, which has an autosomal
dominant mode of transmission with incomplete penetrance,
appear to impair respiratory control function of the retrotrapezoid
nucleus in the rostral medulla in infants with CCAHS
(Chap. 11). By comparison, SRH due to medical conditions
most often is traceable to ventilation-perfusion abnormalities
(Chap. 8) including mechanical ventilatory insuffi ciencies
that are associated with these serious conditions.
How is Primary SRH diagnosed both in newborns and adults? How is secondary SRH diagnosed?
CCAHS is suspected in a newborn who presents with sustained
shallow breathing, cyanosis, and apnea during sleep (Fig. 25.8). In older patients, a diagnosis of idiopathic SRH
is made in adolescents and adults only after excluding medical
conditions that can cause secondary SRH. The syndrome
is characterized by blunted chemoresponsiveness that causes
daytime hypercapnia and hypoxemia despite normal mechanical
properties of the lungs and chest. When left untreated,
these primary alveolar hypoventilation syndromes can progress
to pulmonary hypertension and death.
In SRH secondary to medical conditions, the diagnosis
requires a polysomnogram and/or arterial blood gases that
demonstrate persistent nocturnal hypoxemia and/or hypercapnia
in the absence of obvious obstructive apneas or periodic
breathing in a patient with a predisposing medical, neurologic,
or muscular condition (Table 25.9).
Polysomnograms or ABGs obtained during sleep showing at least one of the following:
An SaO2 during sleep of 5 minutes with a nadir of ≤85%; OR
>30% of total sleep time with SaO2 of <90%; OR
Sleeping ABGs with a Paco2 that is abnormally high or disproportionately increased relative to levels during wakefulness.
What therapeutic approaches are there for Primary and secondary SRH?
Treat underlying cause
Weight loss for obesity
Inhaled steroids and bronchodilators for COPD
Anticholinesterase (i.e., pyridostigmine) for myasthenia gravis
Noninvasive ventilation (i.e., Bilevel PAP)