Sleep Disordered Breathing
In COPD
BY
AHMAD YOUNES
Professor of Thoracic Medicine
Mansoura Faculty of Medicine
Normal Individuals
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During NREM sleep, CO2 production falls but
alveolar ventilation falls proportionately more
and PaCO2 increases slightly .
Recall that PaCO2 = constant × (CO2
production)/(alveolar ventilation);
The fall in ventilation is due to a loss of the
wakefulness stimulus to breathe, decreased
chemosensitivity to hypoxia and hypercapnia,
and increased upper airway resistance.
The increase in PaCO2 results in a mild decrease
in the PaO2.
Normal Individuals
• Because the awake PaO2 value is on the flat portion of the
oxygen-hemoglobin saturation curve , minimal drops in
the SaO2 are noted (e.g., from 97% to 95%).
• The FRC may decrease slightly from wake to NREM sleep
During REM sleep in normal individuals, ventilation is
irregular and periods of reduced tidal volume occur, often
during bursts of REMs. Skeletal muscle hypotonia reduces
the contribution from the accessory respiratory muscles
and respiration depends on the diaphragm.
• During REM sleep, there is typically a decrease in chest
wall movement, likely due to chest wall hypotonia. These
REM-associated physiologic changes result in a slight
increase in PaCO2 and decreases in PaO2 during REM
compared with NREM sleep.
Central apnea
• A central apnea occurs when both airflow
and ventilatory effort are absent.
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE
• COPD is the fourth leading cause of death.
• Patients with COPD may die from
respiratory failure or lung cancer.
• Although they typically present to
physicians with complaints of bronchitis or
dyspnea, they also frequently complain of
poor-quality sleep.
• Daytime hypercapnia is usually associated
with an FEV1 of 30% to 40% of predicted or
less.
Sleep in COPD
1-Sleep is often impaired in both
duration and quality.
2-Many patients also have significant
hypercapnia and hypoxemia at night.
3-Ten percent to 15% of patients may
also have concomitant OSA that
worsens nocturnal gas exchange
(overlap syndrome ).
Sleep in COPD
• The typical pattern of nocturnal oxygen
desaturation in a patient with COPD is that
the baseline sleeping SaO2 falls 2% to 4%
from the awake baseline with minor
fluctuations until much larger drops are
noted during REM sleep.
• In a patient with severe COPD , the
awake SaO2 is mildly reduced at 92%
but falls to the low 80% with sleep.
Further severe falls in the SaO2 occur
during REM sleep (dark bars).
Sleep in COPD
• Many patients with COPD have an increase
in FRC in the upright position
• COPD patients with a significant
component of airways disease could
experience a drop in FRC during REM sleep.
• In COPD, the closing volume (CV) is closer
to the FRC than in normal individuals.
During the hypopneic breathing of REM
sleep, the FRC falls below the CV .
Sleep-Related Changes in Respiration in
COPD
• During supine wakefulness, often start
with low-normal or slightly decreased SaO2
values. Therefore, even the normal fall in
PaO2 with sleep will cause a greater
decrease in the SaO2.
• The onset of NREM sleep is associated with
mild falls in the SaO2 (4–8%) and PaCO2
increases. If obstructive apneas or
hypopneas are present, the degree of
desaturation is worsened.
Sleep-Related Changes in
Respiration in COPD
• During REM sleep, there are more profound
periods of arterial oxygen desaturation
compared with NREM sleep in patients with
COPD.
• These episodes of desaturation are
characterized by long periods of irregular
breathing and reduced tidal volume .
• REM-associated hypotonia reduces the
contribution for the intercostal muscles so
that ventilation depends on the diaphragm.
Sleep-Related Changes in
Respiration in COPD
• Hypoventilation definitely occurs
during periods of nonapneic
desaturation (also called
hypopneic breathing),
• V/Q mismatch is believed to play a
role in REM-associated
desaturation (in addition to
hypoventilation).
Etiology of Abnormal Nocturnal
Gas Exchange
• Patients with COPD often experience
exaggerations of normal sleep-related
changes in ventilation.
• The most severe desaturation occurs
during REM sleep.
• The relative importance of
hypoventilation and ventilationperfusion mismatch is still debated .
Time of Night and Circadian
Variation in Lung Function:
• REM episodes in the early morning have greatest REM
density and the greatest variation in ventilation even in
normal individuals. These REM periods also are typically
longer.
• In the early morning hours, there is greater lower airway
resistance due to circadian changes in bronchomotor
tone that are exaggerated in many patients with COPD.
• An increase in upper airway resistance but not lower
airway resistance during the night occure in patients with
emphysema.
• These factors help explain why the most severe and
longest REM-associated desaturation typically occurs in
the early morning hours.
COPD Types and Respiration
during Sleep:
• lower awake PaO2 and higher
PaCO2 predict more dramatic
changes in gas exchange during
sleep.
• comparing blue bloaters and
pink puffers ,the former were
more likely to desaturate during
sleep .
Sleep Quality in COPD:
• Reductions in total sleep time, stage N3
sleep, and REM sleep.
• The wake after sleep onset (WASO) and
stage N1 sleep are increased as is the
total arousal index.
• Patients often complain of insomnia but
can also complain of daytime
sleepiness if OSA is also present.
Sleep Quality in COPD:
• It is likely that other factors such as
cough, nocturnal dyspnea, and
medication side effects have greater
effect than transient hypoxemia on
sleep quality.
• In many patients, the NOD is less than
15 minutes and confined to the last
few REM periods of the night.
Indication for oxygen therapy:
1. PO2 ≤ 55 mm Hg or SaO2 ≤ 88% at rest
awake (breathing room air, stable medical
condition).
2. PO2 ≤ 55 mm Hg or SaO2 ≤ 88% for at least 5
min while asleep. in a patient with a PaO2 at
≥ 56% or SaO2 ≥ 89% at rest, Oxygen is
provided during sleep only.
3. PO2 < 55 mm Hg or SaO2 ≤ 88% during
exercise in a patient with a PaO2 at ≥ 56%
or SaO2 ≥ 89% at rest. Oxygen provided
during exercise.
Nocturnal oximetry is indicated if the
patient complains of nocturnal
symptoms or has evidence of cor
pulmonale.
• In acute respiratory failure,
administration of high-flow oxygen
can significantly worsen hypercapnia
• It seems prudent to use the lowest
oxygen flow required to maintain
adequate nocturnal oxygenation,
especially in hypercapnic patients.
Complex Sleep Apnea (CompSA)
• CompSA consists of all or predominantly
obstructive apneas which convert to all or
predominantly central apneas when
treated with a CPAP or bilevel devices.
Bronchodilators:
• long-acting inhaled bronchodilators improve
nocturnal oxygenation in COPD patients.
• Theophylline did not worsen sleep quality but
improved the morning FEV1 and SaO2 during NREM
sleep.
• Inhaled ipratropium bromide improved
subjective sleep quality, NOD, and the amount of
REM sleep. Tiotropium given either in the
morning or in the evening improved the SaO2
during REM sleep compared with placebo but did
not improve sleep quality.
Bronchodilators:
• Most clinicians would use a long-acting
beta agonist or anticholinergic in patients
with significant COPD who complain of
nocturnal dyspnea, cough, or poor sleep
quality.
• The use of inhaled corticosteroids does not
improve mortality but, improved the quality
of life, reduced exacerbations, and
improved lung function when added to a
long-acting bronchodilator.
Hypnotics in COPD Patients:
• In nonhypercapnic patients, clinically significant
worsening of gas exchange does not occur with
benzodiazepine receptor agonists.
• The only objective improvement in sleep was an
increase in stage N2. Subjective sleep quality
was also improved .
• The effects of zolpidem and triazolam in mild to
moderate COPD showed that total sleep time was
increased as well as sleep efficiency without an
adverse effect on gas exchange.
Hypnotics in COPD Patients:
• No worsening of nocturnal gas exchange,
an improvement in total sleep time, sleep
efficiency, and the latency to persistent
sleep on ramelteon compared to placebo.
• In summary, the benzodiazepine receptor
agonists are probably safe in
nonhypercapnic nonhypoxemic patients.
However, caution is still required.
• Ramelteon is a safe hypnotic that may be
effective in some patients with COPD.
Nocturnal Noninvasive PositivePressure Ventilation:
For patients with COPD who present with
hypercapnic respiratory failure,
noninvasive positive-pressure ventilation
has proved to be an effective treatment,
often avoiding the need for intubation and
mechanical ventilation.
The results for long-term use are much less
clear. Those COPD patients most likely to
benefit are individuals with substantial
daytime CO2 retention and NOD who are
highly motivated.
Nocturnal Noninvasive PositivePressure Ventilation:
Indications for NPPV in COPD:
1. Symptoms criteria (e.g., fatigue,
dyspnea, or morning headache),
2. Daytime PaCO2 > 55 or 50–54 mm Hg
with NOD, or
3. PaCO2 50–54 mm Hg with recurrent
hospitalization related to episodes of
hypercapnic respiratory failure.
COPD – OSA overlap syndrome
• Patients with the overlap syndrome
(COPD + obstructive sleep apnea) can
develop hypercapnia with higher FEV1
values.
• Oximetry of a patient with the overlap
syndrome show low baseline
sleeping SaO2 and a saw-tooth pattern
consistent with repeated discrete
events.
In a patient with both snoring and moderate COPD. the
baseline is reduced during sleep but the saw-tooth
pattern is suggestive of obstructive sleep apnea. A = period
of REM sleep.
Overlap Syndrome
• OSA is no more frequent in COPD patients
than in the general population. The
prevalence of OSA in COPD patients is the
same as in the general population.
• Because both are common, the combination
is also fairly common.
• The two groups of OSA patients with daytime
hypercapnia include patients with the
obesity hypoventilation syndrome and some
patients with OLS.
Overlap Syndrome
• Patients with OLS tend to have severe
NOD even if they do not have daytime
hypercapnia.
• Patients with COPD usually become
hypercapnic when the FEV1 is around
40% of predicted.
• OLS patients can be hypercapnic with
milder reductions in the FEV1 .
Overlap Syndrome
• Individuals who have the overlap syndrome have
been recognized to have greater risk for
pulmonary hypertension , right heart failure , and
hypercapnia than patients who have either
disorder alone.
The traits possessed by those who have the overlap
syndrome were the classic ‘‘blue bloater’’
phenotype of COPD, in which obesity and snoring
are relatively common.
Overlap Syndrome
• Clinical practice, one often treats
patients with a combination of
COPD, OSA, and severe obesity who
have significant hypoventilation. It
is difficult to know how to label
them because they likely have
components of both OHS and OLS.
Overlap Syndrome
• These patients demonstrated clinical
improvement with positive airway
pressure and had limited symptomatic
improvement with supplemental
oxygen.
• Individuals who had the ‘‘pink puffer’’
did not typically demonstrate OSA and
responded well to supplemental
oxygen but not to positive airway
pressure.
Consequences:
1-Inflammation
Inflammatory mediators are elevated in
OSA, (Significant elevation in (NF-kB) ,
tumor necrosis factor, IL-6, C-reactive
protein , and homocysteine )
• COPD is an inflammatory airways
disorder, and with the inflammatory
mediator elevation seen in COPD,
coexistent OSA could lead to
deterioration of COPD.
2-Quality of sleep
• Poorer quality of sleep in patients
who have COPD and OSA.
• Disturbed sleep in patients who have
COPD has also been demonstrated,
with reduced sleep efficiency and
total sleep time, delay in sleep onset,
and increased WASO
• Insomnia and sleep disruption is well
described in patients who have OSA,
3-Pulmonary hemodynamics
• The mechanism of pulmonary pressure
elevation seems to be relatively severe
hypoxemia and not the inflammatory
aspect of COPD.
• The degree of sleep apnea based on AHI
was a weak predictor of pulmonary arterial
hypertension (PAH), whereas nocturnal
desaturation was a more significant
determinant of the presence of PAH.
• overlap syndrome show elevations in
pulmonary pressure,
4- Cardiac disease and arrhythmia
• In patients who have COPD, premature
ventricular contractions have been
observed to be common in sleep
particularly in those who have nocturnal
SaO2 less than 80% .
• In patients who have OSA, more significant
arrhythmias have been noted. ,the entire
spectrum of cardiac arrhythmias has been
observed in patients who have OSA.
Cardiac disease and arrhythmia
• The most common abnormality, seen in
severe OSA, is marked sinus arrhythmia,
characterized by bradycardia during
apnea, followed by tachycardia on
resumption of respiration.
• OSA is also an independent risk factor for
atrial fibrillation , an arrhythmia that is
common in the COPD population.
• In overlap syndrome ,rhythm disturbances
should be worse in these individuals as a
result of more profound hypoxemia.
5- Quality of life
• Those who had the overlap syndrome had
significantly elevated St. George’s
respiratory questionnaire scores for total
score and for each of the three components
as compared with patients who had COPD
alone.
6-Mortality
• An increase in mortality in patients who have
untreated OSA, with most of this increase
attributed to cardiovascular causes .
• The mortality associated with OSA is significantly
increased with the presence of COPD.
Evaluation
• Testing for sleep apnea is not necessary in all
patients who have COPD.
• Individuals who have COPD who possess typical
risk factors for OSA, such as obesity, chronic
snoring, enlarged neck, daytime sleepiness, and
hypertension, should be evaluated according to
standard screening practices.
• Other individuals who should undergo evaluation
include those who have polycythemia, cor
pulmonale, pulmonary hypertension, and
neuropsychologic impairments.
Evaluation
• Individuals may first come to clinical
attention after initiation of mechanical
ventilation for respiratory exacerbations of
COPD. In such instances, clinical evaluation
for the presence of COPD and risks for OSA
are appropriate.
• Individuals who have known COPD along with
obesity ,chronic snoring, and daytime
somnolence may warrant empiric treatment
while hospitalized with PSG at or soon after
hospital discharge to assess for OSA.
Evaluation
• The most appropriate method for
diagnosis of the overlap syndrome
continues to be routine PSG
• Nocturnal oximetry, although
sufficient for identifying those who
have severe desaturations, is not able
to detect those individuals who have
more subtle sleep-disordered
breathing
Treatment of OLS
• Treatment of patients with OLS with
supplemental oxygen alone can result
in significant increases in nocturnal
PaCO2.
• On room air, there is a saw-tooth
pattern in the SaO2 tracing, this is a
clue that OSA as well as COPD is
present.
Obesity hypoventilation syndrome
• on supplemental oxygen and TcPCO2) has climbed from
approximately 60 mm Hg (top tracing) to just below 90 mm
Hg. Therefore, use of supplemental oxygen in patients with
OLS and significant daytime hypercapnia may worsen
nocturnal hypercapnia.
On supplemental oxygen TcPCO2 has climbed from approximately
60 mm Hg (top tracing) to just below 90 mm Hg. Therefore, use of
supplemental oxygen in patients with OLS and significant daytime
hypercapnia may worsen nocturnal hypercapnia.
Treatment of OLS
• The treatment of OLS includes
treatment of their COPD and CPAP or
BPAP with supplemental oxygen if
needed, oral appliances .
• If significant CO2 retention is present,
most clinicians would use BPAP.
• Some patients with COPD have difficulty
exhaling on CPAP and may be more
adherent to treatment with BPAP.
Treatment of OLS
• Auto-titrating CPAP, though
commonly used in clinical
practice, is not currently
recommended for individuals
who have COPD.
• .
Treatment of OLS
• Patients who have COPD and mild OSA but
significant nocturnal hypoxemia may be
poorly tolerant of CPAP and be best treated
with oxygen and optimum medical
management of their COPD.
• In patients who have more severe forms of
OSA ,treatment with CPAP is beneficial for
improving the AHI, nocturnal hypoxemia
/hypercapnia, ,daytime sleepiness., blood
pressure reduction, and fatal and non-fatal
cardiovascular events
Treatment of OLS
• Because low arterial oxygen may lead
to pulmonary hypertension, cor
pulmonale, impaired cognitive function,
and polycythemia, these data supporte
supplemental oxygen in patients who
have COPD with respiratory failure.
• Careful consideration of concomitant
medical illnesses, such as obesity,
heart failure, and secondary pulmonary
hypertension, should also be made.
Implications in ICU patients
• Patients admitted with the OLS may not be
recognized to have either disorder on
admission.
• Admission for respiratory exacerbation of
COPD is a common ICU diagnosis, and often
presents with respiratory failure and
intubation with mechanical ventilation.
• Patients who have concomitant obesity, a
history of habitual snoring, or hypertension
should be considered at risk for having the
overlap syndrome.
Implications in ICU patients
• These patients are at potentially greater
risk for the consequences of sleep
disruption common in ICU patients and
should be closely monitored on extubation.
• Untreated OSA may be a factor in recurrent
failed attempts at extubation;
consideration of this possibility might
reasonably lead to empiric CPAP or even
early tracheotomy in individuals who
appear likely to have OSA and who
repeatedly fail weaning and extubation.