Sleep Disordered Breathing In COPD

BY

AHMAD YOUNES

Professor of Thoracic Medicine

Mansoura Faculty of Medicine

Normal Individuals• 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 apneaCentral apnea

• A central apnea occurs when both A central apnea occurs when both airflow and ventilatory effort are airflow and ventilatory effort are absentabsent.

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 COPD1-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.

• 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

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 ventilation-perfusion 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 Positive-Pressure 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 Positive-Pressure 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.

•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.

Overlap Syndrome

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.

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