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11. ABNORMALITIES OF BREATHING IN SLEEP

Contents

11.1 Breathing During Normal Sleep
11.2 Snoring
11.3 Obstructive Sleep Apnoea

11.3.1 Pathophysiology of Snoring & Obstructive Sleep Apnoea

11.4 Central Sleep Apnoea
11.5 Primary Alveolar Hypoventilation
11.6 References

11.1 BREATHING DURING NORMAL SLEEP
Important physiological changes occur within the respiratory system during normal sleep. These include an alteration of the sensitivity of the central respiratory controller to changes in arterial levels of oxygen and carbon dioxide (i.e. chemoreceptor feedback) and changes in its sensitivity to feedback from chest wall and respiratory muscle receptors. There is also a fall in the neural output from the respiratory center (i.e. a fall in "respiratory drive"). Furthermore, the fall in muscle tone that occurs in sleep means that the resistance of the upper airway (against which the respiratory muscles must work) increases. During rapid eye movement (REM) sleep, the only active muscle of respiration is the diaphragm - thus if its action is compromised, hyperventilation may be seen in REM sleep. The key abnormalities of breathing during sleep include:
- Snoring
- Obstructive Apnoea
- Central Apnoea (including central sleep apnoea seen in cardiac failure)
- Mixed Apnoea
- Hypoventilation

11.2 SNORING
Snoring is a loud noise usually generated during the inspiratory phase of respiration during sleep by rapid vibration of the soft palate and pharyngeal walls. It is indicative of inspiratory airflow limitation in the oropharynx i.e. that the airway is partially obstructed. In general, the louder the snoring the greater the obstruction. Heavy snorers usually make vigorous efforts to breath (i.e. much greater muscle effort than while awake). Despite extremely large suction pressures (e.g. a pleural pressure of -80 to -100 cmH2O compared to -2 to -5cmH2O normally) the airflow through the oropharynx is often insufficient to maintain blood gas tensions.

Snoring is very common, affecting as many as 30% of an adult male population. Snoring is less common in females but its prevalence increases to the male level after the menopause.

Heavy, habitual snoring (all night, every night) is a risk factor for the development of cardiovascular disease. It is a provoking cause of systemic hypertension and is usually the forerunner of obstructive apnoea. A history of heavy snoring is also an established risk factor for stroke. Its causes are similar to those of obstructive apnoea. Moderate weight gain typically precipitates snoring in many subjects and nasal obstruction does so in others. Alcohol consumption is another important provoking factor and invariably precipitates obstructive apnoea in heavy habitual snorers if taken before sleep.

A 'snoring history' should be part of a medical examination. Because most snorers don't hear themselves, the history of a spouse or bed partner is essential.

11.3 OBSTRUCTIVE SLEEP APNOEA
This is an extreme form of snoring in which complete closure of the oropharynx occurs during sleep. There is no airflow into the lungs (hence apnoea) despite inspiratory efforts by the respiratory muscles. Apnoeas may continue for 10-60 seconds (sometimes longer) and asphyxia develops (a falling PaO2 and rising PaCO2). The apnoea is terminated when asphyxia and increasing respiratory efforts trigger a brief awakening; this leads to a return of muscle tone in upper airway dilator muscles (particularly the tongue muscles) and 4 or 5 loud snoring breaths occur before the subject drifts back into sleep and another apnoea occurs. Events may occur repeatedly over night and there is a wide range of severity.

a. Severe: in these patients sleeping and breathing are mutually exclusive! The cycle of apnoea, then awakening with 4-5 breaths, occurs for the entire sleep period, with between 200 and 400 apnoeic episodes per night. During each apnoea there is a marked fall in oxygen level in the arterial blood, typically to below 80% saturation for most of the night (remember = PaO2 of less than 47mmHg). Although the character of sleep in these patients is abnormal - interrupted and variable - they do have REM-like sleep; it is in this state that the most severe desaturation occurs. These patients often present with cardiac failure, awake respiratory failure or neurologic symptoms (see below), as well as the more typical symptoms of loud snoring, witness apnoeas and excessive daytime somnolence.

b. Moderate: in this group there is repetitive apnoea throughout the night and less severe desaturation. These patients often go on for years without developing other obvious complaints apart from the major symptom of daytime somnolence.

c. Mild: in this group, apnoea tends to occur in epochs throughout the night with periods of loud snoring without apnoea. The runs of apnoea may occur for 10-15 minutes, typically at sleep onset or in REM sleep and are more likely to be dependent on sleep posture (e.g. occur only in the supine position). These patients often have only mild sleepiness but defective short-term memory function appears to be an important consequence.

a. Cause of upper airway obstruction
The oropharynx is a muscular tube which depends on muscle tone for patency. Muscle blocking (in anaesthetics) provides upper airway obstruction in many normal subjects. Many of the 23 pairs of muscles which regulate upper airway patency are activated during the respiratory cycle i.e. they are 'accessory respiratory muscles'. The tongue muscles (genioglossi) form the anterior wall of the oropharynx and are activated during every inspiratory effort. This increase in tone during inspiration counteracts the suction forces (generated by the inspiratory pump muscles - especially diaphragm) of inspiration. During sleep there is a loss of background muscle tone and reduced phasic inspiratory activation of the dilator muscles in normals - thus the upper airway resistance increases.

major underlying cause of sleep apnoea is a physically narrow oropharyngeal airway - often because of fat infiltration of the surrounding tissues. When this underlying narrowing is combined with a loss of muscle tone (in sleep), complete obstruction occurs. However, any cause of neuromuscular weakness of the upper airway (e.g. bulbar palsy) may cause sleep apnoea.

b. Mechanism of Symptoms
Two major events cause the symptoms of sleep apnoea:

i. Sleep fragmentation
Apnoeas are terminated by a reflexly induced arousal (the asphyxia, stimulates chemoreceptors, causing arousal). When this occurs repetitively all night there is major fragmentation of sleep. The subject is unable to proceed through the orderly cycles of sleep. Although the total sleep time may appear greater than normal, it is of poor quality. This sleep fragmentation causes a main symptom - excessive daytime sleepiness.

ii. Repetitive asphyxia
Repeated episodes of unstable respiratory failure (e.g. upwards of 400 episodes of progressive asphyxia to between 80% and 50% saturation every night) is the major cause of the serious medical complications of sleep apnoea. They are:

• Right heart failure - this results from hypoxia-induced pulmonary hypertension
  
• Sustained hypoventilation even while awake
  
• Brain damage
  
• Left heart failure
  
• Cardiac arrhythmias

c. Symptoms and Clinical Presentation
Sleep apnoea is readily diagnosed by the two key symptoms of heavy snoring and excessive daytime sleepiness. However, the physician must enquire about these two symptoms. They are rarely volunteered by the patient. Typically the snoring has been a source of embarrassment and sleepiness is widely regarded as a sign of laziness. Often the sleepiness has developed over such along period, e.g. 2 - 10 years, that the sufferer has no clear idea of what is normal and what is not. A collaborative history from a spouse or bed partner is of great value and should be sought. The spouse will often describe apnoeas - 4 or 5 loud snores and 20-40 seconds of silence repeated over and over all night. The pattern as well as intensity of snoring are important. Occasionally the intensity of snoring decreases when the subject starts to have obstructive apnoea.

i. Snoring:
15-20 year history; more recent change to interrupted pattern.

ii. Excessive Daytime Sleepiness:
At first this is simply an exaggeration of a normal individual's sleepiness. The after luncheon drowsiness becomes a little more marked etc. The tendency to 'nod off in front of the TV' becomes a typical occurrence. In its full form, abnormal daytime sleepiness is readily recognised:

• falling asleep while driving only short distances, e.g. falling asleep while stopped at red lights
  
• falling asleep while talking, eating, etc
  
• waking each morning and still feeling sleepy after breakfast

d. Other Symptoms

• Non-restorative sleep
  
• Restless sleep
  
• Abnormal motor activity in sleep
  
• Morning headache (like that seen in raised CSF pressure)
  
• Episodes of confusion at night or on waking in the morning
  
• Chest pain ('atypical' subcostal or parasternal the result of vigorous obstructed efforts all night)
  
• Dry, sore throat on waking
  
• Impotence
  
• Nocturia - Dementia
  
• Depression
  
• Psychiatric syndromes (aggression, apathy etc)

• Unexplained heart failure (especially RHF)
  
• Nocturnal/morning cardiac arrhythmias
  
• Night choking
  
• Paroxysmal nocturnal dyspnoea
  
• Unexplained polycythemia
  
• Hypothyroidism
  
• Acromegaly
  
• Obesity
  
• Unexplained daytime respiratory failure

f. The Endocrine Syndrome
Sleep apnoea probably occurs in the majority of patients with acromegaly, and is sometimes the presenting symptom. It is the result of macroglossia and mucus membrane swelling in the nasal and oropharyngeal airway. It does not resolve on treatment of the pituitary tumour.

Hypothyroid patients often have sleep apnoea. The 'sleepiness' previously attributed to low metabolic rate is often the result of sleep apnoea. The mechanism is macroglossia and sometimes myopathy affecting the oropharyngeal muscles (the myopathy is usually obvious as it affects other muscles). Most patients have a major improvement of their sleep apnoea when treated with thyroid replacement. However, failure to recognise sleep apnoea can be a cause of early difficulties in the initiation of therapy. Any patient with hypothyroid coma should be strongly suspected of having sleep apnoea. Failure to recognise and treat sleep apnoea in this group of patients is likely to be a major reason why they have such a high mortality.

Obesity
In some patients, severe sleep apnoea is a major cause of failure of weight control. These patients often do well after their sleep apnoea is treated.

g. Other causes of excessive daytime sleepiness

i. Narcolepsy:

• REM onset
  
• vivid dreams
  
• sleep 'attacks'
  
• cataplexy

ii. Drug addiction

iii. Depression

iv. Brain tumour

11.4 CENTRAL SLEEP APNOEA
Central apnoea during sleep is not due to a single disorder. Instead it is best thought of as a manifestation of a variety of clinical conditions which may have unstable breathing as a characteristic. Much of the underlying pathophysiology is yet to be understood.

Central apnoea is characterised on the polysomnogram by an absence of airflow and an absence of respiratory effort (monitored by measuring diaphragm muscle EMG or thoracic and abdominal wall movements).

This may occur during sleep as a result of a variety of neurological processes (e.g. brainstem tumours, strokes, effects of drugs). Central apnoeic events may also be seen as a reflex response to upper airway obstruction of stimulation in small infants.

There is also a well described association between cardiac failure and regular cycles of a crescendo-decrescendo pattern of tidal volume and central apnoea during sleep ("Cheyne-Stokes" respiration).

11.5 PRIMARY ALVEOLAR HYPOVENTILATION
Rare condition in which there is awake hypoventilation which typically becomes extreme (complete apnoea) during sleep. Causes unknown. Characteristically these patients have no evidence of chemoreceptor function (?neurochemical defect). Diagnosis is by exclusion of brainstem, spinal cord and muscle pathology, all of which can cause hypoventilation. Most commonly presents in infancy (e.g. failure to breath at birth; respiratory decompensation with minor infections; unexplained heart failure). Typically misdiagnosed. Even awake these patients may have grossly abnormal blood gases with cyanosis. They are usually confused with cyanotic congenital heart disease. The clue is that they have an elevated PCO2 - i.e. the cyanosis is due to hypoventilation. May present in adult life. Readily treated if diagnosed early (ventilatory support at night).

11.6 REFERENCES

McNamara SG et al. "Obstructive Sleep Apnea" Thorax. 1993 48: 754-763.

Sullivan CE et al. "Pathophysiology of Sleep Apnea." in: Saunders NA, Sullivan CE (eds): 'Sleep and Breathing' 2nd edition. Mercel Deher. 1994. p405.