14: Sleep‐related disorders

CHAPTER 14
Sleep‐related disorders


Abbreviations



AHI
apnoea/hypopnoea index
BiPAP
bilevel positive airways pressure
BMI
body mass index
CPAP
continuous positive airways pressure
CSA
central sleep apnoea
DVLA
Driver and Vehicle Licensing Agency
ECG
electrocardiogram
EDS
excessive daytime sleepiness
EEG
electroencephalogram
EMG
electromyelogram
ENT
Ear, Nose, and Throat
EOG
electro‐oculogram
ESS
Epworth Sleepiness Scale
HDU
high dependency unit
ICU
intensive care unit
IH
idiopathic hypersomnia
IOD
intra‐oral device
LAUP
laser‐assisted uvulopalatopharyngoplasty
MAD
mandibular advancement device
MSLT
multiple sleep latency test
MWT
maintenance of wakefulness test
OSA
obstructive sleep apnoea
OSAHS
obstructive sleep apnoea hypopnoea syndrome
PO2
partial pressure of oxygen
PCO2
partial pressure of carbon dioxide
PLMD
periodic limb movement disorder
PSG
polysomnography
RBD
REM behaviour disorder
RDI
respiratory disturbance index
REM
rapid eye movement
RLS
restless leg syndrome
UARS
upper airways resistance syndrome
UPP
uvulopalatopharyngoplasty

Introduction


In this chapter, there will be a description of normal sleep physiology and the autonomic changes that occur during sleep. The symptoms and conditions that can affect people when they sleep will be discussed. Upper airways resistance syndrome (UARS) and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) are common conditions that present with snoring and excessive daytime sleepiness (EDS). OSAHS can lead to systemic hypertension and can severely impair the individual’s quality of life. Treatment with continuous positive airways pressure (CPAP) can be effective in severe cases, while milder cases may benefit from an intra‐oral device and lifestyle modifications. Rarer causes of hypersomnia include narcolepsy, periodic limb movement disorder, and idiopathic hypersomnia. Central sleep apnoea (CSA), which is much rarer than OSAHS, can be differentiated from OSAHS by the absence of ventilatory drive. These conditions are all classified according to the International Classification of Sleep Disorders.


Sleep physiology


Sleep is essential, but the physiology of sleep and the reasons why it is necessary are poorly understood. Sleep architecture varies with age, hormonal factors, and with external factors, such as sedatives and alcohol, so it can be difficult to define what is normal.


During sleep, consciousness is partly or totally suspended and muscle tone, including that of the respiratory muscles, is reduced. The respiratory centre in the medulla becomes less responsive to cortical, chemical, and mechanical stimuli, resulting in a fall in minute ventilation, a reduction in respiratory rate, a slight reduction in pO2 and a small increase in pCO2. These changes occur predominantly during rapid eye movement (REM) sleep. Individuals with respiratory disease which compromises their breathing when awake can become decompensated during sleep, with nocturnal hypoxaemia and hypercapnia, resulting in ventilatory failure.


The stages of sleep can be divided into non‐rapid eye movement (non‐REM) and rapid eye movement (REM) sleep. An understanding of these stages of sleep has been gained by monitoring brain wave activity during sleep using an electroencephalogram (EEG). An electro‐oculogram (EOG) can accurately differentiate between REM and non‐REM sleep.


Non‐REM sleep


Non‐REM sleep is subdivided into four stages during which the individual goes from a relaxed, but awake, state to being deeply asleep and less able to be roused (Figure 14.1). There is a progressive loss of alpha wave activity, with a slowing in the frequency of, and an increase in the amplitude of the waves measured on EEG. During Stage 2, the individual is completely asleep, and the EEG shows a further decrease in frequency of the waves, with spindles and k‐complexes. During this period there is a decrease in muscle tone, pulse rate, respiratory rate, and temperature. Stages 3 and 4 are characterised by the presence of lower frequency delta waves. Nightmares, parasomnias, sleep walking, and nocturnal enuresis can occur during this stage. Each stage of non‐REM sleep lasts between 5 and 15 minutes.

Flow diagram illustrating the brain wave activity during normal sleep, from awake (beta waves) to REM sleep (“saw tooth” waves), each with graphical representation of their corresponding waveforms on the right.

Figure 14.1 Brain wave activity during normal sleep.


It generally takes about 70 minutes to drift from wakefulness through the stages of non‐REM sleep before entering REM sleep. The individual spends 30 minutes in REM sleep before entering non‐REM sleep again.


REM sleep


REM sleep is characterised by rapid eye movements as demonstrated by EOG monitoring and vivid dreams. EEG demonstrates high frequency, low amplitude waves (Figure 14.1). There are several autonomic changes during REM sleep, including a decrease in ventilatory drive, decrease in body temperature, reduction in muscle tone, and an increase in pulse rate and blood pressure. Apnoeic episodes lasting for up to 20 seconds occur, which can compromise breathing. Each period of REM sleep lasts about 30 minutes after which the individual awakes briefly before returning to Stage 1 of non‐REM sleep. There are four to five cycles of REM sleep during a typical night which occupies 20–25% of total sleep time, predominantly during the second half of the night. REM sleep occupies 80% of sleep in infants and it is postulated that it may be important in learning and memory. Table 14.1 lists the causes of excessive sleepiness during the day (hypersomnia).


Table 14.1 Differential diagnoses of excessive daytime sleepiness (EDS)/hypersomnia.







  • Upper airways resistance syndrome (UARS)
  • Obstructive sleep apnoea/hypopnoea syndrome (OSAHS)
  • Narcolepsy
  • Periodic limb movement disorder (PLMD)/Restless leg syndrome
  • REM behaviour disorder (RBD)/parasomnia
  • Idiopathic hypersomnia (IH)
  • Nocturnal hypoventilation
  • Insomnia
  • Chronic sleep insufficiency
  • Depression

Snoring


Snoring is a common symptom which can cause significant disruption to the sleep of the individual and to their bed partner. It can be a cause of excessive daytime sleepiness (EDS). Snoring can occur without any pathology when it is called “simple”, due to upper airways resistance syndrome (UARS), or obstructive sleep apnoea/hypopnoea syndrome (OSAHS).


Simple snoring


Snoring is the noise made by vibration of the soft tissues in the oropharynx as the individual attempts to inhale air into the lungs against an obstruction. Simple snoring is a common condition which is more prevalent in men because they tend to have more fat deposition around their necks. It increases in prevalence with increasing weight and age. Snoring can be exacerbated by sleeping in the supine position, by taking sedatives and drinking alcohol. Snorers often breathe through their mouth and complain of a dry mouth. When severe, snoring can disturb the individual and their bed partner, and can result in disharmony. It can also cause sleep fragmentation and excessive daytime sleepiness.


Upper airways resistance syndrome (UARS)


Upper airways resistance increases during sleep, even in normal individuals, due to a reduction in the muscle tone of the upper airways and collapse of the upper airways (Figure 14.2). UARS, characterised by snoring and EDS, is at one end of the OSAHS spectrum, with severe OSA being at the other end. There is no accurate estimate of the prevalence of UARS in a population as these individuals do not usually report their symptoms to their doctor.

Graph illustrating the increase in upper airway resistance during sleep, with a line ascending from awake to NREM sleep.

Figure 14.2 Increase in upper airway resistance during sleep.


Oesophageal manometry and pneumotachographic airflow measurements show that while the negative inspiratory oesophageal pressure increases, the oronasal airflow decreases in UARS. Although these periods of upper airways resistance are not sufficient to cause an apnoea (complete cessation of breathing) or a desaturation of more than 4% in the oxygen level, they do result in brief EEG arousals which cause sleep fragmentation and daytime sleepiness. More than 10 EEG arousals/hour is also associated with an increase in diurnal diastolic blood pressure, possibly due to sympathetic activation and changes in intra‐thoracic pressure.


UARS can result from any cause of upper airway obstruction, including enlarged tonsils, large nasal polyps, deviated nasal septum and craniofacial abnormalities, such as a low soft palate, and a long uvula. The male‐to‐female prevalence of UARS is similar, whereas OSAHS is commoner in men. Most individuals with UARS are non‐obese and younger than the average patient with OSAHS. The average age of an individual with UARS is 37.5 years whereas the majority with OSAHS are over 50 years old.


Management of UARS


Management of UARS depends on the cause. If the obstruction can be dealt with by surgery, for example, septoplasty or tonsillectomy, this may improve symptoms. Craniofacial abnormalities are much harder to correct surgically. Patients should be advised to avoid alcohol and sedatives at night and to avoid sleeping in the supine position. Patients were told to sew a tennis ball in the back of their pyjama top to prevent them from rolling onto their back, and this advice is still given by many doctors. An intra‐oral device, such as a mandibular advancement device (MAD), pulls the lower jaw forward and increases the space in the oropharynx (Figure 14.3). When no surgically correctable cause is identified and if a MAD is not helpful, symptomatic individuals may benefit from CPAP.

Image described by caption and surrounding text.

Figure 14.3 Mandibular advancement device (MAD).


Obstructive sleep apnoea/hypopnoea syndrome (OSAHS)


OSAHS is a common, chronic condition characterised by recurrent episodes of upper airway collapse during sleep resulting in hypoxia and sleep fragmentation (Figure 14.4, Figure 14.5). The diagnosis of OSAHS is made when the patient has symptoms of snoring and excessive daytime sleepiness, and a sleep study shows apnoeic episodes and desaturation of oxygen by at least 4% from baseline.

Illustration depicting a normal upper airway.

Figure 14.4 Normal upper airway.

Illustration depicting a narrowed upper airway in apnoea-hypopnoea syndrome.

Figure 14.5 Narrowed upper airway in apnoea‐hypopnoea syndrome.


OSAHS is an independent risk factor for developing systemic hypertension which could increase the risk of cardiovascular and cerebrovascular disease, although there is no direct evidence to suggest this. Retrospective data suggests that morbidity and mortality are greater in patients with an apnoea/hypopnoea index (AHI) of greater than 20/hour. Excessive sleepiness during the day is associated with an increase road traffic accidents. Table 14.2 contains the definitions of AHI from the SIGN Guidelines 2003.


Table 14.2 Definitions.


Source: adapted from SIGN guidelines (2003)





These definitions are arbitrary and exact cut‐offs can vary between laboratories. The AHI is a continuous variable, like blood pressure, so separating normal from abnormal is difficult. The severity of symptoms can vary from night to night and can depend on exogenous factors, such as the amount of alcohol drunk. The severity of the apnoeic episodes measured does not always correlate with the severity of symptoms experienced by the patient.

  • Apnoea: complete obstruction of airways for >10 sec
  • Hypopnoea: >50% obstruction of airways for >10 sec
  • Apnoea/Hypopnoea index (AHI) or Respiratory Disturbance Index (RDI): number of apnoeas and hypopnoeas/hour
  • Mild OSA: AHI 5–14 h−1
  • Moderate OSA: AHI 15–30 h−1
  • Severe OSA: AHI > 30 h−1

Epidemiology of OSAHS


OSAHS is a common condition affecting at least 3–7% of men and 2–5% of women in the general population. It is likely that many more individuals have a high AHI but are asymptomatic. Estimates of prevalence vary greatly between studies because of inconsistencies in the definitions and measurements used in different laboratories.


The prevalence of OSAHS is directly related to the prevalence of obesity in the population. Studies have shown a direct correlation between OSAHS and an increase in BMI, neck circumference, and waist circumference. Fat deposition in the parapharyngeal area causes narrowing of the upper airways and predisposes to airway collapse. In the Wisconsin Sleep Cohort Study it was found that individuals who had a 10% increase in weight had a 32% increase in the AHI and a sixfold increased risk of developing moderate to severe OSAHS compared to those who maintained a stable weight. Weight loss has been shown to improve the severity of OSAHS, and even completely eradicate it.


Several epidemiological studies have shown that the prevalence of OSAHS increases with age in both men and women, reaching a plateau after 60 years, where rates of 18% in men and 7% in women have been reported. This may be due to anatomical changes in the pharynx and soft palate, with increased deposition of fat in the parapharyngeal area.


The male‐to‐female ratio of OSAHS is 2–3:1 in epidemiological studies and 5–8:1 in clinic‐based studies. This discrepancy may be partly because women are more likely to notice snoring in their male bed partners, whereas men under‐report snoring in their female bed partners. Doctors too may be less likely to suspect OSAHS in women.


The reason for a male preponderance is mainly due to greater fat deposition around the neck and upper body compared to women which predisposes to airways narrowing and collapse. Hormonal factors are also implicated as the prevalence of OSAHS increases in women after the menopause, and hormone replacement therapy has been shown to reduce the prevalence of OSAHS in post‐menopausal women. Exogenous androgen therapy can exacerbate the severity of OSAHS, and women with polycystic ovary syndrome have a higher rate of OSAHS. Women have a lower AHI in non‐REM sleep and their apnoeic episodes are of shorter duration, with less severe oxygen desaturations than in men.


The prevalence of OSAHS is broadly similar in different ethnic groups, but the aetiology varies. Differences in craniofacial morphology may be relevant in the Asian and Oriental population, who tend to be less obese than the Caucasian populations of Europe and the USA. The greater prevalence of OSAHS in African Americans over 65 years of age may be due to an increase in the size of the tongue and soft palate. Care must be taken, however, when interpreting data regarding race and prevalence of OSAHS as socio‐economic rather than genetic factors may be implicated.


OSAHS can occur within families, with first degree relatives of those affected having a greater risk of developing the condition. Several studies, including the Cleveland Family Study, have suggested that genetic factors, including inherited abnormalities affecting the control of breathing, may be implicated. However, confounding factors such as obesity and craniofacial or pharyngeal abnormalities within a family could also explain this. Further genetic studies are required to clarify the role of genes in the development of OSAHS.


The prevalence of OSAHS in children reaches a peak at around the age of 5 years and is estimated to be as high as 4% because of tonsillar and adenoid hypertrophy. Children who are sleep‐deprived present with hyperactivity, loss of concentration, poor behaviour, and growth retardation. As children get older, their tonsils and adenoids atrophy, and the prevalence decreases. Tonsillectomy and/or adenoidectomy are possible, but rarely considered.


Pathophysiology of OSAHS


The patency of the upper airway is a dynamic process and reliant on a combination of anatomical features, neuromuscular activity, and whether the individual is awake or asleep. The upper airway is kept open when awake by activation of the pharyngeal dilator muscles and the rings of cartilage in the trachea. In response to negative intra‐pharyngeal pressure, the tone of the main pharyngeal dilator muscle, the genioglossus, increases during inspiration and decreases during expiration. During sleep, particularly REM sleep, the muscle tone is reduced and is insufficient to keep the airway patent. In OSAHS there is also narrowing and vascular engorgement of the upper airway, causing collapse at multiple sites, with reduced or no airflow into the lungs despite continued respiratory effort Alcohol and sedatives cause relaxation of the upper airway dilator muscles, exacerbating the problem.


The reduction in airflow (hypopnoea) or cessation of airflow (apnoea) results in hypoxia which activates the respiratory centre, resulting in an arousal which is accompanied by an increase in pulse, an increase in blood pressure by about 50 mmHg and a surge in catecholamine release. The individual wakes up briefly to breathe, and there is an increase in inspiratory effort to overcome the obstruction, with the diaphragm and intercostal muscles working hard. This results in a breath being taken, often with a snort or grunt. This whole process can occur repeatedly throughout the night, up to 100 times every hour. The repeated arousals cause sleep fragmentation, resulting in poor quality, restless sleep, and excessive sleepiness during the day. Nocturia is associated with OSAHS due to an increase in atrial natriuretic peptide (ANP) levels.


Table 14.3 lists the presenting symptoms of OSAHS. Patients with OSAHS can present with any, or all, of these symptoms, which develop insidiously over many years. Occasionally, the patient may be asymptomatic despite proven OSA on a sleep study. Often it is the partner of the patient who reports loud, persistent, and disturbing snoring, in some cases prompting them to sleep in a separate room. The partner may also report that the patient stops breathing (witnessed apnoeic episodes), and then starts breathing accompanied by grunts and snorts. The patient could be disturbed by his/her own snoring which can wake them up from sleep. Even if an individual has no symptoms, those presenting with resistant hypertension and raised urinary catecholamines suggestive of sympathetic activation should also be investigated for OSAHS. Patients with metabolic syndrome and hypothyroidism are at increased risk of developing OSA.


Table 14.3 Presenting symptoms and signs of OSAHS.







  • Snoring
  • Apnoea (Greek word meaning ‘without breath’), usually witnessed by a partner
  • Restless/disturbed sleep
  • Mouth breathing
  • Dry mouth on waking
  • Nocturnal choking
  • Unrefreshed on waking
  • Morning headache
  • Nocturia
  • Nocturnal sweating
  • Excessive daytime sleepiness
  • Reduced cognition, concentration, memory, and libido
  • Irritability
  • Change in mood
  • Road traffic accidents

Table 14.4 lists the risk factor for, and clinical features of, OSAHS. As well as eliciting a history of snoring and the risk factors for OSAHS, it is essential to ascertain how sleepy the patient is using the Epworth Sleepiness Scale (ESS), which is a validated score that assesses the tendency to fall asleep under various situations (see Appendix 14.A). Ideally, the ESS should be completed by the patient, together with their partner, when they first present, as there is a tendency for the patient to underestimate the severity of their sleepiness. The baseline score is used to monitor improvement once treatment has been initiated.



  • ESS < 11: normal
  • ESS 11–14: mild sleepiness
  • ESS 15–18: moderate sleepiness
  • ESS > 18: severe sleepiness

Table 14.4 Risk factors for and clinical features of OSAHS.























































































































Risk factor History suggestive of Features on clinical examination
Obesity Increase in weight BMI >30 (weight (kg)/height (M2)
Large neck size Large collar size Neck size>17 inches (33 cm)
Retrognathia Craniofacial abnormality Maxillary and mandibular retroposition
Micrognathia Craniofacial abnormality Small mandible
Sedative drugs Use of sedative drugs None
Alcohol use at night Alcohol intake at night None
Enlarged tongue Upper airway obstruction and snoring Macroglossia
Low lying soft palate Upper airway obstruction and snoring Narrowed oropharynx
Long uvula Upper airway obstruction and snoring Long, oedematous uvula
Enlarged tonsils Upper airway obstruction and snoring Large tonsils
Enlarged adenoids Upper airway obstruction and snoring Large adenoids
Nasal pathology Nasal trauma Broken nose
Nasal surgery Septal deviation
Nasal polyps
Reduced nasal inspiratory pressure
Asthma Breathlessness, wheeze Wheeze
Hypothyroidism Weight gain Features of hypothyroidism
Other symptoms of hypothyroidism
Acromegaly Increase in size of head, feet, and hands Features of acromegaly
Marfan’s syndrome Marfan’s syndrome High arched palate
Other Marfanoid features
Down’s syndrome Down’s syndrome Features consistent with Down’s syndrome
Hypertension Usually asymptomatic Hypertension
Diabetes May be asymptomatic Hyperglycaemia on testing glucose
Musculoskeletal disorders Nocturnal difficulty in breathing Scoliosis
Kyphosis
Neuromuscular Disease Symptoms of neuromuscular disease Features of neuromuscular disease
Polycystic Ovary Syndrome Irregular menstrual cycle Obesity
Acne
Hirsutism
Third Trimester of Pregnancy Snoring and EDS during pregnancy Pregnant
Obese

Other causes of excessive sleepiness, such as narcolepsy, should be considered in patients who have a very high score of more than 18. Patients who are excessively sleepy should be strongly advised to stop driving immediately until investigations have been completed and appropriate treatment commenced. They should be advised to inform the DVLA.


Investigations for possible OSAHS



  • Bloods: full blood count, urea, and electrolytes, fasting glucose, fasting lipids, thyroid function.
  • ENT Investigations: nasendoscopy.
  • Cardiac: blood pressure, ambulatory blood pressure monitoring, ECG, and echocardiogram.
  • CXR if respiratory symptoms and/or hypoxia.
  • Arterial blood gases if respiratory symptoms and/or hypoxia.
  • Spirometry if respiratory symptoms and/or hypoxia.
  • Overnight pulse oximetry.
  • Limited sleep study.
  • Full polysomnography (PSG).

Patients suspected of having severe OSA should have investigations and treatment without delay. Patients with co‐morbid conditions, including ischaemic heart disease, arrhythmias, and COPD are at increased risk of fatal events during hypoxic episodes, so should be investigated urgently. Individuals who undertake dangerous tasks, work with machinery, or drive any vehicle (cars, Heavy Goods Vehicles (HGV), trains, buses), should be advised to stop work immediately and be referred for urgent investigations.


Overnight pulse oximetry may be sufficient to make a diagnosis of OSAHS in many patients. A drop of at least 4% or more of the oxygen saturation is considered a desaturation and the total number of desaturations per hour is counted. An increase in pulse rate may indicate an arousal and act as a surrogate marker of an apnoeic episode. However, oximetry alone may not reliably exclude OSAHS in a third of patients. False positive results can occur in those with respiratory disease and hypoxia at rest and those with Cheyne‐Stokes breathing when there are oscillations in the oxygen saturation. Oximetry is also unreliable if tissue perfusion is poor, and can give false negative results in young, thin patients.


A limited sleep study, which can be done overnight in the patient’s own home, is the most commonly used and cost‐effective investigation for those suspected of having OSAHS. The patient is fitted with an oximeter to measure oxygen saturation, thoracic and abdominal belts to detect respiratory movements, oronasal airflow sensors or a thermistor and snore sensors which can measure the frequency and volume of snoring (Figure 14.6, Figure 14.7). This is cheaper than a full polysomnography (PSG) and more convenient for the patient.

Photo displaying a woman being fitted with an oximeter around her body by a man in front of her.

Figure 14.6 An individual being fitted with a home (limited) sleep study.

Photo displaying the middle body of a female patient with an oximeter fitted to the middle finger of her extended left hand for a home (limited) sleep study.

Figure 14.7 An oximeter being fitted for a home (limited) sleep study.


Full polysomnography, including EEG monitoring to determine the stages of sleep, is not necessary in most patients suspected of having OSAHS (Figure 14.8, Figure 14.9). PSG is conducted in a sleep laboratory with trained sleep technicians, usually in a regional sleep centre, so is a time‐consuming and expensive investigation. PSG should be reserved for patients with atypical features, those with neurological symptoms and when a limited sleep study is not diagnostic. The patient is fitted with an oximeter, thoracic and abdominal belts to detect chest and abdominal wall movements, oronasal airflow sensors, snore sensors, ECG to record heart rate, a blood pressure monitor, EEG to record the stages of sleep, EOG to detect rapid eye movement, and EMG to monitor limb movement (usually tibialis). Video recording can be used to correlate the patient’s position and movement with apnoeas and arousals.

ECG tracings with labels Flattening (255 m/cm), Thorax (168μV/cm)Effort, Abdomen (168μV/cm), Pulse (30–120bpm), etc. depicting obstructive sleep apnoea.

Figure 14.8 Home (limited) sleep study tracing showing obstructive sleep apnoea.

Image described by caption and surrounding text.

Figure 14.9 Full polysomnography tracing showing obstructive sleep apnoea.


Diagnosis of OSA


A diagnosis of OSA is made when the AHI is greater than 10/hour in a patient who has symptoms suggestive of OSA as described in Table 14.2. Medical conditions, including hypothyroidism, diabetes, and hypertension should be actively excluded.


Consequences of OSA


OSAHS impairs cognition, mood, and quality of life. This can result in difficulty with work, social activities, and driving.


Initially, the link between OSAHS and systemic hypertension was thought to be due to confounding factors such as obesity and the metabolic syndrome. However, large epidemiological studies and controlled clinical trials have concluded that untreated OSAHS is an independent risk factor for developing systemic hypertension, with up to 60% of patients with OSAHS developing hypertension, often resistant to antihypertensive treatment. Patients with OSAHS were found to have a significantly higher blood pressure than matched controls, and treatment with CPAP resulted in a 5 mmHg reduction in blood pressure over a 24‐hour period; this was most pronounced in patients with the most severe disease. That OSAHS alone results in an increased risk of cardiovascular and cerebrovascular morbidity and mortality has not been shown in any trial yet; a longer period of follow‐up may be required.


It is postulated that recurrent episodes of hypoxaemia result in the formation of reactive oxygen species which damage the vascular endothelium. There is a reduction in nitric oxide levels and an increase in the levels of Endothelin‐1, which results in vasoconstriction and an increase in peripheral vascular tone. There is a strong link between the metabolic syndrome (visceral obesity, insulin resistance, hypertension, and dyslipidaemia) and OSAHS, and apnoeic episodes may be associated with erratic glycaemic control. Individuals with OSAHS have reduced levels of growth hormone and testosterone and increased levels of cortisol, suggesting that the body is in a state of ‘stress’. There is also a surge of catecholamine release with each arousal which may cause further damage to the vascular endothelium. It is thought that the high rates of sudden death during sleep associated with these conditions may be related to undiagnosed OSA.


Patients with COPD and OSAHS (called the Overlap Syndrome) have a high risk of nocturnal hypoxaemia, acute respiratory failure, pulmonary hypertension, and cor pulmonale.


Some obese patients with OSAHS will develop nocturnal hypoventilation and Type 2 Respiratory Failure which can be diagnosed with a full polysomnography and CO2 measurements. These patients will require non‐invasive ventilation (NIV) using BiPAP rather than CPAP. The causes and management of type 2 respiratory failure are discussed in Chapter 13.


OSAHS and driving


Driving when sleepy is extremely dangerous and can result in road traffic accidents. It is estimated that up to a quarter of all road traffic accidents occur due to people falling asleep at the wheel. Epidemiological studies have shown a high prevalence of OSAHS in truck drivers.


The doctor must inform the patient who has OSAHS that they should refrain from driving while excessively sleepy, that it is their duty to inform the DVLA and that it is a criminal offence leading to prosecution if they fall asleep at the wheel. The patient should also be told to inform their insurance company about their diagnosis. The doctor should document the discussion in the notes and inform the patient’s General Practitioner.


Individuals with OSAHS are legally required to inform the DVLA of a diagnosis of OSAHS. The DVLA will send them a questionnaire which they must complete, and their licence will be revoked until they can demonstrate that they are compliant with any treatment and that they are not excessively sleepy. Drivers holding Group 1 Licences (normal car licence) can drive when they are commenced on treatment for OSAHS and are no longer symptomatic. Group 2 Licence Holders (HGV, PSV = Public service vehicle and PCV = passenger carrying vehicle drivers) will be permitted to drive when it has been verified by a sleep specialist that they are using their CPAP for at least three hours each night, that they have a normal ESS and a normal sleep study when using CPAP.


Management of OSA


Patients who are symptomatic and who have moderate or severe OSAHS (AHI > 15 h−1) are more likely to comply with advice and treatment.


Lifestyle changes


Patients who are overweight should be advised to reduce weight by modifying their diet and by exercise. Even a small weight loss can have significant benefits, with weight loss of 10% significantly decreasing the severity of obstructive events. Increasingly, patients who are morbidly obese are having bariatric surgery with significant improvement in the severity of their OSA. Patients should be advised to stop smoking and avoid sedatives, sleeping tablets, and alcohol consumption at night. Patients should also be advised to avoid sleeping in the supine position.


Surgery


Somnoplasty is a common procedure for snoring, but OSA must be excluded prior to surgery. Patients who have a deviated nasal septum, large nasal polyps, large tonsils, or adenoids may benefit from appropriate surgery. Uvulopalatopharyngoplasty (UPPP) and laser‐assisted uvulopalatopharyngoplasty (LAUP) used to be common procedures, whereby parts of the soft palate, uvula, and pharyngeal walls were excised to increase the size of the airway and overcome the obstruction. The results of clinical trials on UPPP have not been favourable, and this procedure is now contra‐indicated. UPPP was associated with an increase in peri‐operative death, significant post‐operative pain, and nasal regurgitation of food without a meaningful reduction in the number of apnoeas. In addition, patients who have had this procedure cannot use CPAP for OSAHS.


Rarely, in severe cases of OSAHS, when all other treatments have failed, tracheostomy can be considered.


Intra‐oral devices


Mandibular advancement devices and tongue‐retaining devices are used to increase the amount of space in the oropharynx.


Mandibular advancement device (MAD)


MAD is recommended for patients with mild OSAHS, UARS, and snoring. It holds the lower jaw forward, thereby increasing the space in the oropharynx. A moulded device can be made at home or a fixed device can be fitted by an orthodontist. Intra‐oral devices are not recommended as first‐line treatment for moderate or severe OSAHS as they have not been shown in cross‐over studies to significantly reduce the number of apnoeas compared to CPAP. However, MADs have been shown to reduce snoring and sleepiness compared to placebo, so should be considered in patients with UARS, mild OSAHS and in those who are unable to tolerate CPAP. Side effects include hypersalivation, tooth pain, jaw pain and temperomandibular joint pain which usually improve over time.


Continuous positive airway pressure (CPAP)


CPAP is the treatment of choice for patients (adults) with moderate and severe OSAHS (AHI > 15 h−1) but is not recommended for children. Randomised controlled trials using sham devices and Cochrane meta‐analysis data have confirmed that compared to intra‐oral devices and lifestyle changes alone, CPAP treatment is effective in reducing apnoeas, improving symptoms of sleepiness and improving quality of life in patients with moderate and severe OSAHS. The more severe the apnoeic episodes are, and the greater the ESS, the more likely the improvement in symptoms with CPAP. The evidence is less clear for mild OSAHS (AHI < 14 h−1), probably because of poor compliance in this group.


Regular use of CPAP for more than three hours each night for several months has been shown to reduce systemic blood pressure, with an average reduction of 4 mmHg in those with severe OSAHS compared to controls. It is inferred that this would lead to a reduction in cardiovascular and cerebrovascular risk.


CPAP treatment for those with OSAHS has been shown to improve sleepiness, driving simulator performance, steering accuracy, and reaction times. Meta‐analysis of trial data and epidemiological data suggests that the use of CPAP is associated with a reduction in road traffic accidents by 83%.


A CPAP device consists of a unit that generates airflow and is connected to either a nasal or full‐face mask via a tube (Figure 14.10, Figure 14.11). A pressure of about 5–15 cm H2O is generated which splints the pharynx open by exerting positive airways pressure, thus preventing the airway from collapsing. A fixed CPAP device delivers air at a constant pressure throughout the night and the pressure required for each patient can be determined by an overnight titration study. Auto‐titrating devices, which continually adjust the pressure delivered throughout the night, are more comfortable and better tolerated, but are more expensive. There is no evidence that their use results in a better outcome. A CPAP device costs £250–£500 and can last for five to seven years. A standard mask costs £100 and lasts for 6–12 months.

Image described by caption and surrounding text.

Figure 14.10 CPAP machine and circuit.

Photo displaying a woman patient fitted with a CPAP machine over the nose and mouth, held by a man beside him.

Figure 14.11 Individual having CPAP fitted.


Claustrophobia, air leaks, and abdominal bloating are the main side effects of CPAP which stop the patient from using it. This can be reduced by ensuring that the mask fits properly and by using a chin support. Dry mouth, nasal congestion, and rhinitis can be reduced by humidification of the air that is breathed in. Damage to the skin, particularly on the bridge of the nose caused by a tightly fitting mask, can be prevented by using a nasal cushion. Epistaxis and paranasal sinusitis are rare complications.


Dedicated and experienced technicians who offer their support and expertise will improve compliance up to 95% for a 3–5 hours usage each night. CPAP machines record the hours of use which is essential when checking compliance, especially when the individual is intending to resume driving. Patients on CPAP should be regularly reviewed, their machines checked, and new masks fitted.


Patients with OSAHS should be carefully assessed prior to a general anaesthetic and regional anaesthesia recommended whenever possible. Sedative and opiate drugs should be avoided if possible. Patients should continue to use their CPAP machine post‐operatively and should be monitored on HDU or ICU.


In patients who remain sleepy despite the use of CPAP, other causes of sleepiness, such as narcolepsy or periodic limb movement disorder, should be excluded. Modafanil, a stimulant working directly on the hypothalamus, can improve the symptoms of sleepiness in some patients, but should not be used as first line therapy for OSAHS.


Narcolepsy


Narcolepsy (meaning ‘to be seized by somnolence’), is a serious sleep disorder which is usually insidious in onset, although occasionally it can develop more acutely over weeks or months. The incidence of narcolepsy is 1:2000, usually in early adolescence. Narcolepsy in children and older people is rare and often overlooked.


Pathophysiology


Primary narcolepsy results from a mutation in the hypocretin receptors in the hypothalamus of the brain. The hypocretin system regulates the sleep‐wake cycle, maintaining wakefulness. Disorders result in excessive sleepiness. Secondary narcolepsy can result from a loss of the hypocretin‐secreting neurones in the hypothalamus due to an autoimmune process (which is associated with HLA phenotype DQB1 0602), viral illness or head injury.


Clinical features


The main feature is EDS resulting in the irresistible need to fall asleep without notice. These episodes are often called ‘sleep attacks’, and short naps of 15 minutes are typically restoring. Cataplexy, which occurs in 65% of patients, is characterised by muscle paralysis for several seconds to a few minutes without loss of consciousness. Minor episodes may manifest as jerking of the face or head and slurring of speech. Episodes of cataplexy may be precipitated by strong emotions such as laughter, surprise, and anger. Other symptoms include parasomnias, sleep paralysis and hallucinations (visual, auditory, and tactile). As the hypothalamus is affected, appetite dysregulation with food cravings can occur, particularly in adolescent females, resulting in huge weight gain.


Investigations


A multiple sleep latency test (MSLT) is a standard measure of daytime sleepiness. It is used to make a diagnosis of narcolepsy and to monitor response to treatment. A normal MSLT score is 10–20 minutes, although it is dependent on how much sleep the individual has had the night before. Patients with narcolepsy will fall asleep within 8 minutes on a MSLT. Full polysomnography will show a reduced latency to REM sleep, with at least two sleep‐onset REM episodes in a series of latency tests during the day. Hypocretin levels in cerebrospinal fluid (CSF) will be very low or undetectable, although this is not an investigation used routinely in clinical practice, but mainly used for experimental purposes.


Management


Lifestyle changes, such as planned short naps during the day and adjustment to the sleep cycle, may help. Employers and family members who appreciate the difficulty of this condition and are flexible can ensure that the individual continues to work and functions as normally as possible.


Modafinil, which stimulates the neurones in the hypothalamus, is the most effective drug for EDS. It is contraindicated if there are serious cardiovascular problems and can cause gastrointestinal upset and headaches. Stimulants, such as dexamfetamine and methylphenidate, can be helpful. Antidepressants, such as venlafaxine and clomipramine, are effective in cataplexy as they suppress REM sleep. Sodium oxybate is very effective, but expensive, and not yet recommended by NICE. Other drugs with less evidence of clinical benefit include melatonin and intravenous immunoglobulins if an autoimmune process is suspected.


Narcolepsy has a variable prognosis. Most patients improve to some extent with lifestyle modifications and medication. Some patients continue to be significantly affected so that they are unable to work or partake in social activities. Patients with narcolepsy must inform the DVLA and can only drive if their symptoms of sleepiness and cataplexy are effectively controlled.


Periodic limb movement disorder (PLMD)


PLMD is characterised by repetitive, involuntary, jerking movements of limbs which occur every 20–40 seconds and can last for many hours. Movement of the lower limbs is more common than that of the upper limbs. This can range from minor movements of feet or significant movements of all four limbs. PLMD occurs during the non‐REM sleep stages, and so is more likely to occur during the first part of the night. Patients may not be aware of these movements which are noticed by their bed partner. These movements can cause sleep disruption and EDS. PLMD is commoner in patients suffering with Parkinson’s disease and narcolepsy and associated with shift working, excessive stress, excessive caffeine intake, benzodiazepine withdrawal, and mental health disorders.


The incidence of PLMD is 4% and is commoner in elderly females. PLMD can be diagnosed with a history from a partner and by a PSG which demonstrates at least three episodes during the night, lasting from a few minutes to an hour, each with at least 30 movements followed by a partial arousal.


Treatment for PLMD includes anti‐Parkinson medications, dopaminergic medication, anticonvulsants, benzodiazepines, and narcotics. Tri‐cyclic antidepressants, alcohol, SSRIs, and caffeine should be avoided.


Restless leg syndrome (RLS)


Restless leg syndrome is characterised by an uncomfortable sensation in the legs which can occur when the patient is asleep or awake. When awake, the patient moves their legs voluntarily to relieve the sensation. Many of these patients (80%) will also have PLMD but the reverse is not true.


REM behaviour disorder (RBD)/parasomnia


RBD is a neurodegenerative disorder, mainly affecting elderly men. Idiopathic RBD is uncommon. Individuals with RBD act out their dreams, sometimes in a violent way, with potential for injuring themselves or their partner. During normal REM sleep the electrical activity, as measured by EEG, is the same as when awake, but there is muscle paralysis. In RBD, the distinction between REM sleep and the awake state is blurred. Episodes of RBD can occur up to four times during a night, especially in the morning hours, when REM sleep occurs more frequently. RBD results in sleep deprivation and is a cause of EDS. There may be a link between RBD and Parkinson’s disease, Lewy body dementia, and multiple system atrophy. A diagnosis is usually made with a partner reporting nocturnal activity and with the use of PSG and a video camera. Clonazepam is the most effective medication for this condition. Antidepressants and melatonin can also help.


Idiopathic hypersomnia (IH)


Idiopathic hypersomnia is a diagnosis of exclusion. Other causes of excessive sleepiness, including the use of medication, alcohol, hypothyroidism, and depression need to be excluded. It is a chronic, debilitating condition characterised by excessive daytime sleepiness which develops insidiously over many years. The true prevalence of IH is unknown. It may be a disorder of the norepinephrine system of the brain or hypersensitivity to GABA. Decreased levels of histamine in CSF has been found in patients with IH.


The individual concerned may sleep up to 18 hours each day and still have difficulty waking up, with disorientation on waking. Unlike narcolepsy, the patient does not fall asleep suddenly, experience episodes of cataplexy, or find short naps refreshing. Anxiety, depression, and reduced appetite may occur. As the diagnosis is one of exclusion, it will require PSG, MSLT, measurement of hypocretin in CSF to exclude narcolepsy, and even a psychiatric review. Management includes stimulants, such as modafanil and amphetamines, although they are not as effective as they are in narcolepsy. Substances that act like histamine, GABA antagonists, clarithromycin, and hypocretin agonists may be suitable wake‐promoting agents in the future.


Insomnia


Insomnia is a common cause of EDS. Stress, excessive caffeine, shift work, and jet lag are some causes of the causes. Chronic insomnia can be hard to cure. Management includes a detailed sleep diary, sleep hygiene advice, ensuring that the sleep environment is conducive to sleeping, and avoiding stimulants at night.


Chronic sleep insufficiency


There are many causes of chronic sleep insufficiency, including long hours at work, shift work and small children who might disrupt sleep. Management comprises of lifestyle modifications.


Central sleep apnoea (CSA)


CSA is much less common than OSAHS. It is due to an absent or reduced ventilatory drive but with no evidence of upper airways obstruction. The most common cause of CSA is due to damage to the brainstem from strokes, tumours, and conditions such as syringobulbia. Ondine’s curse is a congenital form of CSA due to abnormal development of the neural crest. Cheyne‐Stokes breathing, consisting of periods of apnoeas followed by hyperventilation, is associated with left ventricular failure (Figure 14.12).The prolonged circulation time means that the carotid body does not respond quickly to changes in ventilation.

Tabular representation of sleep tracings, with columns labeled obstructive, central, and mixed, and rows labeled airflow, diaphragmatic movement, and oxygen saturation.

Figure 14.12 Sleep tracing showing obstructive, central, and mixed apnoea.


Nocturnal hypoventilation


Nocturnal hypoventilation can be due to a variety of conditions, including neuromuscular and musculoskeletal diseases, which can result in mechanical ventilatory failure. Obesity is another common cause. The patient is usually able to maintain ventilation when awake but decompensates when asleep, resulting in type 2 respiratory failure (hypoxia and hypercapnoea). Causes and management of type 2 respiratory failure are discussed in Chapter 13.

Jun 4, 2019 | Posted by in RESPIRATORY | Comments Off on 14: Sleep‐related disorders
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