Sleep Apnoea Syndrome : Pathophysiology and Management ...

Chapter 11
Sleep Apnoea Syndrome : Pathophysiology and Management

RS Bhatia

Medical Consultant, Hon. Faculty, College of Chest Physicians,
Dept. of Respiratory Diseases, Model Town, Ludhiana

Introduction

Sleep apnoea is a sleep induced pulmonary disorder characterized by snoring and respiratory pauses,1
often accompanied with respiratory obstruction. Two third of patients are obese, and male population
is 20 times more frequently affected as compared to females. Idiopathic sleep apnoea (SAS) afflicts
1% of adult population in USA, affecting more commonly in the age group between 40-60 years.
SAS has become a major research field in pulmonary physiology in the recent years ; nevertheless,
the significant realization of SAS causing morbidity and mortality has not been spotted by physicians
in this part of the country. SAS is defined as the presence of more than five apnoeas or hypoapnoeas
per hour of in a young or middle aged patients sleep in conjunction with atleast two major symptoms.
There is cessation of air flow for atleast 10 seconds and a hypoapnoea as a 50% reduction in thoraco
abdominal movements for atleast 10 seconds. Respiratory disturbance indexed (RDI) is the number of
apnoea or hypoapnoea per hour of sleep. In other words, SAS is diagnosed if respiratory events occur
during both NREM and RM sleep with a RDI of greater than five. Severity of SAS is denoted by RBI and
degree of oxygen desaturation accompanying apnoeic episodes. Mild cases have RDI below 20/hour
with oxygen saturation remaining above 85% while severe cases of SAS have RDI above 50/hour with
oxygen saturation falling bellow 65% or cardiac arrhythmia accompanying apnoeic episode.

There are two types of sleep apnoeas; obstructive variety characterized by frustrated respiratory
efforts to breathe against blocked upper airways; and central apnoea, where there is simple cessation
of breathing without ventillatory efforts i.e. cessation of all airflow simultaneous with cessation of
respiratory muscle activity. And those with obstructive apnoea having no initial respiratory efforts,
when start having thoracic efforts as the apnoea progresses, is called mixed apnoea. All the apnoeas
can occur in SAS, the obstructive variety is the commonest one. Familial tendency in SAS has also
been documented.2 Obstructive variety has only been recognized in the past decade, although it is
as common as asthma.3 Although exact prevalence of obstructive variety is not known, it is roughly
estimated around 1-5%.

Pathophysiology

Almost all the apnoeas originate from airway occulusion around the level of soft palate. There is an

Sleep Apnoea Syndrome : Pathophysiology and Management 79

active contraction of muscles such as genioglossus, geniohyoid and omohyoid with each inspiration.
During sleep, the muscle tone drops, creating a greater tendency of upper airway to narrow on
inspiration. Turbulent flow occurs, resulting in the vibration sound of snoring. If the airway narrows
subcritically, hypoapnea results if the airway occludes almost totally and apnoea results with total
occlusion. Predisposing factors including obesity, enlarged tonsils, hypothyroidism, macro glossia,
retrognathia etc. for pharyngeal encroachment, recurrent rhinitis and deviated nasal septum for nasal
obstruction and alcohol, benzodiazepines etc. for decreased activity of upper airway dilator muscle.
Possibly, upper airway behaving like a starling resistor may tend to collapse within a limited upper
airway segment in sleep apnoea / hypoapnoea patients.4 Anatomical and functional mechanisms lead
to development of critical collapsing pressure, the most important being a small lumen in the upper
airways and the reduction and instability of drive to the dilator and abductors of upper airways. The
latter is the characteristic of REM sleep and light NREM sleep. Excessive day time sleepiness (EDS)
and snoring are the clinical hallmarks of SAS. Most of the patients find falling asleep while being idle
or doing monotonous work such as driving a vehicle on lonely road. Vehicular accidents are likely to
be more in such cases. Children with SAS are likely to lower their potential in studies. Often there is a
history of snoring in these patients is quite old and may be intermittent; absence of snoring, however,
does not exclude SAS. Often history of unsatisfying sleep, unrefreshed awakening, disorientation and
generalized headache. Gradual onset of excessive day time sleepiness means it is underdiagnosed for
years.5 Occasional episodes of nocturnal chocking are quite disturbing. Even homicidal behavior has
been described during sleep apnoea.6 Possibly because of atrial natriuretic peptide secretion being
stimulated by apnoea, nocturia may appear due to excess of salt and water excretion.7 Enuresis has
been documented in younger patients. Recently association of cherubism with OSA and mental
retardation has been documented.8,9 Decrease in libido is yet another problem, impotence in males is
often associated with long lasting and severe SAS, Majority of the patients with SAS are males, role of
testosterone may be important both in hypogonadal patients of both sexes.1

Although SAS is commonly seen in overweight patients yet obesity is not a prerequisite to establish
the diagnosis. When sleep apnoea is associated with a significant tall of 74% in arterial oxygen
saturation, this leads to repeated apnoea. Long standing severe cases, however, precipitate hypoxemic
complications of corpulmonale, secondary polycythemia and day time carbon dioxide retension,
especially in the presence of coexisting pulmonary disease.10 Coexisting systemic as well as pulmonary
hypertension and cardiac arrhythmias have been documented with SAS. Higher incidence of SAS in
COPD as overlap syndrome has been recorded and these patients hence are at higher risk of developing
respiratory insufficiency and corpulmonale.11 Personality changes, impaired memory and motor
performance are quite commonly encountered in SAS. Recently two separate studies have documented
the evidence of a link between obstructive sleep apnoea and insulin resistance, independent of degree
of obesity.12-14 Significant higher levels of fasting glucose and insulin levels have been demonstrated
when compared with weight matched controls. Further studies have identified impaired metabolism
as one of the consequence of sleep loss, suggesting that decrements in sleep duration and / or quality
may increase the severity of metabolic disorders, particularly diabetes mellitus. Sleep disturbances are
common in type 2 diabetes mellitus. Infact there has been a significant association of sleep disturbances
with the presence of dyspnoea, nocturnal cramps, paresthesia and burning of sole.15 But findings of
sleep disturbed breathing in these patients are mostly observed in obese patients with a mean BMI
of 35.6 (SD: 9.9) kg /m2 in an Indian study. Therefore, a large community based epidemiological
study is required to identify the true prevalence of sleep apnoea in Indian population. During clinical
examination, obesity should be noticed, nose and orpharynx should be examined, especially by ENT
surgeon, assessment for hypothyroidism and acromegaly and for complications such as cyanosis and
conjestive cardiac failure should be made. There will be sleep fragmentation also. Observations should
be recorded, leaving the patient alone on the examination table, especially for induction of sleep while
sitting idle (waiting for the doctor).

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When air flow stops at the mouth and nose for a period of 10 seconds or more (apnoea) and is
accompanied by continuing respiratory movements is called obstructive apnoea. And occurrence of
5 apnoeas per hour or more than 35 per night, during sleep, with frequent arousals, unrestful sleep,
followed by daytime hypersomnolence constitutes obstructive sleep apnoea syndrome. The classic
patients with OSAS is an overweight, middle aged person (although it can occur at any age and obesity
is not necessarily present). A majority of these patients have some degree of upper airways obstruction.
Alcohol is often a co-factor. Apnoea is associated with oxygen desaturation and a marked fall in tissue
oxygen concentration during sleep. Typical snoring of OSAS is loud and spouse-disturbing. With the
progress of disease, period of silence may alternate with vigorous breathing efforts of irregular intervals,
with a terminal explosive snore, accompanied with restlessness and flailing of limbs. Recurrent arousals
and insomnia cause unrefreshing effect of sleep, leading to mental fogginess, disorientation and
tiredness during the day. Even headache is noted in 1/5* of these patients. Intermittent snoring and
arousals occur due to combination of hypoxia and hypercapnia.16 Day time excessive sleepness may
result in social consequence due to deterioration in intelligence, impairment of memory and decreased
sense of appropriate judgment. These patients may become instable, irritable and loose temper on little
provocation. Systemic hypertension may be associated in 50% of these patients. Progressive asphyxia
and pulmonary hypertension are also associated. Though pulmonary artery pressure returns to normal
level during wakefullness in majority of cases, the nocturnal event may be accentuated in patients
with obstructive airways disease, associated with sustained daytime hypoxaemia, hypercapnia, and
polycythemia in 10-15% of patients. Such an event leads to right heart failure, cardiac arrhythmias
such as ventricular premature beats and ventricular tachycardia may occur and may cause death
during sleep (but further corroborative data is lacking). Nevertheless, daytime sleepiness has to be
differentiated in case of narcolepsy, hypometabolic states such as hypothermia and hypothyroidism,
uremia, cerebrovascular diseases, depression and use of sedatives.

Management

SAS cannot be diagnosed alone by clinical history or clinical observations, oximetry has been applied by
man to diagnose SAS from the characteristic pattern of recurrent arterial oxyhaemoglobin desaturation.
Again simple pulse oximetry is not disease-pictorial although it may be useful for population screening.
At the same time, false negative results are obtained when oximetry employed even for screening.
Ideal diagnostic choice for SAS includes over night polysomonography, recording oxygen saturation
by an oximeter, thoracoabdominal movement by surface techniques, airflow by temperature or
carbon dioxide sensors, electro encephalogram, electromyogram and electro-occulogram.17 This help
in differentiating other causes of excessive daytime sleep i.e. narcolepsy. It is observed that severity
of apnoea increases as the night progresses, possibly due to lengthening of mean apnoea duration.
Forced oscillation technique has recently been used as a diagnostic tool to accurately & non-invasibly
quantify respiratory obstruction during sleep.18 Elevated serum amyloid a has been suggested to be a
risk factor for cardiovascular & neuronal dysfunction in patients with obstructive sleep apnoea.19

Treatment starts with a piece of advice to loose weight and avoid alcohol and sedative use. This
sufficient for mild form of disorder. Appropriate treatment should be provided for myxodema,
acromegaly, retrognathia and naso-pharyngeal problems. Drug therapy as such has found no place
in the treatment of SAS.1 However, tricyclic antidepressant protriptyline has been used. It is thought
to increase the tone of upper airways muscle and also help in reducing the REP sleep. Tracheostomy
that used to be original 100% effective treatment, has now been obsolete. Increasing the pharynx
size through surgical operation-Uvulopalatopharyngoplasty20 prevents snoring but it is not effective in
treating SAS.

CPAP therapy has been found to be effective treatment in SAS21 using positive pressure between

7.5-20 cm H2O. It works by physically blowing the back of the throat open. It acts by splinting the

Sleep Apnoea Syndrome : Pathophysiology and Management 81

upper airways and preventing it’s collapse during inspiration. Results are equally good using subcritical
pressure with lesser side effect.22 OSAS can be managed using combination of surgical technique and
oxygen therapies.23,24 Continuous positive airway pressure therapy improves subjective & objective
measures of sleepiness more than placebo in OSA.25 Short term beneficial effect on blood pressure &
cardiac functions has been observed in these patients; long term vascular consequences of OSA are
influenced by CPAP is yet to be confirmed.26,27 Regression in left ventricular hypertrophy in patients with
severe OSA has also been observed after six months of nasal CPAP therapy.28 However, CPAP therapy
is ineffective in those who have not been benefited by Uvulopalatopharyngoplasty. Also, cost factor is
another major hurdle in our country. Treatment of central sleep apnoea is more difficult. Often seen in
the elderly, it is associated with a little of snoring. There is a lack of drive to upper airway muscles and
diaphragm, which may be primary or due to reflex elicited by stimulation of mucosal sensory receptors
by passive airway closure. Earlier treatment included diaphragm pacing with tracheostomy. Recently
CPAP has been effectively used Acetazolamide in low dose may reduce the number of apnoeas.29

Suspecting and diagnosis SAS early and referring for sleep clinic, to start earlier benefiting from
modern, effective and straight forward treatments to lead better social life16 is the need of the present
time. President of ACCP Dr Udaya B S Prakash, while describing complications of sleep apnoea
such as hypertension, heart disease & other cardiovascular complications, has remarked that the
advancement in sleep medicine in diagnosing & treatment in the recent years should reach to primary
care & speciality physicians so as to enable them to educate patients on the health effects of sleep
disorders.

References

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