BMH Medical Journal

BMH Med. J. 2020; 7 (Suppl): Early Online. Geriatrics & Gerontology Initiative: International Workshop on Care of the Elderly

Abstract

Longer life expectancy in the elderly is a worldwide phenomenon observed during the last two decades owing to the improvements in socioeconomic status, better health policies and revolutionary efforts in imparting health awareness amongst the general public through print, visual and social media. This lead to the concept of “active aging” by maximizing the health and functional ability of older people to achieve disease and disability free quality living. Extensive studies have been performed to assess factors that may affect active aging, such as metabolic, vascular and neuropsychological factors, and sleep disorders, such as insomnia, Obstructive Sleep apnea hypopnea syndrome (OSAHS) and other sleep related breathing disorders (SRBD).

However, OSAHS and SRBD remains under diagnosed despite the diagnostic and therapeutic advances in this field leading to the evolution of a new specialty of medicine, the sleep medicine. In middle-aged adults, snoring, excessive daytime sleepiness, poorly controlled hypertension, cerebrovascular diseases, depression, accelerated cognitive decline and traffic accidents should prompt screening and an evaluation for the possibility of an undiagnosed OSAHS. Although OSAHS in the elderly seems to have a lower impact on mortality than it does in middle-aged adults, the risk of stroke and new-onset hypertension appears to increase in elderly patients. In addition, the presence of central sleep apnea must prompt a thorough cardiac assessment, even in the elderly. Both elderly and middle-aged symptomatic OSA patients derive equivalent benefits from continuous positive airway pressure (CPAP) treatment.

Keywords: Obstructive sleep apnea hypopnea syndrome, sleep related breathing disorders, Central sleep apnea, Continuous positive airway pressure, Overnight polysomnography

Primer case to the topic

This elderly obese gentleman was admitted to the medical intensive care unit with history of acute chest pain and was found to have extensive anterior wall myocardial infarction and underwent thrombolysis. He was a diabetic on insulin for last eight years and his HbA1C was 10.4 % and he had uncontrolled hypertension and was on dual antihypertensives. His total cholesterol was 312 mg%, LDL 198 mg%, triglycerides 290 mg% and HDL 30 mg%. He was an asthmatic on inhaled medications and used to get occasional systemic steroid bursts during acute episodes. His mother was a hypertensive, diabetic and asthmatic.

After the acute phase of his illness was stabilized, probing in to a detailed history revealed that he had chronic snoring, excessive day time sleepiness, irritability and he had no children and erectile dysfunction. His ESS was 14. His wife disclosed he had severe nocturnal choking episodes and she had witnessed apnea for several seconds to more than a minute on several days and had woke him up from sleep out of her anxiety as he was not literally breathing. This gives us the possible diagnosis of a severe OSAHS and metabolic syndrome which could be part of the entity of Syndrome Z and considering his moderate persistent asthma, he could very well be having a co existent alternate overlap syndrome.

His weight was 121 kg, height 180 cm and BMI was 37.3.kg/m². His neck circumference was 18 inches and his Mallampati score was Grade IV which is typical of OSAHS. He was taken up for a Level 1 polysomnography and the sleep study confirmed the diagnosis (Figure 1).

Figure 1: Polysomnography report summary

The apnea-hypopnea index (AHI-index) of the patient was 87.7 which puts him under the category of severe OSAHS. It has been proved beyond doubt that OSAHS is an independent risk factor for uncontrolled hypertension, metabolic syndrome and endothelial dysfunction related adverse events like coronary artery disease and stroke. This patient was started on CPAP and his condition improved and his diabetes, hypertension and dyslipidaemia also could be controlled with optimal medications after initiating CPAP therapy. He also lost around 15 kg weight in three months.

Introduction

The presentations of OSAHS are quite varied in the elderly. During obstructive episodes, which happen maximally during REM sleep in supine position due to the tongue falling backward and closing the upper airway (Figure 2), and the subsequent efforts to restore pharyngeal patency, patients experience recurrent arousal from sleep, which activates the sympathetic nervous system and results in sleep fragmentation. These acute changes contribute to the increased risk of cardiovascular, metabolic and other consequences, such as excessive day time sleepiness, road traffic accidents, cognitive disturbances and poor quality of life.

Figure 2: Tongue falling back during REM sleep in supine posture

The link between OSAHS, a clinical entity characterized by repeated pharyngeal collapse during sleep, inducing apnea or hypopnea, decreasing oxygen saturation and increasing arterial carbon dioxide tension, and aging, is now well defined and expressed by the age-related physiological changes inducing a progressive rise in the prevalence of OSA in the elderly. Three large epidemiologic studies have demonstrated that the prevalence of OSA in women appears to increase after menopause [1,2,3]. Postmenopausal women are 3 times more likely to have moderate to severe OSA compared with premenopausal women. Women who are on Hormone replacement therapy (HRT) are half as likely to have OSA compared with postmenopausal women who are not on HRT [4].

During normal breathing the sequence of events happening which keeps the upper airway patent in the awake state is as follows:

• Phase 1 (beginning of inspiration): Area of upper airway increase due to activation of dilator muscle

• Phase 2 (remaining part of inspiration): Area of upper airway maintained constant and activity of dilator muscle tending to enlarge airway counterbalances the tendency to collapse due to negative intraluminal pressure.

• Phase 3 (Beginning of expiration): Activity of upper airway dilator muscle decrease, airway widens (due to positive intraluminal pressure at this phase).

• Phase 4 (later half of expiration): Airway dimensions decrease rapidly. This is the most vulnerable phase for collapse.

In the awake state, airway dialator muscle tone of OSAHS patients increase more than in normal individuals to compensate for the anatomic compromise which is lost during sleep and the airways collapse especially in obese OSAHS where the lateral pharyngeal wall is thicker and there is increased deposition of fat.

In the non-obese elderly instead of the fat deposition of the pharyngeal walls causing the airway collapse, the age related decline in muscle mass and the reduced tone of the muscles owing to several other factors like, post stroke state, myasthenia, Parkinsonism, inflammatory and toxic myopathies can lead to the collapse of upper airways more readily in sleep.

Repetitive forced inspiration against a closed upper airway generates very substantial negative pressures in the chest cavity, up to the tune of –65 mm Hg. This leads to increased transmural gradients across the atria, ventricles, and aorta leading to ↑ wall stress, ↑ after load, ↑ atrial size, ↓ diastolic function, thoracic aortic dilatation, and even propensity towards dissection. Sympathetic surges and hypoxia induces endothelin release, systemic inflammation, endothelial dysfunction and hypercoagulability leading to cardiovascular and cerebrovascular events especially triggered by factors like dehydration and hypoxia induced polycythaemia especially in those elderly patients with COPD-OSA overlap.

Bed partner reported witnessed choking episodes and chronic snoring are two important clinical clues towards the possible diagnosis in a large majority of cases. Non restorative sleep (“waking up as tired as when they went to bed”) morning headache, dry or sore throat, daytime fatigue/tiredness, cognitive deficits like memory and intellectual impairment (short term memory defects, lack of concentration), morning confusion, personality and mood changes, including depression and anxiety are the other usual symptoms. But the presentation could be a totally unrelated one which makes it difficult for the treating physician to pick up this entity unless he has a high index of suspicion.

Creating awareness about this entity amongst other specialties

Many of the symptoms are non-specific and have other possible causes [5]. Failure to recognize OSAHS is costly both to the individual and to society. Under diagnosis is thought to cost $3.4 billion in additional medical costs per year [6]. To this figure must be added the cost of losses in productivity, accidents, etc [7,8]. A telephone survey in the UK of approximately 5000 individuals aged 15–100 years found that 31% of those with breathing pauses during sleep had sought medical help more than six times in the previous 12 months compared with 12% of snorers and11.9% of non-snorers. They sought medical treatment from their general practioner for a variety of physical complaints - not obviously related to a sleep problem - more than twice as often as patients without OSAHS [9].

Cardiology

New onset hypertension in the elderly or difficult to control hypertension, Left ventricular hypertrophy, nocturnal angina, myocardial infarction with no other obvious risk factors, arrhythmias, particularly bradyarrhythmias, atrial fibrillation with no other cause, heart failure, progressive exertional dyspnea in non-smokers with evidence of increased pulmonary artery pressure & cor pulmonale especially in an obese patient should alert the treating cardiologist to probe for the presence of a sleep related breathing disorder [10].

Psychiatry

Depression, anxiety, behavioural problems, acute delirium and memory disturbances are the features with which they present to a psychiatrist and hence a thorough evaluation is mandatory before branding the patient as having functional abnormalities and being started on long term medications [11].

Neurology

Headache on waking up in the morning, refractory epilepsy, stroke, impaired rehabilitation post stroke, post-polio syndrome, muscular dystrophies, and autonomic failure syndromes such as Shy Drager syndrome etc are related to sleep related breathing disorders and a thorough history in this regard should be elicited.

Urology

Nocturia, impotence, erectile dysfunction are symptoms related to OSAHS often overlooked as part of obstructive uropathy as in Benign Hypertrophy of Prostate which is a common problem in elderly males.

Other unusual presentations

Hypothyroidism, acromegaly are associated with macroglossia and increased soft tissue mass in the pharyngeal region and thus with an increased risk of sleep disordered breathing (SDB), obese Type II diabetics may have OSAHS which might be missed by the Physician or Endocrinologist. Sore throat, hoarse voice and gastro oesophageal reflux disease might be part of OSAHS and could easily be missed by the Physician, ENT surgeon or Gastroenterologist.

Hepatic steatosis, osteoarthritis, chronic pain syndrome and even multiple myeloma are found to have associations with OSAHS. Polycythaemia is often a perplexing problem faced by the physician which might ultimately be due to a sleep related breathing disorder. Difficult intubation, sensitivity to opioid analgesics and witnessed apneas during recovery are features encountered by the anaesthetist while dealing with this subset of patients who were not previously diagnosed as having sleep related breathing disorder.

Spectrum of Sleep related breathing disorders (SRBD)

1. Snoring with or without excessive daytime sleepiness
2. Upper airway resistance syndrome and Respiratory event related arousals
3. Obstructive sleep apnea-hypopnea syndrome (OSAHS)
4. Obesity hypoventilation syndrome
5. Central Sleep apnea
6. Complex Sleep apnea syndrome
7. Obstructive lung disease with Obstructive sleep apnea (OLDOSA)
8. Metabolic syndrome with OSA (Syndrome Z)
9. Unusual variants like REM sleep related behavioral disorder (RBD), Restless leg syndrome (RLS), Periodic leg movement syndrome (PLMS), Catathrenia etc all can be associated with SRBD.

Snoring with or without excessive day time sleepiness (EDS)

It is estimated that around 35–45% of men and 15–28% of women all over the world report habitual snoring [6,12]. Loud intrusive snoring affects bed partners, family, and even neighbours. Noise pollution and its resulting social disability, relationship disharmony and threatened marriage break up [13] is an important reason why the patient, often pressurized by their partner, seeks medical help. In this case the ‘‘patient’’ is often more correctly the partner as the individual concerned is not aware of any adverse effects from his/her snoring other than the irritation reported by others. Snoring is also the most frequent symptom of OSAHS, occurring in 70–95% of patients [14], but because it is so common in the general population it is a poor predictor of OSAHS [15]. Three quarters of patients who deny snoring turn out to snore when this is measured objectively. Hence whenever possible, an account from a third party should be obtained.

Excessive daytime sleepiness (EDS) is caused by fragmented sleep related to frequent arousals. Like snoring, it is common and a poor discriminator of the patient with OSAHS. 30–50% of the general population without OSAHS report moderate to severe EDS. Several tools are available for measuring sleepiness both subjectively and objectively. A self-administered questionnaire like STOP BANG (mnemonic) with 3 or more positive answers puts the patient under high risk for OSAHS. If Stop Bang score is 3 or more then the chance for moderate OSA (AHI-15-30) is 93% and for Severe OSA (AHI>30) sensitivity is 100%. The components of the questionnaire are as follows:

Snoring - Do you snore loudly (Louder than talking or loud enough to be heard through closed doors)?
Tired - Do you often feel tired, fatigued or sleepy during the day time?
Observed - Has anyone observed you stop breathing during your sleep?
Blood Pressure - Do you have or are you being treated for high blood pressure
BMI - Body mass index>35 ?
Age - Age > 50 years old
Neck Circumference - Neck circumference greater than 40 cm
Gender -Male

There is no gold standard, but the easiest and most practical method of assessment is the Epworth sleepiness scoring system (ESS). An ESS score of 10 or more increases the likelihood of OSAHS in snorers with EDS and likewise the treating physician can streamline those patients with high likelihood of having an OSAHS for referring for a full-fledged overnight polysomnography. This would be a cost effective strategy rather than referring all snorers for a polysomnography. The positive predictive value of the test could be improved by prioritizing those snorers with a neck circumference of more than 17 inches in males and 15 inches in females.

Clinical Evaluation

• BMI > 30 kg/m².
• Neck circumference: A neck circumference over 43 cm in males and 37 cm in females is a common finding in adults with obstructive sleep apnea (OSAHS).
• Skeletal features: Features such as maxillary deficiency and retrognathia may cause OSA.
• Nasal airway: Evaluate nasal airflow, the internal and external nasal valves, nasal turbinates, and presence of a deviated nasal septum. Nasal obstruction contributes to sleep-disordered breathing and also hinders treatment with continuous positive airway pressure.
• Oral examination: Mallampati score (Figure 3) should be noted because higher scores are correlated OSA. An erythematous uvula as a result of vibrational trauma from snoring is a common finding in patients with OSA, and scalloping of the tongue suggests the oral cavity is too small. A high, arched hard palate is a common finding in patients with OSA and indicates the oral cavity is too narrow. Objective measure of snoring can be done using light weight sensors picking up tracheal sounds.

Figure 3: Class 1, full visibility of tonsils, uvula, and soft palate; class 2, visibility of hard and soft palate, upper portion of tonsils and uvula; class 3, soft and hard palate and base of the uvula are visible; class 4, only hard palate visible. (Mallampati classification)

A proper clinical history and evaluation enables the physician to judiciously sort out those snorers who would really benefit from further evaluation. However a good sleep hygiene can considerably reduce the severity of snoring and improve the quality of life of these patients by avoiding pillows, lying on a lateral or prone position, use of nasal steroids in case of chronic allergic rhino sinusitis etc. The “No snore” devices that are available over the counter like straps, pillows and plasters are not currently accepted as a treatment strategy.

Upper airway resistance syndrome (UARS) and Respiratory event related arousals (RERAS)

Recording the apnea (defined by the American Academy of Sleep Medicine (AASM) as the cessation of airflow for at least 10 seconds) and hypopnea as peak signal excursions drop by at least 30% of pre event baseline using nasal pressure transducers and flow assessment thermal devices (Diagnostic study) for at least 10 sec and causing a 3% drop in saturation, is the basis of an OPSG in making a diagnosis of OSAHS based on the apnea-hypopnea index (AHI) and whether it is Central or Obstructive events are characterized by absent or continued thoracoabdominal effort respectively in the setting of partial or complete airflow cessation. Mixed events have both obstructive and central features. They generally begin without thoracoabdominal effort and end with several thoracoabdominal efforts in breathing.

Supposedly a continuum, the next group in the spectrum of SRBD patients includes the milder forms of OSAHS which is termed as Respiratory event related arousals (RERAS) characterized by sequences of breaths characterized by increasing respiratory effort (which can be recorded by esophageal manometry),inspiratory flattening in the nasal pressure or positive airway pressure (recorded by positive airway pressure device flow channel),increase in end-tidal partial pressure of carbon dioxide (PaCO2) leading to an arousal from sleep. In other words, a RERA is an event characterized by increasing respiratory effort for 10 seconds or longer leading to an arousal from sleep but one that does not fulfill the criteria for a hypopnea or apnea. Respiratory effort related arousals (RERAs >5/h) or> 30% TST (Total sleep time) with flow limitation associated with EDS (ESS>10) and AHI <5 are categorized as UARS (Figure 7).

The clinical significance of UARS and RERAs is that they are also associated with the various problems like poorly controlled hypertension, cardiovascular and cerebrovascular events as seen in OSAHS and hence addressing these problems have a beneficial effect on the long term outcome of these co morbidities. The various management strategies amongst this subset of patients include general measures like avoiding alcohol/sedatives, adhering to good sleep hygiene, positional therapy, while the medical measures include nasal steroids.

Figure 4: Hypnogram showing repeated arousals and snore with AHI <5, but the respiratory disturbance index was more than AHI which suggests the possibility of UARS.

Dental measures like the oral expansion focussed orthodontic appliances in selected cases following cephalometry and CT/MRI assessment of the upper airway morphology and selecting the appropriate appliance as per the dimensions required for the patient should be custom made.

Drug induced sleep endoscopy (DISE) of the upper airway which is to localize the site of maximum collapse during inspiratory efforts especially during sleep is a good guide to surgeons who plan for a minimally invasive surgical ablation of the tissues to avoid collapse of the airway like radiofrequency ablation (RFA), Laser assisted uvulopalatopharyngoplasty (LAUP) etc.

Pure surgical procedures like uvulopalato pharyngoplasty(UPPP), septoplasty, turbinectomy, tonsillectomy, might be successful in carefully selected cases. A successful empirical trial of CPAP CPAP may be tried by titrating against the snoring/ arousal index as against the usual titration against AHI and assessing the improvement in daytime sleepiness supports the initial diagnosis.

Obstructive Sleep apnea hypopnea syndrome (OSAHS)

OSAHS is the most common type of sleep apnea. The site of obstruction in most patients is the soft palate in the mouth. This region has no rigid structure, such as cartilage or bone, to keep the airway open. As a person with OSAHS falls asleep, the muscles that hold the airway open during the day relax. The airway collapses and becomes obstructed. Tissue pressure that causes this collapse is referred to as critical closing pressure (Pcrit). When the airway closes, breathing stops, leads to awakening & opens up the airway. Because the person is continuously awakening to open his airway, he does not reach the deep stage of rapid eye movement (REM) sleep, which the body needs to rest and replenish its strength.

Obstructive apnea (OSA) may generate negative intrathoracic pressure that increases left ventricular transmural pressure and left ventricular after load. The negative pressure also draws more blood into the thorax and increases right ventricular preload. Intermittent hypoxia related to OSA will also impair cardiac contractility and diastolic relaxation. OSA patients also have attenuated endothelium-dependent vasodilatation and decreased circulating markers of nitric oxide. These effects, together with increased sympathetic vasoconstrictor activity and inflammation, will predispose to hypertension and atherosclerosis. In addition, platelet activation and aggregability are increased and predispose to thrombotic disease. Epidemiological studies indicate that OSA can initiate or promote cardiovascular disease such as hypertension, coronary heart disease, Heart failure, cardiac arrhythmias (bradyarrhythmias, atrial fibrillation and ventricular ectopy) and cerebrovascular disease. Tumours exposed to acute cyclic hypoxic stress show enhanced angiogenesis, perfusion and metastatic dissemination and hence OSAHS is implicated in the release of oxygen free radicals at the subcellular level leading to DNA damage and carcinogenesis [33,34].

OSAHS is associated with several components of the metabolic syndrome, mainly insulin resistance and abnormal lipid metabolism. Sleep restriction causes insulin resistance by inducing a pro-inflammatory state (increased release of interleukin-6 and tumour necrosis factor (TNF-α). Epidemiological studies have shown that sleep related hypoxaemia is associated with glucose intolerance independent of age, sex, BMI and waist circumference. The metabolic syndrome can be triggered by intermittent hypoxia and sleep fragmentation/ deprivation. The metabolic syndrome can be due to the release of free fatty acids, angiotensin II and adipokines by adipose tissue, which may damage the pancreas, leading to insufficient insulin release and apparent insulin resistance. Mean and nadir SaO2 during sleep are independent predictors of the metabolic syndrome in overweight children and adolescents.

In patients with OSA, disruptions of autonomic activity have been described [16] and are now recognized to contribute to cardiovascular risk in the elderly [17]. While the mechanisms explaining this association remain unclear, it is presumed that autonomic hyperactivity might be considered to be a marker of new-onset hypertension [18]. Diurnal baroreflex control alteration is also associated with sleep-related autonomic overactivity in the elderly [19,32] and increases the incidence of cardiovascular complications in elderly OSA patients. OSA is associated with an increased cardiovascular mortality related to cyclic oxygen desaturations followed by rapid re-oxygenation, causing oxidative stress, inflammation and sympathetic over activation. To prove this hypothesis, six studies including 11, 932 patients were identified and analysed. The pooled HR (95% CI) of all-cause mortality was 1.19 (1.00–1.41) for moderate OSA and reached 1.90 (1.29–2.81) for severe OSA. The pooled HR (95% CI) of cardiovascular mortality was 1.40 (0.77–2.53) for moderate OSA and 2.65 (1.82–3.85) for severe OSA. With CPAP treatment, patients had the same cardiovascular mortality rate as healthy subjects (HR 0.82, 95% CI 0.50–1.33), suggesting that severe OSA is a strong independent predictor for future cardiovascular and all-cause mortality and that CPAP treatment reduces the mortality risk in moderate OSA group [20,25].

The current gold standard diagnostic tool in clinical practice for assessing OSAHS, particularly in the elderly, is Level-1 Overnight polysomnography (OPSG), which is a fully attended multi parametric study in a sleep lab, as it allows for a more accurate diagnosis of OSA and other age-related sleep disturbances (Figure 5). However, only a minority of patients at risk for OSA has access to OPSG, owing to its technical requirements, labour-intensive procedures and cost. A Level-2 study is a full unattended polysomnography with >7 channels of monitoring and sleep staging. Whereas a Level-3 OPSG is a home based unattended, portable study and monitors >4 channels, including ECG or heart rate, oxygen saturation and at least 2 channels for respiratory movement and airflow, with no sleep staging.

Figure 5: Patient undergoing Level-1 fully monitored Overnight polysomnography

Due to increasing demand, a good alternative for diagnosing OSA is a portable respiratory monitoring system (Figure 6), that is known for its accuracy, easy management and lower cost [21] and also as a valid tool for the diagnosis of OSA [22] in clinical settings and in the elderly [23], for whom oximetry could represent a simple alternative for the detection of OSA [24].This is grouped as Level-3 OPSG but has the disadvantage of lack of proper sleep staging which is important in many sleep disorders.

Figure 6: Level-3 portable home based OPSG

Obstructive apnea is a complete blockage of the airway despite efforts to breath for more than 10 seconds culminating in an EEG evidence of an arousal and is termed apnea (Figure 7). If the nasal pressure signal excursions drops by more than 30% of baseline with 4% desaturation(or alternatively more than 50% drop in amplitude of flow with 3% desaturation) and the duration of the event lasts for at least 10 seconds and at least 90% of the time of the event the 30% amplitude criteria persists and this ultimately leads to an EEG arousal, is termed as hypopnea. Notice that the patient efforts gradually increases and ends in an arousal which causes the airways to open and the saturation by this time drops considerably leading to a sympathetic surge which is the proposed mechanism for the various sleep related health events.

The total number of apnea and hypopnea events happening throughout the total sleep time of an individual is calculated per hour and is recorded as the AHI. If along with these events we add the other minor respiratory events which can result in an arousal, like the RERAs, then the total number of respiratory disturbances occurring on an hourly basis over the total sleep time is known as the Respiratory disturbance index (RDI).

Figure 7: Schematic representation of a Polysomnographic recording of an Obstructive event

In this hypnogram, (Figure 8), the first four lines are related to the EEG of the patient which is the basis for staging the sleep, next line is the actual number of arousals that occurred, followed by snores, heart rate fluctuations, leg movements, periodic leg movement sequences, apnea-hypopnea, desaturations and body positions. All these have to be analysed objectively and then the final results are interpreted based on the AHI and maximum desaturations.

Figure 8: Typical hypnogram which is a single page graphical representation of the various sleep related parameters recorded overnight.

The common SRBD patterns usually encountered are as follows (Figure 9)

Figure 9: Schematic representation of common sleep related breathing patterns

Based on the AHI obtained (Figure 10), the severity of OSAHS is graded as follows:
AHI     0-5           Normal
             5-15         Mild
            15-30        Moderate
             >30          Severe

Figure 10: Sleep report-summary of respiratory events

The mild variant of OSAHS can be managed with weight reduction protocol and sleep hygiene techniques while the moderate and severe OSAHS warrants definitive management in the form of CPAP as the treatment of choice since it counteracts Pcrit and stabilizes the breathing pattern. Grote et al in the journal of hypertension published their study showing clear cut correlation between uncontrolled hypertension with increasing severity of OSAHS [26].The seventh Joint National Committee for management of hypertension in 2003 has recognized OSAHS as an independent risk factor for the development of hypertension. It was also established by randomized controlled trials that for the proper control of hypertension in OSAHS patients along with optimized anti-hypertensive there must be proper management of OSAHS by nasal CPAP therapy [27,28]. CPAP reduces sleepiness and may be of importance in elderly OSA patients, as improved attention capacity could delay cognitive dysfunction and prevent traffic accidents [29,30].

How CPAP works?

Sullivan first described the use of nasal CPAP to treat OSA. It is the gold standard treatment for patients with sleep disordered breathing. There is a flow generator and a valve which modulates the pressure between 5 cm of H20 to 25 cm of H20. It has the advantage of being a non-invasive, portable option for daily use in these patients. It acts as a pneumatic splint in opening up the collapsed upper airway. It is available in a less expensive manual pressure setting form where the pressures are set based on the titration study done and an expensive auto titrating CPAP in which the flow sensors in the machine senses the obstruction and titrates the pressure accordingly on a breath to breath basis which might change based on the body positions and the stage of sleep. Thus an OSAHS patient who is supine and in REM sleep requires much more pressure than a patient who is sleeping prone or on his sides.

Choosing the right interface for the right patient as there are nasal masks, oronasal masks, nasal pillows, full face mask, helmets etc available for delivering CPAP. This is important in ensuring the CPAP compliance as an ill-fitting mask may end up causing nasal bridge ulcer and renders the patient non-compliant for CPAP therapy.

Regular use of CPAP caused 5 mm of Hg drop in diastolic BP and 42% reduced risk for stroke, 14% risk reduction for coronary artery disease over 5 year period. As per the Wisconsin sleep cohort, those who were not on CPAP was associated with the following long term effects [31,32],

• 2.5 times risk for Congestive Cardiac failure
• 1.3 times risk for Coronary artery disease
• 1.6 times risk for Cerebrovascular accidents
• 1.2 times chance for resistant HTN

Hence for ensuring proper adherence for CPAP therapy, a regular follow up and analysis of the inbuilt smart card of the machine is essential to note the number of hours of CPAP used on a daily basis by the patient for the last several days with additional information like the technical details including the average pressure delivered for abolishing events, mask leak etc. Most of the latest automatic CPAP machines have heated humidification which prevents mouth drying and drying up of secretions which again improves the compliance and hence a major revolutionary therapy in averting major organ related events in the elderly.

Obesity hypoventilation syndrome (OHS)

Obesity is considered as an epidemic and obese elderly population does have their share of sleep related hypoventilation. OHS is a chronic condition associated with impairments of body structures or functions, leading to a decrease in daily life activities, a lack of social participation, and a higher risk of hospitalization and death. Despite its severity, OHS is largely under diagnosed even in obesity clinics.

Obesity hypoventilation syndrome (OHS) is defined as the combination of obesity (BMI ⩾30 kg•m−2), daytime hypercapnia (arterial carbon dioxide tension (PaCO2) ⩾45 mmHg) and various types of sleep disordered breathing after ruling out other disorders that may cause alveolar hypoventilation (obstructive or restrictive pulmonary diseases, chest wall disorders, neuromuscular diseases, severe hypothyroidism and congenital central hypoventilation syndrome) [35].

It has been proposed to add the presence of an arterial base excess >3 mmol/L or a standard bicarbonate concentration >27 mmol/L in the absence of another cause of metabolic alkalosis to the definition as there is high sensitivity of bicarbonate in detecting OHS. 70–90% of patients with OHS also have OSAH syndrome (OSAS) while 10–15% of sleep apnea patients referred to the sleep lab have diurnal hypercapnia and can be classified as having OHS [36]. Many of them may be admitted for acute hypercapnic respiratory failure (AHRF) due to obesity hypoventilation and might have had similar episodes of AHRF in the past but had not been treated by home noninvasive ventilation (NIV) or CPAP after their first episode. This highlights that OHS is under diagnosed or that the diagnosis is dramatically delayed.

Diagnosis

OPSG shows prolonged apneas, hypopneas and/or episodes of severe continuous desaturation during REM sleep suggestive of REM sleep hypoventilation. Adding transcutaneous carbon dioxide tension (PtcCO2) monitoring to PSG is helpful to confirm the presence of episodes of sleep hypoventilation. A decrease in lung volumes (vital capacity, total lung capacity and FRC) has been reported as a determinant of daytime hypercapnia in obese patients. This restriction is associated with decreases in total respiratory system compliance and lung compliance, and with an increase in work of breathing. The decrease in lung volume is usually related to fat mass, and intrathoracic and abdominal fat distribution. These fat deposits could have direct mechanical effects on respiratory function by impeding diaphragm motion, and changing the balance of elastic recoil between the chest wall and lung. Another possible mechanism may involve the low-grade inflammation associated with excess visceral and intrathoracic adiposity that might induce specific muscle impairment [37].

Hypoventilation is more pronounced during REM sleep and the severity of REM sleep hypoventilation is associated with a blunted awake ventilatory response to carbon dioxide. In obese subjects, circulating leptin levels, a potent stimulator for ventilatory drive, are often higher than in non-obese subjects. These results suggest that a central resistance to leptin may occur in obesity and particularly in OHS. A possible mechanism for this central resistance could be deficient leptin transport through the blood–brain barrier [38,39]. The three main strategies available to clinicians for the management of OHS are PAP therapies (CPAP and/or NIV), body weight losing strategies and rehabilitation. “Nonresponders” to CPAP are classically more obese (BMI >40 kg•m−2), with a higher PaCO2, a lower PaO2 and more severe oxygen desaturation during the night. General consensus is that obese subjects with a BMI >40 kg•m−2 in whom nonsurgical approaches have failed or subjects with a BMI >35 kg•m−2 and having weight-related co morbidities are candidates for bariatric surgery. Common surgical procedures include vertical banded gastroplasty (VBG), adjustable gastric banding, Roux-en-Y gastric bypass (RYGBP) and biliopancreatic diversion with or without duodenal switch. CPAP adherence is again crucial to achieve treatment goals. One open study compared the improvement in daytime PaCO2 with CPAP and NIV treatments, after selecting patients with predominantly nocturnal central hypoventilation to be treated by NIV and those with predominantly obstructive events to use CPAP [40]. The AASM recommends using bilevel pressure support in spontaeneous mode as a default modality. A Cochrane review of 26 trials measuring the impact of 21 drugs on respiratory drive and OSAHS, including acetazolamide, medroxyprogesterone, aminophylline, theophylline, protriptyline and paroxetine, concluded that there was insufficient evidence to recommend drug therapy as a treatment for OSAHS [41].

Central Sleep apnea

Central sleep apnea/hypopnea refers to the cessation or reduction of ventilation lasting for ≥10 s (in adults) due to a transient loss of neural output to the respiratory muscles. It can be seen in high altitude or without any co morbidities when it is termed idiopathic CSA.A periodic pattern of waxing and waning of ventilation with periods of hyperventilation alternating with central apnea/ hypopnea is termed Cheyne-Stokes respiration (CSR) (Figure 11).

Figure 11: Cheyne Stokes Respiration (CSR) pattern

Repetitive episodes of apnea in the absence of respiratory effort, is caused by an altered ventilatory motor output. At least three consecutive cycles of cyclical crescendo and decrescendo change in breathing amplitude and at least one of the following is required to make a diagnosis of CSR:

i) Five or more central apnea/hypopnea per hour of sleep.
ii) This particular pattern has duration of at least 10 consecutive minutes.

The prevalence of CSA in the general population is not known. However, it seems to be significantly less common than OSA, as <5% of patients referred to a sleep laboratory reveal predominant CSA. In contrast, a relatively high prevalence of CSA/CSR is observed in association with various conditions including CHF, pulmonary hypertension, ischemic stroke, neuromuscular disease, obesity hypoventilation syndrome and opioid use, or during initiation of CPAP therapy in certain patients with OSA. Hence the chances for encountering the same in the elderly population is more so than in the general group. The pathophysiology of CSA is considered as due to three mechanisms, respiratory centre control instability, due to an increased chemical drive, so that the prevailing PaCO2 is close to the apnea threshold, a prolonged circulation time as in heart failure (HF), altered respiratory mechanics as in neuromuscular and OHS. Sleep-related breathing disturbances should be suspected in all patients with HF who suffer from nocturnal dyspnea, nonrefreshing sleep or daytime sleepiness. Particular risk factors for CSA/CSR include: severe HF, elder age (≥60 years), male sex, hypocapnia, atrial fibrillation, CSR observed during the day.

Cheyne-Stokes respiration in congestive heart failure and high altitude, hypothyroidism are all non-neurologic/ non hypercapnic causes for CSA whereas Shy-Drager syndrome, CVA, myasthenia gravis, neuromuscular disease, bulbar poliomyelitis, brain stem infarction, and encephalitis are hypercapnic/ neurologic variants of CSA. This distinction is helpful in devising the management strategies in these patients. Hypercapnic CSA and hypoventilation disorders are characterized by a reduction in the minute volume due to insufficient respiratory drive, impaired translation of breathing impulses to the muscles, or abnormalities of musculoskeletal function or morphology. By contrast, respiratory drive or the sensitivity of the chemoreceptors to metabolic changes is increased and often leads to chronic hyperventilation in non-hypercapnic CSA [42].

The questions about survival and severe cardiac events over the long-term are being addressed in two large international, multicentre RCTs (SERVE-HF and ADVENT-HF) [43]. After optimization of medical management for the underlying inciting co morbidities the ventilatory strategies are designed as follows:

i) CPAP reduces CSA by 50%, which may be due to an improvement in left ventricular function.

ii) ASV (Adaptive servo ventilation) or ACMV (Anti cyclic modulated ventilation) with mandatory breaths seems to be the best option to counterbalance the ventilatory instability in CSR.

iii) Obstruction of the upper or lower airways: airway obstruction can be addressed by increasing intra luminal pressure using CPAP or BPAP in the spontaneous mode (BPAP-S).These modes stabilize the upper airway, help avoid collapse of the small airways in COPD and improve the ventilation–perfusion mismatch. The reduction of the expiratory pressure in BPAP may ease respiration for the patient. Expiratory pressure relief algorithms apply different levels during early and end-expiration. Reduced ventilatory drive can be addressed by the application of mandatory breaths. Pressure support ventilation with target volume (also known as average volume assured pressure support (AVAPS) are newer modes which ensures normalizing the breathing patterns in complicated sleep related breathing disorders associated with CSA.

Hence a judicious combination of optimal medication and non-invasive ventilatory mode selection enables the physician to abolish all sleep related CSA/CSR events capable of increasing the mortality in those elderly patients with various co morbidities leading to these complex breathing patterns.

Complex Sleep apnea syndrome

In some patients diagnosed with OSA, a CSR/CSA breathing pattern may emerge during initial CPAP therapy (Figure 12). The clinical relevance of this phenomenon, referred to as treatment-emergent CSA, is still a matter of debate, as studies suggest that CSA disappears in the majority of OSA patients during prolonged CPAP therapy. However, persistent residual CSA may disturb sleep quality and may lead to CPAP intolerance in OSA patients. ‘‘Complex Sleep Apnea’’ may merely reflect difficulty adjusting to the CPAP with repeated ‘‘transitional’’, sleep-onset central apneas, inadequate titration or over titration of CPAP, or substantial mask leak. Higher pressures leading to mask leak, sleep fragmentation and resultant drop of PaCO2 below the “apneic threshold”, triggering central apneas. Loss of upper airway muscle tone, acute lung inflation also contributes to emergence of central apneas (Figure 13). Following central hypercapnia ventilatory hyper responsiveness causes PaCO2 levels to fall below the apneic threshold triggering a central apnea.

Figure 12: Use of CPAP leading to emergence of CSA which follows increasing pressure, mask leaks and sleep fragmentation (Complex Sleep apnea)

Figure 13: Shaded area corresponds to CSA events when the flow increases and mask leak proportionally rises (red line).

Once the peripheral chemoreceptors sense an apnea related rise in the PaCO2 level above the apnea threshold, hyperventilation recurs driving PaCO2 level below the apnoea threshold and the cycle continues. In those not responding to prolonged CPAP therapy, Adaptive Servo Ventilation (ASV) is the choice for such patients. In this mode of pressure support (PS) ventilation, the inspiratory pressure support is increased during hypopnoeic or apneic phases of CSR whereas PS is reduced to a minimal level during hyperpneic phases.

Obstructive lung disease with Obstructive sleep apnea (OLDOSA)

About 16.8% of COPD patients have OSAHS while amongst the OSAHS patients there is a large majority of COPD patients who are classified as the COPD-OSAHS overlap syndrome, as this subset of patients tend to develop more severe and accelerated pulmonary artery hypertension as compared to either diseases alone when there was no overlap. Interestingly similar overlap existed with Asthmatics as well and they were considered as Alternative overlap syndrome and later the Asthma COPD overlap (ACO) group also was found to have overlap with OSA phenotypes and hence collectively all these obstructive airway disease –OSAHS overlaps are now known as OLDOSA or Obstructive lung disease-OSA syndrome [44].

In COPD patients with OSAHS, hypercarbia results in blunted response of respiratory muscles and respiratory centre to hypoxia and COPD with near-maximal ventilatory capacity on the contrary, even a mild increase in UAR (upper airway resistance) like snoring increases the work of breathing and results in arousals. COPD, on the other hand cannot compensate for UAR by altering inspiratory time and leads to early arousals and increased sleep fragmentation. So both has the potential to worsen each other’s course and results in poor control of both disease processes. Axial coupling between upper airway, lower airways and lung parenchyma exists. There is increasing evidence that the collapse of the upper airway occurs during expiration and there is loss of the axial coupling. REM recumbent posture and hyperinflated lungs in this posture causing reduction in FRC (Functional residual capacity) and inefficient accessory muscle use to maintain ventilation.

Ventilation perfusion mismatch of emphysema, increased nocturnal vagotonia, wall edema, C- fibre stimulation results in more narrowing of airway calibre during sleep. All these are the proposed mechanisms for hypoxia in a COPD-OSAHS overlap patient. OSA alone has a 20% chance for development of cor pulmonale as compared to COPD which has a 30% chance for the same. While in case of Overlap, the chances for developing cor pulmonale get catapulted to 80%.The five year survival drops to 30 % in such patients.

So screening for overlap is a must when we deal with obese COPD patients, COPD patients with snoring or on LTOT with day time headache. It is always prudent to look for comorbid COPD/Asthma in OSA patients.

CPAP is the first line therapy for overlap syndrome. Daytime hypercapnia and nocturnal hypoxemia despite supplemental oxygen therapy are indications for nocturnal BiPAP, regardless of the presence of OSA. The five year survival increased from 26% to 71 % for those on CPAP with supplemental O2 vs LTOT (Long term oxygen therapy) alone [45]. Bariatric surgery for morbid obesity improves both Asthma and OSA.

Metabolic syndrome with OSA (Syndrome Z)

Vascular risk factors have been shown to be independent predictors of adverse events; they will show at least additive effects in combination and possibly potentiate each other. One such cluster is a quartet of risk factors which includes systemic hypertension, insulin resistance, hyperlipidaemia (hypertriglyceridemia and low HDL), and central obesity which has been defined as metabolic syndrome or “Syndrome X”. OSAHS with syndrome X is known as Syndrome Z [46] (Figure 14).

Figure 14: Various components of Syndrome X being linked to OSAHS to form Syndrome Z

There exist a circadian variation in risk of cardiovascular events is paralleled by changes in heart rate, blood pressure, and autonomic balance. In normal subjects there is a preponderance of vagal influences during sleep, although the relative balance between sympathetic and parasympathetic nerve activity varies between non-REM and REM sleep with relatively greater and more variable sympathetic nerve activity in REM. Awakening from sleep is associated with a rapid increase in sympathetic nerve activity and a relative reduction in vagus nerve activity. Increased platelet agreeability has been shown to occur in the morning and is believed to be due to increased sympathetic nerve activity [47]. It is possible that the circadian distribution of acute coronary events is different in patients with OSA with, for example, a disproportionate proportion of events occurring during sleep. The influence of obstructed breathing during sleep may also carry over into the early hours after awakening.

These relationships should lead physicians to consider that patients with OSAHS may have co-existent modifiable cardiovascular risk factors and, conversely, that OSAHS should be suspected in patients with poorly controlled hypertension, central obesity, insulin resistant diabetes, or dyslipidaemia. Prompt initiation of CPAP therapy in those with OSAHS have undoubtedly lead to the better control of hypertension, diabetes, dyslipidaemia and has translated in to lesser organ related adverse outcomes.

Unusual variants

The list of other related disorders are too long and beyond the scope of this discussion as entities like narcolepsy, idiopathic hypersomnolence, SOREM (Sleep onset REM), Sleep wake disorders, parasomnias, bruxism, night terrors, nocturnal enuresis, somnambulism, insomnia, rhythmic masticatory movement activity (RMMA) which is associated with bradypnea and prolonged expiration have to be evaluated by multidisciplinary dedicated sleep centres. However REM sleep related behavioural disorder (RBD), periodic leg movement syndrome (PLMS), restless leg syndrome (RLS), catathrenia etc all can be associated with SRBD especially in the elderly and more or less can present as social problems and partner oriented adjustment disorders as 64% RBD cases are reported to have history of partner assault in sleep and hence has to be properly dealt with or made aware of.

As an illustration the following case is discussed:

An elderly diabetic who was on Insulin and oral hypoglycemic agents for last several years presented with excessive day time sleepiness, irrelevant talk, disturbed sleep and muttering in sleep. He used to enact his dreams and even screamed and shouted once in a while in his sleep and even kicked his wife so as to make her fall out of the bed during an instance when he dreamt of fighting a thief. Interestingly he could recollect the dreams and the response he had to these stimuli. His clinical and detailed neurological examinations were within normal limits except for features of diabetic neuropathy.

Figure 15: Tibial muscle jerks suggestive of PLM

His OPSG showed increased tibial muscle activity in the form of jerks lasting for 0.5 to 5 seconds (Figure 15) and at a rate of 15 or more per hour of sleep is supportive of the diagnosis of periodic limb movement disorder (PLMD) which cannot be explained by another disease process. It also revealed enhanced EMG activity during REM sleep which is a REM related behavioural disorder (RBD), which is a sleep related leg movement disorder (SRLMD) (Figure 16 and 17). There was also few recorded snores as well.

Figure 16: REM sleep phase with chin and tibial muscle activity suggestive of RBD

Figure 17: Chin muscle and leg muscle enhanced activity in the same patient

So though this was suspected as a case of OSAHS, it turned out to be a case of primary snoring, REM related behavioral disorder (RBD) and periodic leg movement disorder (PLMD) in a case of diabetic neuropathy causing frequent arousals and related sleep fragmentation.

RBD is the loss of normal voluntary muscle atonia during REM sleep is otherwise termed RSWA (REM sleep without atonia) and the EEG should not be showing any seizure activity. RBD is a potential marker for the later development of neurodegenerative disorders characterized by alpha-synuclein deposition and more than 50% of idiopathic RBD later on developed neurodegenerative parkinsonism with a mean latency period of 13 years [48]. Clonazepam 0.5 mg at bed time is found to be effective in RBD and some studies have shown benefits with melatonin 3-6 mg taken orally at bed time which might restore the RBD related desynchronisation of circadian rhythm. Levodopa is also prescribed in those patients in whom RBD is considered as a harbinger of Parkinsonism.

Yet another interesting situation is catathrenia where the person makes a groaning sound during prolonged expiration for > 2s, in REM sleep and can mimic CSAS. This moaning sound has a sexual connotation which makes it socially unacceptable and puts the patient in perplexing situations. They have high arousal index, headache and excessive somnolence. They tend to have normal BMI. Bradypnea, crescendo-decrescendo pattern of moaning following an arousal has to be differentiated from CSAS by synchronous audio-video recordings. Vocalisation differentiates it from CSAS/ expiratory snorers. Being a glottic phenomenon, the diagnosis of pharyngeal muscle dysfunction could be ruled out. CPAP or oral appliances based on patient preferences are successfully used as a treatment in this rare variant.

Conclusion

OSA is a highly prevalent, chronic condition that is frequently associated with modifiable risk factors and multiple medical co morbidities in the elderly. Effective management of OSA requires a comprehensive, multidisciplinary, patient-centred approach that addresses not only the sleep disordered breathing events but also includes evaluation for and treatment of related medical co morbidities and strategies to optimize treatment adherence. Integrated care for OSA involves collaboration between health professionals from a variety of disciplines.

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Obstructive Sleep Apnea And The Spectrum Beyond In The Elderly Patients