«PEKKA TIIHONEN Novel Portable Devices for Recording Sleep Apnea and Evaluating Altered Consciousness Doctoral dissertation To be presented by ...»
Sleep apnea is defined as a repetitive cessation of airflow in spite of breathing efforts. A sleep apnea event can be classified into three categories (obstructive, mixed or central) according to the strength and existence of respiratory efforts during the apnea event. A sleep apnea patient can suffer from all types of apneas, however central apneas are rare. In addition to apnea events, the patient can experience hypopnea events which are classified as partial obstruction of airflow associated with decrease in blood oxygen saturation.
In middle aged men, the estimated prevalence of sleep apnea or sleep apnea syndrome has been reported to vary from 9 to 24% (Ancoli-Israel 1991, Young 1993, Bearpark 1995, Marin 1997, Bixler 1998). In certain subgroups patients with (hypertension, coronary artery disease and bariatric surgery candidates) the prevalence is much higher (Andreas 1996, Worsnop 1998, Gottlieb 1999, Frey 2003, O'Keeffe 2004, Valham 2008). For example, O’Keeffe (2004) found that 77% of candidates for bariatric surgery suffered from sleep apnea. There are many risk factors for obstructive sleep apnea, the most common of which include being overweight, a male, and having a family history of the disease. Sleep apnea has several undesirable consequences but the cardiovascular sequelae are the most serious (Wilcox 1998, Shahar 2001, Marin 2005, Valham 2008). Marin (2005) reported that untreated severe sleep apnea increased the risk of fatal cardiovascular events by more than 500% during a 12 year follow-up.
Portable monitoring (PM) or respiratory polygraphy (RP) has recently been accepted as an alternative to overnight polysomnography (PSG) (Thurnheer 2007) for the evaluation of suspected obstructive sleep apnea. It has been reported in a number of papers that the PM is appropriate for the recording of sleep apnea (Whittle 1997, Ballester 2000, Portier 2000, Lloberes 2001, Gagnadoux 2002, Dingli 2003, Douglas 2003, Ahmed 2007, Collop 2008a, Collop 2008b, Kayyali 2008). Portable monitoring has several advantages: increased accessibility, better patient acceptance, convenience
of home recording, low cost and applicability to telemedicine. However, it also has several disadvantages including potential for data loss, misinterpretation of the results due to limited data such as misinterpretation of wake time as sleep, and for inappropriate use of automatic scoring (Douglas 2003, Collop 2009). Unfortunately, the proportion of unsuccessful PM recordings with current commercial ambulatory devices has been reported to be rather high (5.6 to 23.4%) (Whittle 1997, Portier 2000, Gagnadoux 2002, Dingli 2003). This causes unnecessary lengthening of queuing times and an increase in costs.
The main objective of Study I of this thesis was to design, construct and evaluate a compact, technically reliable and easy-to-use eight-channel recording device suitable for clinical use in hospital and at home. The objective of Study II was to evaluate a new commercial PM device for home recordings and to estimate its potential for telemedical applications. The aim of Study III was to investigate the reliability of automatic analysis of sleep apnea events compared to manual analysis of the same data.
Many conditions can cause altered consciousness or coma (e.g. head injury, heart disease, diabetes, sedatives or other drugs) (Posner 2007). Monitoring the level of consciousness or depth of sedation is essential in modern intensive care units and emergency rooms (Jordan 1999). Traditionally, electroencephalography (EEG) has been used to gather information on the state of the brain. However, conventional EEG is merely a passive method for recording the resting or background state of the brain.
Somatosensory, auditory and visual evoked potentials have been used to collect additional information on the responses of the brain to sensory stimuli. In particular, long latency auditory evoked potential measurements appear to hold promise for evaluation of cortical functions and the depth of sedation or coma (Yppärilä 2002a, Yppärilä 2002b, Haenggi 2004, Yppärilä 2004a, Yppärilä 2004b). However, despite the clear diagnostic potential for recording of event-related potentials (ERPs) in the intensive care unit (ICU) no portable devices for this purpose exist.
For this reason, the aim of Study IV was to design, construct and evaluate a compact, technically reliable, battery-operated, auditory ERP device suitable for use in the ICU.
In summary, the four main aims of this thesis are 1) to develop and evaluate a portable monitoring device for recording of sleep apnea, 2) to evaluate the clinical potential of its successor, 3) to investigate the reliability of automatic analysis of sleep apnea events and 4) to develop a portable device for evaluating the level of consciousness with auditory evoked potentials.
A sleep apnea event is defined as a total respiratory cessation lasting longer than 10 seconds during sleep. A hypopnea event is defined as a reduction of respiratory air flow associated with a desaturation event. Obstructive sleep apnea is characterized by repetitive episodes of upper airway obstruction that occur during sleep. Apnea events having an initial central component followed by an obstructive component are called mixed apnea events (AASM 2005, AASM 2007). Sleep apnea syndrome (SAS, i.e.
sleep apnea combined with daytime sleepiness due to nocturnal respiratory arrest or repeated nocturnal awakening) has been reported to increase the risk of car accidents, cardiovascular diseases, stroke, hypertension, even death. Milder consequences may include excessive daytime sleepiness, psychological problems and a reduction in the quality of life.
2.1 Symptoms and prevalence of sleep apnea
Typical symptoms of sleep apnea are snoring, choking and gasping. A significant relationship between snoring and sleep apnea has been detected (Viner 1991, Flemons 1994, Maislin 1995, Netzer 1999, Duran 2001, Young 2002). However, the high prevalence of snoring without sleep apnea in the general population makes it an unreliable indicator of sleep apnea. Witnessed apneas or bed partner’s reports of choking or gasping are important preliminary information for use in the diagnostics.
The estimates of the prevalence of witnessed apneas in the general adult population vary from 3.8% to 6% (Ohayon 1997, Duran 2001, Teculescu 2005). However, the diagnostic gain from witnessed apneas is limited by the facts that not everyone has a bed partner and that people may be poor reporters of abnormal respiratory events (Haponik 1984).
The prevalence of obstructive sleep apnea is high and comparable to that of several other important chronic diseases such as asthma, chronic obstructive pulmonary disease, type 2 diabetes and coronary artery disease (AHA 1994). In a population study conducted in Wisconsin, the prevalence of moderate or severe OSA in middle-aged (age 30 – 60 years) men was 24% compared to 9% for women (Young 1993), (Table 2.1).
Similar estimates have been reported in several studies (Lavie 1983, Duran 2001, Ip 2001). The prevalence of sleep apnea is significantly age-dependent (Ancoli-Israel 1991). Bixler (1998) found that the prevalences of sleep apnea in men in age groups of 20 – 29, 30 – 39, 40 – 49 and 50 – 59 years were 0.4%, 1.5%, 2.8% and 5.4%,
respectively. The prevalence was found to decrease in the groups of 60 to 69 years and t 70 years (4.2% and 2.5%, respectively) (Bixler 1998).
The prevalence of sleep apnea has been shown to be strikingly high in certain patient subgroups (Table 2.2). In individuals suffering from hypertension, values in the range 30 to 40% have been found (Worsnop 1998, Kryger 2005). In middle-aged adults with drug-resistant hypertension, the prevalence of OSA may be even greater than 80% (Logan 2001). Patients with coronary artery disease display a high prevalence (50%) of OSA (Andreas 1996). Central, obstructive, and mixed patterns of sleep apnea are commonly observed in hypothyroidism (VanDyck 1989).
Table 2.1: The prevalence of sleep apnea in the normal population.
2.2 Risk factors of obstructive sleep apnea The etiology of sleep apnea is not fully understood (Deegan 1995, McNicholas 1998) and the role of obesity is somewhat unclear (McNicholas 1998, Vgontzas 2000). One theory suggests that the development of sleep apnea is caused by enlargement of soft tissues surrounding the upper airway, increasing the risk of airway collapse during sleep (Billington 2002). At least 60 to 70% of patients with obstructive sleep apnea are obese (Millman 1991). In particular, visceral fat increases the risk of sleep apnea (Shinohara 1997). A large neck circumference is a clear indicator of central obesity and a major risk factor of OSA (Davies 1992, Mortimore 1998). It has been reported that a ten percent increase in weight is associated with a 32% increase in AHI, whereas a ten percent weight loss decreases AHI by 26% (Peppard 2000). Males have a higher risk of OSA than females (Schwab 1999). There is also a racial component; African-Americans and Asians have a greater risk for OSA than Caucasians (Ancoli-Israel 1995, Redline 1997, Li 1999).
Several studies have demonstrated that there is family aggregation of OSA pointing to the importance of genetic factors in disease development (Pillar 1995, Redline 1995).
The heritability of the propensity for OSA has been found to range from 30% to 35% (Palmer 2003, Carmelli 2004). Nasal obstruction during sleep (Carskadon 1997), Kuopio University Publications C. Natural and Environmental Sciences 261: 1 - 79 (2009)
- 18 Sleep Apnea alcohol intake before sleep (Mitler 1988) and habitual smoking (Wetter 1994, Kashyap
2001) are clear risk factors of OSA (Table 2.3). Other risk factors include hypothyroidism, acromegaly, use of benzodiazepines or other relaxants, upper airway structural abnormalities (such as large tonsils) and use of exogenous testosterone (Al Lawati 2009).
Table 2.2: The prevalence of sleep apnea in patients suffering from cardiovascular diseases, hypertension or obesity.
Table 2.3: The most common risk factors of obstructive sleep apnea and their relative strength as estimated by the author on the basis of the literature.
2.3 Consequences of sleep apnea Heavy snoring, morning headache, interrupted nocturnal sleep and excessive daytime sleepiness are common symptoms of OSA. Excessive daytime sleepiness (ESD) may cause serious accidents in tasks demanding continuous alertness (e.g., car driving). Several studies have shown that sleep apnea has serious cardiovascular consequences (Wilcox 1998, Shahar 2001, Marin 2005, Valham 2008) (Table 2.4). In men, severe OSA increases significantly the risk of fatal and non-fatal cardiovascular events (Marin 2005), (Figure 2.1).
Epidemiological studies (Young 1993, Duran 2001, Bixler 2005) estimate the prevalence of EDS to range from 8% to 30% in the general population. EDS itself is not necessarily a sign of sleep apnea, because there are several underlying etiologies for
EDS. Furthermore, it is important to note that people often underestimate their sleepiness (Engleman 1997).
Table 2.4: The strength of connection between obstructive sleep apnea and its various consequences as estimated by the author on the basis of the literature.
The Epworth sleepiness scale (ESS) has been introduced as a method to identify and quantify the symptoms of sleep apnea (Johns 1991). The ESS scale extends from 0 to
24. The normal range is from 2 to 10, and apnea patients have scores from 4 to 24.
Although the ESS score has been shown to discern patient groups with different severities of the disease, it does not provide reliable information on the severity of the disease in a single individual (Gottlieb 1999).
In a recent study, sleep apnea was found to be associated (independently of other risk factors) with an almost tripled risk of stroke (Valham 2008). In addition, autonomic instability and hypertension have been found to be related to sleep apnea (Shepard 1992, Kansanen 1998, Salo 2000).
Figure 2.1: The cumulative percentage of individuals with new fatal and non-fatal cardiovascular (CVS) events in controls, mild and severe OSA patients.
Figure redrawn from the study of Marin (2005).
2.4 Laboratory diagnostics of obstructive sleep apnea 2.4.1 Clinical diagnosis of sleep apnea syndrome There are more than 70 different types of sleep disorders (AASM 2005) and differentiating between these disorders requires well-defined diagnostic criteria. If a sleep disorder is not explained by a medical or neurological disorder or by medication or substance use, the disorder in question may be obstructive sleep apnea. Complaints of Kuopio University Publications C. Natural and Environmental Sciences 261: 1 - 79 (2009)
- 20 Sleep Apnea daytime sleepiness and bed partner’s reports of loud snoring and breathing interruptions may represent an indicator of OSA. In polysomnography more than five apneas or hypopneas per hour of sleep is an indication of sleep apnea. The diagnostic criteria of obstructive sleep apnea syndrome (OSAS) in adults set by the American Academy of Sleep Medicine (AASM) are presented in Figure 2.2 (AASM 2005).
The severity of sleep apnea can be divided into three classes (Nieto 2000). The dividing line between normal and OSA is five apneas and / or hypopneas per hour of sleep (AHI). OSA is mild if the number of apneas and hypopneas per hour of sleep is equal or greater than five and smaller than 15. The disorder is severe if AHI is greater than 30. The moderate category is located between the mild and severe categories. The severity limits are shown in Table 2.5. According to the Finnish national guidelines, the limit between mild and moderate is 16 instead of 15. In this work, the Finnish national limits have been used. Despite published recommendations (Nieto 2000), the diagnostic criteria of OSA vary from sleep laboratory to sleep laboratory. For example, in some studies, an AHI of ten has been used as the value differentiating normal subjects from OSA patients (Ancoli-Israel 1991, Bearpark 1995, Marin 1997, Bixler 1998).