Selective indication for positive airway pressure (PAP) in sleep-related breathing disorders with obstruction.

Positive airway pressure (PAP) is the therapy of choice for most sleep-related breathing disorders (SRBD). A variety of PAP devices using positive airway pressure (CPAP, BiPAP, APAP, ASV) must be carefully considered before application. This overview aims to provide criteria for choosing the optimal PAP device according to severity and type of sleep-related breathing disorder. In addition, the range of therapeutic applications, constraints and side effects as well as alternative methods to PAP will be discussed. This review is based on an analysis of current literature and clinical experience. The data is presented from an ENT-sleep-laboratory perspective and is designed to help the ENT practitioner initiate treatment and provide support. Different titration methods, current devices and possible applications will be described. In addition to constant pressure devices (CPAP), most commonly used for symptomatic obstructive sleep apnoea (OSA) without complicating conditions, BiPAP models will be introduced. These allow two different positive pressure settings and are thus especially suitable for patients with cardiopulmonary diseases or patients with pressure intolerance, increasing compliance in this subgroup considerably. Compliance can also be increased in patients during first night of therapy, patients with highly variable pressure demands or position-dependent OSA, by using self-regulating Auto-adjust PAP devices (Automatic positive airway pressure, APAP). Patients with Cheyne-Stokes breathing, a subtype of central sleep apnoea, benefit from adaptive servo-ventilation (ASV), which analyzes breathing patterns continually and adjusts the actual ventilation pressure accordingly. This not only reduces daytime sleepiness, but can also influence heart disease positively. Therapy with positive airway pressure is very effective in eliminating obstruction-related sleep diseases and symptoms. However, because therapy is generally applied for life, the optimal PAP device must be carefully selected, taking into account side effects that influence compliance.

1. Introduction

Sleep disorders are common. If disorders occur regularly over extended periods of time, they can cause considerable discomfort and sickness. Sleep medicine, which began almost 40 years ago, investigates epidemiology, etiology, pathogenesis, clinical symptoms, diagnostics and therapy of sleep related diseases. Significant progress has been achieved in recent years in a number of areas, especially in the understanding and development of treatment for sleep related breathing disorders (SRBD). Continuous positive airway pressure (CPAP) has allowed for effective and non-invasive treatment of obstructive sleep apnoea [1], [2]. According to the revised international classification of sleep disorders (ICSD-R) [3], published by the American sleep disorders association (ASDA) in 2001, sleep apnoea syndrome (SAS) belongs to the SRBD subgroup of hypersomnia. Major symptoms include daytime sleepiness, sleep „attacks“ (hypersomnia) and obstructive snoring with partial or total collapsing of the upper airways. This leads to a reduction in concentration and alertness, which in turn leads to an increased accident risk at work and in traffic [4]. Because sleep related breathing disorders are widespread [5], [6], [7] and associated with cardio-vascular and respiratory diseases, the social and economic ramifications are immense [8], [9], [10], [11].

Patients with SRBD often present to ENT-practitioners because the pathology is produced in the upper airways. ENT-support of patients not only includes possible surgical intervention, but also diagnosis and treatment of SRBD. However, cooperation with other contributing specialties, like internal medicine, pneumology, family practice, neurology, psychiatry, psychotherapy and pediatrics remains important.

The gold standard for treatment of obstructive sleep apnoea syndrome (OSAS) is nightly application of positive airway pressure (PAP) [12], [13]. To achieve maximum therapeutic success and compliance, it is important for the ENT-practitioner to be familiar with the mechanisms of treatment, different types of devices and ventilation forms (nasal continuous airway pressure, Continuous positive airway pressure (nCPAP), bilevel positive airway pressure (BiPAP) or automatic positive airway pressure (APAP)), indications and guidelines for therapy initiation. This study is designed to provide a broad overview of current standards.

Manufacturers of PAP-devices do not always use the terms ventilation and breathing uniformly when referring to PAP-therapy, so quotations may contain imprecise terminology. CPAP refers to spontaneous breathing that is supported by continuous positive airway pressure to keep collapsing airways open. It is therefore not a ventilation technique, but rather a form of spontaneous breathing. Other devices, such as BiPAP (BiPAP-T and BiPAP-ST), are ventilation devices (see chapter 5).

2. Definitions of sleep related breathing disorders (SRBD)

In order to make research comparable, parameters must be clearly defined. A number of definitions have evolved in the last 40 years in sleep medicine. Apnoea is a complete stop of oro-nasal air flow and is considered pathologic, if longer than 10 seconds in length and occuring more than 5 times per hour [14], [12]. Apnoea can be subdivided according to breathing effort. Paradox breathing excursions occur during obstructive apnoea, as air flow is stopped by an obstruction of the upper airways. In central apnoea, effort is lacking. Mixed apnoea begins with a central component and is followed by obstruction [15].

Hypopnoea is not as clearly defined. There is general agreement that a reduction of air flow must have a length of at least 10 seconds for adults. There is no agreement on how much reduction in air flow is necessary for definition or if effort, oxygen desaturation or arousals should also be considered. Most sleep labs in Germany have a working definition including a reduction of oro-nasal air flow of at least 50% for at least 10 seconds, followed by oxygen desaturation of at least 4%. Meoli et al., however, recommended the following definition to the American Academy of Sleep Medicine based on studies: “Hypopnoea in adult patients is defined as an abnormal respiratory event lasting at least 10 seconds with at least 30% reduction in thoroco-abdominal movement or airflow as compared to baseline, and with at least a 4% oxygen desaturation” [16]. Because an apnoea-hypopnoea-index of ≥5 per hour is associated with an increased risk for cardio-vascular disease, they recommend considering hypopnoea in the appraisal of sleep related breathing disorder.

Snoring (primary snoring, ronchopathy, heavy snoring) is a sound generated by turbulence in airflow, caused by vibration of the soft palate and pharynx. A loss of muscle tone is involved, and generally occurs during inspiration. Pathologic influences on breathing, heart or circulation have not been observed [17].

Sleep-apnoea-syndrome (SAS) refers to regular apnoea and hypopnoea during sleep, combined with excessive daytime sleepiness and cardio-pulmonary dysfunction [12].

Incomplete obstruction of the upper airways leads to in increase in airway resistance defined as upper airway resistance syndrome (UARS). Unlike SAS, an increase in effort leads to sufficient ventilation. Negative effects on heart, circulation, sleep quality through flow-limitation and arousals are comparable to those producing OSA. Because oxygen desaturation does not occur and hypopnoea is infrequent, UARS is diagnosed by observing respiratory arousals. The gold-standard for measurement of intra-thoracic pressure changes is through esophageal pressure probes [18].

3. Epidemiology

Studies show a prevalence for sleep apnoea between 1% and 4% (1-2% for women and 3-4% for men) [19], and is therefore similar to widely spread diseases like diabetes mellitus. Because there are no standardized instruments for diagnosis, however (subjective sleepiness scores, polygraphy and polysomnography) these figures are not certain. Estimates are also dependent upon SAS-definitions, which may vary in parameters such as apnoea-index (AI) and AHI as well as clinical symptoms [20], [6], [7].

4. Classification, clinical symptoms and diagnostic standards

The revised international classification of sleep disorders (ICSD-R), published by the American sleep disorder association (ASDA) in 2001 [3], classifies intrinsic sleep disorders, obstructive and central SAS and central alveolar hypoventilation syndrome as sleep related breathing disorders (SRBD). There are SRBD with and without obstruction. Obstructive sleep apnoea is generated by the upper airways, apnoea without obstruction is caused by central disorders. Depending on the severity of obstruction, 3 diseases can be differentiated: primary snoring, upper airway resistance syndrome (UARS) and obstructive sleep apnoea. According to Moore, the three diseases represent varying degrees of the same disorder [21]. Obstructive sleep anpnoea is characterized by periodical obstructions of the upper airways during sleep, which leads to alveolar hypoventilation with oxygen desaturation and CO2 increase. Diagnostic criteria also include excessive daytime sleepiness, loud and irregular snoring, cessation of breathing or sleep pattern disruptions in polysomnography (PSG). There are no clear criteria for classification of severity. Definition of severity according to apnoea alone is not always helpful, because apnoea does not always correlate to symptoms. The American academy of sleep medicine published the following classification in 1999 [22]:

Mild OSAS: AHI 5-20

Moderate OSAS: AHI 21-50

Severe OSAS: AHI > 50

Threshold for OSAS: AHI > 5 + hypersomnia

Classification according to subjective discomfort is difficult. On the one hand, apnoea can occur during REM-sleep in healthy individuals, and on the other hand, even partial obstructions can fragment sleep patterns. Guilleminault defines sleep apnoea as occurring if more than 5 apnoea events take place per hour or more than 30 during total length of sleep [23]. The apnoea index (per hour) is not always helpful for classification. It is therefore advisable to consider clinical symptoms and discomfort, risk factors for cardio-vascular disease and compliance when selecting treatment forms.

Diagnosis of SRBD includes several parameters which are regulated in steps by the BUB-guidelines („Richtlinien zur Bewertung medizinischer Untersuchungs- und Behandlungsmethoden gemäß § 135 Abs. 1 des Fünften Buches Sozialgesetzbuch“) [24]. The first step includes taking the patient history using standardized forms and tests used to verify sleep disorders. The Epworth sleepiness scale (ESS) and Pittsburgh sleep quality index (PSQI) are examples. In the second step the patient is inspected. After that, cardio-respiratory polysomnography may be used.

5. Positive airway pressure (PAP) is the gold standard for treatment of SRBD

In order to better understand how positive airway pressure influences sleep related breathing disorders and to differentiate these from ventilation in anaesthesiology or intensive-care settings the different modes of ventilation will be briefly reviewed. SI-units (Systeme International d´unites) are the standard units used in science. The SI-unit for pressure is pascal (Pa) and is defined as newton per square meter (N/m2). Many manufacturers of respirators still use the older unit, “centimetre Wassersäule” (cm WS, 1 cm WS = 0.981 hPa) in manuals and menus. For simplicity, 1 cm WS has been defined in this study as equivalent to 1 hPa.

There are three general types of ventilation, which differ primarily in the amount of breathing effort done by the patient and respirator: controlled mechanical ventilation (CMV), pressure supported ventilation (PSV) and spontaneous ventilation (SV) [25]. Non-invasive ventilation (NIV) refers to ventilation using a mask. This method is used most commonly in SRBD, acute or chronic lung disease or in weaning. Invasive methods require intubation or tracheotomy. These methods are applied primarily in intensive care.

During controlled mechanical ventilation (CMV) ventilation is achieved completely through a respirator. Ventilation can be volume-controlled (VCV) or pressure-controlled (PCV) (Figure 1 (Fig. 1) and 2 (Fig. 2)). Inspiration is initiated regardless of possible spontaneous breathing. Synchronization between patient and device is not possible, expiration is achieved passively. The ventilation device performs all breathing effort for inspiration and regulates timing and volume parameters of every breath. Heavy sedation is frequently required, and often leads to a decrease of blood pressure. Catecholamines are often necessary to stabilize pressure. Because this ventilation form is very invasive, weaning can be very difficult and be accompanied by hemodynamic disturbances, intestinal and kidney disorders and even barotrauma.

Figure 1

Pressure-time and flow-time-diagram of volume-controlled ventilation showing controlled ventilation method with specified breath-volume. Pressure changes according to variations in resistance and compliance. Modified according to Oczenski et al.

Figure 2

Pressure-time and flow-time diagram showing pressure-controlled ventilation (PCV) showing controlled ventilation with constant pressure during inspiration and expiration. Modified according to Oczenski et al.

Assisted ventilation supports spontaneous breathing and can be divided into intermittent mandatory ventilation (IMV) (Figure 3 (Fig. 3)), synchronized intermittent mandatory ventilation (SIMV) and inspiration assistance. Assisted ventilation methods differ in timing between spontaneous breathing and breathing generated by the device according to defined criteria. In inspiration assistance, the ventilation device is triggered by the negative pressure generated by a patient breath. This form of ventilation is also referred to as assisted spontaneous breathing (ASB) or pressure support ventilation (PSV) (Figure 4 (Fig. 4)). This method is used primarily for weaning and home ventilation therapy. Frequency, inspiration flow and duration of assistance are determined by patient breathing. Intensity of breathing support and trigger threshold can be programmed and are independent from spontaneous breathing patterns.

Figure 3

Pressure-time diagram of intermittent mandatory ventilation (IMV), combining spontaneous breathing and controlled ventilation. Modified according to Oczenski et al.

Figure 4

Pressure-time and flow-time-diagram of assisted spontaneous breathing (ASB) showing assisted, pressure-supported flow-regulated breathing assistance. Modified according to Oczenski et al.

Continuous positive airway pressure (CPAP) is applied during spontaneous ventilation (SV). Breathing effort during inspiration and expiration is done by the patient. Treatment of SRBS is one of the main indications for non invasive positive airway pressure (PAP) ventilation using a nasal mask (nCPAP) (Figure 5 (Fig. 5)). BiPAPTM is a registered trademark of Respironics Inc., Australia, and refers to a ventilation system using a higher pressure setting for inspiration (inspiratory positive airway pressure, IPAP) and a lower pressure setting for expiration (expiratory positive airway pressure, EPAP) during each breath. Because this form assists spontaneous breathing patterns, it is referred to as “S”-mode. If, in addition to IPAP and EPAP, breathing frequency and the ratio of inspiration duration to expiration duration (I/E-Ratio) is determined, ventilation is referred to as “T”-mode. A combination of “S” and “T”-modes is referred to as “ST”-mode (assisted/controlled ventilation). This involves determining minimal breathing frequency and a set I/E-Ratio. As long as spontaneous breathing frequency remains above the minimal setting, breathing is only pressure assisted (“S”-mode). If frequency falls below the minimal setting, for example because of hypoventilation or apnoea, the device switches to “T”-mode for controlled ventilation (Figure 6 (Fig. 6)). Spontaneous pressure assisted ventilation (“S”-Mode) is the most common non-invasive form of mask-ventilation for treatment of acute respiratory insufficiency. nCPAP, BiPAPTM, “S”-Mode and “ST”-Mode are non-invasive ventilation methods frequently used in sleep-medicine (see Chapter 5.3). Assisted ventilation with BiPAPTM, in which every breath is assisted during inspiration, must be carefully distinguished from BIPAP-methods used in intensive-care that allow spontaneous breathing at all pressure levels [26].

Figure 5

Pressure-time diagram of Continuous Positive Airway Pressure (CPAP) showing spontaneous breathing with positive pressure in inspiration and expiration. Modified according to Oczenski et al.

Figure 6

BiPAP-“ST” ventilation. Modified according to Becker et al.

5.1 Mechanisms of PAP

Although PAP is not therapeutic, it remains the therapy of choice for sleep apnoea by removing obstruction in the upper airways [12], [13], [27], [28], [14]. Positive airway pressure applied by nasal mask (nCPAP) prevents collapsing of the upper airways, the cause of sleep apnoea, through pneumatic splint (Figure 7 (Fig. 7)). Becker et al. were able to demonstrate this by video endoscopy of the pharynx during CPAP therapy [29]. The result of CPAP is thus purely passive [30]. Initially, it was believed that airway-flow or pressure receptors triggered contraction of pharynx muscles as an airway reflex-mechanism. This could not be substantiated in studies [31]. Another possible explanation for the effects of CPAP is that pharynx muscle tone is increased through an activation of pulmonary pressure receptors during CPAP-induced increase in lung volume. This is still controversial, however [32]. CPAP devices filter (for dust and bacteria), compress and inflate air into the upper airways through a tubing and mask. Constant pressure must be maintained in the entire system. To prevent CO2-retention, the mask has an expiration-valve. Ventilation pressure is regulated and maintained electronically and can be programmed to special breathing patterns in devices such as bilevel and APAP (Figure 8 (Fig. 8)).

Figure 7

Pneumatic splint using CPAP for obstructive SRBD

Figure 8

Pressure-time diagram for different types of CPAP ventilation showing differences in pressure development.

5.2. Goals of PAP

Reduction of SRBD-symptoms and associated risk factors for morbidity and mortality of cardio-pulmonary disease is the goal of PAP therapy. There is no consensus about which and to which degree cardio-respiratory polysomnographic parameters should be influenced to prove successful treatment with PAP. Possible parameters include:

reduction of the apnoea/hypopnoea index (AHI)

reduction of desaturations per hour of sleep, as indicated by the Desaturation index

reduction of daytime sleepiness as indicated by Epworth sleepiness scale (ESS), the multiple sleep latency test (MSLT) or the maintenance of wakefulness test (MWT)

an improvement of sleep patterns as shown by an increase in deep sleep phases (NREM 3 and 4) over light sleep phases (NREM 1 and 2), an increase in REM phases, an increase in sleep latency and a reduction or removal of arousals

an improvement in cardio-pulmonary symptoms or parameters, such as reduction of hypertension or arrhythmia or pathological blood gas values

an increase in quality of life.

nCPAP should be combined with behaviour changes designed to achieve weight loss or improve sleeping habits. The correlation between sleep apnoea and adiposity is certain, but by no means linear. Thus even a slight loss in weight can lessen symptoms dramatically in one case, yet at the same time, even a substantial decrease in weight may not have any positive effects on a severe case of sleep apnoea. Good sleep habits include avoiding alcohol consumption in the evening, avoiding sleeping medicines, not sleeping on a full stomach and sleeping at regular times.

5.3. CPAP-Therapy

5.3.1. Manual pressure titration using nasal continuous positive airway pressure (nCPAP)

The pressure required for effective therapy is determined during one or more polysomnographic investigation (Figure 9 (Fig. 9)). This is necessary to determine the pressure setting that is high enough to eliminate apnoea, hypopnoea and snoring on the one hand, and low enough to ensure good patient compliance. The efficacy must be demonstrated in all sleep phases and sleep positions [33]. Titration can be performed in a number of ways, but is most often performed manually using nCPAP devices. In this case, polysomnographic parameters are observed by trained personnel and the ideal pressure determined under supervision of the physician. There are no uniform guidelines or titration protocols for manual titration. Criteria for titration include: apnoea, hypopnoea, oxygen desaturation, snoring and respiratory arousals. The use of flow parameters is controversial. On the one hand they are extremely sensitive, showing reduction during pressure changes as low as 1 hPa, before parameters such as snoring, desaturation and respiratory disorders are affected [34]. On the other hand, limitations in flow do not correlate with patient compliance, to MWT or sleep structure patterns [35]. Titration can be performed in an ascending or descending approach. Most sleep labs titrate in an ascending manner, starting with an initial pressure of 3-5 hPa in differing pressure and time intervals, until titration criteria have been satisfied. Effective therapeutic pressure is reached, when shown to be sufficient in the first REM sleep phase and in the supine position. The results of differing titration methods can lead to pressure differences of up to 2 hPa. Bureau and Series were able to demonstrate a reduction of therapeutic pressure between 0.6 and 1.5 hPa when using a combination of initial ascending titration followed by descending titration as compared to ascending titration alone [36]. However, the time required for the combined method is 5-6 hours. Patients generally profit from better long term compliance because of the lower effective therapeutic pressure. The authors therefore recommend titration under in-patient conditions with cardio-respiratory polysomnography.

Figure 9

CPAP therapy (pressure = 7 hPa): Pressure variations in spontaneous breathing under increased airway pressure.

During calculated titration, the expected effective pressure is determined by analyzing parameters such as neck circumference, BMI and AHI. This method is described as allowing CPAP adjustment in out-patient settings and is not suitable for patients with risk factors [37].

CPAP therapy depends on a constant pressure during inspiration as well as expiration. Diaphragm movements during inspiration create a vacuum which reduces mask pressure (Figure 10 (Fig. 10)), so titrated pressure values are higher than the actual pressure necessary to keep the airways open. New generations of constant pressure devices (nCPAP) avoid this phenomena by electronically adjusting pressure to remove dips [38].

Figure 10

Inspiratory pressure loss during CPAP. Modified according to Rostig

Another method for titration divides the in-patient night polysomnography into a diagnostic and a titration part using a split night protocol. This method is used in the USA as a cost-effective treatment of SRBD without cardiopulmonary risk factors.

Many patients find positive airway pressure uncomfortable before sleep onset. Pressure ramps have been developed by many manufacturers to raise pressure after a set time interval. Ideally, the patient is asleep before therapeutic pressure is reached. A rise in compliance hat not yet been demonstrated in studies [12].

5.3.2. PAP-devices with two pressure settings: bilevel positive airway pressure (BiPAP)

For most patients with mixed or predominantly central sleep apnoea, nCPAP is not effective because the disease is not caused by pharyngeal obstruction. Many of these patients require very high pressure settings that can make exhaling difficult. Furthermore, about 5% of all treated patients with sleep apnoea do not tolerate nCPAP [39]. Devices are available for these patients, typically those with high BMI, with expiration pressure set considerably lower than inspiration [40]. Inspiration pressure is at least equal to the pressure necessary for nCPAP treatment. During inspiration, the airways are more likely to collapse than in expiration. Thus the pressure can be decreased during expiration without causing obstruction. Devices have an integrated flow sensor that adjusts pressure for inspiration and expiration separately. Pressure is switched to expiration levels when a specified reduction in gas-flow is detected. Assisted or controlled pressure limited ventilation are possible utilizing a mask. If ventilation is assisted (triggered by flow or spontaneous breathing) it is referred to as BiPAP-S (spontaneous) or “S-mode”. A second option allows a minimal breath frequency to be programmed. If this frequency is not reached, the device automatically switches from spontaneous to controlled ventilation. This is referred to as BiPAP-ST (spontaneous/timed). If ventilation is controlled only, it is referred to as BiPAP-T (timed). Most devices can perform in different modes. Trigger frequency can be varied as well. “S-mode” is usually chosen for patients requiring high inspiration pressures. “ST-mode” is often used for patients with central apnoea. There are no long term prospective studies available for these devices yet, so recommendations are lacking as to what pressure justifies choosing an “S-mode” or how many central apnoea events require “ST-mode”. Figure 11 (Fig. 11) shows an excerpt from a well adjusted BiPAP-S. Figure 12 (Fig. 12) shows the principles involved in BiPAP-ST therapy: The first breath is triggered by the patient (“S-mode”). After apnoea without obstruction, the frequency limit has not been reached, so controlled ventilation is initiated (“T-mode”).

Figure 11

BiPAP-therapy (IPAP = 12 hPa, EPAP = 7 hPa) showing good adjustment but tachypnoea during first night of treatment.

Figure 12

BiPAP-ST treatment (IPAP = 10 hPa, EPAP = 5 hPa, Frequency 10/min, I:E-ratio 1:3): Pressure-controlled breathing (“T-mode”) initiated after central apnoea during pressure-assisted spontaneous ventilation (“S-mode”).

Patients with high nCPAP pressure settings or with difficulty exhaling against positive pressure should benefit from increased comfort and compliance. Despite the fact that initial compliance of PAP is better using BiPAP-devices [41], these have not been recommended as a routine substitute for nCPAP [42]. Although effective therapeutic pressure may be lower than nCPAP, an improvement in daily use could not be demonstrated in a randomized study [43].

5.3.3. Automatic positive airway pressure (APAP): automatic titration and automatic therapy

The most marked developments have occurred in the “smart” PAP sector. Thus, most recent literature has focused on these devices. A current critical review of the literature has been published by Littner et al. [33]. Devices performing automatic titration must be distinguished from devices performing long-term automatic therapy. This generation of devices contains a sensor that detects changes in air flow or pressure, and adjusts to correct differences quickly. Figure 13 (Fig. 13) shows an excerpt from APAP-treatment of a patient with posture dependent OSAS. Pressure is increased in increments in constant pressure mode, decrease is infinitely variable (Figure 14 (Fig. 14)). APAP devices can be set at BiPAP mode as well (Figure 15 (Fig. 15)). The optimal pressure setting can be adjusted according to need, thus reducing mean actual pressure levels. The goal is to increase comfort and patient compliance. APAP is especially useful for the treatment of posture related OSAS. These devices can also be used for automatic titration of therapeutic pressure. In other words, the device adjusts pressure automatically, until the minimal pressure necessary to eliminate respiratory disturbances in all body positions and sleep phases is reached. In order to reduce costs, pressure titration is often performed in an out-patient setting in the USA, using APAP. A number of algorithms are used to enable the device to recognize respiratory disturbances and is being constantly refined by manufacturers. For example, devices can detect acoustic vibrations from snoring (Figure 16 (Fig. 16)), or reductions in air flow. Other devices measure impedance in mask or airways or a combination of parameters. Sleep medicine practitioners generally are not aware of the algorithms involved in devices, and there are nor guidelines available, as to which algorithms should be used for different indications. It is therefore also difficult to compare the efficacy of different algorithms. Farre et al. performed an in vitro comparison of different algorithms used for artificial breathing patterns [44]. The results are not conclusive. The benefit of APAP devices for therapy and for automatic titration has been evaluated in numerous studies [45], [46], [47], [48], [49], [50], [51]. Most studies confirm long-term benefits similar to nCPAP, with patients benefiting from a reduction of arousals and an increase in REM and deep sleep phases. However, a possible increase in micro arousals caused by frequent pressure changes has also been reported [52], [35]. Although the evidence from current studies is not conclusive enough to issue general guidelines for therapy of SRBD [53], some patients do profit from APAP [54]. Long-term compliance after automatic titration has been shown to be comparable to compliance after manual titration [55]. APAP has shown advantages in length of therapy for patients with high pressure requirements and patients with alcohol consumption [56], [57]. The American academy of sleep medicine has developed guidelines for the use of auto-titrating continuous positive airway pressure devices for treatment of adults with OSAS [33]: indication is limited to OSAS diagnosed by cardio-respiratory polysomnopraphy, excluding patients with heart failure, chronic obstructive lung disease, nightly oxygen desaturations of other etiology (obesity hypoventilation syndrom) or patients without snoring (if devices use a snoring algorithm). Furthermore, APAP devices are not recommended for split night protocols and automatic pressure titration using APAP is recommended only under supervised cardio-respiratory polysomnography. Unsupervised therapy with APAP should be supervised at onset of treatment under cardio-respiratory polysomnographic conditions. Controls are required for APAP therapy and, if necessary, treatment should be changed to nCPAP. In a current meta-analysis, the Deutsche Gesellschaft für Schlafforschung und Schlafmedizin (DGSM) does not recommend unsupervised automatic CPAP titration in out-patient settings [35]. In summary, more expensive APAP devices may be cost efficient, if hospital resources or personnel costs can be reduced during automatic titration or treatment of patients with posture-associated or REM-associated OSAS. The above mentioned limitations should be followed carefully.

Figure 13

APAP-treatment: Automatic pressure increase from 3 to 6 hPa in two steps within 2.5 minutes.

Figure 14

APAP-treatment: Continuous automatic pressure reduction from 8 to 7 hPa in 2.5 minutes.

Figure 15

APAP-treatment: Automatic therapy in Bi-level mode with two pressure settings. The device regulates pressure automatically as pressure requirements change, during different sleep stages and body positions.

Figure 16

APAP-treatment: Automatic pressure increase from 4 to 5 hPa in constant-pressure mode, after flattening. The pressure is still insufficient to remove flattening!

5.3.4. Adaptive support (servo-)ventilation (ASV)

Finally, devices will be described that are used for PAP-therapy of SRBD without obstruction. Because many patients show an overlap of disease, and many PAP devices are becoming increasingly versatile, sleep labs have begun treating patients with severe heart failure and Cheyne-Stokes breathing, or who require home-ventilation therapy to treat global respiratory insufficiency caused by COPD. About 50% of all patients with heart failure suffer from SRBD with Cheyne-Stokes breathing or OSAS. Both diseases can develop simultaneously, but Cheyne-Stokes breathing is the most common form of SRBD in patients with severe left-ventricular dysfunction. Cheyne-Stokes breathing is characterized by cycles of increasing and decreasing breath-depth and repeating apnoea without obstruction (Figure 17 (Fig. 17)). Oxygen desaturation and catecholamine discharge are the result, causing further strain to the heart. The exact etiology of Cheynce-Stokes breathing is still unknown, but it is assumed that heart failure causes a disturbance in central breathing centers. Patients with Cheyne-Stokes breathing have a lower long-range survival [58]. Adaptive Servo-Ventilation with the AutoSetCS-device (AutoSetCSTM, ResMed, Sydney, Australia) has been newly developed to treat Cheyne-Stokes breathing. The device analyzes breathing patterns and pressure is regulated for each breath, providing variable pressure support. If apnoea or hypopneoa is detected, then a variable pressure amplitude is applied in addition to constant expiratory pressure. Mask leakage disturbs the algorithm, so full face masks are required. Figure 18 (Fig. 18) shows 3 polysomnographic excerpts from treatment of a patient with left-ventricular disease and Cheyne-Stokes disease, using an AutoSetCSTM-device. In the middle, data shows the adjustments in breathing pattern made by the device. Because of the great flexibility, ASV-CS-therapy is superior to oxygen-treatment, nCPAP- or bilevel-therapy [59]. A number of studies have shown a decrease in morbidity for effective treatment of Cheyne-Stokes breathing with AutoSetCSTM. An increase in heart function was observed, as well as a general increase in strength and life quality [60], [61], [62].

Figure 17

Cheyne-Stokes-Breathing as seen in a patient with heart failure.

Figure 18

Cheyne-Stokes-Breathing in patient with heart failure. Ventilation therapy using AutoSetCS®, ResMed, Sydney, Australia (AutoSetCS®-Ventilation pressure).

5.3.5 Intermittent self-ventilation (ISV)

The four main types of disorders include SRBD, primary hypoventilation (impaired breathing stimulus), disorders of accessory breathing muscles (fatigue) and gas exchange disorders [63]. Two or three disorders can occur in the same patient and make ventilation therapy challenging. In this case, patients presenting in a sleep lab should be seen by a participating lung specialist. Primary hypoventilation may be amplified in sleep or, in some cases, only occur during sleep. The increase in life-expectancy achieved by oxygen therapy has been further improved by the introduction of intermittent self-ventilation [64]. The most common cause for global respiratory insufficiency is fatigue of accessory breathing muscles, leading to hypercapnea and hypoxemia. In order to prevent complete exhaustion of breathing muscles, hypoventilation occurs. This frequently occurs at night. There are many causes for fatigue of the breathing muscles, including neuromuscular disorders (amyotrophic lateral sclerosis, ALS), anatomical restrictions (scoliosis), obstructive lung disease (COPD) or compliance related disorders like fibrosis of the lung. The therapeutic principle aims in assisting the muscular breathing system through ISV in controlled mode. The central breathing center can be trained to reduce its activity during ventilation. The length of time during which ISV is performed per day varies according to the degree of muscle fatigue. Usually the whole night and part of the day is required, with maximum ventilation not exceeding 15 hours per day [65]. Because pCO2 is usually highest at night, patients with hypercapnea require nightly ventilation. ISV can increase quality of life and mobility. Most devices used today are similar in design to nCPAP-devices used to treat SRBD. However, ISV devices are usually fully programmable ventilation devices that function more like intensive-care ventilation units. Ventilation is non-invasive and uses common nasal and facial masks. Ventilation is performed as intermitted positive Pressure Ventilation (IPPV) and always occurs in controlled mode, as this is the only reliable way to assist exhausted muscles [65]. For first night treatment, blood gas analysis, pulsoxymetry and transcutaneous pCO2 should be readily available. If SRBD is suspected as well, cardio-respiratory polysomnography is required. Ventilation settings should be set by qualified personnel, and a physician trained in CPR should be nearby. If there is acute respiratory distress, patients are usually treated in an intensive-care unit for the first night. ISV has helped many patients with severe hypoventilation avoid intubation or tracheotomy in recent years, and thus improved life quality [65].

5.4. Selective indications for treatment with PAP

Because a large number of PAP-devices are available to treat SRBD, long-term prospective studies are often lacking to supply reliable data, and innovations are constantly being introduced by manufacturers, there are no clear guidelines available for selecting PAP devices. However, there are a number of recommendations in form of consensus statements for indication of different PAP-devices for treatment of SRBD [12], [14], [16], [27], [33], [35], [39], [42], [59], [63], [64]. The newly organized “Gemeinsame Bundesausschuss” also “regulates” device selection in Germany through the “BUB-Richtlinien” [24].

Criteria for choosing the best PAP-therapy for treating different SRBD:

There is a general consensus, that the choice should consider clinical as well as sleep lab parameters [12], [14]. In general, 5-10 episodes of apnoea or hypopnoea per hour of sleep are considered to be pathologic. Hypersomnia and cognitive dysfunction correlate with nightly arousals and desaturations during sleep, can be influenced by the general health condition of the patient or cardio-respiratory comorbidity. The goal of PAP-therapy has been described above (point 5.2). It is unclear, however, if there should be a preferred order for pathological parameters treated. The main goal should be to remove all obstruction, increase sleep quality and improve oxygen saturation as well as blood-gas parameters and breathing work [35].

According to Loube et al. [42], CPAP-therapy is indicated for patients with a RDI≥30 because of the increased risk for cardio-vascular disease, regardless of clinical symptoms. If RDI is between 5 and 30, then CPAP-therapy is indicated if clinical symptoms such as daytime sleepiness, cognitive dysfunction, insomnia or known cardio-vascular disease (high blood pressure, Chronic Heart Disease, stroke). An RDI of 5 has been designated as the threshold for CPAP-therapy based on the observation that even light forms of OSAS can be effectively treated with CPAP, reducing adverse symptoms like daytime sleepiness [66]. Furthermore, RDI≥5 is associated with increased cardio-vascular disease [16]. Non-symptomatic patients with mild OSAS and no cardio-vascular disease should not be treated with CPAP [42]. Bilevel-devices in “S”-mode (BiPAP-S) should be used for patients with high nCPAP pressure levels and patients with breathing problems during CPAP therapy. If SRBD is associated with COPD and nightly ventilation disturbances or central apnoea caused by heart failure, then Bilevel ventilation in “ST”-mode is necessary (BiPAP-ST) [35], [42]. Intelligent APAP devices can be used for automatic titration or automatic PAP-therapy, when performed under supervision in a sleep lab, for patients with posture-related OSAS or REM-associated OSAS. Restrictions include heart failure, COPD, nightly oxygen desaturations (Obesity hypoventilation syndrom) or lack of snoring (if device uses a snoring algorithm). APAP-devices are usually not suited for split-night protocols [33].

Patients suffering from severe heart failure and Cheyne-Stokes breathing with or without OSAS benefit from adaptive support (servo) ventilation (ASV) [35]. This form of ventilation therapy improves heart function, physical fitness and life quality.

If the accessory respiratory muscles are dysfunctional, due to neuromuscular disease (ALS) with pCO2 increase, or there is restrictive lung disease (scoliosis), obstruction (COPD) or compliance reduction (lung fibrosis), intermittent self-ventilation may be necessary [63].

The guidelines for indication of ventilation therapy reflect only a portion of the current literature. Many associations revise recommendations regularly based on the latest literature and manufacturer innovations. Figure 19 (Fig. 19) provides an overview of indications as presented above.

Figure 19

Indications for ventilation therapy of SRBD and comorbidities.

5.5. Equipment – devices, masks, humidifiers

According to § 128 SGB V, application of medical devices is regulated by compulsory health insurance. An association of health insurance agencies provides a list of viable devices and regulates financing [67]. The list is organized according to product groups. At the moment the list includes 18 615 products. PAP-devices are listed in product group 14: “Inhalation- and Ventilation devices”, group 24 “Lung” subgroup 07: “Systems for therapy of sleep apnoea”. Requisite technical standards are described in detail, including safety standards. Devices must be approved by authorized institutes and instruction manuals must be produced in German. Devices with one pressure setting must hold constant pressure between 4 hPa and at least 15 hPa, with titration steps of 1 hPa difference in CPAP devices. Pressure difference between inspiration and expiration may not exceed 0.5 hPa.

For BiPAP devices, the same upper and lower pressure requirements apply, with titration steps of 1 hPa for inspiration. The setting of unequal expiration and inspiration settings must be possible.

Integrated humidifiers must be able to be completely dismantled and thermally disinfected. The humidifier must be securely built in to the device and allow the use of cold or warm air, and reach a humidity of at least 70% to 90%. All parts must allow complete rinsing and drying.

External humidifiers must be completely functional and fulfil the same cleansing and humidity requirements specified above.

Masks must be fitted to patients, allow complete dismantling and cleansing as well as thermal disinfection. Clear materials should be used to allow detection of contaminations. Materials should be break resistant and masks must fit devices produced by different manufacturers. Masks should be as soft and pliable as possible, and the edges should not become hard, and must be delivered including all necessary accessories (for example straps).

BiPAP-devices are required to show actual pressure on an analogue or digital display. Pressure settings must be secured against accidental adjustment and pressure must be held at a sufficient therapeutic level. Devices must record and show length of use (in hours and therapy nights) and have tolerance limits for pressure fluctuation. Devices should be quiet (< 30 dB (A)) at 10 hPa effective pressure and 1 meter distance, without tubing system and require minimal or no maintenance (maximum once a year). The lower pressure parameters should not be less than 4 hPa and must allow increase in 1 hPa steps. Devices must include easy to remove and clean filters for dust and bacteria. The complete tubing system required for use must be included in the accessories, and guarantee must extend for at least one year [68].

There are presently 23 PAP-devices from 16 manufacturers listed in product group 14.12.07.0 “Systems for therapy of sleep apnoea, nCPAP-devices” in the list of viable medical devices (Table 1 (Tab. 1)). 12 devices from 8 manufacturers are listed in product group 14.12.07.1 “Systems for therapy of sleep apnoea, nCPAP-dvices (2 pressure settings)” (Table 2 (Tab. 2)) and 8 devices from 5 manufacturers for product group 14.24.07.2 “Systems for therapy of sleep apnoea, nCPAP-devices (one pressure setting) with integrated humidifier” (Table 3 (Tab. 3)). Product group 14.24.07.3 lists oral devices. Product group 14.24.07.4 lists “Special nCPAP-devices (2 pressure settings) with integrated humidifier (7 devices from 6 manufacturers, Table 4 (Tab. 4)). Masks are listed in subgroup 14.24.07.5 “Confectioned masks for nCPAP- / Ventilation therapy” and includes 14 masks from 6 manufacturers. “Cold / Warm air humidifiers for nCPAP-therapy” are listed in groups 14.24.07.6 and 14.24.07.7, but only warm air humidifiers are recommended. APAP devices are listed in subgroup 14.24.07.8 and 14.24.07.9 (Table 5 (Tab. 5)). At present, 14 APAP devices from 7 manufacturers are listed. 14.24.09.1 lists 29 ventilation systems, controlled / assisted for intermittent ventilation therapy that are also allowed for bilevel-device therapy of sleep apnoea (Table 6 (Tab. 6)). Lists are constantly updated as required by § 128 SGB V. Detailed lists are designed to assist the practitioner in choosing the appropriate device and may be downloaded at: http://www.vdak-aev.de/vertragspartner/Sonstige_Vertragspartner/.

Table 1

NCPAP-Devices (one pressure setting). Hilfsmittelverzeichnis-Nummer 14.24.07.0

Table 2

NCPAP-Devices (two pressure settings). Hilfsmittelverzeichnis-Nummer 14.24.07.1

Table 3

NCPAP-Devices (one pressure setting) with integrated humidifier. Hilfsmittelverzeichnis-Nummer: 14.24.07.2

Table 4

NCPAP-Devices (two pressure settings) with integrated humidifier. Hilfmittelverzeichnis-Nummer: 14.24.07.4

Table 5

NCPAP-Devices (automatic pressure setting). Hilfsmittelverzeichnis-Nummer: 14.24.07.8

Table 6

Ventilation systems, assisted/controlled, ventilation devices for intermittent ventilation. Hilfmittelverzeichnis-Nummer: 14.24.09.1

6. Long-term results

Long-term results may be judged by patient compliance or efficacy and depends heavily upon patient acceptance, since therapy is usually applied for life. Subjective impairment at onset, reduction of symptoms and minimal side effects through PAP-therapy are important criteria for compliance. Side effects are usually related to high pressure levels. If therapy is discontinued, symptoms of apnoea return within days, as Kribbs et al. were able to demonstrate [69]. Only a minority of patients manage to reduce symptoms completely through weight loss alone. CPAP-therapy is usually continued. Compliance rates differ highly in current literature and are best explained by differing definitions of compliance. Sometimes the term acceptance is used, without specifying actual hours or nights of use. Different methods are applied to determine use of the device, including symptom-scores, documentation of hours of use and repeated polysomnographic tests. Questionnaires are used to determine subjective use of devices, but many devices also allow the hours of use to be recorded.

According to literature, long-term acceptance of treatment (> 1 year) for CPAP-therapy ranges from 68% to 79%. Average time of use for positive compliance is described as a minimum of 3 hours per night [70], [71], [72]. Meslier et al. describe long-term compliance rates of 78% [73]. 86% of 3225 nCPAP users used the device for more than 4 hours per night after more than one year. According to a study by Pieters et al., 21 of 192 patients discontinued therapy [74]. One problem with the above mentioned figures is that compliance was only determined for long-term patients using nCPAP. This does not reflect the actual acceptance of therapy for all patients requiring PAP-therapy. Including patients who reject nCPAP-therapy could lower compliance rates [75]. To determine efficacy of treatment, the goal of nCPAP-therapy must be considered, including parameters such as disease symptoms and reduction of cardio-respiratory risk factors. Numerous studies show differing results. PAP should show an improvement in sleep quality, as seen in sleep profiles. Deep sleep phases increase (Non-REM III and IV) as well as REM-phases. Daytime sleepiness is reduced and quality of life increased [70], [76]. Subjective sleepiness is recorded using the ESS and should show significant changes [77], may, however, be caused by placebo-effect [19]. The Apnoea-Hypopnoea-Index is reduced significantly in nCPAP-treated patients with OSAS and arterial oxygen saturation increases [77], [78], [79]. nCPAP-therapy is therefore considered effective in reducing apnoea, hypopnoea and desaturations in patients with OSAS [19]. The initial reduction of pathologic sleep parameters is retained during long-term use. Body weight is generally constant during long-term therapy [35]. Although apnoea causes micro-arousals with a sudden rise in blood pressure [80], a general positive effect for patients with hypertension could not be shown in 24-hour blood pressure measurement after CPAP-use [81].

The main factors influencing compliance are the use of humidifiers, early intervention for problems with the mask and intensive guidance of patients [82]. APAP-devices can increase compliance as well, by reducing effective mask pressure [33]. In all studies, a subgroup of patients is described that does not tolerate PAP-therapy for treatment of SRBD. These patients need to be informed about alternative therapies (through operations or alternative devices).

7. Risks and adverse side effects

Adverse side effects may include cardio-respiratory disturbances caused by positive airway pressure or topical problems caused by the mask. As is the case with all forms of positive pressure ventilation therapy, CPAP-therapy may cause hemodynamic disturbances. Fietze et al. found 2 out of 5 patients with central apnoea to develop arrhythmia. One patient with central hypoventilation and one patient with impending heart failure developed arrhythmia as well [83]. Stammnitz et al. describe severe disturbances like long central apnoea or hypoventilation with desaturations up to 20% which were found associated with arrhythmia in 5 out of 502 sleep lab patients [84]. Positive airway pressure increases lung tidal volume. Right ventricular preload is reduced by a reduction in venous backflow. In addition compression of pulmonary vessels is assumed to increase right-ventricular afterload. Thus cardiac output and cardiac index are lowered especially in patients with severe sleep apnoea [85], [86]. This reduction of cardiac output is generally lower when Bilevel-ventilation is used, because mean effective pressure is generally lower than in nCPAP [39]. In cases of latent heart failure, extremely low blood pressure or bullous lung disease, nCPAP-therapy should be initiated under intensive-care supervision [87]. PAP-therapy can induce breathing disorders as well. In REM-phases, for example, hypoxemia may occur. This is believed to be the result of inadequate CPAP-pressure, which fails to remove obstruction [88]. In the first nights of therapy, a shortened REM-latency, an increase in REM-time and an increase in REM-phases is often observed. This is referred to REM-Rebound and reflects the fragmentation of sleep phases SRBD patients have experienced prior to treatment because muscle-tone is reduced and hypoxemia due to hypopnoea is increased in REM-sleep. This can be especially dangerous. Hypoxemia may develop despite adequate ventilation pressure and is often associated with COPD or restrictive lung disease. It is therefore imperative that therapy is initiated under polysomnographic supervision [88]. Central sleep apnoea is the most common breathing disturbance during nCPAP-therapy and is usually followed by an arousal with hyperventilation. Examples for nCPAP and BiPAP-S findings are shown in Figures 20 (Fig. 20) and 21 (Fig. 21). Apnoea can occur in multiple sequences or as a solitary event, and takes place most often in sleep phases NREM I and II [89]. Central apnoea under PAP-treatment is not associated with apnoea observed prior to treatment. The etiology is not fully understood at present and is being studied by a work group for “Pathophysiology of breathing” of the German Association for Sleep Research and Sleep Medicine. For these cases, BiPAP-ST-mode is a viable alternative for therapy.

Figure 20

CPAP-therapy (CPAP = 7 hPa): Device unaffected by central apnoea.

Figure 21

BiPAP-S-treatment (IPAP = 10 hPa, EPAP = 5 hPa): Device unaffected by central apnoea, spontaneous pressure-assisted ventilation resumed after 15 sec. pause.

Very rare topical side effects of nCPAP-therapy in the upper airways includes rhino-liquorrhea, pneumocephalus and bacterial meningitis during acute sinusitis [90], [91]. Most side effects, however, involve mask fit, or irritations of skin or mucous membranes. A common problem is the development of pressure sores on the nose, forehead or upper lip (Figure 22 (Fig. 22)). Leakage can cause conjunctivitis. About a third of all patients suffer from dry mucous membranes of the nose and mouth, burning sensations or nasal obstruction [92]. The incidence of these side effects may be as high as 65% [93], [94], [95]. Pepin et al. found 50% of 193 patients treated with nCPAP suffering from mask disturbances (allergies, leakage, pressure sores), 24% eye irritations, 65% dryness in mouth and nose, 35% increased mucous secretion and 25% with nasal obstruction [93]. In a retrospective analysis, Verse et al. found that 71% of 92 patients treated with nCPAP suffered from sleep disturbances, 47.5% suffered from dryness of mouth, 46.3% dryness of nasal membranes, 41% suffered from pressure sores, 38.8% suffered from incrustation of the nose and 26.3% suffered from hearing loss. The intensity of symptoms was greatest for recurring sinusitis, clausterphobia and dryness of nose and mouth [94]. Often, patients are on medications that can cause similar symptoms (i.e. diuretics, anti-hypertensives), so that it is difficult to correlate side effect and causative agent [94]. Conditions such as deviation of the nasal septum, allergic hypertrophy of the turbinates, or chronic sinusitis may require surgical intervention before or after initiation of nCPAP-therapy. Kuhl et al. describe 2 out of 41 patients, in which surgery was necessary to improve nasal airflow, after nCPAP-therapy failed [95]. Other authors describe up to 25% of nCPAP patients requiring surgery before therapy is successful [96].

Figure 22

Typical pressure ulcer caused by nCPAP-mask.

The main cause of nasal disturbances is leakage from the mouth [97], [98]. The mucous membranes of the nose have a great capacity to warm and humidify ambient air during breathing. About one third of the moisture loss produced by exhaling can be compensated by the nose during inspiration. If leakage through the mouth occurs, the flow rate during breathing is increased considerably during nCPAP-therapy. As a result, the mucous membranes are no longer capable of humidifying the air sufficiently. Dryness leads to discharge of leucotrienes and vasoactive substances that cause swelling of the membranes and an increase in nasal resistance [99]. This reaction can also be interpreted as a non-specific hyperreactive reaction to mechanical irritation through the ventilation air flow. CPAP-compliance can be improved considerably through humidifiers using warm air by reducing side effects [100], [101]. Warm air humidifiers are more frequently required for patients over age 60, taking medications that cause dryness, with chronic diseases of the mucous membranes or after uvulo-palato-pharyngoplasty (UVPP). In these cases, humidifiers can be considered at initiation of treatment [102]. However, the use of humidifiers is not without risks. Intensive Care patients receiving controlled ventilation suffer from increased nosocomial infections contracted from contaminated ventilation devices or tubing systems. OSAS-patients with nCPAP have an increased risk for inflammatory diseases of the respiratory tract, compared to patients without ventilation treatment. Ventilation systems have been shown to be contaminated with potentially pathogenic micro-organisms if patients neglect cleaning the humidifier [103]. It is therefore imperative to instruct the patient carefully in the use and maintenance of the device and accessories. Another option to treat nasal mask disorders is to apply PAP using a full-face (oro-nasal) mask [104]. Compliance tends to be lower than nor nasal masks, however. Manufacturers are constantly improving masks, so other solutions may be expected in the future, including allergic and pressure sore problems. In recent years, patient comfort has been increased considerably. A special type of nasal mask has been developed to treat patients with clausterphobia. This nasal mask uses nasal pillows placed directly into the nostrils. In the past, patients often complained about the noise generated by devices [92], [105]. New devices are much quieter. Careful mask selection helps reduce noise generated by leakage air flow. The success of conservative ENT treatment of mucous membrane disorders for CPAP users can not be appraised, for lack of studies. Patient expectations tend to be very high. Treatment is usually initiated according to experience with similar ENT-disorders. Rinsing with saline solutions, for example, can be recommended for dryness or crust development. Saltwater saline sprays now available at pharmacies can be used. Not only does rinsing provide gentle mechanical cleansing, it also stimulates cilial activity of the nasal membranes. The use of special rinsing devices or nebulizers may be beneficial. Ultrasound nebulizers are not generally recommended, since the small aerosol size is not effective for nasal membranes. Nasal ointments are especially effective in preventing dryness in noses with excessive crusts. The moisture is trapped under the ointment film and softens crusts, which can be removed without further damage. There are a number of recipes and commercial products available. The ointment base is usually responsible for the efficacy, and not the additives, which are usually highly diluted. Because essential oils may cause dryness, they are generally not recommended. Hyperplasia of the turbinates or mucous membranes caused by ventilation leads to obstruction. Topical steroid nasal sprays may prove effective in this case, as well as in treating obstruction caused by allergic rhinitis or chronic sinusitis [106]. Adverse side effects may also include dryness or fungus infections. Treatment should therefore only be initiated for nasal dryness without crusts and discontinued as soon as adverse side effects are observed. If treatment is not effective, surgery of the nasal turbinates may be considered. This may be performed as a resection of the medial surface and posterior ends (conchotomy) or include fracturing or resecting the turbinate bone (lateroposition, turbinoplasty). High-frequency methods like APC-coagulation or even laser (CO2-, Diode-, Nd-YAG-laser) may be used. These methods have been shown to be especially gentle. They lead to scaring of the cavernous bodies, while retaining cilial function and mucous surfaces. They can be performed in an out-patient setting, as the review of current literature by Mlynski shows [107].

8. Progression of SRBD and alternative therapy

Progression of SRBD is closely linked to body weight and age. Studies have shown AHI-values to double in 10 years, when evaluated independently from BMI. If only clinical symptoms are used, prevalence decreases after the age of 60 [108]. This correlates with clinical experience of sleep labs, showing a peak in OSAS around the age of 50. It is not clear, however, if this effect is caused by a reduction of breathing disorders or if elderly patients are merely more indolent [109]. The influence of body weight on the severity of OSAS is generally appreciated. Peppard et al. were able to show an increase in AHI of 32% in 4 years for patients with a weight increase of 10%. The converse effect, AHI-reduction of 26% for weight loss of 10% in 4 years was also observed. Clinical experience also shows that OSAS often becomes clinically apparent after a sudden increase in body weight (Figure 23 (Fig. 23)). It is unclear, however, if this sudden increase in weight is the cause or the effect of OSAS [110]. Sampo et al., however, could show effective of treatment of OSAS by weight loss in few of their 216 overweight patients. A correlation between AHI and BMI was not observed [111].

Figure 23

Symptoms of OSAS in relation to weight and age. Notice the sharp increase in BMI before OSAS becomes symptomatic. Modified according to Lugaresi et al.

After determining the individual risk-profile of the patient, the goal of treating SRBD must be to eliminate pharyngeal obstruction during sleep and the symptoms and disorders caused thereby. Alternative treatments must be compared to the gold standard of nCPAP-therapy and are usually sufficient only for treatment of mild forms of OSAS, upper airway resistance syndrome (UARS) or obstructive snoring. For detailed descriptions of possible procedures, see other articles in this series.

Sleep hygiene should always be the first step in treatment, and includes changes in sleeping habits, such as weight loss, avoiding sleep medicines and alcohol and keeping regular sleep patterns.

Patients with mild OSAS may show posture dependency. In this case, apnoea occurs in the supine position and not in side positions. There is no universally accepted definition of posture dependent OSAS. Some authors define the term as an increase in AHI of 2 times in the supine position, as compared to side positions [112]. In these cases, position training or the use of special vests that obstruct changes into the supine position my be helpful. Alarms that cause waking if the pathologic position is assumed should not be used, since they disturb sleep structure.

The use of medications in treating fully developed OSAS has not been successful. Progesteron, Protriptylin, Acetazolamid, Octreotid or transdermal Nicotine have all been tested, and are no longer recommended. The most commonly used medication is Theophyllin. Although the exact mechanisms are not understood, Schäfer et al. recommended an evening dose of Theophyllin for mild forms of SAS with closely monitored follow up as early as 1996 [113]. Modafinil has been recommended recently for cases of lingering daytime sleepiness despite CPAP. In a current study, Black et al. were able to demonstrate an increase in sleep latency and lower ESS scores for patients treated with Modafinil compared with patients treated with CPAP only [114].

9. Social and economic aspects

Since the first description of OSAS, about 40 years ago, the costs for diagnosis and treatment of SRBD have risen dramatically. Although the positive effect of PAP-therapy is widely recognized, it is unclear how effective treatment may reduce health costs in general. SAS is widely prevalent, affecting between 1% and 4% [7], [19], and generating costs for health insurance companies and society. There is a wide consensus about the correlation between SRBD, daytime sleepiness and an increase in traffic accidents [4], [115]. Mortality is also high for SRBD-patients and is most likely caused by comorbidities [116], [117], [118]. Comorbidity with cardio-vascular and pulmonary diseases is described in large meta-studies [19].

It seems fairly certain, that OSAS patients without treatment generate higher costs than treated patients. Kryger et al. describe a group of 97 untreated SAS patients that showed 2.8 times as many days in hospital and a increase in costs between $ 100,000 and $ 200,000 compared to a control group [119]. Another study of 238 untreated OSAS patients showed yearly hospital costs of $ 2720 compared to a control-group with costs of $ 1384. Costs correlated to severity of SRBD [120]. Bahammam et al. researched medical expenses and days spent in hospital for 2 years for 238 treated patients. Compared to the control-group of untreated OSAS-patients, costs dropped 33% and days in hospital showed significant reduction from 1.27 to 0.54 days per patient per year [121]. The American academy of sleep medicine (AASM) has published a position paper justifying the expenses caused by diagnosis and treatment of OSAS, despite a lack of conclusive data at present. In a recommendation to the health insurance industry, the AASM concludes that a treated patient with OSAS does not have a higher risk profile and should not be required to pay excessive rates [122].

In Germany, diagnosis and therapy of OSAS are controlled by compulsory health insurance. Until 2004, treatment was regulated by “NUB-guidelines for out-patient polygraphy”. Before the introduction of Diagnosis Related Groups (DRG´s), diagnosis and treatment with polysomnography was covered by daily in-patient rates. DRG´s are now used. In 2004, the DRG´s used were E 63, with and a factor of 0.322 for at least 2 nights, and E 63 B, with a factor of 1.60 for one night. Since 2004, diagnostic steps have been specified by “BUB-guidelines”, mandatory for compulsory heath insurance [24]. Steps 1, 2 and 3 include history, inspection and out-patient polygraphy. Step 4 regulates the more expensive in-patient cardio-respiratory polysomnography. Step 4 is limited to cases, where steps 1-3 have provided inconclusive information about whether CPAP-therapy is necessary. The German Association for Sleep Research and Sleep Medicine has strongly criticized the initiation and therapy with PAP, as well as follow-ups, without cardio-respiratory polysomnography. Financial constraints caused by DRG`s seem to make the use of split-night protocols unavoidable. This procedure was rejected by a majority vote at the yearly convention of the chapter “Nächtliche Atumungs- und Kreislaufstörungen (SNAK)” of the German association for pneumonology and the “apnoea” work group of the German association of sleep Research and sleep medicine (DGSM) in January 2005. In Germany, two nights are considered best for titration, in order to achieve long-term compliance. Professional medical indication, diagnosis through cardio-respiratory polysomnography and titration in a supervised sleep lab, are considered the prerequisites for the use of PAP in SRBD [27]. The first follow-up control should take place 3 months after initiation of therapy. Long-term follow-up is important because an adaptation of the central sleep centers with changes in sleep patterns is possible. Changes in obstruction of the upper airways, through a reduction of swelling, for example, may occur during treatment as well. Pressure may often be reduced as much as 2 hPa [123].

10. Scientific medical associations and self-help groups

AASM - American academy of sleep medicine http://www.aasmnet.org/

ASAA - American sleep apnea association http://www.sleepapnea.org/

ATS - American thoracic society http://www.thoracic.org/

BSD - Bundesverband schlafapnoe Deutschland BSD e.V. http://www.bundesverband-schlafapnoe-deutschland.de/

BSS - British sleep society http://www.sleeping.org.uk/

DGHNO - Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie http://www.hno.org/

DGP - Deutsche Gesellschaft für Pneumologie http://www.pneumologie.de/

DGSM - Deutsche Gesellschaft für Schlafforschung und Schlafmedizin http://www.dgsm.de/

ESRS - European sleep research society http://www.esrs.org/

ÖGSM - Österreichische Gesellschaft für Schlafmedizin und Schlafforschung http://www.schlafmedizin.at/

SSSR - Swiss society of sleep research sleep medicine and chronobiology http://www.swiss-sleep.ch/index.html

SRFS - Société Française de Recherche sur le Sommeil http://sommeil.univ-lyon1.fr/SFRS/index.html

11. Abbreviations

AHI - Apnoea-hypopnoea-index

AI - Apnoea-index

ASV - Adaptive servo ventilation

BMI - Body-mass-index

cm - centimeter

cm WS - centimeter Wassersäule

COPD - chronic obstructive lung disease

CPAP - Continuous positive airway pressure

EEG - Elektroencephalogramm

EKG - Elektrocardiogramm

EMG - Elektromyogramm

EOG - Elektrooculogramm

ESS - Epworth sleepiness scale

Fig. - Figure

hPa - Hektopascal

ICD - International classification of diseases

ICSD - International classification of sleep disorders

LAUP - Laser-assisted uvulo-palatoplasty

MSLT - Multiple sleep latency test

MWT - Maintenance of wakefulness test

NREM - Non rapid eye movement

NREM I-II - Sleep phase I-II, „light sleep“

NREM III-IV - Sleep phase III-IV, „deep sleep“

NUB - Neue Untersuchungs- und Behandlungsmethoden

OSA - Obstruktive sleep-apnoea

OSAS - Obstructive sleep-apnoea-syndrome

OSAHS - Obstruktives sleep-apnoea-hypopnoea-syndrome

pCO2 - Partial pressure of carbon-dioxide

PLMS - Periodic leg movement syndrome

pO2 - Partial pressure of oxygen

PSG - Polysomnography

RDI - Respiratory disturbance index

REM - Rapid eye movement, sleep phase

s - second

SAHS - Sleep-apnoea-hypopnoea-syndrome

SAS - Sleep-apnoea-syndrome

SRBD - Sleep related breathing disorders

Tab. - Table

UARS - Upper-airway-resistance-syndrom

UPPP - Uvulo-palato-pharyngoplasty