Somnologie 2017 · 20 (Suppl s2): p97–p180 DOI 10.1007 ... · suspected central sleep apnea –...

S97Somnologie · Suppl s2 · 2017

S3-Guideline on Nonrestorative Sleep/Sleep Disorders - Chapter on “Sleep-Related Respiratory Disorders”German Sleep Society (Deutsche Gesellschaft für Schlafforschung und Schlafmedizin, DGSM)

Somnologie 2017 · 20 (Suppl s2): p97–p180DOI 10.1007/s11818-016-0093-1Published online: November 29, 2016© Springer Medizin Verlag Berlin 2016

Table of Contents1. Summary1.1 What’s new?1.2 New recommendations

regarding the Guideline on “Nonrestorative Sleep,” Chapter on “Sleep-Related Breathing Disorders” of 2009

1.2.1 Perioperative management1.2.2 Obstructive sleep apnea1.2.3 Central sleep apnea1.2.4 Sleep-related hypoventilation/

hypoxemia2. Introduction3. Diagnosis3.1 General3.2 Non-instrument-based

diagnosis3.2.1 Questionnaires and

performance and vigilance tests

3.2.2 Clinical examination3.2.3 Instrument-based diagnosis3.2.4 Polysomnography3.2.5 Polygraphy for Sleep-Related

Respiratory Disorders3.2.6 Monitoring for sleep-relates

respiratory disorders with reduced systems.

4. Principles of the creation of the indication for the treatment of sleep-related respiratory disorders

5. Obstructive sleep apnea syndrome

5.1 Obstructive sleep apnea5.2 Clinical symptoms5.3 Epidemiology5.4 Predisposing and triggering

factors5.5 Family history, genetics

5.6 Start, progression, complications

5.7 Daytime sleepiness5.8 Cardiovascular risk5.9 Arterial hypertension5.10 Stroke5.11 Heart failure5.12 Diabetes mellitus5.13 Malignant diseases5.14 Perioperative complications5.15 PAP treatment methods5.15.1 Nighttime positive pressure

breathing5.15.2 Modified positive pressure

treatment methods5.15.3 Compliance5.16 Telemonitoring of sleep-related

respiratory disorders5.17 OSA in pregnancy5.18 OSA in elderly people5.19 Obstructive sleep apnea and

dementia5.19.1 Treatment of obstructive sleep

apnea in people with dementia5.20 Non-CPAP methods of treating

obstructive sleep apnea5.20.1 Weight reduction5.20.2 Non-operative weight

reduction5.20.3 Operative weight reduction5.20.4 Lower jaw braces5.20.5 Treatment with medication5.20.6 Treatment with medication in

patients with residual daytime sleepiness receiving CPAP treatment

5.20.7 Method to increase muscle tone

5.20.8 Treatment with oxygen5.20.9 Positional therapy5.20.10 Surgical treatment

6. Central sleep apnea syndrome

6.1 Central sleep apnea with Cheyne-Stokes respiration

6.1.1 Main findings6.1.2 Epidemiology6.1.3 Diagnosis6.1.4 Treatment6.1.5 Respiratory stimulants

and CO2

6.1.6 Unilateral stimulation of the phrenic nerve

6.1.7 Oxygen6.1.8 Continuous Positive Airway

Pressure6.1.9 Bilevel Positive Airway

Pressure6.1.10 Adaptive servo ventilation6.2 Central sleep apnea without

Cheyne-Stokes respiration6.2.1 Main findings6.2.2 Diagnosis6.2.3 Treatment6.3 Central sleep apnea with

periodic breathing at a high altitude

6.3.1 Main findings6.3.2 Treatment6.4 Centrals sleep apnea caused

by medication, drugs or substances

6.4.1 Main findings6.4.2 Treatment6.5 Primary central sleep apnea6.5.1 Main findings6.5.2 Epidemiology6.5.3 Treatment6.6 Central sleep apnea as

a consequence of treatment6.6.1 Main findings6.6.2 Epidemiology

S3-Guideline on Sleep-Related Respiratory Disorders

Somnologie · Suppl s2 · 2017S98

6.6.3 Diagnosis6.6.4 Treatment7. Sleep-related

hypoventilation/sleep-related hypoxemia

7.1 Obesity hypoventilation syndrome (OHS)

7.1.1 Main findings7.1.2 Diagnosis7.1.3 Treatment7.2 Sleep-related hypoventilation

caused by a physical illness7.2.1 Main findings7.2.2 Start, progression,

complications7.2.3 Diagnosis7.2.4 Treatment8. Legal consequences9. Glossary10. Appendices10.1 Annex A: Guideline report10.2 Annex B: Tables10.3 Annex C: Algorithms10.4 Annex D: Addendum11. Bibliography


Composition of the guideline group, involvement of stakeholders

Steering committee and published – Prof. Dr. med. Geert Mayer, Schwalm-stadt-Treysa

– Prof. Dr. med. Michael Arzt, Regensburg – Prof. Dr. med. Bert Braumann, Cologne – Prof. Dr. med. Joachim H. Ficker, Nuremberg – Prof. Dr. med. Ingo Fietze, Berlin – PD Dr. med. Helmut Frohnhofen, Essen – PD Dr. med. Wolfgang Galetke, Cologne – Dr. med. Joachim T. Maurer, Mannheim – Prof. Dr. med. Maritta Orth, Mannheim – Prof. Dr. rer. physiol. Thomas Penzel, Berlin – Prof. Dr. med. Winfried Randerath, Solingen – Dr. med. Martin Rösslein, Freiburg – PD Dr. rer. physiol. Helmut Sitter, Marburg – Prof. Dr. med. Boris A. Stuck, Essen

Authors – Prof. Dr. med. Geert Mayer, Schwalm-stadt-Treysa

– Prof. Dr. med. Michael Arzt, Regensburg – Prof. Dr. med. Bert Braumann, Cologne – Prof. Dr.med. Joachim H. Ficker, Nuremberg – Prof. Dr. med. Ingo Fietze, Berlin – PD Dr. med. Wolfgang Galetke, Cologne – Dr. med. Joachim T. Maurer, Mannheim – Prof. Dr. med. Maritta Orth, Mannheim – Prof. Dr. rer. physiol. Thomas Penzel, Berlin – Prof. Dr. med. Dr. med. dent. Hans Peter Pistner, Erfurt

– Prof. Dr. med. Winfried Randerath, Solingen – Dr. med. Martin Rösslein, Freiburg – PD Dr. rer. physiol. Helmut Sitter, Marburg – Prof. Dr.med. Boris A. Stuck, Essen

Editorial work – Dr. rer. nat. Martina Bögel, Hamburg

1. Summary

1.1 What’s new?

– Polygraphy can be used in patients with high pre-test probability (snoring, respiratory disorders observed by others and somnolence during the day).

– In the case of a cardiovascular disease with no typical SRRD symptoms, a reduced system with 1-3 channels can be used.

– In the past 20 years, an increase in the prevalence of OSA of 14-55% has been observed.

– Sleep-related respiratory disorders frequently occur in patients with heart failure. They are also associated with

increased morbidity and mortality in patients who are subjectively not hypersomniac.

– There is a link between OSA and malignant diseases.

– During telemonitoring the legal limits of admissible consultation and treatment options in accordance with Section 7 (4) of the Muster-Berufsordnung für Ärzte (Professional Code of Doctors Working in Germany) (MBO-Ä) should be complied with.

– Obstructive sleep apnea in the mother can harm the neonate.

– Untreated sleep apnea increases cognitive deterioration in patients with dementia.

– Patients with a high likelihood of developing a SRRD and a high risk of accident should receive a diagnosis as quickly as possible and if necessary should start to receive treatment quickly.

Reference to the current algorithms (see Annex C)

– Algorithms for treating patients with suspected obstruction of the upper respiratory tract

– Algorithms for treating patients with suspected central sleep apnea

– Algorithms for handling patients with cardiovascular diseases and sleep-related respiratory disorders.=

– Algorithms for treating patients with obstructive sleep apnea

1.2 New recommendations regarding the Guideline on “Nonrestorative Sleep,” Chapter on “Sleep-Related Breathing Disorders” of 2009

1. Diagnosisa. The STOP-BANG questionnaire

was included in the diagnostic spectrum.

2. Clinical examinationa. Examination of the oral cavity,

tooth status, if applicable a teleradiograph should be carried out to evaluate the cranial morphology.

3. Polygraphya. should only be used where the

pre-test likelihood of diagnostic evidence and the determination of the severity of sleep-related respiratory disorders is high (A).

1.2.1 Perioperative managementa. Questions on OSA should be

part of a preoperative patient history (B).

b. In the case of the existence of a previously unknown OSA, a sleep medicine diagnosis clarification should be carried out. It is necessary to weigh up the urgency of an operation and the need for or type of sleep medicine diagnosis clarification on a case-by-case basis (B).

c. If the patient has OSA and this needs treating, CPAP treatment started beforehand should be continued or started in the perioperative phase if the urgency of an operation permits this (B).

d. The selection of the patient history procedure and the type and duration of any postoperative monitoring that may be necessary should be based on the type and severity of the operation and the perioperative need for analgesics, the severity of the (suspected) respiratory disorder and the individual risk constellation of the patient including the concomitant diseases associated with OSA (B).

1.2.2 Obstructive sleep apnea1. Treatment:

a. Structured patient training should be carried out for the initial approach (B).

b. The patient should be supplied with the treatment device immediately after the adjustment to respiratory treatment (B).

c. A requirement for the use of bilevel procedures should be an



attempt to administer CPAP or APAP treatment (B).

d. APAP and CPAP can both be used to adjust treatment or for long-term treatment of OSAS (A).

e. APAP should not be used in patients with central respiratory disorders and hypoventilation at night (B).

f. Other respiratory support treatments or other suitable treatments should be used for patients whose condition cannot be controlled using CPAP (A).

g. An initial control should be carried out within the first six weeks clinically, where applicable with the help of at least one six-channel polygraph. Further regular controls should be carried out at least once a year (B).

h. Measures to reduce body weight should be recommended to all patients with excess weight as a concomitant treatment measure (A).

i. Lower jaw braces (LJB) can be used in patients with mild to moderate obstructive sleep apnea (AHI ≤ 30/h) as an alternative to positive pressure procedures. This applies in particular to patients with a body mass index of less than 30 kg/m2 and position-dependent sleep apnea (A).

j. The adjustment of LJB should be carried out with dental and sleep medicine expertise (A).

k. The effect of treatment with LJB should be checked by doctors qualified in sleep medicine on a regular basis, for example once every six months (A).

l. Non-electric procedures and myofunctional exercises can be considered in individual cases (B).

m. A tonsillectomy should be carried out in patients with tonsillar hyperplasia and oropharyngeal obstruction, particularly if other treatment

(CPAP, MAD) is not possible or this is not sufficiently well tolerated (A).

n. Neural stimulation of the hypoglossal nerve can be used in patients who do not have any anatomical abnormalities and who have moderate to severe OSA if positive pressure therapy cannot be used under the above-mentioned conditions. It should only be used in patients with CPAP intolerance or ineffectiveness with an AHI of 15–50/h and an obesity severity level of ≤ I if no concentric obstruction has been documented in the sleep endoscopy (B).

o. In patients with corresponding anatomical results with a small lower jaw and a narrow cranial structure (distance between the base of the tongue and the back of the throat, also known as the posterior airway space PAS < 10 mm in the teleradiograph image), a preliminary displacement of the upper and/or lower jaw (bimaxiliary advancement) should be considered, particularly if other treatment (CPAP, LJB) is not possible or this is not sufficiently well tolerated (A).

1.2.3 Central sleep apnea1. Diagnosis

a. In patients with central sleep apnea, where possible the internal medicine, pharmacological and neurological causes should be clarified (A).

2. Treatmenta. Guideline-compliant treatment

of the heart failure should be carried out to treat central sleep apnea in patients with heart failure and reduced left-ventricular function (HFrEF).

b. In patients with symptomatic moderate to severe central sleep apnea and HFrEF (LVEF ≤ 45%), treatment methods on which no randomized, long-

term studies have been carried out, such as the unilateral stimulation of the phrenic nerve and O2, should only be used within the scope of prospective studies (B).

c. A reduction of the dose of the opiates should be considered in opiate-induced sleep apnea (B).

d. Positive pressure procedures should be adjusted on an individual basis in patients with opiate-induced sleep apnea and their efficiency should be checked using a polysomnograph (A).

e. In addition to the PSG, the introduction and control of treatment should also include a capnography (A).

1.2.4 Sleep-related hypoventilation/hypoxemia1. Diagnosis

a. The diagnosis of sleep-related hypoventilation should be made in the event of clinical suspicion or a predisposed underlying disease by means of arterial or capillary blood analysis overnight or by means of nightly transcutaneous or end tidal CO2 measurement. An arterial blood gas analysis carried out during the day is needed to diagnose an obesity hypoventilation syndrome. An overnight oximetry test in combination with a measurement of the CO2 overnight should be carried out to diagnose sleep-related hypoxemia (A).

b. In patients with a body mass index of > 30 kg/m2 and symptoms of sleep-related respiratory disorders, examinations should be carried out to determine the venous bicarbonate when the patient is awake, the arterial or capillary pCO2 or the transcutaneous/end tidal CO2 in order to rule out concomitant hypoventilation during sleep (A).


c. In patients with neuromuscular diseases or diseases of the chest wall, where the is a vital capacity of < 50% hypoventilation during sleep should be ruled out before starting ventilation treatment (A).

2. Treatmenta. If hypoventilation at night

persists when the patient is using CPAP, non-invasive pressure-supported ventilation (with or without target volumes) should be introduced (B).

b. In patients with OHS, bariatric operations should be considered after measures to reduce weight have been exhausted (B).

2. Introduction

Sleep-related respiratory disorders (SRRD) occur exclusively or primarily when the patient is asleep. They have a disruptive effect on sleep and impair its restorative function. Characteristic patterns of distorted breathing include apneas and hypopneas with or without pharyngeal obstruction and hypoventi-lation. Depending on the type of respi-ratory disorder the patient has, it may be associated with hypoxemia or cause hypercapnia and acidosis.

ICSD-3 [9, 10] distinguishes 5 diagnos-tic categories, the designations of which are based on the patterns of breathing distorted during sleep and the underlying pathomechanism (see Tab. B.1). Within these five categories, a total of 18 clinical pictures are describes in the ICSD-3.

The pathogenesis of sleep-related re-spiratory disorders is based on central nervous and/or neuromuscular pro-cesses which lead to a change in central breathing regulation and/or the tone of the musculature in the upper respiratory tract. In addition to the category-specific patterns of distorted breathing, individ-ual sleep-related respiratory disorders are also characterized by further disease features which are based on predisposi-tion-related or triggering factors in com-bination with the changes which occur

as a result of breathing events and conse-quential damages. This can be different aspects such as symptoms of insomnia, somnolence during the day or long-term metabolic, endocrine, neurological, psy-chiatric, cardiovascular or pulmonary consequences. The combination of the factors triggered in each case, the change in sleep during the night and the short-term and long-term consequences result in typical symptoms and results for the respective diagnosis. These can range from nonrestorative sleep and somno-lence during the day with an increased risk of accident to cor pulmonale, car-diac arrhythmias, arterial hyperten-sion, atherosclerosis, heart attack, heart failure and stroke. This explains why in many patients it is not the sleep at night which is distorted or perceived to be dis-torted but rather the secondary diseases and their symptoms which justify a sus-pected diagnosis of sleep-related respi-ratory disorders. The severity and type of SRRD is important for a diagnosis to be made and a decision to be taken on treatment. Clinical symptoms and co-morbid diseases also have to be taken into account.

The prompt detection and treatment of for example obstructive SRRDs decreas-es the risk of accidents, improves the quality of life and reduces the morbid-ity and mortality of the person affected considerably. Nowadays, the assumption is made that for example untreated ob-structive sleep apnea leads to an increase in costs in the healthcare system. On the other hand, the effective treatment of obstructive sleep apnea is a cost-efficient measure from a health economics per-spective [29, 143, 274, 440, 467].

3. Diagnosis

3.1 General

The diagnosis of sleep-related respira-tory disorders is made in order to start efficient, needs-oriented and economic treatment with low levels of side effects. The diagnostic tools are based on the pathophysiology, the consequences and the concomitant diseases of sleep-relat-ed respiratory disorders. They are used to determine the severity and any con-

comitant disorders, and are intended to estimate the extent of the consequenc-es. They comprise the patient history, questionnaires for self-assessment, out-patient and in-patient multi-channel devices, video recordings, clinical lab-oratory diagnostics and both non-in-strument-based and instrument-based performance diagnostics. They are all or in combination used for making a diag-nosis and controlling treatment; they are also necessary for a social medicine eval-uation and assessment.

The diagnosis procedures are com-bined, used simultaneously or one after the other, as a supplement or exclusive-ly and with different resource input in terms of time, staff, organization and materials, depending on the case. The guidelines for the selection of certain instruments presents the “sleep-related respiratory disorders” algorithm with its decision-making pathway. The algo-rithm is based on the algorithm in the DGSM S3 Guideline “Nicht erholsamer Schlaf/Schlafstörungen” (Nonrestorative sleep/sleep disorders)[286]. In 2014, the DGSM Guideline was supplemented by a position paper submitted by expert associations DGP and DGSM, and the professional associations [122, 378, 379]. Furthermore, the DGSM Guideline was supplemented by a position paper by the DGK predominantly regarding the sig-nificance in patients with cardiovascular diseases [330].

Evaluations and examinations to pro-vide evidence of questionnaires, sensi-tivity and specificity and quantitative information to increase the reliability of testing (pre-test and post-test likelihood) are available for some instrument-based procedures. Some procedures are used on the bases of the general, currently recognized level of knowledge and find-ings (e.g., patient history questions). Some have been validated for special groups of patients (e.g., Epworth Sleepi-ness Scale, Berlin Questionnaire, MSLT/MWT, STOP, STOP-BANG).

In accordance with the ICSD-3 pub-lished in 2014, a distinction is made be-tween five main groups of sleep-related respiratory disorders (see Tab. B.1).



An overview of sleep medicine diag-nosis procedures and their application is set out in Tab. B.2 (see Annex B).

3.2 Non-instrument-based diagnosis

3.2.1 Questionnaires and performance and vigilance testsSleep medicine symptoms are primarily determined through the patient histo-ry, but also via self-assessment ques-tionnaires or interviews in the case of sleep-related respiratory disorders. An overview of the common procedures can be found in Tab. B.3.

The most commonly used instrument to determine sleepiness is the Epworth Sleepiness Scale (ESS) [220]. It is always used if information on the reduction in attention and concentration during the day is required over an extended period of time.

The Pittsburgh Sleep Quality Index (PSQI) [79], the Berlin Questionnaire [313] and in recent years also the STOP-BANG questionnaire [333] are used in major international studies. The diag-nostic value of these questionnaires in the sense of a prediction compared to each other and in comparison with poly-somnography is currently being investi-gated ([133, 413]; see Tab. B.4).

The neck circumference and hip circumference are recorded as a high-ly simplified examination to predict sleep-related obstructive respiratory disorders. Further anthropometric pro-cedures such as cephalometry, digital photo evaluation, and pharyngometry are currently being tested. To date, none of the procedures has achieved sufficient evidence for a diagnosis to be made. Un-der certain conditions, the likelihood of the existence of sleep-related respiratory disorders can be increased. This includes being male and the ratio between “hip size and height” [36].

In a meta-analysis comprising 10 stud-ies (n = 1484 patients), what are known as “STOP” studies (snoring, tiredness, observed apneas and high blood pres-sure) in combination with the BMI, age and neck circumference (“BANG” ques-tionnaires) showed the highest method-

ological quality for screening in patients with OSAS [1].

Quantitative attention and vigilance tests in order to gain an objective over-view of the somnolence during the day and of the reaction time include the psy-chomotor vigilance test (PVT), the Os-ler Test, the Divided Attention Steering Test (DASS) and other procedures [417]. Various investigations have been carried out on PVT [40]. Fewer have been car-ried out on the other procedures. The use of these procedures is possible to record sleepiness under certain condi-tions, but the diagnostic value has yet to be sufficiently proven.

The clinical guidelines of the Task Force der American Academy of Sleep Medicine (AASM) summarizes the eval-uation, the management and the long-term care of adults OSAS patients as follows:

Questions on OSAS and on cardiovas-cular concomitant diseases (e.g., arterial hypertension, cardiac arrhythmias, etc.) should be part of each clinical patient his-tory. If there is any cause to suspect that a patient has OSAS, an extensive sleep medicine evaluation should be carried out. The diagnostic strategy comprises a detailed sleep medicine patient history and clinical examination and objective testing (polysomnography, polygraphy) and clarification of the patient’s diagno-sis. Treatment measures and alternatives should be agreed with the patient. The OSAS should be recorded as a chronic disease. It requires multi-disciplinary long-term management [131].

3.2.2 Clinical examinationThe clinical examination should aim to identify anatomical changes in the upper respiratory tract or in the region of the skull which could (also) be responsible for the development of the OSA. This clinical examination should look at the nose, the oral cavity and the throat as well as the skeletal morphology of the skull. The clinical examination should be expanded if symptoms are indicated or relevant pathologies are expected in these regions. In order to do it, it can be necessary to include colleagues from other specialties with the relevant qual-

ifications (ENT, oral and maxillofacial surgery, specialist dentists).

Recommendations – A clinical examination of the nose should be carried out to evaluate the flow-relevant nasal structures. This can also include an endoscopic evaluation.

– The examination of the oral cavity and the throat is particularly important and should be carried out (B).

– If treatment with a pro-generation splint is considered, an estimation of the possible lower jaw protrusion should be carried out and the dental status recorded. This could be supplemented by a panorama layer image (PLI, OPG) being taken (B).

– In the diagnostic clarification of the OSA, an orientating assessment of the skeletal morphology of the skull should be carried out (B). This can include the creation of a lateral teleradiograph image (FRS) in order to evaluate the Posterior Airway Space (PAS), among other areas.

3.2.3 Instrument-based diagnosisThe need for an instrument-based diag-nosis of obstructive sleep apnea can be determined by the pre-test likelihood. The pre-test likelihood increases if several symptoms occur simultaneously or the patient has certain comorbidities. This means an increased or high likeli-ness of the patient having sleep apnea before a test is carried out based on the patient having characteristic signs and symptoms, some of which are reported by the patient themselves and some by the person they share a bed with. This includes:

– increased daytime sleepiness, – obesity, – hypertension, cardiac arrhythmias, – the person they share a bed with observing gaps in breathing during the night,

– loud, irregular snoring, – libido problems and erectile dysfunction,

– restless sleep, – fatigue in the mornings, diffuse, dull headaches, xerostomia,


– non-specific psychological symptoms such as fatigue, poor performance, change in character, poor intellectual performance.

A quantitative evaluation of the pre-test likelihood in terms of a standardization has yet to be carried out. As a result, there is still no quantitatively justified division of the degree of severity. Vali-dated questionnaires e.g., STOP, STOP-BANG, and the Epworth Sleepiness Scale are used to determine the pre-test likelihood [413].

3.2.4 PolysomnographyThe basic tool and the reference for sleep medicine diagnostics in the sleep labo-ratory is monitored cardiorespiratory polysomnography, by common agree-ment now known as polysomnography (PSG) for short. In this procedure re-cords the physiological signals which are needed for a quantitative evaluation of sleep, sleep disorders and diseases as-sociated with sleep in accordance with ICSD-3 (see Tab. B.5).

Evidence from the polysomnography (AASM manual) has been evaluated in extensive overview works (Tab. B.6). The division of sleep stages predominantly corresponds to the old classification by Rechtschaffen and Kales [382], [412]. Ambiguities are reduced and the reli-ability is increased [115]. A chapter on central nervous activation (arousal) uses the definitions from a previous recom-mendation paper [60]. Further chapters set out the recording and the evalua-tion of parameters of the EKG [87] and of leg movements. The motor patterns such as periodic leg movements, brux-ism and REM sleep behavioral disorders are precisely defined [460]. There are definitions of apneas and hypopneas of various kinds in nightly respiratory dis-orders. The reference method to record the obstructive respiratory activity is the esophageal pressure measurement. In-duction plethysmography is recognized as a non-invasive method with compa-rable results [384]. In order to recog-nize hypoventilation during sleep, the CO2 concentration must be continually determined. The most commonly used procedure for this is the transcutaneous

determination of the CO2 partial pres-sure (tcPaCO2) [384]. Polysomnography also includes the recording of the body position and a precisely synchronized video recording of the sleeping person [198]. AASM manual were updated slightly in 2012 (Version 2.0) and 2014 (Version 2.1), 2015 (Version 2.2), 2016 (2.3) in order to take into account new knowledge [48, 49, 50, 51].

Through monitored polysomnog-raphy, sleep disorders with changes in the physiological parameters can be in-vestigated and indicated quantitatively with a severity. With current comput-er-aided technology, polysomnography represents a manageable instrumental effort. It requires staff specifically trained in sleep medicine to carry out the mea-surement and evaluate the biosignals. Sleep medicine training and qualifica-tions have been established for medical technical staff, psychologists and natural scientists and for doctors at an addition-al training level. For doctors, the training to become a “specialist qualified in sleep medicine” comprises suitable specialist training with the opportunity to obtain the additional title of “sleep medicine specialist” or training on the diagnosis and treatment of sleep-related respira-tory disorders in accordance with BUB guidelines which is equivalent in scope and content. Non-specialist doctors and natural scientists can obtain evidence of their qualification as DGSM somnolo-gist.

The AASM manual [48, 198] permits the division into the stages of awake, REM, N1, N2, N3. There are national and international recommendations on the equipment and staff requirements in a sleep laboratory, compliance with which is a requirement for sleep labo-ratories to be accredited by expert sleep medicine associations [348].

Tab. B.6 provides an overview of the evidence-based data on PSG. Evidence has been provided of the validity and reliability of the visual evaluation. It cor-responds to the current requirements in terms of the quality of a visual evalua-tion of biosignals [114, 115]. In the sleep medicine findings report it is necessary to document whether the recording and the evaluation of the polysomnography

were carried out in accordance with the criteria of Rechtschaffen and Kales [382] or in accordance with the AASM crite-ria [49, 198]. The AASM Guidelines are updated around every two years, most recently in 2016 (version 2.3).

3.2.5 Polygraphy for Sleep-Related Respiratory DisordersSimplified, portable systems are avail-able for the diagnosis of sleep-related respiratory disorders ([11, 97, 145]; see Tab. B.7).

The portable diagnosis systems are divided into four categories by number of channels recorded. For the most part, they are systems with 4 to 6 channels with no measurement of the sleep EEG (synonym: polygraphy systems).

Polygraphy systems with an adequate selection of biosignals, very good signal recording and very good signal process-ing can reduce the number of false posi-tive diagnoses [104, 105]. A preliminary selection of the patients using a targeted patient history can increase pre-test like-lihood significantly and also reduce the number of false-positive diagnoses.

Using polygraphy, it is fundamental-ly possible to distinguish between OSA and CSA. However, when doing so it is necessary to take into account that the method has not been validated for this.

The polygraphy systems for the di-agnosis of sleep apnea must record the airflow using a thermistor or dynamic pressure sensor by means of induction plethysmography, the oxygen saturation using suitable pulse oximetry (averaging with a sufficiently high resolution), pulse frequency and body position [105]. Us-ing the SCOPER system method, the number of channels is insignificant and the recording of the functions is the fo-cus (S = sleep, C = cardiovascular, O = oximetry, P = position, E = effort, R = re-spiratory; [105]). There are several class-es of quality for each function. Sleep can be estimated from its actigraphy or other surrogate parameters and depending on the question may not have to be derived from a sleeping EEG. The SCOPER sys-tem is now used for classification in the polygraphy systems.

The evaluation of the polygraphy must be carried out in accordance with



the current rules of polysomnography [49] and enable a visual evaluation and processing of artefacts. The implemen-tation of a visual evaluation must be indicated in the documentation. The evidence-based recommendations for polysomnography are used for sampling rates and other technical specifications of the polygraphy systems (see Tab. B.5).

Polygraphy systems should be used by specialists trained in sleep medicine who can record and evaluate the pre-test likelihood, the symptoms and the co-morbidities to diagnose sleep-related respiratory disorders. In Germany, in ac-cordance with the BUB-Richtline [388] (Guideline on Methods for Ambulatory Care), sleep medicine training is a re-quirement to charge for polygraphy in accordance with EBM. Polygraphy sys-tems can be used to diagnose obstruc-tive sleep apnea, but not in patients with comorbid pulmonary, psychiatric or neurological diseases, not if the patient has other sleep disorders such as central sleep apnea, and not in patients with PLMD (periodic limb movement dis-order), insomnia, circadian sleep-wake cycle disorders or narcolepsy [122, 378, 379]. The polygraphy systems enable a distinction to be made between central and obstructive apneas. If the patient

primarily has hypopneas, polygraphy systems do not always enable a definitive differentiation to be made between cen-tral and obstructive sleep apnea and they are therefore not validated in this case. As a result of the lack of EEG channels, polygraphy systems are inferior to poly-somnography because the severity of the sleep-related respiratory disorder cannot be estimated as precisely, a sleep-related respiratory disorder cannot be ruled out with certainty and possible differential diagnoses of sleep-related respiratory disorder cannot be diagnosed. Without an EEG analysis, physiological irregular-ities of the breathing rhythm in the tran-sition between being asleep and being awake (known as “apneas while falling asleep”) may incorrectly be diagnosed as sleep apnea and lead to false positive results.

3.2.6 Monitoring for sleep-relates respiratory disorders with reduced systems.Systems which only record 1 to 3 chan-nels (pulse oximetry, long-term EKG, ac-tigraphy, oronasal airflow measurement) result in up to 17% false negative and up to 31% false positive findings [392], which is why their use to make a defini-tive diagnosis or to rule out sleep-related respiratory disorders is not recommend-ed (see Tab. B.7).

More recent selected systems with just 1-3 channels meet the SCOPER criteria and show a diagnostic sensitivity and specificity in meta-analyses correspond-ing to a 4-6 channel polygraphy [489]. Some systems increase pre-test likeli-hood of sleep-related respiratory disor-ders [330, 486].

Recommendations – After the above-mentioned pre-test likelihood has been recorded, the instrument-based diagnosis can be carried out in the 3 categories of preliminary diagnosis, confirmation diagnosis or differential diagnosis (C).

Polysomnography – Polysomnography in the sleep laboratory with monitoring by staff trained in sleep medicine is recommended as a basic tool and reference method (A).

– Polysomnography should be carried out in accordance with the current recommendations. This includes the recording of sleep EEGs, EOGs, EMGs, EKGs, airflow, snoring, breathing effort, oxygen saturation, body position, and video (A).

– The videometry should be carried out to diagnose parasomnias and movement disorders during sleep and differential diagnostic delimitation from some forms of epilepsy (A).

Prognostic bene�ts

e.g., reduction in cardiovascular risk

factors, reduction in metabolic risks, etc.

Side e�ects

e.g., sleep disorders, psychosocial

consequences, costs, “inconvenience” to the

patient, etc.

Comorbidities

e.g., cardiovascular diseases, metabolic

diseases, concomitant sleep medicine

diseases, etc.

Fig. 1 Individual indications for polysomnography. Various aspects such as pre-test probability, comorbidities, the possible prognostic usefulness and the risk of side effects relating to the respective approach must be considered during the management of indications [187]


Polygraphy for Sleep-Related Respiratory Disorders

– Polygraphy systems with a reduced number of channels can be used provided they record at least oxygen saturation, airflow, breathing effort, heart rate or pulse and body position (A). They should only be used where the pre-test likelihood of diagnostic evidence and the determination of the severity of sleep-related respiratory disorders is high (A).

– Polygraphy systems should be used by specialists trained in sleep medicine who can record and evaluate the pre-test likelihood, the symptoms and the comorbidities to diagnose sleep-related respiratory disorders (A).

– Polygraphy should generally be used to diagnose SRRDs in patients with comorbid disorders relevant to this diagnostic task and not as a replacement for PSG (A). The evaluation of the signals recorded must be carried out visually by trained staff. Simply evaluating the results using what is known as automatic scoring is not currently recommended (A).

– Cardiorespiratory polysomnography is recommended for a diagnosis that excludes sleep-related respiratory disorders; the polygraphy is not sufficient (A).

– PG and PSG are not sufficient to clarify a diagnosis of ventilatory insufficiency (A).

Reduced monitoring for sleep-related respiratory disorders

– Polygraphs with fewer criteria than those set out above can provide information on the existence of sleep-related respiratory disorders and increase the pre-test likelihood. They are not to be recommended as sole measures for the diagnosis of sleep-related respiratory disorders (A).

– A polysonography for differential diagnosis is indicated in the event of low pre-test likelihood or in patients with a history of suspected other sleep medicine diseases such as OSA (A). In order to carry out a differential diagnosis of the causes

of the obstructive sleep apnea, individual patients should be offered a dental and specialist radiological examination by dentists, orthopedic surgeons specializing in the jaw or oral and maxillofacial surgeons trained in sleep medicine, including a teleradiograph examination to investigate the possibility of treatment with lower jaw braces or a corrective osteotomy of the jaw.

– A teleradiograph examination is recommended to recognize skeletal anomalies. The posterior airway space (PAS) should be estimated using the extension of the lower edge of the lower jaw. In the case of low values of less than 10 mm, the assumption can be made that the patient has a suspected narrowing of the respiratory tract. Further confirmation can be attempted by means of three-dimensional imaging of the upper respiratory tract or by means of a transnasal video endoscopy. A requirement for the creation of a lower jaw brace (LJB) is that the patient has sufficient teeth with at least eight resilient teeth in the upper and lower jaw or an equivalent implant. In order to do this, a panorama layer image should be taken and a decision made by a dentist well versed in sleep medicine (B).

– If the patient has high-risk cardiovascular diseases (arterial hypertension, heart failure, atrial fibrillation, cerebrovascular diseases) without all of the typical symptoms, single-channel or double-channel registration is possible. If this registration shows that the patient is suspected of having an OSA, further diagnostic procedures using polygraphy or polysomnography are indicated (C). - Controls of a patient’s progression and treatment can be carried out using a polygraph. PSG controls may be necessary in the case of patients with questionable treatment success, patients with high levels cardiovascular risk and in patients with other diseases which impede sleep (C).

4. Principles of the creation of the indication for the treatment of sleep-related respiratory disorders

Sleep-related respiratory disorders (SRRD) are common, and there are a wide range of effective treatment op-tions to treat them. These are set out in detail and discusses in other parts of this guideline. The results of studies on diag-nosis and treatment are critically evalu-ated and systematically assessed in the relevant chapters. These evidence-based recommendations form the basic frame-work of medical decisions on the treat-ment of patients with SRRDs. However, the “medical art” involved in the care of specific individual patients is not only “clear use of clear knowledge on clear material for a clear purpose” [223], but rather goes well beyond a precise knowl-edge and the correct application of ev-idence-based recommendations of this type. The intention is therefore to set out the individual indication for the treat-ment of sleep-related respiratory disor-ders in principle below.

The indication for treatment (but also for no treatment!) of an SRRD always re-lates to a patient in his or her individual physical, mental and social situation. It is therefore not only dependent on the type and extent of the respective SRRD and the resulting risk of complication but also on the symptoms of the patient in question and the resulting psychologi-cal strain, the performance requirements and the desire of the specific patient for treatment. The indication for treatment can in individual cases be very simple if for example an obstructive sleep ap-nea syndrome is causing a high degree of psychological strain as a result of the tendency to fall asleep during the day. In this case, the evidence-based recom-mendations in this guideline apply and allow a relatively simple decision to be made about the “correct” treatment recommendation. It is more difficult to identify an indication if the individual prognosis is complicated by comorbidi-ties. It can be the case that a wide range of further symptoms and restrictions in terms of performance occur in mul-



timorbid and/or elderly patients in ad-dition to the sleep-related respiratory disorder, so even successful treatment of hypersomnia caused by an SRRD would not lead to a tangible advantage for the patient. An indication solely on the basis of even a careful instrument-based diag-nosis is not possible.

The indication is significantly more difficult in individual cases of oligo-symptomatic or asymptomatic patients in whom the treatment of a sleep-related respiratory disorder would not lead to a short-term or medium-term allevia-tion of symptoms. There is an indication for treatment in these patients too if it is necessary to prevent cardiovascular or metabolic complications. In a situation of this type, the possible indirect side ef-fects of treatment of the SRRD and the “stress” for the patient associated with any treatment must be weighed up care-fully against the expected future benefits ( Fig. 1).

The possible benefits of treatment of SRRD in patients with pronounced car-diovascular comorbidities are mostly significantly higher than in patients with only a few cardiovascular risk factors or none at all. Exceptions to this are often elderly patients or seriously ill patients with a poor short-term prognosis in whom the prognostic benefit of treating an SRRD which is in principle possible may no longer be effective in the specific case.

A patient’s individual preference plays a role in particular when it comes to tak-ing into account possible side effects of treatment and the subjective experience of the “inconvenience” caused by treat-ment, as the subjective experience of the “inconvenience” of treatment can vary greatly from individual to individual. Sleep medicine-related comorbidities may play an important role if, for ex-ample, an insomniac patient is meant to receive treatment with CPAP which in-creases their insomnia symptoms.

The treatment effects of the treat-ment of sleep-related respiratory disor-ders set out in the individual chapters of this guideline form the solid basis for the attending physician’s prognosis and indication. Ultimately, however, it is necessary to make a new decision in

each individual case in which the scope of the study data can be applied to the individual patient and considerations can be made about the effect the indi-vidual situation will have on the type of treatment. The evidence set out in the corresponding chapters of this guideline can only be sensibly applied on the basis of sufficient medical experience, a solid understanding of pathophysiology and comprehensive information about the medical, physical and social situation of the individual patient.

The indication for the treatment of sleep-related respiratory is not made in a legal vacuum. For example, in Vol-ume V of the Social Insurance Code “needs-oriented and uniform care corre-sponding to the generally recognized level of medical knowledge” is required (Sec-tion 70 of Volume V of the Social Insur-ance Code). But here, too, the “generally recognized level” is defined as “medical knowledge on the basis of evidence-based medicine” (Section 5 (2) of the Rules of Procedure of the Federal Joint Commit-tee). When interpreting legal specifica-tions regarding the application in a spe-cific individual case, this guideline and the above-mentioned statement can be used for the indication.

5. Obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome com-prises two diagnoses. Obstructive sleep apnea in adults will be described in the following section. Obstructive sleep ap-nea in children is not addressed in this guideline.

5.1 Obstructive sleep apnea

According to ICSD-3 [10], obstructive sleep apnea (OSA) is diagnosed if the respiratory disorder cannot be explained by any other sleep disorder or medical disease or by medications or other sub-stances and the patient has either an AHI > 15/h (result ≥ 10 s in each case) sleeping time or an AHI ≥ 5/h sleeping time in combination with typical clinical symptoms or relevant comorbidities.

5.2 Clinical symptoms

Main findings Day sleepiness through to involuntary falling asleep is the leading clinical symptom of obstructive sleep apnea, although there are people who are affected who are not sleepy or they state that they do not experience that as a symptom of the disease or do not ex-plicitly notice it. Day sleepiness causes a defective performance an impairs cog-nitive performance and social compati-bility and quality of life over the course of the disease (see Signs and Symptoms) Other people report a history of the pa-tient stopping breathing. The main di-agnostic result is the Apnea Hypopnea Index (AHI) which indicates the num-ber of apneas and hypopneas per hour. This makes the diagnosis more objective and determines the severity of the OSA when looked at together with the clinical symptoms and the comorbid diseases. From an AHI of > 15/h and < 30/h the sleep apnea is deemed to be moderate; from an AHI of > 30/h it is deemed to be severe.

Additional findings Scares at night with short-term shortness of breath, snoring (in 95% of those affected), symptoms of insomnia with frequent waking in the night, palpitations at night, nycturia, night sweats, enuresis, waking at night choking, holding breath or gasping, drowsiness in the morning and headaches both at night and in the morning may occur. Exhaustion, mem-ory impairment, impotence, personality changes, depressive disorders and the occurrence of automatic behavior are possible symptoms during the day or while awake. Viewed in isolation, how-ever, these symptoms only have a low specificity [118, 192, 246, 258, 270, 454, 495].


5.3 Epidemiology

There are relatively few population-based sleep laboratory studies. The prevalence data have not been corrected to reflect the clinical symptoms as relevant com-ponents for the evaluation of the severity of the disease as the resulting require-ment for treatment.

In the Wisconsin study, obstructive sleep apnea with clinical symptoms was identified in 2% to 4% of adults aged be-tween 30 and 60 [494]. 58% of the pa-tients were obese. In Great Britain, 0.5% to 1% the middle-aged men had mod-erate to severe sleep apnea [316]. To-day in the USA these figures are 13% of men and 6% of women [350]. We iden-tified an increase in the prevalence of obstructive sleep apnea of 14%-55% in the past 20 years. According to ICSD-3, 3%-7% of adult men and 2%-5% of adult women have sleep apnea syndrome. In-dependently of this, the prevalence is twice to three times higher in patients with cardiovascular diseases than in the normal population. Men are more com-monly affected than women [364, 497]. The prevalence increases in older peo-ple [364]. More than half (53%) have an AHI > 15/h [406] and almost 80% have an AHI > 5/h [497].

The prevalence data are mostly based on older investigations in the USA, Spain, Brazil, Hong Kong, India and Australia [258]. Initial German data are expected from the SHIP cohort [455].

5.4 Predisposing and triggering factors

Factors which determine the occurrence of obstructive sleep apnea are primar-ily BMI, age, gender and craniofacial features. Other factors are smoking, al-cohol, pregnancy, chemoreceptor sen-sitivity in the region of the breathing regulation and existing diseases such as rheumatism, acromegaly, hypothyroid-ism, and polycystic ovary syndrome [292, 497].

5.5 Family history, genetics

Although a sleep apnea-inducing gene has not yet been able to be identified and there are only certain associations to the chromosomes 1p, 2p, 12p and 19p and to the ApoE4 complex, there are suspi-cions that the disease can be inherited. Approximately 35% of the variability of OSA can be traced back to genetic fac-tors [383]. If one parent has OSA, the risk of the child having it increases by 2-3 times [164] compared to children whose parents do not have sleep apnea. A specific sleep apnea gene has not yet been identified [450].

5.6 Start, progression, complications

Obstructive sleep apnea has a natural development progression depending on age, BMI and the history of snoring [364]. The incidence increases between the ages of 35 and 65 [497]. The extent of the respiratory disorders during the night and daytime sleepiness are respon-sible for possible complications.

5.7 Daytime sleepiness

OSA patients with daytime sleepiness are 3-7 times more likely to have a traffic accident [292, 425]. OSA and daytime sleepiness are, however, not strongly correlated [425]. Sleepiness is common in the general population [494, 497] and a concomitant symptom of many oth-er diseases and circumstances, so it has a low specificity as a symptom [465].

5.8 Cardiovascular risk

Obstructive sleep apnea has been asso-ciated with coronary heart disease and atrial fibrillation [126, 153, 154, 225, 294, 369, 400, 430]. The link to other cardi-ac arrhythmias is as yet unclear [371]. These links have been proven for both OSA patients in the general population [364] and OSA patients with cardiovas-cular diseases [425]. Links to pulmonary hypertension [202], diabetes mellitus [139, 199], kidney failure [2] and athero-sclerosis [128] are likely but have not yet been proven or have only been proven

for sub=groups of patients [20, 21, 127, 127, 168, 297, 425, 472].

5.9 Arterial hypertension

There are confirmed links between ob-structive sleep apnea and arterial hyper-tension, particularly resistant hyperten-sion [34, 37, 42, 138, 177, 276, 347, 425, 456], and in patients with concomitant cardiovascular diseases [169], with heart failure [168, 213, 227, 407, 463, 499], with stroke [41, 346, 385, 394, 449], with coronary heart disease [168, 197], with atrial fibrillation, [154] and with mortal-ity [84, 185, 275, 276, 278, 280, 425, 498].

The effects of CPAP treatment on ar-terial blood pressure were investigated in a meta-analysis of 32 randomized and controlled studies in which “active high pressure therapy” (CPAP, lower jaw braces, anti-hypertensive drugs) were compared with a “passive group” (sham CPAP, anti-hypertensive drugs, weight loss). Under effective CPAP pres-sure both the systolic and the diastolic blood pressure were able to be reduced significantly (p < 0.001), although the values were clinically negligible (sys-tolic BP 2.5 ± 0.5 mm Hg, diastolic BP 2.0 ± 0.4 mm Hg). The higher the initial AHI were, the greater the percentage by which the blood pressure was able to be reduced during treatment with CPAP [138]. In a meta-analysis, Bratton et al. [67] add that good compliance improves the effect on the blood pressure and the blood pressure-lowering effect of CPAP is comparable to the effect of intraoral lower jaw brace treatment.

In patients with good compliance (use for at least 4 hours per night), the inci-dence of the development of hyperten-sion decreases [38]. Additional weight reduction is also sensible [98].

Sleep apnea increases the risk of cardi-ac and cerebrovascular diseases. Various studies also show a reduction in the car-diac and cerebrovascular risk as a result of the treatment of SRRD, although there are as yet no randomized, controlled studies [167, 258]. In multimodal treat-ment concepts in patients with cardio-vascular diseases, treatment of a night-time respiratory disorder should always be considered.



5.10 Stroke

The guidelines [167] for the primary prevention of stroke name sleep-related respiratory disorders as one of the risk factors for a stroke occurring and rec-ommend the implementation of a poly-somnography in patients who snore a great deal, are excessively sleepy in the day, have vascular risk factors and a BMI > 30 kg/m2 and have treatment-refrac-tory arterial hypertension (class 1, evi-dence grade A). A multicenter, random-ized, controlled treatment study with a follow-up period of five years showed an improvement in the functional con-sequences of stroke and a reduction in mortality in patients with ischemic stroke and moderate to severe sleep ap-nea being treated with CPAP [341, 342]. A current meta-analysis confirms the link between moderate to severe sleep apnea and stroke [126]. However, insuf-ficient evidence has been provided to show that the treatment of sleep apnea reduces the risk of a stroke.

5.11 Heart failure

Sleep-related respiratory disorders that occur frequently in patients with heart failure, obstructive and central sleep ap-nea (see CSA) are also associated with increased morbidity and mortality in patients who subjectively do not expe-rience hypersomnia [95, 210, 252, 463]. Patients with heart failure with particu-larly obstructive sleep apnea should be directed to treatment depending on the AHI, as should comparable OSA pa-tients without heart failure.

The effects of CPAP on left ventricular function in patients with OSAS was ex-amined in a meta-analysis of 10 random-ized, controlled studies. Patients with OSAS and an existing disorder of left ventricular function experienced a sig-nificant improvement in the left ventric-ular ejection fraction during treatment with CPAP, those OSAS patients who did not have a disorder of left ventricu-lar function only improved marginally. A significant correlation was identified between the initial AHI and the left ven-tricular ejection fraction [438].

5.12 Diabetes mellitus

Due to the high coincidence of OSAS and type 2 diabetes, patients with type 2 diabetes should have a sleep medicine examination [28, 409]. A meta-analy-sis of the effects of CPAP treatment on blood sugar and insulin resistance did not show an improvement in fasting blood sugar in diabetes or non-diabetics 3 and 24 weeks after the start of CPAP treatment. Insulin resistance only im-proved in non-diabetics with mild to moderate OSAS [490, 491]. The impact on insulin resistance is also described by Feng et al. [139].

A further meta-analysis of the effects of CPAP treatment on glucose metabo-lism showed that CPAP did not affect the plasma insulin level, insulin resistance, the adipo-leptin value or the HbA1c value [186].

When managing SRRD patients with an underlying cardiovascular disease, the distinction between obstructive and central sleep apnea should always be considered. In order to do this, the expertise of a doctor qualified in sleep medicine is required [289].

5.13 Malignant diseases

There is a link between OSA and ma-lignant diseases and their progression. Evidence has, however, yet to be pro-vided on the impact of CPAP treatment [85, 257, 317, 338].

5.14 Perioperative complications

In addition to the risks caused by asso-ciated diseases, patients with OSA have a particular risk constellation during surgery:

the perioperative mortality of OSA patients does not appear to be elevated if differentiated perioperative manage-ment is carried out for these patients [266, 303, 304]. However, there are nu-merous indications that OSA patients have an increased risk of various periop-erative complications of systemic anal-gesia with opioids and sedation or a gen-eral anesthetic are administered [451].

Respiratory tract management (mask ventilation and/or intubation) appears to be more difficult in these patients in the intraoperative phase, and the cate-cholamine requirement appears to be elevated [233, 419, 431].

In a meta-analysis of thirteen studies with 3942 OSA patients evidence was able to be provided that there was a sig-nificantly higher risk of cardiovascular events, decreases in oxygen through to acute respiratory failure and the need for the patient to be moved to an intensive care ward after an operation in patients with OSA [229].

There are indications that be iden-tifying and treating an OSA before an operation the increased risk of the above-mentioned complications occur-ring can be reduced at least in part [175, 310].

A particular challenge for the periop-erative treatment team is that OSA is not diagnosed before treatment in the ma-jority of surgical patients [141, 381].

There are currently only few guide-lines and recommendations from med-ical specialist associations regarding the optimal perioperative management of patients with (suspected) OSA [172, 224]. In 2015, the German Anesthesi-ology and Intensive Medicine Associa-tion and the German Association of Ear, Nose and Throat Medicine and Surgery on the Head and Neck published a joint position paper on ENT operations and operations on the upper respiratory tract containing recommendations for the perioperative management of this group of patients [390].

For ambulatory operations, the Amer-ican Society of Ambulatory Anesthesia recommends the following procedure: patients with diagnosed OSA and opti-mal treatment of the concomitant dis-eases can have operations in an ambula-tory environment on condition that they are able to tolerate a CPAP device in the postoperative phase. Patients in whom there are indications of an OSA on the basis of their history whose concomitant diseases are also being treated in an op-timal manner can receive operations in an ambulatory environment on condi-tion that the pain which occurs after the


operation is not treated with opioids. Pa-tients in whom the concomitant diseases are not being treated sufficiently well are not suitable for operations in an ambula-tory environment [224].

There are currently insufficient data on the risk of perioperative complica-tions in patients with other non-ob-structive SRRDs such as CSA [108]. The perioperative management of these pa-tients should therefore take into account the individual situation with a consider-ation of the underlying and concomitant diseases (see Tab. B.8).

Recommendations – Questions on OSA should be part of a preoperative patient history (B).

– In the case of the existence of a previously unknown OSA, a sleep medicine diagnosis clarification should be carried out. It is necessary to weigh up the urgency of an operation and the need for or type of sleep medicine diagnosis clarification on a case-by-case basis (B).

– If the patient has OSA and this needs treating, CPAP treatment started beforehand should be continued or started in the perioperative phase if the urgency of an operation permits this (B).

– The selection of the patient history procedure and the type and duration of any postoperative monitoring that may be necessary should be based on the type and severity of the operation and the perioperative need for analgesics, the severity of the (suspected) respiratory disorder and the individual risk constellation of the patient including the concomitant diseases associated with OSA (B).

5.15 PAP treatment methods

Treatment of nighttime respiratory disorders is based on the number of pathological breathing events per hour of sleep, the form of apnea (central, ob-structive, hypoventilation) and the clin-ical symptoms, primarily daytime sleep-iness and the impairments, risks and comorbid diseases caused by this.

The aim of treatment in accordance with the definition of obstructive sleep apnea (OSA) according to ICSD-3 is undisturbed sleep, characterized by an AHI of fewer than 15 events per hours of sleep with no symptoms of daytime sleepiness.

Before treatment of the sleep-related respiratory disorders, the clarification of possible factors which may impact the diseases is combined with the aim of carrying out behavioral measures.

The treatment measures listed below can generally be used both in an isolat-ed manner and in combination with one another.

5.15.1 Nighttime positive pressure breathingThe most common form of treatment for all severities of obstructive sleep ap-nea if nighttime positive airway pressure (PAP) in the form of the continuous PAP mode (CPAP, “continuous PAP”) [5, 29, 247, 315, 316, 396, 474]. The in-dications for the introduction of CPAP treatment arise from the synopsis of the patient history, polysomnograph and in-strument-based results and the concom-itant diseases which occur, particularly if a worsening of these can be assumed in the event of a failure to provided positive pressure treatment [378, 379].

The indication for the introduction of positive pressure therapy is present from an AHI of ≥ 15/h.

The introduction of CPAP treatment can be considered in patients with an AHI of 5-15/h with one or more of the symptoms or concomitant diseases men-tioned below:a) excessive daytime sleepiness

(ESS > 10) or falling asleep in monotonous situations,

b) cognitive deficits of symptoms of depression as a result of an SRRD,

c) cardiovascular diseases such as arterial hypertension, coronary heart disease, cardiac arrhythmias, status post stroke among others.

In patients with an AHI < 5/h, CPAP treatment is only indicated if symptoms (as described above) continues despite the diagnosis and treatment of other dis-eases. The initial application of positive pressure ventilation should be carried out in a sleep laboratory under contin-uous monitoring, and the possibility of immediate intervention by a doctor. Two nights of polysomnograph pro-cedures are generally sufficient to de-termine the settings. Initiation of PAP using a polysomnograph is sensible in order to cover other masked sleep dis-orders such as insomnia, PLMD (peri-odic leg movements) RBD (REM sleep behavior disorder) or central respiratory disorders and to be able to control the pressure efficiency depending on the position of the body and the stage of sleep. The aim of CPAP adjustment is to improve or normalize the sleep structure with sufficient percentages of REM and deep sleep and to eliminate waking re-actions, improve or normalize the ven-tilation parameters with a reduction of the respiratory events and consecutive pathological decreases in oxygen to the physiological level.

In order to manage the introduction of treatment, there are increasing numbers of RCTs (randomized, controlled trials) which show that in certain sub-groups of patients the adjustment of CPAP/APAP can be carried out without a polysomno-graphical control in a sleep laboratory. This procedure is effective in terms of respiratory disorders [144, 244] and day-time sleepiness [93, 100], but no better than the levels being set in the sleep lab-oratory [391]. The costs of adjusting the settings in an ambulatory environment are somewhat lower in the American healthcare system, but the subsequent costs of care are then sometimes higher [234]. Further studies need to be carried out in countries including Germany to identify the predictors of the success of this procedure and validate the long-



term success. Patients with a suspected additional sleep disorder in addition to the OSA or with an increased comor-bidity and questionable compliance and implementability of the PAP treatment should continue to be treated in the sleep laboratory. The recommendation on treatment mode and the pressures to be applied in the positive pressure thera-py should be made be a doctor qualified in sleep medicine.

Automatic (APAP, auto-bilevel, ASV) procedures can be used to set the posi-tive pressure treatment, but many titra-tion can be used too. The scientifically justified clinical guidelines for manual CPAP titration are as follows:1. Sufficient clarification, instruction

and adjustment of the treatment,2. Titration of the CPAP pressure to

a level at which apneas, hypopne-as, RERAs and snoring no longer occur,

3. Start of titration at 4 mbar (CPAP) or IPAP 8/EPAP 4 mbar (bilevel),

4. max. CPAP: 15 mbar, max. IPAP: 20 mbar (bilevel), IPAP/EPAP Dif-ference: min. 4, max. 10 mbar,

5. Increase the pressure as needed by 1 mbar at a time interval of at least 5 minutes,

6. The pressure is increased if at least 2 obstructive apneas, 3 hypopneas or 5 RERAs or 3 minutes of loud snoring occur,

7. Switch to bilevel in the event of an intolerance of CPAP or pressure > 15cmH2O,

8. Treatment objective: RDI < 5/h, min. oxygen saturation > 90%,

9. Optimal titration: RDI < 5/h for at least 15 min., incl. REM and no arousal,

10. Good titration: RDI ≤ 10/h or reduction by 50% with a baseline RDI of < 15/h, incl. REM and no arousal,

11. Sufficient titration: RDI > 10/h, but at 75% of the initial value, particu-larly in patients with severe OSAS or patients with optimal settings who did not experience REM sleep at night,

12. Unacceptable titration: does not meet any of the criteria above and

13. a second night of adjustment of the settings is needed if the criteria for optimal or good settings are not met in the first night [248].

There is no more effective treatment to remedy all forms of respiratory disor-ders than positive pressure treatment, with the exception of a tracheotomy in severe, life-threatening cases [247, 396]. CPAP does not only reduce and remove the respiratory disorder, but also day sleepiness [67, 159, 163, 247, 287], leading to an average reduction in the Epworth Sleepiness Scale (ESS) of around 2.5 points [67] and to an increase in the average sleep latency of approxi-mately 0.93 minutes in the multiple sleep latency test (MSLT) [344]. The sleepier patients are before the start of treatment, the more obvious the improvement it. When determining the quality of life (QoL), too, there was a significant in-crease in terms of the dimensions of physical activity and vitality [159, 163, 217, 247, 287]. Further scientifically confirmed effects are the improvement in sleep structure and mood and the re-duction in the risk of an accident [5, 396, 425, 445]. The effects of CPAP treatment on daytime sleepiness, cognition, blood pressure and quality of life depend on the duration of use of the treatment de-vice during the time spent sleeping [19, 468]. There was no positive effect on the weight, but rather weight gain can occur during treatment [129]. Concomitant weight reduction measures are therefore essential with this indication.

Under CPAP, the average blood pres-sure in OSA patients decreased by ap-proximately 2 mmHg depending on the severity of the OSA and the arterial hypertension [34, 42, 67, 163, 177, 247, 301], and in hypertensive patients by approximately 7 to 10 mmHg [43, 300, 351]. The blood pressure reducing effect of CPAP is more clearly in treatment-re-fractory hypertension [281]. Predictors for an even clearer treatment effect in-clude the severity of the disease and good CPAP compliance. Although there are no randomized clinical trials on this, a range of cohort-based long-term stud-ies indicate that good use of CPAP has a positive impact on survival [83, 275].

CPAP decreases the burden of cardiac arrhythmias, particularly atrial fibrilla-tion [369] and the LVEF in patients with severe OSA [396]. Further positive ef-fects caused by CPAP can be seen in the markers for inflammation and oxidative stress [21, 106, 396].

5.15.2 Modified positive pressure treatment methodsModified long-term treatment meth-ods include automatic APAP treatment [305, 396], bilevel S/T treatment [247, 396], pressure-delayed treatment (pres-sure relief in the in and/or out phase of expiration) and a combination of these methods. There is a lack of clinical trials to recommend these methods in gen-eral [179]. Automatic PAP procedures in particular showed themselves to be equal to standard CPAP treatment in long-term use and [111] and are there-fore increasingly being used in patients with moderate to severe OSA with no comorbid diseases or risk factors [307, 309]. However, it is not possible to calcu-late the effective continuous minimum pressure in advance [396]. The Canadian Thoracic Society, for example, recom-mends CPAP as the primary treatment of OSAS (recommendation level IB). APAP is an alternative effective form of treatment in OSAS patients with no co-morbidities [144].

In general, APAP appears to improve compliance (by 11 min) and daytime sleepiness (0.5 in the ESS) more than CPAP [201]. The clinical significance of these changes, however, is questionable and in summary APAP has not yet pro-vided any evidence of being better than CPAP in short-term or long-term care [33, 67, 155, 201, 307, 345, 396, 423, 485]. The same is true of what is known as the “pressure relief ” mode. Further research is needed to provide further recommen-dations for clinical practice [3].

The current general recommendations for the use of APAP devices are as fol-lows:1. diagnoses should not be made

using APAP.2. it should not be used in patients

with severe cardiopulmonary diseases, nighttime decreases in


oxygen which are not due to an OSAS or central sleep apnea.

3. Pressure titration using APAP is possible to determine the effective pressure with or without (in the case of moderate to severe OSA with no comorbidity) polysomnog-raphy.

4. For check-up examinations in patients whose diseases are already being controlled with CPAP [307].

Patients in whom a higher CPAP pres-sure is no longer tolerated or cannot be applied (e.g., COPD patients) who have central apneas or in whom these devel-op under positive pressure treatment (complex apneas) whose subjective compliance is inadequate or in whom optimal treatment success if not able to be achieved for other reasons should be switched to alternative procedures such as APAP or bilevel treatment or auto ser-vo ventilation (taking into account the indication) [247, 248]. In patients with known hypoxemia, oxygen can also be administered with careful monitoring of the blood gases in the adjustment phase [248]. Treatment with oxygen alone is not recommended [267, 323].

The type of sleep-related respiratory disorder the treatment success, the co-morbid diseases and the patient’s com-pliance are all key elements when select-ing the individual treatment mode. From a health economics perspective, CPAP is a cost-effective treatment [287], but it is not superior to lower jaw braces in all groups of patients. In patients with mild to moderate sleep apnea, the selection of the appropriate treatment method lies in the hands of the doctor qualified in sleep medicine. CPAP treatment should al-ways be tried first in patients with severe sleep apnea (see also Tab. B10 and B.11).

5.15.3 ComplianceThe Cochrane Analysis of 2009 on CPAP compliance used as an endpoint the im-pact on CPAP compliance, the influence of mechanical interventions (air humid-ification) (n = 1), auto-CPAP (n = 13), bi-level PAP (n = 3), and patient titrated CPAP [n = 1] [423].

In addition to this, the impact of pa-tient training, support provided to the

patient and behavioral therapy mea-sures was also investigated and revised in the current Cochrane Analysis of 2014 [484]. Supportive measures lead to a longer CPAP usage period of 50 mins/night, an increase in the number patients who use their device for more than 4h per night (from 59 to 75/100 patients) and to a lower rate of discontinuation. Explanatory measures increase the usage period by approximately 35 mins and also lead to an increase in the number of patients who use their device for more than 4h per night (from 57 to 70/100 pa-tients) and to a lower rate of discontin-uation. Behavioral therapy improves the usage period by 104 minutes and also leads to an increase in patients who use their device for more than 4h per night (from 28 to 47/100 patients). The treat-ment of a coexisting sleep disorder is also important for compliance [47, 386]. The mask standard continues to be the nasal mask [468].

In addition to a reliable diagnosis in the sleep laboratory, the severity of the disease, daytime sleepiness and the first week of use of the treatment are critical for compliance [272, 468]. The improve-ment in daytime sleepiness, perfor-mance, quality of life and blood pressure contribute significantly to compliance. If compliance is poor or questionable on two or more nights in the first week of treatment, a careful follow-up and sup-port are necessary [247, 248]. Ultimate-ly, 5-50% of patients who have started on CPAP discontinue their treatment in the first seven days. Annual long-term con-trols are generally recommended [247].

Further compliance factors are the environment, the clarification of the diagnosis of the disease and treatment including a change in lifestyle, the inclu-sion of the partner, the careful selection and adjustment of the mask, the efforts to get used to the treatment the day be-fore the first night on CPAP and the rec-ognition and treatment of claustropho-bia, in addition to high respiratory tract resistance in the nose [298, 386, 468]. These variables make up approximately 4-25% of the variance in the use of CPAP [477]. The degree of hypoxemia at night does not have an impact on compliance [468]. During the use of the treatment,

the following measures can improve compliance, although there is as yet no evidence of this [92]: Humidification and warming of the air [247, 318], close follow-up examinations with a recorded of the use of CPAP, the problems and complications and the opinion of the partner, the objectivization of possible residual sleepiness and the prompt treat-ment of this [191, 259] and retitration if the treatment effect is insufficient or switching to an alternative treatment method [35]. Close follow-up care is also important as in addition to rhinitis incorrect mask positioning and a lack of comfort, for example the pain caused by the pressure of the mask, skin irritation, leakages and sounds are common side ef-fects of CPAP treatment but are easy to remedy.

The information on compliance varies greatly and there are few current studies. The assumption can be made that inter-national compliance is approximately 40-60%. Between 29-83% of OSA pa-tients regularly use their treatment less than 4h a night. Around 70% of patients use the treatment around 5.3h (4.4-6.2) per night in the first four years [468]. Adherence (65-80%) and acceptance (85%) [258] in Europe are higher than in the USA.

Reasons for the very different com-pliance information are the above-men-tioned influence factors, which are taken into account and controlled in a coun-try-specific manner, including depend-ing on the quality of sleep medicine care.

Deficiencies to date: The definition of compliance is based on the doctor’s perspective. User sensitivity and specif-ic features and the special medical need play a subordinate role ([464]; see Tab. B.9).

Check-up examinations The interval, necessary scope and outcome of check-up examinations are not yet clearly de-fined [484].



An official statement by the American Thoracic Society (ATS) on the control of CPAP adherence determined the follow-ing, among other things [403] (expert opinion):1. The measurement of CPAP use

through nighttime ventilation pres-sure is sensible. although the effect on compliance is not clear.

2. Pressure monitoring should rou-tinely be read.

3. A uniform technical standard for pressure monitoring for the identi-fication of apneas, hypopneas and mask leakages is required.

4. Documentation on CPAP adher-ence between the 7th and the 90th day after the start of treatment is required. Regular controls should be carried out for the duration of time that the patient is using the CPAP device.

5. The nomenclature for CPAP adher-ence must be standardized by the manufacturer. The AHI flow is the parameter for the remaining respi-ratory events (see also Tab. B.9).

5.16 Telemonitoring of sleep-related respiratory disorders

The technical options made available by telemonitoring have developed signifi-cantly in the past few years. For example, it is now possible to transfer the patient’s usage data from the PAP device to a cen-tral server night by night and there to re-cord parameters of treatment adherence (duration of use, regularity of use) or other parameters relevant to treatment (e.g., leakages) automatically. In this way, in a further step it is possible to care for the patient via telemedicine and for ex-ample to train them, advise them or mo-tivate them in a targeted manner via the telephone or using internet-based mea-sures, or to arrange an on-site interven-tion. The effects of telemonitoring have not yet been the subject of much scien-tific investigation. A number of studies show entirely positive effects on night-time duration of treatment [62, 148, 203, 245, 426]. Other studies were not able to provide any evidence of favorable effects of a telemedicinal intervention [296].

The telemedicine concepts offered and investigated to date vary in some cases significantly in terms of the data recorded, the type of data transmission, data storage and data evaluation and above all in terms of the intervention on the patient which results from the data analysis, so the results of various tele-medicinal scenarios cannot be directly compared with one another. Other tele-medicine applications such as telethera-py, teleconsultation and telediagnostics have not yet been evaluated sufficiently and should not be used in the routine care of patients with sleep-related respi-ratory disorders.

To date, telemonitoring has only been developed for positive pressure (PAP treatment) of patients with obstructive sleep apneas. An application in ventila-tion medicine (NIV treatment) has thus far been ruled out. To date there have also been no studies which show that telemonitoring techniques are suitable for the initial process of adjusting the settings on a PAP device or for the initial selection of a mask.

Since the use of telemonitoring in patients with sleep-related respiratory disorders includes medical services, the doctor who specializes in sleep medicine sets out the type and scope of the record-ing and determination of data in coordi-nation with the patient. Telemonitoring in SRRDs requires a binding treatment concept to be ensured on the basis of complete care for the patient including personal doctor-patient contact at the instigation of the attention sleep medi-cine physician.

The legal limits of admissible and in-admissible consultation and treatment options in accordance with Section 7 (4) of the Muster-Berufsordnung für Ärzte (Professional Code of Doctors Working in Germany) (MBO-Ä) should be com-plied with. [76].

5.17 OSA in pregnancy

According to an American morbidity/mortality study (1998-2008), the prev-alence of sleep-related respiratory dis-orders in pregnant women is low at 0.7 per 10,000 (1998) and 7.3 per 10,000 (2009). In the literature, the prevalence in women of childbearing age is gen-erally given as 0.7-7%, and in pregnant women as 11-20%, in other words sig-nificantly higher. It is known that OSA is associated with a higher risk of pre-ec-lampsia, eclampsia, cardiomyopathies, diabetes mellitus and pulmonary em-bolisms [269, 339]. Mortality increases five-fold. Being overweight increases the risk. Obstructive sleep apnea also harms the neonate [96]. Reduced movements during pregnancy can be a sign of this [59]. According to a Cochrane Analysis of health programs before and during pregnancy in overweight women, there have, however, been no scientific studies on this subject [334]. This also included CPAP treatment in patients with sleep apnea. Controlled studies are required to recommend short-term or long-term treatment of sleep-related respiratory disorders during pregnancy.

5.18 OSA in elderly people

The prevalence of obstructive sleep ap-nea increases with age [14]. The values given, however, fluctuate wildly (20 to 40%) and are among other things de-pendent on the sub-group of patients being investigated and the AHI limit used [13, 497]. A conservative estima-tion assumes a doubling of the preva-lence in old age [13]. Prevalence figures of up to 70% are given for residents of homes. In principle, diagnostic and ther-apeutic management corresponds to that for obstructive sleep apnea in younger patients. Older people with obstructive sleep apnea benefit from treatment in terms of their daytime sleepiness, QoL [283] and prognosis [337]. Age is no rea-son to refuse treatment.


5.19 Obstructive sleep apnea and dementia

No randomized controlled studies on the incidence of dementia in patients with obstructive sleep apnea have been carried out.

Two prospective cohort studies of 2636 elderly men and 298 elderly wom-en all without cognitive impairment at the start of the study investigate the effect of obstructive sleep apnea on brain per-formance. In men, there was a signifi-cantly greater loss in brain performance after an average of 3.4 years if they had obstructive sleep apnea with addition-al hypoxemia [57]. In the women with obstructive sleep apnea and hypoxemia the risk of developing a mild cognitive impairment (MCI) or dementia was in-creased by a factor of 1.85 (95% CI 1.11-3.08) over the course of 4.7 years after adjusting for other risk factors [487]. Furthermore, evidence was provided of a significant reduction in the instrumen-tal activity of daily life in elderly women with untreated sleep-related respiratory disorders [427].

5.19.1 Treatment of obstructive sleep apnea in people with dementiaIn a small, randomized, controlled study people with mild and moderate dementia and obstructive sleep apnea (AHI > 10/h) were effectively treated with sham CPAP. The acceptance of CPAP treatment was initially high, but 25% of patients dis-continued the study after randomiza-tion [101].

After three weeks of treatment, the patients who had effectively been treated with PAP treatment showed a significant improvement in their daytime sleepiness and a significant improvement in brain performance [15].

This means that untreated obstructive sleep apnea with additional hypoxemia increases the risk of cognitive deterio-ration in both men and women. CPAP treatment decreases daytime sleepiness in people with mild and moderate de-mentia and improves global brain per-formance.

Recommendation – An attempt should be made to provide PAP treatment to patients with mild and moderate dementia and obstructive sleep apnea (B).

Recommendations – CPAP treatment is the reference method in the treatment of obstructive sleep apnea syndrome.

– CPAP treatment should be carried out in patients with moderate and severe sleep apnea (AHI > 15/h) (A).

– CPAP treatment can also be considered in patients with mild sleep apnea with an AHI ≤ 15/h with a cardiovascular risk and/or daytime sleepiness (C).

– Structured patient training should be carried out for the initial approach (B).

– The decision on the treatment mode should be made by a doctor qualified in sleep medicine (A).

– The patient should be supplied with the treatment device immediately after the adjustment to respiratory treatment (B).

– The selection of the device, the mask, additional tools and the initial adjustment by staff qualified in sleep medicine is recommended (C).

– The introduction of CPAP treatment or modified positive pressure procedures should be carried out under polysomnographic control in a sleep laboratory (A).

– The final adjustment to the settings should be carried out with the same device and the same mask type that the patient actually receives (A).

– A requirement for the use of bilevel procedures should be an attempt to administer CPAP or APAP treatment (B).

– APAP and CPAP can both be used to adjust treatment or for long-term treatment of OSAS (A).

– APAP should not be used in patients with central respiratory disorders and hypoventilation at night (B).

– Other respiratory support treatments or other suitable treatments should be used for patients whose condition cannot be controlled using CPAP (A).

– An initial control should be carried out within the first six weeks clinically, where applicable with the help of at least one six-channel polygraph. Further regular controls should be carried out at least once a year (B).

– Polygraphical or polysomnographical controls should be carried out in the event of subjective symptoms or clinical or technical problems (A).

Notes Appendix C includes the OSAS algorithm, the CSA algorithm, the SRRD algorithm and cardiovascular diseases and the OSAS treatment algorithm.

5.20 Non-CPAP methods of treating obstructive sleep apnea

5.20.1 Weight reductionA risk factor for OSA is being over-weight. Weight reducing measures up to and including an operation can therefore be supportive strategies in the treatment of moderate to severe OSA in patients who are overweight.

5.20.2 Non-operative weight reductionA 10-15% weight reduction leads to an approximately 50% reduction in the AHI in male patients who are moderately overweight [497]. Reference has there-fore been made to the positive effects of weight reduction in overview works and meta-analyses [12, 46, 183, 404]. In the interim period, randomized, controlled studies have also been published which compare various weight reduction inter-ventions (e.g., intensive diet-based mea-sures with low calorie liquid food with or without a program for increased physi-cal activity or to modify the lifestyle) with control treatment [147, 219, 447]. These intensive weight reduction pro-grams led to an improvement in the OSA both subjectively and objectively and the likelihood of successful treatment was higher than that of the control group. While there is therefore plenty of evi-dence of the positive effects of successful weight reduction, the fundamental lim-itations in terms of treatment remain. The unclear prospects of the success of long-term, stable weight reduction, the fact that substantial conservative weight



reduction requires a high degree of per-sonal effort and commitment which can-not be provided with any degree of regu-larity outside of studies and the fact that weight reduction in many cases merely results in an improvement rather than an elimination of the OSA are all problem-atic elements.

Intensive measures to ensure con-servative reduction of the body weight should however be recommended to all patients with excess weight as a concom-itant treatment measure. This is consis-tent with the recommendations of oth-er specialist associations and societies [131, 367, 375].

5.20.3 Operative weight reductionBariatric surgery has become increas-ingly common in the past few years and the indications for operations to reduce weight have gradually applied to lower and lower BMI values. The weight re-duction associated with bariatric sur-gery generally leads to a reduction in the intensity of the respiratory disorder in patients with concomitant OSA [322]. Reviews and meta-analyses have been able to show the positive effects of bar-iatric surgery on OSA [72, 171, 398]. Despite the documented effect on AHI, for example, many patients still have an OSA which requires treatment even af-ter bariatric surgery, so corresponding polysomnographic controls are neces-sary [171]. In a randomized study, the superiority of operative weight reduc-tion over conservative weight reduction in terms of the weight loss was able to be demonstrated. The reduction in the AHI was greater but the difference was not statistically significant [124].

The indication for bariatric surgery is generally not made solely on the ba-sis of the OSA and requires a differ-entiated assessment of the obesity and the individual comorbid disorders. Specialized facilities are therefore the only ones qualified to identify the indi-cation. A recommendation for bariatric surgery in general or specific operative techniques can therefore not form part of this guideline. If a morbidly obese pa-tient has an OSA as a concomitant dis-order, this should be taken into account when identifying the indication. A signif-

icant improvement in the sleep-related respiratory disorder can be expected as a result of the operation.

Recommendation – Measures to reduce body weight should be recommended to all patients with excess weight as a concomitant treatment measure (A).

5.20.4 Lower jaw bracesTreatment with lower jaw braces (Syn-onyms: oral appliance [OA], mandibular advancement device [MAD], mandib-ular repositioning device [MRD]) im-proves night-time respiratory disorders and reduces the associated health and social impairments [131, 262, 358]. In-traoral lower jaw braces and non-inva-sive, silent, easy to transport and well tolerated.

Although the superiority of CPAP to reduce AHI in moderate to severe OSA has been proven, current studies show a comparable effectiveness in terms of daytime sleepiness, high blood pressure, cardiovascular mortality, neurocognitive function, and quality of life [262, 358]. In this context, a subjectively higher compliance of lower jaw braces com-pared to CPAP was able to be demon-strated [358].

Lower jaw braces can be used as an alternative in patients with mild to mod-erate OSAs. They can also be considered for use in by patients with severe sleep apnea who do not tolerate CPAP or re-fuse it or in whom CPAP treatment can-not be used despite all supportive mea-sures being exhausted [131, 262, 314, 358, 367, 375, 378, 379].

Characteristics of patient selection that have a positive effect on treatment success must be further evaluated in studies [277, 367]. The effectiveness de-pends on the severity of the OSA, the individual anatomy, general medical parameters and the type and adjustment of the LJB used [131, 314, 375]. The in-dication should be critically assessed in patients with an AHI > 30/h and/or a BMI > 30.

The mechanism of action of the LJB is the expansion and stabilization of the upper respiratory tract by means of a preliminary displacement of the lower jaw and the tension in the suprahyoid tissue caused by this with the effect of increasing the volume in the respiratory tract at the level of the velum, the base of the tongue, and the epiglottis. According to current study data, the LJB should be manufactured on the basis of individual impressions, anchored in a bimaxillary manner and be able to be reproduced by the person providing treatment at incre-ments of single millimeters [4, 277, 378, 379]. The LJB should ensure a secure fit and be easy to position. The optimal therapeutic position should be individ-ually determined on the basis of a pre-liminary displacement of a minimum of 50% of the maximum possible lower jaw protrusion [4, 277].

After titration, the effectiveness should be confirmed and evaluated at regular intervals by a polygraph or polysomno-graph [131, 375, 247]. LJB can be used as permanent treatment. Temporary discomfort in the teeth and the mus-cles and increased salivation may occur [375]. The clinical examination and ad-justment of LJB should be carried out by a person with expertise in dentistry and sleep medicine [131, 158, 378, 379]. Pos-sible side effects on the stomatognath-ic system such as changes in the biting position and the tooth position should be considered and evaluated in advance and during treatment with the patient in addition to the medical check-up exam-inations by a dentist specializing in sleep medicine [131, 158, 378, 379]. Although not previously described in scientific literature, changes in the jaw cannot be entirely ruled out.


Recommendations – LJB can be used in patients with mild to moderate obstructive sleep apnea (AHI ≤ 30/h) as an alternative to positive pressure procedures. This applies in particular to patients with a body mass index of less than 30 kg/m2 and position-dependent sleep apnea (A).

– In patients with a higher AHI and/or a BMI > 30 kg/m2, LJB can be considered if positive pressure treatment cannot be used despite all supportive measures having been exhausted (C).

– The adjustment of LJB should be carried out with dental and sleep medicine expertise (A).

– The effect of treatment with LJB should be checked by doctors qualified in sleep medicine on a regular basis, for example once a year (A).

5.20.5 Treatment with medicationThe data on treatment of OSA with med-ication is inconsistent and the evaluation is more difficult. A distinction should be made between the treatment of an underlying disease with medication and the possible effects on an OSA caused or made once by this underlying disease and the treatment of an OSA with medi-cation, regardless of the existence of oth-er diseases. Positive effects on individual aspects of obstructive sleep apnea during treatment of an underlying disease were able to be identified in selected studies. In this context, reference is made, for example, the treatment of obesity [124] with medication or the treatment of al-lergic rhinitis with fluticasone propio-nate nasal spray [232].

However, there is no convincing ev-idence of efficacy on the treatment of OSA itself with medication, [88, 284, 305, 422], and the data is heterogeneous. No list has been prepared of individual studies which are available for individual preparations and as RCTs. This also ap-plies to the tabular overview.

It is therefore not possible to make a recommendation for the treatment of OSA with medication. This is consistent with the recommendations of other spe-cialist associations and societies [131, 367, 375].

Recommendation – Treatment of OSA with medication cannot be recommended (A).

5.20.6 Treatment with medication in patients with residual daytime sleepiness receiving CPAP treatmentThere are only very few, mostly retro-spective investigations of the prevalence of this clinical picture. An average of around 10% of all CPAP patients suf-fer from persistent daytime sleepiness despite effective CPAP treatment once all possible causes such as insufficient use, leakages, other sleep disorders, and other organic or psychological causes of daytime sleepiness have been ruled out [157]. To date, no predictors of the occurrence of persistent sleepiness in patients being treated with CPAP have been able to be identified.

In seven placebo-controlled studies, 1,023 patients were treated with 200 or 400 mg of modafinil or armodafinil. The results showed a significant, clinical-ly relevant yet moderate improvement in daytime sleepiness in subjective and objective parameters compared to a pla-cebo. Relevant undesirable effects, in particular an increase in arterial blood pressure, were not observed, so use was recommended [200, 254].

In late 2010, the European Medicines Agency withdrew authorization for modafinil for the treatment of residu-al daytime sleepiness in patients with OSA, despite effective CPAP treatment, because there was a lack of large, pla-cebo-controlled studies and sufficient pharmacovigilance data and there were doubts about residual sleepiness as a clinical entity. The inverse hista-mine-3 receptor agonists pitolisant and MK-0249 have not yet been investigated in terms of their ability to decrease resid-ual sleepiness in patients with OSA, or at least have not been investigated suffi-ciently [188].

Recommendation – Modafinil (“off-label”) can be considered to treat residual daytime sleepiness in patients with OSA receiving CPAP treatment if other causes have been ruled out (C).

5.20.7 Method to increase muscle toneSeveral attempts have been made to use various treatment or training methods to increase muscle tone in the upper respiratory tract in order to reduce the collapsibility of the respiratory tract and treat OSA. The treatment and training methods are only comparable to a very limited extent, and there is often a lack of prospective, controlled studies with sufficient case numbers. For some meth-ods, however, there are also random-ized, controlled clinical trials, includ-ing the method for intraoral electrical stimulation [373], regularly playing a didgeridoo [363] and the use of myo-functional exercises [174]. For intraoral electrical stimulation, superiority in the RCT mentioned was only able to be proven in terms of a reduction in snor-ing, while no difference was able to be shown between the treatment groups in terms of the occurrence of respiratory events or in terms of daytime sleepiness. For playing a didgeridoo and myofunc-tional exercises, however, a significant superiority of the intervention group over the control group was able to be demonstrated both in terms of respirato-ry events (AHI) and in terms of daytime sleepiness (ESS). A review carried out of myocardial exercises with nine clinical trials in adults came to the conclusion that a reduction in AHI of approximate-ly 50% can be achieved through the ex-ercises [81]. However, the reliability of the data is often limited because of the often small treatment groups and the short follow-up periods. Electrical sur-face stimulation to increase muscle tone is therefore not able to be recommended. Non-electrical methods such as the play-ing of a didgeridoo and myofunctional exercises cannot be recommended as the sole treatment of OSA on the basis of the study data available to date, but they can be considered in individual cases. An improvement in respiratory disorders and symptoms is possible provided the non-electrical methods are used by the patient on a regular basis.



Recommendations – Electrical surface stimulation to increase muscle tone should not be carried out (B).

– Non-electric procedures and myofunctional exercises can be considered in individual cases (B).

5.20.8 Treatment with oxygenThe use of night-time treatment with ox-ygen to prevent or improve desaturation associated with the respiratory events has been investigated in numerous con-trolled and uncontrolled treatment stud-ies. Comparisons are generally either made between treatment with O2 and control treatment with ambient air or between O2 and CPAP treatment. In all of the comparative randomized and co-hort studies, in all cases a higher average oxygen saturation was able to be deter-mined, and in the majority of the stud-ies, a minimally lower number of respi-ratory events was able to be determined in patients receiving night-time oxygen treatment in comparison with ambient air [6, 58, 151, 166, 230, 243, 360, 421].

In the randomized studies, which compared the effects of the adminis-tration of O2 with CPAP treatment, no difference was identified in terms of the average night-time oxygen saturation, but a significant superiority in terms of AHI was observed in the CPAP group [39, 263, 267, 300, 323, 357]. The supe-riority of treatment with O2 compared to ambient air in terms of the parameters mentioned and CPAP treatment com-pared to the administration of O2 was able to be confirmed in a meta-analysis [295].

Treatment with oxygen alone in pa-tients with obstructive sleep apnea can therefore improve the night-time oxy-gen saturation significantly, but is infe-rior to CPAP treatment because of the lack of or minimal effect on the number of respiratory events. The administra-tion of oxygen alone at night further-more potentially brings with it the right of prolonging respiratory events and in-creasing hypercapnias. To date, no con-vincing effects in terms of the daytime symptoms were able to be demonstrated in OSA patients.

Recommendation – Night-time oxygen treatment alone should not be used to treat OSA (A).

5.20.9 Positional therapyThe position-dependency of the respi-ratory events in patients with OSA is a known phenomenon. Lying in a supine position appears to be the most vulner-able sleeping position in this group of patients. Depending on the manifes-tation, a distinction is made between a supine position-based and a supine position-dependent OSA, with various definitions being used for this. The term position-dependent (“positional”) OSA is often used if the AHI in a supine po-sition is more than twice as high as in other sleeping positions. Preventing the patient from lying in the supine posi-tion has a fundamental therapeutic po-tential in patients who only experience respiratory disorders when in the supine position, and those in whom the AHI is lower or does not require treatment in other body positions. Methods or tools used to prevent the patient from lying in a supine position vary greatly in their structure and in the reliability in terms of preventing the patient lying in a su-pine position. As with all other tools, the problem here is that of compliance. The success of any measures to treat the posi-tion of patients with OSA should funda-mentally be examined objectively.

Three randomized studies and a me-ta-analysis which builds on these are available for a comparison between po-sition-based and CPAP treatment. The study by [420] compared one-month treatment using a modified “tennis ball” method with CPAP treatment. A reduc-tion in the AHI was able to be achieved in both groups. CPAP treatment was found to be superior in terms of reduc-tion in the AHI and improvement in average oxygen saturation, while com-pliance and the side effect profile were more favorable in the positional therapy group. There was no significant differ-ence in terms of the parameters of day-time sleepiness and quality of life.

As far back as 1999 Jokic et al. were able to provide evidence of a significant reduction in the subjective and objec-tive target parameters in both treatment

arms using a similar tool [222]. CPAP treatment proved to be superior to po-sitional therapy in terms of reduction in AHI and improvement in the mini-mum oxygen saturation, but there were no differences in terms of the daytime sleepiness and the vigilance or in terms of psychomotor test procedure.

Permut et al. used a type of plas-tic block that was strapped to the back using a belt, the aim of which was to prevent the patient from lying in a su-pine position in a more reliable manner than the “tennis ball” method [355]. In their collective they were able to identi-fy a significant reduction in the AHI in both groups, with CPAP treatment being significantly superior to the positional therapy group In terms of the percentage of patients whose AHI was able to be re-duced to a value of less than 5, however, both treatments were equal.

A meta-analysis of the three studies mentioned comes to the conclusion that CPAP treatment is superior to positional therapy in terms of reduction of the AHI and improvement in night-time oxygen saturation but that the remaining sleep medicine value investigated did not vary between the groups and the clinical rel-evance of the slight advantage in terms of respiratory parameters is questionable [190].

Recommendation – For patients with mild to moderate position-dependent OSA, treatment to prevent them lying in a supine position can be considered if other treatment recommended in this guideline is not possible or is not sufficiently well tolerated (C).


5.20.10 Surgical treatmentIn surgical treatment, a distinction is made between resective and non-re-sective operation methods and the procedures to shift the facial skeleton (osteotomies). A further procedure is tracheotomy, which reliably removes the OSA [80] but should be seen as the last resort. Operations to improve nasal breathing should be taken into account in another context as they generally do not improve the respiratory disorder but do reduce daytime sleepiness, snoring and the CPAP pressure needed and im-prove general acceptance of CPAP treat-ment [261].

Resective procedures include all sur-gical measures which aim to remedy or correct obstructions or obstacles to the airflow through resection in the re-gion of the upper respiratory tract. In a randomized study with a high-quali-ty method uvulopalatopharyngoplasty (UPPP) was highly significantly supe-rior to just waiting over a period of six months with a reduction of the AHI of 60% compared to 11% and a decrease in the > 50% to an AHI < 20 in 59% vs. 6% [70]. The probability of success increas-es as the side of the tonsils increases and the size of the tongue decreases [260]. In the case of patients with very large ton-sils, simply removing the tonsils can be sensible in individual cases.

Overall, there is an increase perioper-ative and postoperative risk associated with resective procedures, which how-ever has decreased significantly in more recent studies [82]. There is no certainty regarding whether the initial effect of operative measures decreases over time because of inconsistent data [69, 459]. Lasting side effects such as changes in the voice and swallowing problems are possible [82]. A tonsillectomy and uvu-lopalatopharyngoplasty can be recom-mended to patients with mild to mod-erate OSA if they have suitable anatomy, particularly if they do not tolerate CPAP treatment, as they are superior to a lack of treatment with acceptable side effects. The significance of the many modifica-tions of the UPPP (e.g., uvula flap, z pala-toplasty, relocation pharyngoplasty, han-UPPP, lateral pharyngoplasty, expansion sphincteroplasty) is as yet unclear and

corresponding studies should be carried out [439]. Laser-assisted uvulopalato-plasty (LAUP) leads to a reduction in the AHI to under 10/h in just 50% of cases and there are postoperative side effects in up to 60% of cases [483]. Similar re-sults were achieved in the long term over a period of an average of 11 years [165]. LAUP is therefore not recommended.

Non-resective procedures aim to re-duce the collapsibility of the pharyngeal respiratory tract by moving pharyngeal structures or inserting implants. There are data with sufficient evidence for soft palate implants, radio frequency surgery in the soft palate and the base of the tongue, hyoid suspension, tongue sus-pension and stimulation therapy of the upper respiratory tract.

As minimally invasive operations, ra-dio frequency ablation (RFA) and soft palate implants are more tolerable than the resective operations [99, 136]. To date, evidence has only been provid-ed of a 31%, short-term reduction in sleepiness in patients receiving RFA us-ing the Epworth Sleepiness Scale (ESS) [136]. While there is good evidence to show that RFA of the soft palate reduces snoring in patients with primary snoring [31], no effect in patients with OSA was able to be shown following a single ses-sion of treatment in a placebo-controlled study [32]. To date, there has been no confirmed evidence of an effective effect of radio frequency treatment of the base of the tongue with the exception of in-dividual studies [482]. A change in taste was not able to be identified either sub-jectively or objectively [132]. For soft palate implants, considerable evidence has been provided of a slight to moder-ate efficacy in terms of the reduction of snoring and the OSA, with an extrusion being reported in almost 10% of patients [99, 285].

A further treatment approach is stim-ulation of the hypoglossal nerve, re-sulting in the genioglossus nerve being activated in a manner in which the respi-ratory tract is considerably more open. The aim of this is to remedy a functional disorder of the muscles in the respira-tory tract in patients with OSA directly. The treatment is used in patients with moderate to severe OSA. According to

feasibility studies, a multicenter study with randomized withdrawal of treat-ment after 12 months was recently pub-lished. In this study, the stimulation of the hypoglossal nerve synchronously with breathing had a lasting treatment ef-fect in patients with moderate to severe OSA and the respiratory disorder reap-peared to the original extent after treat-ment was withdrawn [434]. The morbid-ity of the procedure is low. The method can be considered if CPAP treatment is not available or is refused.

What is known as multi-level surgery is currently being propagated to a great extent, but here too there are a lack of data providing evidence of success con-firmed by controlled studies, although a relatively constant response rate of 50-70% (weighted mean 66.4%) is being reported in all case series [264]. The re-sponse rates do not differ if tongue sus-pension is used for the retrolingual oper-ation instead of the most commonly used procedure of genioglossus advancement with or without hyoid suspension [178]. In a randomized study Babadamez et al. [30] were not able to show any signifi-cant differences between the groups in three different tongue resections each in combination with a UPPP [30]. The re-sponse rate may decrease over a period of five years [196].

Other procedures which have been validated except for the small amount of evidence include hyoid suspension, midline glossectomy (cold surgery, laser, robot-assisted), and linguoplasty [152, 483]. The following methods are not recommended for obstructive sleep ap-nea which requires treatment: Laser-as-sisted soft palate surgery, uvula capping, “cautery-assisted palatal stiffening oper-ation,” “injection snoreplasty,” radio fre-quency surgery in the tonsils, “transpal-atal advancement pharyngoplasty” and isolated genioglossus advancement.



Osteotomies to enable a preliminary displacement of the upper and lower jaw (maxillo-mandibular advancement) enlarge the pharyngeal respiratory tract, thereby increasing the pharyngeal mus-cle tone. Both effects reduce the collaps-ibility of the pharynx synergistically. They can be a highly effective form of treatment for OSA in patients with con-genital abnormalities (including Pierre Robin sequence, Crouzon syndrome, Apert syndrome) or in patients with an-atomical abnormalities of the upper re-spiratory tract such as microgenia (small lower jaw), mandibular retrognathia (the lower jaw is in a position that is further backward relative to the front base of the skull) and the associated narrow sagit-tal structure of the cranium, but also in normognathian patients. A preliminary displacement of 10 mm is deemed to be necessary. In a meta-analysis of 627 pa-tients a substantial improvement in the AHI of 86% was indicated; and AHI < 5 is achieved in 43.2% of cases [194]. The treatment effect remained unchanged in the series with long-term data after more than 2 years. No difference in the efficacy compared to ventilation thera-py was seen in either cohort studies or in a randomized study [359, 453]. Tran-sient paresthesias (changes in sense) of the second and/or third trigeminal nerve branches are often indicated as undesir-able effects [194], although evidence of these was only still able to be found in 14% of patients after 12 months. Aes-thetic effects are classified as either pos-itive of neutral by more than 90% of pa-tients [359].

In general, surgical forms of treatment are difficult to evaluate at a high level of evidence as the operative techniques are selected on an individual basis de-pending on the anatomy and function of the upper respiratory tract and are correspondingly difficult to standard-ize and only a few centers offer the full range of treatments [91]. Blinding is of course not possible with many operative techniques. However, there are increas-ing numbers of controlled and random-ized studies which compare the surgical treatment methods with CPAP, place-bo or simply waiting. However, to date there have only been a small number

of studies with high levels of evidence for each type of operation. The results therefore have to be checked in further studies. Data on long-term effects are available for osteotomies, tracheotomy, laser-assisted uvulopalatoplasty (LAUP), uvulopalatopharyngoplasty (UPPP) and multi-level surgery. No statements about the long-term effects can be made for practically any of the other surgi-cal procedures. The effect of operative treatment methods on cardiovascular parameters and daytime symptoms has not yet been tested in qualitative stud-ies. However, cohort studies have shown a positive effect. In comparison to a con-trol group only treated with behavioral recommendations, daytime sleepiness was significantly lower three years after surgical treatment [395]; compared to a healthy control group, a normalization of the serum leptin and nitrogen monox-ide values and the endothelium-depen-dent vasodilation was successfully able to be achieved three months after suc-cessful UPPP [255, 265]; TNF-a and IL-6 as inflammatory markers were signifi-cantly reduced three months after UPPP with a septoplasty compared to a healthy control group [107]. In an epidemio-logical cohort study of 444 patients, the mortality in patients with OSA was able to be reduced significantly and compa-rably with CPAP treatment as a result of UPPP compared to an untreated control group [279].

If surgical procedures are used in patients with OSA, they should not be carried out without a sleep medicine di-agnostics procedure. The predictors for the success of an operation and therefore the selection criteria when choosing ap-propriate surgical treatment in patients with OSA have to be developed separate-ly for each intervention. They sometimes vary considerably and are not present for all operations. Only obesity is a neg-ative predictor, but with different and in some cases unknown threshold values depending on the intervention. It is not possible to predict the complete remov-al of an OSA by means of an operation on an individual basis. The resective and non-resective procedures are in princi-ple not without risk [150, 264]. In gener-al, therefore, with the exception of oste-

otomies and where the patient’s anatomy is suitable tonsillectomy and uvulopal-atopharyngoplasty, they are not to be recommended as primary treatment measures [439]. In individual cases, the minimally invasive procedures may have a threshold value. In the case of anatom-ical abnormalities such as hyperplasia of the adenoids or tonsils or welling caused by inflammation or neoplasias in the pharynx, it can be necessary to wait and see what the effect of the treatment nec-essary is on the extent of the OSA in the individual case.

Recommendations – Operations to improve nasal breathing should be considered in patients with impeded nasal breathing and resulting CPAP intolerance.

– A tonsillectomy should be carried out in patients with tonsillar hyperplasia and oropharyngeal obstruction, particularly if other treatment (CPAP, MAD) is not possible or this is not sufficiently well tolerated (A). If necessary, they can be combined with a uvulopalatopharyngoplasty (C).

– Neural stimulation of the hypoglossal nerve can be used in patients who do not have any anatomical abnormalities and who have moderate to severe OSA if positive pressure therapy cannot be used under the above-mentioned conditions. It should only be used in patients with CPAP intolerance or ineffectiveness with an AHI of 15-50/h and an obesity severity level of ≤ I if no concentric obstruction has been documented in the sleep endoscopy (B).

– In patients with corresponding anatomical results with a small lower jaw and a narrow cranial structure (distance between the base of the tongue and the back of the throat, also known as the posterior airway space PAS < 10 mm in the teleradiograph image), a preliminary displacement of the upper and/or lower jaw (bimaxillary advancement) should be considered, particularly if other treatment (CPAP, LJB) is not possible or this is not sufficiently well tolerated (A).


– Operations on the soft palate which resect the muscles are not to be recommended (A).

– A number of further operative procedures can be sensible depending on the anatomical results in individual cases (C).

Note see Tab. B.10 and B.11

6. Central sleep apnea syndromeThis group of sleep-related respiratory disorders is characterized by a disorder of breathing regulation and/or the trans-fer of the impulses to the thoracic skele-ton system. In central sleep apnea (CSA) there is no airflow despite an open or passively collapsed upper respiratory tract, so no effective ventilation occurs. There is a lack of inspiratory breath-ing effort for the entire duration of the suspended airflow [48, 198]. In patients with central hypopneas, there is a de-crease in breathing effort and breathing flow. In contrast to obstructive respirato-ry disorders, there are no signs of para-doxical breathing [377].

There is no agreement in the litera-ture about the number of central events which are still considered to be normal. In uninterrupted sleep, central apne-as can occur in the transition between being asleep and awake without having a pathological significance. This fact must be taken into account when diag-nosing central events.

In CSA, a distinction is made between hypercapnic and non-hypercapnic forms. Hypercapnic respiratory disor-ders are characterized by a decrease in the breathing impetus or the transfer or implementation of the impulses on the breathing muscles (neuromuscu-lar diseases, opiate-induced CSA). In non-hypercapnic forms of CPA, there is mostly an increased breathing impetus and/or an increased chemosensitivity (CSA at altitudes, CSA with or without Cheyne-Stokes respiration [CSR] in pa-tients with cardiovascular/cerebrovascu-lar diseases and kidney failure). In this group, CSAs in patients with heart fail-ure, with nephrological and neurological diseases (including in the initial phase after a stroke) or under opioids and oth-

er medications which have a depressive effect on breathing are of particular epi-demiological significance as the primary form.

The forms of central sleep apnea in adults are described in this chapter.

6.1 Central sleep apnea with Cheyne-Stokes respiration

CSA in combination with CSR is char-acterized by a crescendo/decrescendo breathing pattern of the tidal volume with central sleep apnea or hypopnea during the nadir of the breathing efforts [425]. Three successive cycles of this type are deemed to be CSR if the cycle length (length of the apnea/hypopnea plus the length of the ventilation/hyper-ventilation phase) is at least 40 s (typ-ically 45-90 s) and there are 5 or more central apneas of hypopneas per hour of sleep with a crescendo/decrescendo breathing pattern over a recording dura-tion of at least two hours [48, 198]. This alternative occurrence of hyperventila-tion and hypoventilation causes fluctua-tions in the arterial oxygen and carbon dioxide levels. The hypoxemias caused by apnea and hypoventilation in com-bination with the increased breathing effort during hyperventilation can lead to an increased number of arousals and therefore lead to fluctuations in the heart rate and the blood pressure and to frag-mented sleep [65].

6.1.1 Main findingsMost patients with CSA and CSR have heart failure with either restricted or maintained systolic function. CSA with CSR can also occur in patients with chronic kidney failure [242] and in pa-tients in the early phase after a stroke [320, 411]. Consequences of CSA in combination with CSR can include day-time sleepiness, tiredness, night-time dyspnea, nycturia and insomnia [25, 55, 205]. These symptoms can be further en-hanced by the underlying disease.

6.1.2 EpidemiologyIn patients with heart failure and a re-duced left ventricular ejection fraction (HFrEF), the occurrence of CSA with CSR (apnea-hypopnea index ≥ 15/h) was reported in 21-37% of the patients. The more severe the HFrEF, the more often a CSA occurs. Women are affect-ed significantly less commonly than men [208, 416, 424, 500]. Advances in the treatment of heart failure have not significantly changed the prevalence of CSA with CSR in HFrEF patients [500]. In this group of patients CSA with CSR is occurring increasingly in men in the age group > 60 and in people who have atrial fibrillation and an arterial pCO2 < 38 mm Hg during the day [205, 416].

Approximately 18 to 30% of patients with heart failure but retained left ven-tricular function (HFpEF) have CSA with CSR [52, 94, 189, 405]. The percent-age of central apneas and hypopneas as a ratio to obstructive apneas and hypo-pneas increases as the restriction of the diastolic function increases [457].



In patients who have had a stroke the CSA with CSR varies considerably (3% and 72%) [41, 61, 68, 221, 340, 411]. CSA with CSR can occur particularly frequently in patients in the early phase after a stroke (up to 72%) [340, 411]. In this group of patients, other than the ex-tent of the stroke the CSA with CSR also depends on an underlying heart failure [320, 411]. These diseases are often com-bined respiratory disorder with phases of central breathing events during NREM sleep alternating with obstructive events during REM sleep or in the supine po-sition.

6.1.3 DiagnosisCSA with CSR is diagnosed if the diag-nosis criteria A or B, C and D and met (ICSD-3): Occurrence of one or more of the following symptoms: Daytime sleep-iness, disorders of falling asleep and sleeping through the night, waking up frequently in the night, waking up with shortness of breath, snoring or pauses in breathing observed.A. Heart failure, atrial fibrillation/

flutter or a neurological disease.B. In polysomnography (diagnosis of

titration of treatment with positive airway pressure), ≥ 5 central apneas and/or hypopneas per hour of sleep [48]. > 50% of all apneas and hypopneas are classified as central and there is a CSR breathing pattern [48].

C. The disease cannot be explained by another sleep disorder or medications (e.g., opioids).

D. The differentiation of central from obstructive apneas and hypopneas is possible by measuring the breathing effort using inductive plethysmography (in the case of any doubt by measuring the pressure in the esophagus) and by measuring the airflow using a nasal dynamic pressure sensor [48, 102, 198, 321, 377, 428, 471]. The semi-quantitative measurement of the airflow using an oronasal thermistor is much less sensitive [321].

6.1.4 TreatmentThe treatment of the underlying disease, for example heart failure, is an import-ant component of treatment of CSA with CSR. This measure can improve or even remove the CSA with CSR [27, 273, 327, 418, 424].

6.1.5 Respiratory stimulants and CO2

Respiratory stimulants such as theophyl-line [209] and acetazolamide [208, 214] or the administration of CO2 - either directly or by means of an increase in clearance volume ventilation - [231, 268] reduce the occurrence of central breath-ing events during sleep in patients with heart failure. However, these treatment approaches cannot be recommended for the treatment of CSA with CSR as there is a lack of data on long-term safety.

6.1.6 Unilateral stimulation of the phrenic nerveTreatment of a CSA with or without CSR by means of unilateral stimulation of the phrenic nerve reduces the frequency of respiratory events and the waking re-action in some patients [361, 502]. The literature research did not show any ran-domized studies of cardiovascular end-points.

6.1.7 OxygenA partial reduction of central apneas and hypopneas of 37 to 85% can be achieved in patients with a stable HFrEF treated with 2-4 liters of oxygen/minute [16, 22, 27, 149, 180, 206, 240, 268, 399, 410, 429, 442, 444, 501]. The normalization of the oxygen saturation through the admin-istration of oxygen is associated with an increase in the PCO2 and persistent periodic breathing [268]. Without an oxygen saturation, these persistent re-spiratory events are often not classified as hypopnea [48]. Both randomized and non-randomized studies show no signif-icant influence on left ventricular ejec-tion fraction [16, 22, 501].

6.1.8 Continuous Positive Airway PressureContinuous Positive Airway Pressure can lead to a variable reduction in cen-tral apneas and hypopneas of approxi-mately 50%, an improvement in the left ventricular ejection fraction [27, 66, 312, 356] and an improvement in the quality of life [312, 356]. Furthermore, CPAP treatment leads to a reduction in sym-pathicus activation and biomarkers of heart failure (e.g., Brain Natriuretic Pe-tide, BNP) in patients with heart failure [23, 27, 66, 116, 170, 207, 241, 312, 352, 356, 417, 442, 443, 492]. In this group of patients, CPAP does not lead to a sig-nificant improvement in the quality of sleep [393]. In a randomized long-term study, CPAP treatment did not improve transplant-free survival in patients with HFrEF and CSA with CSR [66]. A post-hoc analysis of the study, patients with HFrEF whose central apneas and hypo-pneas were suppressed to less than 15/h showed a significant increase in left ven-tricular ejection fraction and improved transplant-free survival [23]. HFrEF patients with persistent CSA with CSR receiving CPAP treatment have an ele-vated mortality rate [23]. CPAP treat-ment should be stopped in patients with persistent CSA being treated with CPAP [23]. Hemodynamic side effects can occur when starting positive airway pressure in patients with severe HFrEF (e.g., New York Heart Association class III/IV and/or average arterial pressure < 60 mm Hg) [24, 329, 402]. CPAP can therefore be considered in some patients with symptomatic moderate to severe CSA and HFrEF (LVEF ≤ 45%). This applies to patients with severe daytime symptoms, an additional obstructive component of sleep apnea and a signifi-cant reduction in the apneas and hypo-pneas with CPAP.

6.1.9 Bilevel Positive Airway PressureTreatment with Bilevel Positive Airway Pressure (Bilevel-PAP) with no back-ground frequency does not offer any advantages over treatment with CPAP in patients with HFrEF in terms of the suppression of central respiratory events [235, 319]. Control of the CSA with CSR


is achieved in individual cases with pres-sure-controlled ventilation procedures with a background frequency (Bilev-el-PAP ST treatment; [125, 140, 226, 442, 475, 476]). While CPAP and adap-tive servo ventilation (ASV) lead to an increase in the arteriocapillary PCO2 (by 4.3 and 3.6 mm Hg) in HFrEF patients with hypocapnic CSA with CSR (PCO2 ≤ 33.6 mm Hg), Bilevel-PAP ST (set breathing frequency 2 beats/minute less than the spontaneous breathing rate) does not change the PCO2 [442]. With Bilevel-PAP ST there is therefore a con-tinuation of the hyperventilation [442]. In a randomized study with HFrEF pa-tients with CSA, the Bilevel-PAP ST group shows a similar increase in left ventricular ejection fraction (26% to 31%, P < 0.01) as the group with adap-tive servo ventilation (25–27%) [140].

6.1.10 Adaptive servo ventilationAdaptive servo ventilation (ASV) sup-presses central apnea and hypopneas more effectively than oxygen, CPAP or Bilevel-PAP ST [27, 408, 442]. In a me-ta-analysis, ASV reduced the AHI by 31 [95% confidence interval -25 to -36]/h and by 12-23/h more in comparison with CPAP treatment [27]. ASV normal-izes the PCO2 in patients with HFrEF with hypocapnic CSA [442]. Adaptive ventilation procedures are also effective in patients with the combination of cen-tral sleep apnea and obstructive sleep apnea [8, 374].

A meta-analysis investigated the ef-fects of treatment with ASV on heart function in patients with HFrEF and CSA with CSR [408]. Six non-random-ized [182, 184, 238, 239, 328, 493] and four randomized studies [140, 228, 352, 376] were included in the analysis. ASV improved the left ventricular ejection fraction and the distance walked in six minutes. The majority of the random-ized studies showed that ASV treatment did not improve the left ventricular ejec-tion fraction compared to a control in-tervention (treatment with medication and treatment using a device of the heart failure, CPAP or Bilevel-PAP ST) [25, 140, 228, 352, 376]. Randomized stud-ies consistently show that ASV reduces the Brain Natriuretic Peptide (BNP) or

NT-proBNP in patients with HFrEF and CSA with CSR [25, 228, 352, 376].

Most long-term observational studies of patients with HFrEF with and with-out CSA indicate that CSA with/without CSR is an independent predictor of in-creased mortality [95, 113, 181, 210, 216, 252, 330, 387, 417, 499]. One cause of the mortality risk could be the increased fre-quency of malignant ventricular rhythm disorders in patients with HFrEF and CSA [53]. In clinical registers, HFrEF patients with severe, treated CSA (CPAP or ASV) have a lower mortality risk [113, 216] and risk of ventricular arrhythmias [56] than patients with severe, untreated CSA.

The effects of ASV treatment in pa-tients with severe, chronic HFrEF (pre-dominantly New York Heart Association class III, LVEF < 45%) and CSA on the long-term prognosis were investigated in a large, randomized study [109]. The ASV group showed a 28% increased risk of mortality compared to the control group [110]. The risk of death as a result of a cardiovascular disease was elevated by 34% in the ASV group [110]. The use of ASV treatment is therefore contra-indicated in patients with symptomatic heart failure (NYHA class II-IV) and reduced left ventricular ejection fraction (LVEF ≤ 45%) and moderate to severe CSA. This means that the left ventric-ular ejection fraction must be deter-mined before starting ASV treatment in patients with CSA. Mechanisms which can contribute to the mortality risk in patients with HFrEF (LVEF < 45%) and CSA as a result of ASV have not yet been clearly identified.

6.2 Central sleep apnea without Cheyne-Stokes respiration

In this case, the central sleep apnea oc-curs as a secondary effect in patients with underlying neurological or internal diseases. Demyelinating, inflammatory and tumor-based diseases of the central nervous system and disorders of the au-tonomous nervous system such as dia-betes mellitus and heart and kidney fail-ure can cause this type of central sleep apnea.

6.2.1 Main findingsThe symptoms of the respective under-lying disease and the consequences of sleep fragmentation can be identified. These may be both daytime sleepiness and insomnia.

6.2.2 DiagnosisCentral apneas occur in light and REM sleep; the increased occurrence of arous-als can lead to sleep fragmentation.

6.2.3 TreatmentThe focus is on treatment of the under-lying disease. There are no systematic examinations of the treatment effects in this form of central sleep apnea.

6.3 Central sleep apnea with periodic breathing at a high altitude

The definition of high altitude periodic breathing (HAPB) is not standardized, so it is difficult to compare studies. There is often a periodical pattern with an al-ternation between hyperventilation and hypoventilation leading to apnea. An increase in hypoxia and a worsening of existing central sleep apnea at high alti-tude can occur in patients with existing sleep apnea.

6.3.1 Main findingsTiredness, exhaustion, and shortness of breath.

Periodic breathing occurs from a clin-ical perspective. Diagnosis using instru-ments is mostly not possible.

6.3.2 TreatmentSafe treatment involves immediate

descent [324, 365], with heights of less than 2500 o 4000 meters needing to be reached. In healthy patients, acetazol-amide can reduce HAPB [142]. There are also positive reports of dexamethasone in patients who are sensitive to high-alti-tude pulmonary edema [326]. These can be avoided in part through the use of ac-etazolamide and predominantly avoided using a combination of acetazolamide and auto-CPAP [253]. Tab. B.14 pro-vides information about studies on high altitude periodic breathing.



6.4 Centrals sleep apnea caused by medication, drugs or substances

Data on the impairment of breathing are primarily available for opiates, and these are mostly case series and retrospective studies. Most investigations look at the chronic use of opiates for pain therapy of methadone programs for heroin addicts. Opiates affect central breathing regula-tion, muscle activity in the upper respi-ratory tract and chemosensitivity [251]. In addition to the characteristic type of atactic breathing, opiates and other sub-stances which have a depressive effect on breathing (e.g., sodium oxybate) can lead to obstructive hypopneas, a de-crease in breathing rate, central apneas, prolonged hypoxias or periodic breath-ing even in the case of chronic use [134, 161, 302, 441, 461, 462, 469]. This applies in particular to the combination of seda-tive substances and those with a depres-sive effect on breathing [161].

6.4.1 Main findingsThe consequences of sleep fragmenta-tion can be both daytime sleepiness and insomnia.

6.4.2 TreatmentTo date there are minimal data on opti-mal treatment. In any case, it is neces-sary to check whether discontinuation or reduction of the opiates is medically possible and reasonable [117]. If the re-spiratory disorders continued, positive pressure methods can be used. There are different results from case series and non-randomized studies. CPAP treat-ment can only be promising in individ-ual cases where there are obstructions in the upper respiratory tract. Adaptive servo ventilation and non-invasive ven-tilation can be used in patients with an impairment of chemosensitivity and breathing regulation [7, 135, 211, 215, 372].

6.5 Primary central sleep apnea

Owing to the unknown etiology, it is known as idiopathic sleep apnea and is not the result of Cheyne-Stokes respira-tion (ICSD-3).

6.5.1 Main findingsThe main element is repeatedly waking up at night as a result of the cessation of breathing, often accompanied by short-ness of breath. The consequences of sleep fragmentation can be both daytime sleepiness and insomnia [64].

6.5.2 EpidemiologyThe rare clinical picture mostly occurs in middle-aged people, possibly more com-monly in men than in women [389]. No statements on prevalence are available.

6.5.3 TreatmentClinical case descriptions report the suc-cessful use of invasive and non-invasive ventilation procedures during sleep. No controlled studies on the effectiveness of these procedures are available. There is largely a lack of clarity regarding the demographic and epidemiological data and data on the treatment effects of the ventilation procedures used.

– Primary central sleep apnea in premature children (in pediatric guideline)

– Primary central sleep apnea in premature infants (in pediatric guideline)

6.6 Central sleep apnea as a consequence of treatment

Central sleep apnea which occurs in patients who predominantly have OSA (without treatment) receiving treatment with CPAP, APAP or Bilevel which is a new development should be called central sleep apnea as a consequence of treatment. The term central sleep apnea as a consequence of treatment should only be used to describe CSA which per-sists when PAP treatment is used.

Furthermore, the avoidable causes of CSA should be ruled out during treat-ment with PAP. This includes elevated treatment pressure, apneas following hy-perventilation, apneas following arousal, incorrect classification of obstructive and central hypopneas, impaired respi-ratory breathing [311]. Incorrect diag-noses can also occur as a result of the different division of obstructive and cen-tral respiratory disorders over the night in the case of split-night measurements. Starting treatment with positive pressure but also with other methods can lead to the occurrence of CSA in the initial phase as the individual CO2 sensitivi-ty and apnea limit have to be gradually adjusted to the new situation [121, 250, 256, 377]. The pathophysiology, the sig-nificance in terms of quality of life and the prognosis of CSA as a consequence of treatment have not yet been the sub-ject of scientific investigation.

6.6.1 Main findingsNo specific symptoms are known. Night-time shortness of breath and uninten-tional removal of the mask can occur more frequently than in OSA [366].

6.6.2 EpidemiologyCSA as a consequence of treatment occurs rarely in patients with healthy hearts with OSA in the night of diag-nosis during treatment with PAP (1%) [473]. Where patients have underlying heart failure CSA occurs more common-ly as a consequence of treatment (18%) [54].

6.6.3 DiagnosisPolysomnography during treatment with PAP.


6.6.4 TreatmentTo date there are date from a small num-ber of randomized and some retrospec-tive and non-randomized investigations. In these, adaptive servo ventilation was significantly superior to continued CPAP treatment or non-invasive venti-lation with Bilevel ST in suppressing the central respiratory disorders [71, 120, 249]. Like CPAP and APAP, Bilevel can even increase central respiratory disor-ders [8, 219, 299, 306, 308]. However, the clinical significance still needs to be developed.

Recommendations – Central sleep apnea – CSA without CSR – CSA with CSR – In patients with central sleep apnea, where possible the internal medicine, pharmacological and neurological causes should be clarified (A).

– Guideline-compliant treatment of the heart failure should be carried out to treat central sleep apnea in patients with heart failure and reduced left-ventricular function (HFrEF).

HFpEF – In patients with heart failure with maintained left ventricular function HFpEF (LVEF > 45%), treatment of the CSA should be carried out using CPAP or ASV (B).

– In patients with HFpEF (LVEF > 45%), treatment with oxygen can be used to treat symptomatic CSA if CPAP or where there is an indication for this ASV have failed (C).

HFrEF – Treatment with ASV should not be administered to patients with moderate to severe CSA and symptomatic HFrEF (LVEF ≤ 45%) (A).

– CPAP treatment can be considered in some patients with symptomatic moderate to severe CSA and HFrEF (LVEF ≤ 45%).

– In patients with symptomatic moderate to severe central sleep apnea and HFrEF (LVEF ≤ 45%), treatment methods on which no randomized, long-term studies have been carried

out, such as the unilateral stimulation of the phrenic nerve and O2, should only be used within the scope of prospective studies (B).

– Alternative forms of treatment such as Bilevel in spontaneous timed (ST) mode, acetazolamide of theophylline should not be used in normocapnic or hypocapnic central sleep apnea in patients with heart failure (B).

Recommendations for central sleep apnea with high altitude periodic breathing

– Acetazolamide can be recommended to decrease CSA/HAPB and to improve the night-time oxygen saturation at high altitude in healthy people (C).

– Combination treatment using acetazolamide and CPAP can be recommended to avoid the worsening of CSA/HAPB in patients with known sleep-related respiratory disorders (C).

Recommendations for centrals sleep apnea caused by medication, drugs or substances

– A reduction of the dose of the opiates should be considered in opiate-induced sleep apnea (B).

– Positive pressure procedures should be adjusted on an individual basis in patients with opiate-induced sleep apnea and their efficiency should be checked using a polysomnograph (A).

– In individual cases, positive pressure procedures and the administration of oxygen can be used in combination (C). In addition to the PSG, the introduction and control of treatment should also include a capnography (A).Recommendation on idiopathic CSA

– Treatment can be carried out using non-invasive ventilation methods or spontaneous breathing methods with a background frequency (C).

Recommendations for CSA as a consequence of treatment

– Known triggers (e.g., excessive treatment or a split night) should be excluded (A).

– In CSA that requires treatment as a consequence of treatment with normocapnia or hypocapnia, the patient should be switched to treatment with ASV (B).

See also Tab. B.12-B.17. The CSA algo-rithm is set out in Appendix C.

7. Sleep-related hypoventilation/sleep-related hypoxemiaIn contrast to ICSD-2, ICSD-3 [10] differentiates between sleep-related hypoventilation and sleep-related hy-poxemia. Within sleep-related hypoven-tilation a distinction is made between six different entities, while there is no sub-division of sleep-related hypoxemia (see Tab. B.18). According to ICSD-3, a patient has sleep-related hypoxemia if the polysomnography or the night-time pulse oximetry document an oxy-gen saturation of ≤ 88% over a period of ≥ 5 minute and the patient is not expe-riencing sleep-related hypoventilation. Sleep-related hypoxemia is generally the result of an internal or neurolog-ical disease and cannot be explained by a sleep-related respiratory disorder, although this may occur at the same time. Some patients with sleep-related hypoxemia also have hypoxemia during the day.

Owing to the clinical significance, this section looks exclusively at obesity hy-poventilation syndrome and sleep-relat-ed hypoventilation caused by a physical disease.

7.1 Obesity hypoventilation syndrome (OHS)

The following are used as diagnostic cri-teria:a. Hypercapnia (PaCO2 during the day

> 45 mm Hg)b. Body mass index (BMI) > 30 kg/m2

c. Hypoventilation is not primarily defined by another disease

In some definitions, a sleep-related re-spiratory disorder must also be present, most commonly (in 90% of cases) this is obstructive sleep apnea (OSA).



Depending on the study, the preva-lence of OHS in patients with an OSA varies between 4 and 50%; in patients with a BMI > 30 kg/m2 the development of OHS can be assumed with a frequen-cy of 10-50%.

7.1.1 Main findingsSince 90% of patients have obstruc-tive sleep apnea, OHS patients often complain of symptoms of OSA such as non-restorative sleep, daytime sleepiness and disorders of concentration. This can lead to the symptoms exclusively being attributed to OSA and the diagnosis of OHS being overlooked. In comparison with OSA patients or obese patients, OHS patients more commonly suffer from shortness of breath and present to clinical facilities more commonly with peripheral edema, pulmonary hyper-tension and pulmonary heart disease. The hospitalization rate, the morbidity and the mortality of OHS patients are all elevated compared to eucapnic patients with a BMI > 30 kg/m2. In addition to respiratory complications such as an ele-vated need for invasive ventilation in the hospital, cardiovascular sequelae such as arterial hypertension, heart failure, pul-monary heart disease and angina pecto-ris contribute to the elevated morbidity. As a result, the quality of life in patients with OHS is reduced considerably.

7.1.2 DiagnosisA blood gas analysis should be carried out in patients with a BMI > 30 kg/m2 to provide evidence of hypercapnia in the day. However, hypoventilation manifests before the full picture is achieved with hypercapnias during sleep, so a night-time determination of the PCO2 (arteri-al, capillary, transcutaneous, end-tidal) is needed in patients with a BMI> 30 kg/m2 [36, 37, 38]. A polysomnography is needed to provide evidence of the sleep-related breathing disorder.

7.1.3 TreatmentCPAP treatment alone is not sufficient in some OHS patients, so only a short-term attempt to carry out CPAP treat-ment with simultaneous transcutaneous measurement of the CO2 monitored in a sleep laboratory or a ventilation unit is

justified. If the CO2 measured transcuta-neously during the night is more than 55 mm Hg for longer than five minutes or the night-time oxygen saturation is less than 90% for longer than 10 minutes, the patient must be switched to non-inva-sive ventilation (NIV). Otherwise there should be a re-evaluation of the CPAP treatment after three months. If the pa-tient has experienced a clinical improve-ment and normocapnia, the CPAP treat-ment can be continued, if not the patient should be switched to NIV.

Oxygen reduces the respiratory drive and increases the transcutaneous CO2 at least in acute situations. There is no evidence of a chronic situation, so treat-ment with O2 cannot be recommended. In contrast to this, non-invasive venti-lation (NIV) improves the respiratory response, the blood gases, the micro-structure and macrostructure of sleep, the quality of life, hemodynamic param-eters and the survival of OHS patients. This treatment should therefore be used primarily or if CPAP treatment is inef-fective. NIV with fixed pressure support and with a specification of target volume have proven to be effective. Comparison studies show various results. Weight re-duction is to be seen as a key causal mea-sure in patients with OHS, although ven-tilation treatment should not be delayed. If conservative approaches to weight reduction fail, bariatric operations can be used. Evidence of a reduction in body weight and an improvement in lung function and blood gases has been able to be provided in patients following bar-iatric surgery.

7.2 Sleep-related hypoventilation caused by a physical illness

Typical diseases from the respective area are indicated in italics and in brackets:a. Sleep-related hypoventilation in

patients with parenchymal lung disease (interstitial lung diseases),

b. Sleep-related hypoventilation in patients with vascular lung pulmonary disease (pulmonary hypertension),

c. Sleep-related hypoventilation in patients with an obstruction of the upper respiratory tract (COPD),

d. Sleep-related hypoventilation in patients with neuromuscular diseases or diseases of the chest wall (kyphoscoliosis, post-tuberculosis syndrome, post-polio syndrome, muscular dystrophies).

7.2.1 Main findingsThe patient’s symptoms are uncharacter-istic and often overshadowed by those of the underlying disease. Since the fo-cus is on the impairment of ventilation, patients typically complain of dyspnea when exercising, decreased physical per-formance, commonly leg edemas and also headaches as a result of hypercap-nia. Disorders of sleeping through the night and waking up with shortness of breath are the most common symptoms related to sleep. Daytime sleepiness can also be one of the main symptoms. There have been no systematic examinations of the main symptoms and sleep-related symptoms.

7.2.2 Start, progression, complicationsThe underlying disease causes a de-creased capacity and/or increased bur-den on the breath pumping apparatus which was not able to be compensated for in earlier stages of the disease. As the underlying disease advances, hypoven-tilation with phases of hypercapnia ini-tially occur during REM sleep which lead to metabolic compensation in the form of bicarbonate retention; this then also decreases the respiratory response to hypercapnia. As the disease progress-es, hypoventilation/hypercapnia occur in NREM sleep too, and ultimately the full picture of hypercapnic respiratory failure while awake develops.

7.2.3 DiagnosisBy definition, the diagnosis of manifest alveolar hypoventilation during the day is made using arterial blood gas analysis. An examination of pulmonary function and the measurement of the strength and resilience of the respiratory musculature are also sensible for further diagnostics while the patient is awake. EKGs, labora-tory tests and chest x-rays and where ap-plicable an echocardiography test should be carried out depending on the patient’s


history and the clinical findings. Regard-less of the underlying disease, hypercap-nias during the day regularly transition into hypoventilation at night and later in non-REM sleep too [44, 137, 370], which can worsen the patient’s prognosis [146, 466]. Observational studies indicate that hypercapnia at night is an indicator of the degree of severity of the disease and the long-term prognosis [74].

Since the uncharacteristic symptoms of alveolar hypoventilation are often falsely attributed solely to the underly-ing disease, there is a risk of overlooking the early phases of chronic ventilation insufficiently with hypoventilation sole-ly at night, thereby delaying sufficient treatment. It is therefore necessary to carry out a measurement of the respi-ration at night in patients with corre-sponding risks of the occurrence of sec-ondary alveolar hypoventilation. From a vital capacity of < 50 target% the risk in patients with restrictive disorders increases significantly [370]. Simply carrying out pulse oximetry is not suffi-cient to provide evidence of sleep-relat-ed hypoventilation. Night-time arterial PaCO2 measurements are not practica-ble. A transcutaneous or end tidal pCO2 measurement in combination with the polygraph is therefore required to pro-vide evidence of sleep-related hypoven-tilation.

The hypercapnia measured in the transcutaneous capnometry provides direct evidence of the hypoventilation [432]. Simply carrying out a continuous registration of the CO2 at night has the significant disadvantage that is remains unclear whether the patient has reached the REM stage of sleep. The procedure to provide positive evidence of hypoventi-lation is therefore good, but it is not suit-able to rule this out. A polysomnography is therefore indicated in patients with night-time symptoms with no evidence of hypoventilation.

7.2.4 TreatmentIn the case of both chronic underlying diseases, treatment is mostly not suffi-cient to remedy the hypoventilation. From a treatment perspective, non-in-vasive ventilation (NIV) is therefore carried out during the sleep using a mast

with the aim of increasing the alveolar ventilation and avoiding hypoventila-tion. The main criteria for the start of long-term NIV treatment in a patient with sleep-related hypoventilation caused by a physical disease are symp-toms and consequences of the ventila-tion insufficiency such as dyspnea and edema and limitation in quality of life caused by non-restorative sleep as a re-sult of disorders sleeping throughout the night and furthermore

– in patients with sleep-related hypoventilation as part of an obstruction of the lower respiratory tract:

� repeated, severe (i.e. associated with respiratory acidosis) exacerbations which require hospitalization or

� a day PaCO2 ≥ 50 mm Hg or � a night-time PaCO2 ≥ 55 mm Hg

or an increase in the CO2 mea-sured transcutaneously at night ≥ 10 mmHg

� in addition to this, long-term NIV can also be considered immediately after an acute exacerbation which requires ventilation.

– in patients with sleep-related hypoventilation within the scope of a neuromuscular disease or a disease of the chest wall:

� a day PaCO2 ≥ 45 mm Hg or � a night-time PaCO2 ≥ 50 mm Hg

or an increase in the CO2 mea-sured transcutaneously at night ≥ 10 mmHg

The aim of the ventilation is normo-capnia achieved by the remedying of the hypoventilation through ventilation while the patient is sleeping and the re-duction in PaCO2 through to normocap-nia during the day. Introduction can be during the day or at night. As the initial settings progress, the effectiveness of the ventilation must be checked during spontaneous breathing and during ven-tilation and it must be amended to in-clude the night-time measurements.

Treatment is generally carried out as Non-Invasive Ventilation (NIV) via a nasal or mouth and nose mouth during the entire period of sleep. Since REM sleep is a particularly critical phase, the effectiveness of the ventilation during

sleep should be documented by means of the transcutaneous CO2 measurement (PtcCO2) plus a polygraph. A polysom-nography is indicated in the case of un-certainty regarding the night-time hy-poventilation during REM sleep.

The NIV can be given as assisted, as-sisted-controlled or purely controlled ventilation. There are no data regarding the superiority of one method. Patients with neuromuscular diseases and diseas-es of the thoracic skeleton often tolerate the controlled mode subjectively very well while patients with COPD mostly prefer the assisted mode. Optimal, indi-vidually adjusted settings are key to the good acceptance and success of treat-ment.

There are only a few controlled stud-ies of the effects of NIV with high-qual-ity methods (see Tab. B.19 and B.20). In the case of slowly progressing muscle diseases, kyphoscoliosis and post-tuber-culosis conditions, NIV achieves a dra-matic clinical improvement both as an acute treatment and in the long term, so controlled studies on these diseases are now ethically dubious. While these patients previously died of respiratory failure, life expectancy with NIV can be almost normal [78, 176, 204, 271, 380, 414, 452]. Correspondingly, the quality of life also improves significantly during treatment with NIV, the hospitalization rate decreases and the symptoms are re-duced [9, 63]. In some cases, the phys-iological parameters such as blood gas and lung function were even able to be normalized [354, 401, 466]. There is an unrestricted indication for treatment for the diseases mentioned.

In the case of rapidly progressive neu-romuscular diseases such as for example Duchenne muscular dystrophy, there is one controlled study and several case series showing a significant advantage of NIV in terms of survival [63, 130, 397, 415], but the progression of the under-lying disease restricts the positive effects of NIV. An individual indication for ventilation treatment is required in these patients. The ethical discussion of the ac-ceptance of invasive ventilation that may eventually necessary should therefore be had as early as possible.



Patients with COPD represent the largest group of patients who meet the indication criteria for NIV. Shorter, con-trolled investigations in patients receiv-ing NIV showed improved quality of life, a reduction in the hospitalization rate, an improvement in sleep quality and an improvement in physical stress and the blood gases [75, 89, 156, 237, 293, 446]. Several controlled studies, albeit with significant shortcomings, were not able to show a reduction in mortality for the group of patients treated with NIV [103, 160, 437, 479].

In a meta-analysis [436] of seven studies, no evidence of differences in the BGA, pulmonary function or quality of life was found. A key point of criticism of these studies was the lack of substan-tial reduction in the PaCO2 as a result of NIV treatment. In a randomized, con-trolled study, however, the life expectan-cy of COPD patients receiving NIV was significant but with a lower quality of life [288]. The German multicenter study on stable COPD patients in the GOLD IV stage with hypercapnia during the day confirmed the improvement in mortality as a result of the NIV [236]. In this study, there was a significant reduction in the PaCO2 during the day as a result of ven-tilation treatment. On the basis of this data, an attempt should be made to treat using NIV in patients with COPD with the above-mentioned indication criteria. The effects of treatment and compliance should be checked after around three months and a decision should be made about the continuation of treatment.

For more details on the treatment of chronic respiratory failure, reference is made to the S2 guideline “Non-Invasive and Invasive Ventilation as Treatment of Chronic Respiratory Failure” from the German Phenomenology Society [480].

Recommendations on diagnosis – The diagnosis of sleep-related hypoventilation should be made in the event of clinical suspicion or a predisposed underlying disease by means of arterial or capillary blood analysis overnight or by means of nightly transcutaneous or end tidal CO2 measurement. An arterial blood gas analysis carried out during

the day is needed to diagnose an obesity hypoventilation syndrome. An overnight oximetry test in combination with a measurement of the CO2 overnight should be carried out to diagnose sleep-related hypoxemia (A).

– In patients with a body mass index of > 30 kg/m2 and symptoms of sleep-related respiratory disorders, examinations should be carried out to determine the venous bicarbonate when the patient is awake, the arterial or capillary pCO2 or the transcutaneous/end tidal CO2 in order to rule out concomitant hypoventilation during sleep (A).

– Transcutaneous capnometry is recommended as the most sensitive method to provide evidence of sleep-related end tidal hypercapnia. It can be carried out in combination with a polygraph or a polysomnograph (C).

– In patients with neuromuscular diseases or diseases of the chest wall, where the is a vital capacity of < 50% hypoventilation during sleep should be ruled out before starting ventilation treatment (A).

– Polysomnography is the diagnostic standard for the exclusion and differential diagnosis of sleep-related respiratory disorders within the scope of sleep-related hypoventilation of hypoxemia (A).

Treatment – An attempted can be made to carry out treatment with CPAP in patients with OHS with CO2 monitoring (C).

– If hypoventilation at night persists when the patient is using CPAP, non-invasive pressure-supported ventilation (with or without target volumes) should be introduced (B).

– Simply treating with oxygen cannot be recommended in patients with OHS (A).

– In patients with OHS, bariatric operations should be considered after measures to reduce weight have been exhausted (B).

– The introduction of non-invasive ventilation is recommended in symptomatic patients with an obstructive of the lower respiratory

tract, neuromuscular diseases or diseases of the chest wall with hypercapnia when awake (PaCO2 ≥ 50 mm Hg in diseases with obstruction of the lower respiratory tract or ≥ 45 mm Hg in patients with neuromuscular diseases or diseases of the chest wall) or when asleep (PaCO2 ≥ 55 mm Hg or ≥ 50 mm Hg or PtcCO2 changed ≥ 10 mm Hg compared to the normocapnic waking state) (A).

8. Legal consequences

Obstructive sleep apnea increases the risk of a road traffic accident two or three times [162, 195, 335, 336]. Treatment with CPAP reduces the risk of an accident [335, 336, 445]. Patients with a high probability of a sleep-related respiratory disorder and a high risk of accident (daytime sleepi-ness and previous accident or near-miss [26]) should have an instrument-based diagnostic procedure carried out as soon as possible and treatment started quickly once the diagnosis is confirmed [433]. In Germany, patients with “measurable, ab-normal daytime sleepiness” should not drive cars. Only if the symptoms are no longer present after treatment should the patient be able to drive again (Appendix 4 of the Driving License Regulation). In order to assess a person’s suitability to drive, the doctor carrying out the exam-ination is instructed to ask about diseases with elevated levels of daytime sleepiness (e.g., sleep disorders) and if he has a spe-cific reason to suspect that the person has a disease of this type he should carry out further diagnostics [45]. In addition to questionnaires, this should also include examination methods to check central nervous activation and attention and if necessary a driving test should be car-ried out where the doctor has significant doubts about the patient’s ability to drive. A statement on this was written in No-vember 2015 by the DGSM.

On July 1, 2014, the “European Par-liament and the Council on Driving Li-cences” passed the following regulation on the ability of patients with obstructive sleep apnea to drive (Official Journal of the European Union, L194, 2014; http_eur-lex.europa):


Drivers who are suspected to have moderate (AHI 15-29/h) and severe (AHI > 30/h) obstructive sleep apnea syndrome should have an authorized medical examination before being issued with or renewing a driving license. They should be banned from driving until the diagnosis has been confirmed. Peo-ple with moderate to severe OSA with evidence of a well-controlled syndrome and good compliance with appropriate treatment and improvement in daytime sleepiness can be issued a driving license once an authorized medical statement has been made on this. They should have a medical examination at intervals of at least three years (driving license group 1) and one year (driving license group 2) for the degree of treatment compliance and continuity and continuous good vig-ilance when on medication.

In accordance with the “principles of medical case” valid since 2009 (previ-ously “guide to expert medical activi-ties”), sleep apnea syndrome is allocated the following degree of damage (DOD) in social compensation law and in the law on the severely disabled:

– without the need for continuous nasal positive pressure ventilation: DOD 0-10%,

– with the need for continuous nasal positive pressure ventilation: DOD 20%,

– if the patient is unable to receive nasal positive pressure ventilation: DOD 50%.

Consequences and complications (e.g., cardiac arrhythmias, hypertension, pul-monary hypertension) should also be taken into account.

In patients with obstructive sleep ap-nea, an inability to work is an exception as there are suitable treatment methods as a result of which as a minimum a re-duction in symptoms can be expected [123].



Glossary

AASM American Academy of Sleep Medicine

AHI Apnea Hyponea Index

APAP Automatic Positive Airway Pressure

ASV Adaptive servo ventilation

ATS American Thoracic Society

AWMF Arbeitsgemeinschaft der Wissenschaftlichen Mediz-inischen Fachgesellschaften (Working Group of Scientific Medical Societies)

BdP Bundesverband der Pneu-mologen (Federal Association of Pneumonologists)

BMI Body mass index

BUB Richtlinie zu Untersuchungs- und Behandlungsmethoden der vertragsärztlichen Versorgung (Guideline on Investigation and Treatment in Contract Medical Care)

COPD Chronic obstructive pulmo-nary disease

CPAP Continuous positive airway pressure

CSR Cheyne-Stokes respiration

DASS Divided Attention Steering Test

DEGAM Deutsche Gesellschaft für All-gemein-und Familienmedizin (German Society of General and Family Medicine)

DGAI Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin (German Society of Anesthesiology and Intensive Medicine)

DGAV Deutsche Gesellschaft für Allgemein- und Viszeralchir-urgie (German Society of General and Visceral Surgery)

DGHNOKHC Deutsche Gesellschaft für Hals-, Nasen- und Ohr-enheilkunde, Kopf- und Halschirurgie (German Soci-ety for ENT Medicine, Head and Neck Surgery)

DGIM Deutsche Gesellschaft für Innere Medizin (German Soci-ety of Internal Medicine)

DGK Deutsche Gesellschaft für Kardiologie (German Cardiol-ogy Society)

DGKFO Deutsche Gesellschaft für Kieferorthopädie (German Jaw Orthopedics Society)

Glossary

DGMKG Deutsche Gesellschaft für Mund-Kiefer-Gesichtschirur-gie (German Society of Oral, Jaw and Facial Surgery)

DGN Deutsche Gesellschaft für Neurologie (German Neurol-ogy Society)

DGP Deutsche Gesellschaft für Pneumologie und Beat-mungsmedizin (German Society of Pneumonology and Respiratory Medicine)

DGPPN Deutsche Gesellschaft für Psychiatrie, Psychothera-pie und Nervenheilkunde (German Society of Psychi-atry, Psychotherapy and Neurology)

DGSM Deutsche Gesellschaft für Schlafforschung und Schlafmedizin (German Sleep Society)

DGZS Deutsche Gesellschaft Zahnärztliche Schlafmedizin (German Dental Sleep Medi-cine Society)

EBM Evidence-based medicine

EEG Electroencephalogram

EOG Electrooculogram

ERJ European Respiratory Journal

ERS European Respiratory Society

ESC European Society of Cardi-ology

ESRS European Society of Sleep Research

FRS Fernröntgenbild (teleradio-graph)

GOLD Global Initiative for Chronic Obstructive Lung Disease

HFrEF Heart failure with reduced ejection fraction

ICSD International Classification of Sleep Disorders

LAUP Laser-assisted uvulopalato-plasty

LVEF Left ventricular ejection fraction

MAD Mandibular advancement device

MCI Mild cognitive impairment

MRD Mandibular reposition device

MSLT Multiple sleep latency test

MWT Multipler Wachbleibetest (multiple staying awake test)

NIV Non-invasive ventilation

Glossary

NYHA New York Heart Association

OHS Obesity hypoventilation syndrome

OSA Obstructive sleep apnea

OSAS Obstructive Sleep Apnea Syndrome

PAP Positive airway pressure

PAS Posterior airway space

PLMD Periodic limb movement disorder

PSQI Pittsburgh Sleep Quality Index

PVT Psychomotor Vigilance Test

QoL Quality of Life

RCT Randomized controlled trial

RBD Sleep behavior disorder

RDI Respiratory disturbance index (AHI + flow limitation)

RFTA Radiofrequency ablation

SRRD Sleep-Related Respiratory Disorders

SCOPER- Sleep, cardiovascular,

system oximetry, position, effort, respiratory

SGB Sozialgesetzbuch (Social Insurance Code)

Sham Feigning

SRS Sleep Research Society

STOP Snoring, tiredness, observed apneas, high blood pressure

STOP-BANG Snoring, tiredness, observed apneas, high blood pressure + BMI, age, neck circumference

TcpCO2 Transcutaneous carbon dioxide

LJB Lower Jaw Brace

UPPP Uvulopalatopharyngoplasty

Sus. Suspected

WASM World Association of Sleep Medicine

WFSRS World Federation of Sleep Research Societies

St. P. Status post

CSA Central sleep apnea

9. Glossary10. Appendices


10.1 Annex A: Guideline report

10.1.1 Scope and purposeThis guideline on sleep-related respira-tory disorders is an update to the chapter on “sleep-related respiratory disorders” of the S3 guideline on non-restorative sleep/sleep disorders published in 2009 in the journal Somnologie [286].

Since the guideline was last published, a large number of evidence-based stud-ies have been added which all need to be taken into account. The scope of the scientific knowledge has increased sig-

nificantly, so “sleep-related respirato-ry disorders” will appear as a separate guideline.

Sleep-related respiratory disorders include obstructive sleep apnea, central sleep apnea and sleep-related hypoventi-lation/sleep-related hypoxemia.

This guideline is aimed at medical and non-medical professionals (e.g., psy-chologists, natural scientists), nursing staff, self-help groups and interested lay-men.

10.1.2 Composition of the guideline group, involvement of stakeholders. Steering Committee and Publisher

– Prof. Dr. med. Geert Mayer, Schwalmstadt-Treysa

– Prof. Dr. med. Michael Arzt, Regensburg

– Prof. Dr. med. Bert Braumann, Cologne

– Prof. Dr. med. Joachim H. Ficker, Nuremberg

– Prof. Dr. med. Ingo Fietze, Berlin – PD Dr. med. Helmut Frohnhofen, Essen

– PD Dr. med. Wolfgang Galetke, Cologne

– Dr. med. Joachim T. Maurer, Mannheim

– Prof. Dr. med. Maritta Orth, Mannheim

– Prof. Dr. rer. physiol. Thomas Penzel, Berlin

– Prof. Dr. med. Winfried Randerath, Solingen

– Dr. med. Martin Rösslein, Freiburg – PD Dr. rer. physiol. Helmut Sitter, Marburg

– Prof. Dr. med. Boris A. Stuck, Essen

Authors – Prof. Dr. med. Geert Mayer, Schwalmstadt-Treysa

– Prof. Dr. med. Michael Arzt, Regensburg

– Prof. Dr. med. Bert Braumann, Cologne

– Prof. Dr. med. Joachim Ficker, Nuremberg

– Prof. Dr. med. Ingo Fietze, Berlin – PD Dr. med. Helmut Frohnhofen, Essen

– PD Dr. med. Wolfgang Galetke, Cologne

– Dr. med. Joachim T. Maurer, Mannheim

– Prof. Dr. med. Maritta Orth, Mannheim

– Prof. Dr. rer. physiol. Thomas Penzel, Berlin

– Prof. Dr. med. Dr. med. dent. Hans Peter Pistner, Erfurt

– Prof. Dr. med. Winfried Randerath, Solingen

– Dr. med. Martin Rösslein, Freiburg – PD Dr. rer. physiol. Helmut Sitter, Marburg

– Prof. Dr. med. Boris A. Stuck, Essen

Editorial work Dr. rer. nat. Martina Bögel, Hamburg

The following professional groups and patient representatives were involved in order to ensure that the guidelines groups were representative.

Tab. A.1 Elements of the systematic development of the guideline

Logic (clinical algorithm)

Consensus

Evidence

Decision analysis

Tab. A.2 Elements of the systematic development of the guideline

Degree of recommendation

Levels of evidence

A 1a, 1b, 1c

B 2a–c, 3a, 3b

C 4.5

Different degrees of evidence may be applied as part of the consensus process in justified cases

1

Clinical condition

1

Decision:

1

Activity

1Logical numbering sequence

Tab. A.3 Study forms, Oxford Level of Evidence

Levels of evidence Description

1a Evidence through systematic review of randomized controlled studies (RCT)

1b Evidence through suitable planned RCT

1c “All or nothing” principle

2a Evidence through systematic review of well=planned cohort studies

2b Evidence through well-planned cohort study/RCT-compliant quality (for example <80% follow-up)

2c Evidence through outcome research studies

3a Evidence through systematic review of well-designed control case studies

3b Evidence through case control study

4 Evidence through case series/cohorts and case control studies of moderate quality

5 Expert opinion without explicit critical evaluation or based on physiological models, laboratory research results or “first principles”



Medical expert associations – Bundesverband der Pneumologen (BdP, representative C. Franke)

– Deutsche Gesellschaft für Allgemein-und Familienmedizin (DEGAM1, comment by E. Baum with no formal mandate)

– Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV, representative M. Schlensak)

– Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI, representative, M. Rösslein)

– Deutsche Gesellschaft für Geriatrie (DGG, representative H. Frohnhofen)

– Deutsche Gesellschaft für Hals-, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie (DHHNO, representative B.A. Stuck, representative: M. Herzog)

– Deutsche Gesellschaft für Innere Medizin (DGIM, representative H. Bonnemeier)

– Deutsche Gesellschaft für Kardiologie (DGK, representative, M. Arzt)

– Deutsche Gesellschaft für Kieferorthopädie (DGKFO, representative B. Braumann)

– Deutsche Gesellschaft für MundKiefer-Gesichtschirurgie (DGMKG, representative H. Pistner)

– Deutsche Gesellschaft für Neurologie (DGN, representative G. Mayer)

– Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP, representative W. Randerath)

– Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde (DGPPN, representative P. Geisler)

– Deutsche Gesellschaft für zahnärztliche Schlafmedizin (DGZS, representative S. Schwarting)

Patient organizations – Allgemeiner Verband Chronische Schlafstörungen Deutschland e. V. (AVSD) (German General Association of Chronic Sleep Disorders), H. Rentmeister

– Federal Association of Sleep Apnea and Sleep disorders (BSD), W. Waldermann

1 Note: For staffing reasons, the expert associ-ation was not able to take part in the consen-sus conferences, so there are only comments in the ongoing correspondence.

10.1.3 Methodical procedureThe AWMF provided support through-out the guideline development process. The coordination of the consensus con-ferences was carried out in accordance with the nominal group process by mod-erated by PD. Dr. Helmus Sitter.

As it is an S3 guideline, the consen-sus program includes the following ele-ments:

Logical analysis (clinical algorithm), formal consensus finding, evidence-based results, decision analysis For an S3 guide-line, a clearly defined question is used to bring about a solution with condition-al logic (if-then logic) in several steps. Clinical studies and meta-analyses are included in the creation of an evidence base. Graphical algorithms are used to make the process simple, clear and un-derstandable.

10.1.4 Drawing up the guideline/gaining consentThe first version of the guideline was drafted under the guidance of the peo-ple responsible for the guideline, Geert Mayer and the authors of the individual chapters.

This version was used as the basis of the first consensus meeting on Novem-ber 27, 2015 in Frankfurt. The following people were present:

Michael Arzt, Martina Bögel, Hen-drik Bonnemeier, Bert Braumann, Ingo Fietze, Christian Franke, Helmut Frohn-hofen, Wolfgang Galetke, Peter Geisler, Michael Herzog, Joachim T. Maurer, Ge-ert Mayer, Maritta Orth, Thomas Pen-zel, Hans Pistner, Winfried Randerath, Martin Rösslein, Susanne Schwarting, Helmut Sitter, Werner Waldmann.

The following people were present at the second consensus meeting, which took place on April 7, 2016 in Frankfurt: Michael Arzt, Martina Bögel, Henrik Bonnemeier, Bert Braumann, Joachim H. Ficker, Ingo Fietze, Helmut Frohn-hofen, Wolfgang Galetke, Joachim T. Maurer, Geert Mayer, Maritta Orth, Hans Pistner, Winfried J. Randerath, Martin Rösslein, Matthias Schlensak, Helmut Sitter, Boris A. Stuck.

10.1.5 Systematic literature researchGeneral search criteria: The literature re-search was carried out for all studies that had been published up to April 2014 in the Pub-Med database and Cochrane Li-brary. Current literature up to December 2015 was also taken into account provid-ed it met the criteria set out below and was deemed to be important. The update to the AASM Manual, which was pub-lished in 2016, was the only exception. The following were defined as inclusion criteria:

publications in German or English, prospective or retrospective clinical tri-als, randomized controlled trials, con-trolled clinical trials, systematic reviews, meta-analyses, guidelines of the AWMF and of European and North American expert associations (practice guidelines, guidelines) in German or English. The exclusion criteria were defined as: Origi-nal works, published in a language other than English or German, animal experi-ments, letters to the editor, case reports, expert opinions, reviews which were not a systematic summary of the literature but rather provided a general overview of the subject.

Since many evidence-based guidelines on SRRDs have been published around the world, in January 2014 the decision was taken to include guidelines which had already been published in the liter-ature and to evaluate these on the basis of the above-mentioned perspectives in order not to cite all of the literature available and selected literature and in order to avoid double work. The search strategy was as follows: Search “sleep apnea syndrome, sleep apnea central” Limits: Publication Date to 2014/04, Humans, Clinical Trial, Meta-Analysis, Practice, Guideline, Randomized Con-trolled Trial, Review, Controlled Clinical Trial, Guideline, English, German. Snor-ing was included as an additional search criterion, as it can be an initial stage of SRRD: “snoring and OSA,” “Snoring in adults,” “snoring and sleep-related breathing disorders,” “snoring.” Addi-tional search terms for published guide-lines of SRRD were: Practical guidelines, standard of practice papers, practice parameters, consensus papers, position


papers and/or sleep apnea, sleep related breathing disorders, snoring, Homep-ages von AASM, SRS, WASM, WFSRS, Dental Sleep Medicine, ATS, ESRS, ERS, American Academy of Otolaryngology and Surgery AAO-HNS, Oceanic Sleep Society, Canadian Sleep Research Soci-ety, ERJ, ESC, AWMF Leitlinien anderer Gesellschaften, Cochrane, HTA reports. There was a total of 502 relevant entries.

10.1.6 EvaluationThe evaluation of literature has been carried out by two independent experts in line with the Oxford Centre for evi-dence-based medicine levels of evidence (2001).

10.1.7 Clinical algorithmsA total of 4 clinical algorithms were cre-ated (s. Appendix C):

– the diagnostic approach for obstructive sleep apnea,

– the diagnostic approach for central sleep apnea,

– the diagnostic approach for sleep-related breathing difficulties and a presence of cardiovascular comorbidities,

– the therapeutic approach for obstructive sleep apnea.

The algorithms were created by the Steering Committee and approved to-gether with the specialist companies.

10.1.8 External assessment and approvalThe guideline has been discussed and approved by the chairmen of participat-ing medical specialist companies.

10.1.9 Editorial independenceFinancing of the guideline Creation of the guideline and implementation of the consensus conferences was realized exclusively with means of the German Association for Sleep Research and Sleep Medicine (DGSM).

The illustration and handling of poten-tial conflicts of interest has been doc-umented with the aid of standardized forms issued by the AWMF. All partici-pants have answered the necessary ques-tions. Information regarding conflicts

of interest has been critically examined by 2 members of the Steering Commit-tee. It was decided that those affected by possible conflicts of interest in specific part areas would not take part in voting processes concerning this subject. 3 Par-ticipants abstained from voting on the subject of neurostimulation processes; 1 participant on the subject of APAP.

10.1.10 Preparation and implementationThe guideline is distributed via the pro-fessional journal Somnologie and can be inspected online on the website of the AWMF (http://www.awmf.org/ awmf-online-das-portal-der-wissen-schaftli-chen-medizin/awmf-aktuell. html).

10.1.11 Period of validity and updating processThe guideline will remain valid for 3 years from its date of publication



10.2 Annex B: Tables

Tab. B.1 Diagnoses of sleep-related breathing difficulties according to ICSD-3 [10]

Main group Sub-group ICD-10-CM

Obstructive sleep apnea Obstructive sleep apnea in adults G47.33

Obstructive sleep apnea in children G47.33

Central sleep apnea syndrome Central sleep apnea with Cheyne-Stokes respiration R06.3

Central sleep apnea for organic reasons without Cheyne-Stokes respiration G47.37

Central sleep apnea with periodic breathing at great height G47.32

Centrals sleep apnea with medication or substances G47.39

Primary central sleep apnea G47.31

Primary central sleep apnea in children P28.3

Primary central sleep apnea in premature infants P28.4

Central sleep apnea as a consequence of treatment G47.39

Sleep-related hypoventilation Obesity hypoventilation syndrome E66.2

Congenital central alveolar hypoventilation syndrome G47.35

Late-onset central hypoventilation with hypothalamic dysfunction G47.36

Idiopathic central alveolar hypoventilation G47.34

Sleep-related hypoventilation with medication or substances G47.36

Sleep-related hypoventilation with organic disorders G47.36

Sleep-related hypoxia Sleep-related hypoxia G47.36

Isolated symptoms and norm variants Snoring R06.83

Catathrenia –

Tab. B.2 Diagnostic processes for the various categories of sleep-related breathing disorders

Questionnaires Performance vigilance tests

1–3 channel polygraphy

4–6 channel polygraphy

Polysomnography

Obstructive sleep apnea (+) (+) (+) + +

Central sleep apnea (+) – (+) (+) +

Hypoventilation – – – (+) +

+ Use recommended, (+) use possible under certain conditions, – the method is neither recommended nor rejected here, there is no evidence for use, it is not possible, uneconomical or pointless

Tab. B.3 Questionnaires and instruments of vigilance diagnostics. The validated instruments give rise to complaints, poor condition, symptoms and various behavior patterns

ESS Berlin Q STOP-BANG Waist to height

PVT, Osler, DASS

MSLT/MWT

Obstructive sleep apnea (+) (+) (+) (+) (+) (+)

Central sleep apnea – (+) – – – (+)

Hypoventilation – – – – – (+)

+ Use recommended, (+) use possible under certain conditions, – the method is neither recommended nor rejected here, there is no evidence for use, it is not possible, uneconomical or pointless


Tab. B.4 Values originate from two studies [353, 413]. The “clinical score” consists of snoring, age, blood pressure, male gender [145]

AHI ≥ 5 AHI ≥15 AHI ≥ 30

Sensitivity Specificity Positive predicative value



ESS > 10 – – – 39.0 71.4 64.8 46.1 70.4 68.7

Berlin-Q 86 25 91.7 91 28 73.4 89 18 45.9

STOP-BANG 90 42 93.7 93 28 73.9 96 21 48.6

Clinical score 33 83 95.0 35 78 77.5 36 72 50.0

Polygraphy 87 67 96.2 77 95 97.1 50 93 84.8

Tab. B.5 Recommended channels for cardiorespiratory polysomnography. Specified are the function to be investigated, the associated biosignals, the necessary technology and its technical specification with regard to the optimal scanning rate and filter settings

Function Parameters Technology Optimal scanning rate (Hz) Filter (Hz)

Sleep EEC, EOC Electrodes 500 0.3-35

EMG Electrodes 500 10-100

Breathing Airflow Ram pressure, thermistor 100 0.1-15

Breathing effort Induction plethysmography 100 0.1-15

Oxygen saturation SaO2 25 –

Carbon Dioxide tcPaCO2 25 –

Snoring Microphone 500 –

Cardial EKG Electrodes 500 0.3-70

Motion EMGM.tibialis Electrodes 500 10-100

Body position Position sensor 1 –

Video Video camera 5 –

Tab. B.6 Meta-analysis for cardiorespiratory polysomnography in the sleep laboratory with monitoring

Study title Author Year Country Study type Outcome Levels of evidence

Rules for scoring respiratory events in sleep: Update of the 2007 AASM manual for the scoring of sleep and associated events

Berry et al. [48] 2012 USA Update of meta-analysis Redline et al. [384] with regard to sensors, recordings, evaluation

Breathing evaluation 1a

The scoring of arousal in sleep Bonnet et al. [60] 2007 USA Meta-analysis of 122 studies after review of 2415 studies

Arousal evaluation 1a

The scoring of cardiac events during sleep

Caples et al. [87] 2007 USA Meta-analysis of 14 studies after review of 285 studies

EKG and circulation 1a

Digital analysis and technical specifications

Penzel et al. [349] 2007 USA Meta-analysis of 119 studies after review of 154 studies

Technology, automatic sleep evaluation

1a

The scoring of respiratory events in sleep

Redline et al. [384] 2007 USA Meta-analysis of 182 studies after review of 2298 studies

Breathing evaluation 1a

The visual scoring of sleep in adults

Silber et al. [412] 2007 USA Meta-analysis of 26 studies after evaluation of more than 1,000 studies

Sleep stage evaluation 1a

Movements in sleep Walters et al. [460] 2007 USA Meta-analysis of 44 studies after review of 81 studies

Movement evaluation 1a



Tab.B.7 Studies for polygraphy for sleep apnea

Study title Author Year Country Study type Pat. number

Outcome Levels of evidence

Executive summary on the systematic review and practice parameters for portable monitoring in the investigation of suspected sleep apnea in adults

Am. Thoracic Soc [11] 2004 USA Meta-analysis of 51 studies

– Portable monitoring may increase or reduce the pre-test probability of sleep apnea undercertain conditions

1

Practice parameters for the use of portable monitoring devices in the investigation of suspected obstructive sleep apnea in adults

Chesson et al. [97] 2003 USA No formal me-ta-analysis, as stud-ies are too different. Formal evaluation of study evidence

– Portable monitoring may increase or reduce the pre-test probability of sleep apnea under certain conditions

1

Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients

Collop et al. [104] 2007 USA Meta-analysis of 291 studies

– Portable monitoring for sleep apnea is possible with 4–6 channels, carried out by sleep researchers

1a

Obstructive sleep apnea devices for out-of-center (OOC) testing: technolo-gy evaluation

Collop et al. [105] 2011 USA Polygraphy equip-ment evaluation with systematic literature review

– – 1

Home diagnosis of sleep apnea: a systematic review of the literature

Flemmons et al. [145] 2003 USA Meta-analysis of 35 high quality studies

– Portable monitoring of sleep apnea is possible, not with comorbidities and other sleep disturbances

1a

Systematic review and meta-analysis of the literature regarding the diagnosis of sleep apnea

Ross et al. [392] 2000 USA Meta-analysis of 71 studies after review of 937 studies, HTA report

7572 Up to 17% incorrect negative results and up to 31% incorrect positive results

1a

Diagnosis of obstructive sleep apnea by peripheral arterial tonometry: meta-analysis

Yalamanchali et al. [489] 2013 USA Meta-analysis of 14 studies

909 Portable monitoring with Watch-PAT apparatus allows diagnosis of obstructive sleep apnea with high pre-test probability

1a


Tab.

B.8

Pe

riope

rativ

e co

mpl

icat

ions

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

patie

nts (n)

Inte

rven

tion

Des

ign/

end

poin

tsLe

vels

of

evid

ence

Corre

a et

al.

[108

]20

15US

ASy

stem

atic

revi

ewZS

A pa

tient

sN

umbe

r of s

tud-

ies:

8–

Prev

alen

ce, m

echa

nism

s, pe

riope

ra-

tive

man

agem

ent

3a

Gros

s et a

l. [1

72]

2014

USA

Guid

elin

es o

f the

Am

eric

an S

ocie

ty o

f An

esth

esio

logi

sts

––

––

–

Fink

el e

t al.

[141

]20

09US

APr

ospe

ctiv

e ob

serv

a-tio

nal s

tudy

Adul

t sur

gica

l pat

ient

s28

77–

Prev

alen

ce O

SAPo

stop

erat

ive

com

plic

atio

ns2b

Gupt

a et

al.

[175

]20

01US

ARe

tros

pect

ive

case

-con

trol

stud

yO

rtho

pedi

c pa

tient

s with

or

with

out O

SA20

2Pr

eope

rativ

e CP

AP tr

eat-

men

t

Post

oper

ativ

e co

mpl

icat

ions

Am

bula

tory

per

iod

3b

Josh

i et a

l. [2

24]

2012

USA

cons

ensu

s sta

tem

ent

of th

e So

ciet

y fo

r Am

-bu

lato

ry A

nest

hesia

––

––

–

Kaw

et a

l. [2

29]

2012

USA

Retr

ospe

ctiv

e ca

se-c

ontr

ol st

udy

Adul

t non

-car

dios

urgi

cal

patie

nts w

ith P

SG47

1–

Post

oper

ativ

e co

mpl

icat

ions

Am

bula

tory

per

iod

3b

Kim

and

Lee

[233

]20

06So

uth

Kore

aRe

tros

pect

ive

case

-con

trol

stud

yO

SA p

at. w

ith u

vulo

pala

toph

a-ry

ngop

last

y18

0–

Inci

denc

es o

f diffi

cult

intu

batio

n3b

Lock

hart

et a

l. [2

66]

2013

USA

Pros

pect

ive

coho

rt

stud

yAd

ult s

urgi

cal p

atie

nts

14,9

62–

Post

oper

ativ

e m

orta

lity

afte

r 20

days

/1 y

ear

2b

Mok

hles

i et a

l. [3

03]

2013

USA

Retr

ospe

ctiv

e co

hort

st

udy

Adul

t bar

iatr

ic su

rger

y pa

tient

s91

,028

–Ho

spita

l mor

talit

y Am

bula

tory

per

iod

Card

ial c

ompl

icat

ions

Re

spira

tory

com

plic

atio

ns

2b

Mok

hles

i et a

l. [3

04]

2013

USA

Retr

ospe

ctiv

e co

hort

st

udy

Elec

tive

surg

ery

patie

nts

1,05

8,71

0–

Hosp

ital m

orta

lity

Ambu

lato

ry p

erio

d Ca

rdia

l com

plic

atio

ns

Resp

irato

ry co

mpl

icat

ions

2b



Tab.

B.8

Pe

riope

rativ

e co

mpl

icat

ions

(con

tinue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

patie

nts (n)

Inte

rven

tion

Des

ign/

end

poin

tsLe

vels

of

evid

ence

Mut

ter e

t al.

[310

]20

14US

AM

atch

ed co

hort

an

alys

isPa

t. w

ith k

now

n O

SA w

ith/

with

out C

PAP

trea

tmen

t vs.

pat.

with

unk

now

n O

SA

17,8

42CP

APCa

rdia

l com

plic

atio

ns re

spira

tory

co

mpl

icat

ions

2b

Rave

sloot

et a

l. [3

81]

2012

Net

herla

nds

Pros

pect

ive,

m

ulti-

disc

iplin

ary,

singl

e-ce

nter

obs

er-

vatio

nal s

tudy

Adul

t bar

iatr

ic su

rger

y pa

tient

s27

9–

OSA

pre

vale

nce

OSA

pre

dict

ors

2b

Röss

lein

et a

l. [3

90]

2015

Germ

any

Posit

ion

pape

r D

GHN

OKH

C/D

GAI

––

––

–

Siya

m a

nd B

enha

mo

[419

]20

02Fr

ance

Retr

ospe

ctiv

e ca

se-c

ontr

ol st

udy

Surg

ical

pat

ient

s11

3–

Inci

denc

es o

f diffi

cult

intu

batio

n3b

Stie

rer e

t al.

[431

]20

10US

APr

ospe

ctiv

e ob

serv

a-tio

nal c

ohor

t stu

dyAm

bula

tory

surg

ical

pat

ient

s21

39–

OSA

pre

vale

nce

Post

oper

ativ

e co

mpl

icat

ions

2b

Vasu

et a

l. [4

51]

2012

USA

Syst

emat

ic re

view

Surg

ical

OSA

pat

ient

sN

umbe

r of s

tud-

ies:

11–

Post

oper

ativ

e co

mpl

icat

ions

2a (Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies:

2b–3

b)


Tab.

B.9

St

udie

s for

the

impr

ovem

ent o

f CPA

P co

mpl

ianc

e, C

ochr

ane

anal

ysis

2011

, stu

dies

from

200

9

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nPa

tient

sIn

terv

entio

nD

esig

n/en

d po

ints

Effec

t on

CPAP

com

plia

nce

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Antic

et a

l. [1

8]20

09In

tern

atio

nal

Rand

omiz

ed,

cont

rolle

dO

SAn

= 19

5CP

AP n

ew

set-

up,

follo

w-u

p:

3 m

onth

s

Inte

rven

tion:

Auto

CPA

P se

t-up

, pul

se

oxim

etry

, mon

itorin

g th

roug

h sle

ep m

edic

ine

trai

ned

nurs

e

ESS:

no

diffe

renc

es

Com

plia

nce:

no

diffe

renc

es

com

pare

d w

ith p

lace

bo?

Inte

rven

tion

1: C

osts

low

er

than

pla

cebo

?

lb

1. P

olys

omno

grap

hic

diag

nost

ics (

1 ni

ght)

and

CPAP

se

t-up

(1 n

ight

), m

onito

ring

by sl

eep

phys

icia

n

Dam

jano

vic

et a

l. [1

12]

2009

Inte

rnat

iona

lPl

aceb

o co

ntro

lled,

pa

ralle

l, ra

ndom

ized

OSA

n =

100

CPAP

/APA

P ne

w se

t-up

, fo

llow

-up

3 m

onth

s, 9

mon

ths

Inte

rven

tion

1:

EDUC

ATIO

N: S

tand

ard

inst

ruct

ion

plus

CPA

P/AP

APIn

terv

entio

n 2:

Trai

ning

, m

onth

ly v

isits

at h

ome

(6 m

onth

s)

Re-e

xam

inat

ion:

Inte

rven

tion

1: 6

8%In

terv

entio

n 2:

88%

, p <

0.0

5Pe

riod

of u

se:

Inte

rven

tion

1:4.

6 ±

0.4

h/ni

ght

Inte

rven

tion

2:5.

7 ±

0.2

h/ni

ght,

p <

0.05

Day

s of u

se (%

):In

terv

entio

n 1:

57.

0 ±

5.9

Inte

rven

tion

2:80

.4 ±

2.8

, p <

0.0

–N

o di

ffere

nces

in p

erio

d of

us

e be

twee

n CP

AP a

nd A

PAP

lb

Del

laca

et a

l. [1

19]

2010

Inte

rnat

iona

lM

onito

ring

stud

yO

SA10

CPAP

, titr

atio

n in

resid

entia

l en

viro

nmen

t

1. T

elem

etry

: –

base

d on

conv

entio

nal

GPRS

cellp

hone

– re

late

d ob

serv

atio

n an

d tit

ratio

n of

CP

AP p

ress

ure

Tele

met

ric p

ress

ure

titra

tion:

–Si

gnifi

cant

impr

ovem

ent/

norm

aliz

atio

n of

ven

tilat

ory

para

met

ers

llc

2. a

fter 1

wee

k of

po

lyso

mno

grap

hic

cont

rol i

n th

e sle

ep la

bora

tory

Ambu

lato

ry p

olys

omno

grap

hy:

–no

rele

vant

cha

nge

of

tele

met

rical

ly a

djus

ted

CPAP

pa

ram

eter

s



Tab.

B.9

St

udie

s for

impr

ovin

g CP

AP co

mpl

ianc

e, C

ochr

ane

anal

ysis

2011

, stu

dies

from

200

9 (c

ontin

ued)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nPa

tient

sIn

terv

entio

nD

esig

n/en

d po

ints

Effec

t on

CPAP

com

plia

nce

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Holm

dahl

et a

l. [1

93]

2010

Inte

rnat

iona

lRa

ndom

ized

, co

ntro

lled

OSA

200

Regu

lar v

isits

, fo

llow

-up

2 ye

ars

Inte

rven

tion

1. A

nnua

l visi

ts fr

om sl

eep

med

icin

e nu

rsin

g sp

ecia

list

2. A

nnua

l visi

ts fr

om p

hysic

ian

+ pu

lse o

xim

etry

Both

gro

ups:

99%

hig

hly

satis

fied

with

CPA

PQ

ualit

y of

life

: id

em in

1 a

nd 2

lb

Men

delso

n et

al.

[296

]20

14In

tern

atio

nal

Mul

ti-ce

nter

, ra

ndom

ized

,co

ntro

lled

OSA

107

OSA

Stan

dard

inst

ruct

ion:

Mas

k ad

just

men

tAu

to-C

PAP

Afte

r 2 d

ays q

uest

ioni

ng

rega

rdin

g ad

here

nce,

side

eff

ects

by

sleep

spec

ialis

t4

wee

ks: R

ead-

out o

f dat

a,

pers

onal

disc

ussio

n w

ith sl

eep

spec

ialis

t2.

Tele

mon

itorin

g Sm

artp

hone

(inp

ut o

f blo

od

pres

sure

, CPA

P ad

here

nce,

qu

ality

of l

ife) +

tele

met

ric

feed

back

3rd

End

poin

t:RR

set-

up

–Bl

ood

pres

sure

ch

arac

teris

tics s

ame

for

both

gro

ups

–no

impr

ovem

ent i

n bl

ood

pres

sure

set-

up th

roug

h te

lem

edic

ine

lb


Tab.

B.9

St

udie

s for

impr

ovin

g CP

AP co

mpl

ianc

e, C

ochr

ane

anal

ysis

2011

, stu

dies

from

200

9 (c

ontin

ued)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nPa

tient

sIn

terv

entio

nD

esig

n/en

d po

ints

Effec

t on

CPAP

com

plia

nce

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Smith

et a

l. [4

23]

2009

Inte

rnat

iona

lRa

ndom

ized

, pl

aceb

o co

ntro

lled,

fo

llow

-up:

6 m

onth

s

OSA

, new

se

t-up

97M

ADIn

terv

entio

n:ED

UCAT

ION

1. In

stru

ctio

n re

gard

ing

CPAP

us

e2.

Dia

ry:

Perio

d of

use

, sid

e eff

ects

, po

sitiv

e eff

ects

3rd

Audi

o ta

pe, m

ask

adju

stm

ent i

nstr

uctio

n,

brea

thin

g pa

tter

n, re

laxa

tion

thro

ugh

mus

icPl

aceb

o:Au

dio

tape

with

info

rmat

ion

1 m

onth

:H

ighe

r adh

eren

ce in

in

terv

entio

n gr

oup

(p <

0.0

1)37

6 m

onth

s:N

o di

ffere

nces

in co

mpl

ianc

e be

twee

n bo

th in

terv

entio

n gr

oups

lb

Spar

row

et a

l. [4

26]

2010

Inte

rnat

iona

lRa

ndom

ized

, co

ntro

lled

OSA

250

CPAP

Com

plia

nce

impr

ovem

ent

Inte

rven

tion

1: n

= 1

24In

tera

ctiv

e an

swer

mac

hine

w

ith fe

edba

ck2.

n =

126

Plac

ebo:

Gene

ral h

ealth

info

rmat

ion,

vi

a th

e te

leph

one

CPAP

use

:In

terv

entio

n 1

vs.

inte

rven

tion

26

mon

ths:

CPAP

use

1 h

long

er p

er n

ight

12 m

onth

s:CP

AP u

se 2

h

lb



Tab.

B.1

0 Cu

rrent

syst

emat

ic re

view

s (SR

) and

met

a-an

alys

es (M

A) fo

r the

trea

tmen

t of o

bstr

uctiv

e sle

ep a

pnea

(OSA

)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

stud

ies

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Ahre

ns e

t al.

[4]

2011

Inte

rnat

iona

lRe

view

OSA

14O

A vs

. OA

OA

vs. P

lace

boAH

I, RD

IO

As m

ore

effec

tive

than

pl

aceb

o pr

otru

sion

is cr

ucia

l Ve

rtic

al o

peni

ng h

as n

o in

fluen

ce

1-5

Anan

dam

et a

l. [1

2]20

13In

tern

atio

nal

Met

a-an

alys

isO

SA9

Cons

erva

tive

wei

ght

redu

ctio

nBM

I, AH

IW

eigh

t red

uctio

n im

prov

es B

MI

and

AHI

1-4

Bäck

et a

l. [3

2]20

09In

tern

atio

nal

Revi

ewSn

orin

g30

RFTA

soft

pala

te v

s. pl

aceb

oSn

orin

g, u

ndes

ired

effec

tsSn

orin

g be

com

es m

oder

ate,

al

thou

gh si

gnifi

cant

ly re

duce

d w

ith lo

wer

mor

bidi

ty th

an

LAUP

or i

njec

tion

snor

epla

sty.

Effec

t fal

ls af

ter m

ore

than

12

mon

ths

1b–4

Bakk

er a

nd M

arsh

all [

33]

2011

Inte

rnat

iona

lRe

view

m

eta-

anal

ysis

OSA

7CP

AP v

s. fle

xibl

e CP

AP,

air h

umid

ifica

tion

Com

plia

nce

No

com

plia

nce

impr

ovem

ent

thro

ugh

flexi

ble

CPAP

1a

Brat

ton

et a

l. [6

7]20

15In

tern

atio

nal

Met

a-an

alys

isO

SA51

CPAP

vs.

no C

PAP

MAD

vs.

no M

AD

CPAP

+ M

AD v

s. no

CP

AP, n

o M

AD

Bloo

d pr

essu

re (R

R)

chan

ges s

ysto

l., d

iast

ol.

prio

r to

and

durin

g tr

eatm

ent

CPAP

vs.

no C

PAP

RR

syst

ol./d

iast

ol. s

igni

fican

t M

AD v

s. no

MAD

RR

syst

ol./d

iast

ol. s

igni

fican

tCP

AP v

s. M

AD

no d

iffer

ence

sin

RR

redu

ctio

n

1a

Brat

ton

et a

l. [6

7]20

15In

tern

atio

nal

Revi

ew

met

a-an

alys

isO

SA67

CPAP

vs.

MAD

Slee

pine

ss

ESS

CPAP

vs.

MAD

: mor

e eff

ectiv

e

Day

-tim

e sle

epin

ess m

ore

effec

tive

M

AD: m

eani

ngfu

l tre

atm

ent

alte

rnat

ive

for C

PAP

into

lera

nce

1a


Tab.

B.1

0 Cu

rrent

syst

emat

ic re

view

s (SR

) and

met

a-an

alys

es (M

A) fo

r the

trea

tmen

t of o

bstr

uctiv

e sle

ep a

pnea

(OSA

) (co

ntin

ued)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

stud

ies

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Cam

acho

et a

l. [8

0]20

14In

tern

atio

nal

Revi

ewO

SA18

Trac

heos

tom

yAI

, CAI

, AHI

, OD

I, da

y-tim

e sle

epin

ess

TT re

liabl

y re

ctifi

es O

SA w

ith

rega

rd to

bea

ting

diso

rder

s and

da

y-tim

e sle

epin

ess;

cent

ral

apne

a >

no lo

nger

det

ecta

ble

14 w

eeks

afte

r TT;

from

BM

I 45

obe

sity

hypo

vent

ilatio

n sy

ndro

me

poss

ible

reas

on fo

r pe

rsist

ently

incr

ease

d O

DI

4 an

d 5

Capl

es e

t al.

[82]

2010

Inte

rnat

iona

lRe

view

, (m

eta-

anal

ysis)

OSA

36M

MA

(9),

UPPP

(15)

, LA

UP (2

), RF

TA (8

), Pi

llar (

2)

AHI,

day-

time

sleep

ines

s, un

desir

ed e

ffect

sM

oder

ate

evid

ence

: LAU

P w

ithou

t effe

ct. L

ow e

vide

nce:

M

MA

with

pro

noun

ced

effec

t, UP

PP, R

FTA

and

Pilla

r with

m

oder

ate

effec

t. Co

mpl

icat

ion

rate

s hav

e de

crea

sed

in la

ter

stud

ies

1b–4

Choi

et a

l. [9

9]20

13In

tern

atio

nal

Met

a-an

alys

isO

SA

(sno

ring

with

out

OSA

)

7 O

SA(7

snor

ing)

Pilla

r sof

t pal

ate

impl

ant

vs. p

lace

boAH

I, ES

S, (s

norin

g),

extr

usio

n ra

te fo

r all

14 st

udie

s

Pilla

r im

plan

ts re

duce

AHI

, ESS

(fo

r OSA

) and

snor

ing

with

m

oder

ate

effec

t ove

r a p

erio

d of

3 to

29

mon

ths m

axim

um.

Extr

usio

ns a

re d

escr

ibed

in

9.3%

of p

atie

nts

1b–4

Don

g et

al.

[126

]20

13In

tern

atio

nal

Met

a-an

alys

isO

SA17

OSA

S (m

ediu

m se

verit

y)an

d^C

AD^s

trok

e -^

gene

ral h

eart

co

nditi

ons

–O

SAS

and

gene

ral h

eart

co

nditi

ons:

O

R 2.

48, 9

5% C

I 1.9

8–3.

1 –

OSA

S an

d CA

D

O

R 1.

37, 9

5% C

I –

OSA

S an

d st

roke

:

O

R 1.

37, 9

5% C

I 0.9

5–1.

98

3a



Tab.

B.1

0 Cu

rrent

syst

emat

ic re

view

s (SR

) and

met

a-an

alys

es (M

A) fo

r the

trea

tmen

t of o

bstr

uctiv

e sle

ep a

pnea

(OSA

) (co

ntin

ued)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

stud

ies

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Dra

ger e

t al.

[129

]20

15In

tern

atio

nal

Met

a-an

alys

isO

SA25

CPAP

vs.

no C

PAP

BMI p

rior t

o an

d du

ring

CPAP

BMI i

ncre

ase

durin

g CP

AP2a

Farr

ar e

t al.

[136

]20

08In

tern

atio

nal

Met

a-an

alys

isO

SA16

RFTA

soft

pala

te, b

ase

of to

ngue

or b

oth

vs.

plac

ebo

or c

ase

serie

s

AHI,

ESS,

und

esire

d eff

ects

Mod

erat

e re

duct

ion

of A

HI a

nd

ESS,

cont

inue

d ov

er 2

4 m

onth

s in

cas

e se

ries.

Cont

rolle

d st

udy

with

com

para

ble

effec

t on

qual

ity o

f life

and

day

-tim

e sle

epin

ess a

s for

CPA

P an

d be

tter

than

pla

cebo

1b–4

Fava

et a

l. [1

38]

2014

Inte

rnat

iona

lRe

view

and

m

eta-

anal

ysis

OSA

31 RCTs

CPAP

vs.

activ

e/pa

ssiv

e tr

eatm

ent

RR lo

wer

ing

Effec

t on

stud

y en

d po

int C

PAP:

sig

nific

ant R

R lo

wer

ing

1

Fran

klin

et a

l. [1

50]

2009

Inte

rnat

iona

lM

eta-

anal

ysis

OSA

and

sn

orin

g4

LAUP

(2),

RFTA

bas

e of

tong

ue (1

) or s

oft

pala

te (1

) vs.

wai

ting

or

plac

ebo

Day

-tim

e sle

epin

ess,

AHI,

snor

ing,

und

esire

d eff

ects

(a

lso u

vulo

pala

topl

asty

an

d uv

ulop

alat

opha

ryn-

galp

last

y)

LAUP

and

RFT

A ba

se o

f ton

gue

with

out e

ffect

in d

ay-t

ime

sleep

ines

s and

AHI

, RFT

A sif

t pal

ate

redu

ced

snor

ing.

N

o ra

ndom

ized

stud

ies a

re

avai

labl

e fo

r all

othe

r sur

gica

l pr

oced

ures

, the

refo

re n

ot

incl

uded

in th

e an

alys

is.

Diffi

culty

swal

low

ing

afte

r uv

ulop

alat

opha

ryng

alpl

asty

or

uvu

lopa

lato

plas

ty su

rger

y in

31%

or 2

7% o

f cas

es,

resp

ectiv

ely.

Com

plic

atio

n ra

tes

have

dec

reas

ed in

late

r stu

dies

1b (e

ffect

ive-

ness

) and

4

(UW

)

Gree

nbur

g et

al.

[171

]20

09In

tern

atio

nal

Met

a-an

alys

isO

SA12

Baria

tric

surg

ery

BMI,

AHI

Baria

tric

surg

ery

impr

oves

BM

I an

d AH

I1-

4


Tab.

B.1

0 Cu

rrent

syst

emat

ic re

view

s (SR

) and

met

a-an

alys

es (M

A) fo

r the

trea

tmen

t of o

bstr

uctiv

e sle

ep a

pnea

(OSA

) (co

ntin

ued)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

stud

ies

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Hand

ler e

t al.

[178

]20

14In

tern

atio

nal

Revi

ewO

SA27

Tong

ue su

spen

sion

(6),

all o

ther

wor

k w

ith

UPPP

AHI

Tong

ue su

spen

sion

alon

e w

ith re

spon

se ra

te o

f 36.

6%,

in co

mbi

natio

n w

ith U

PPP

as g

ood

as g

enio

glos

sus

adva

ncem

ent a

nd h

yoid

su

spen

sion

(62.

1% v

s. 61

.6%

)

Hech

t et a

l. [1

86]

2011

Inte

rnat

iona

lRe

view

and

m

eta-

anal

ysis

OSA

S6

(3 p

aral

lel,

2 cr

oss-

over

, 1

cont

rolle

d)

CPAP

, ran

dom

ized

and

no

n-ra

ndom

ized

CPAP

effe

ct o

n –

gluc

ose

met

abol

ism –

insu

lin re

sista

nce

No

effec

t on

stud

y en

d po

ints

5 Le

vel 1

11

Leve

l 3

Hira

i et a

l. [1

90]

2010

Inte

rnat

iona

lM

eta-

anal

ysis

OSA

3Po

sitio

n tr

eatm

ent

vs. C

PAP

AHI,

ESS,

02

satu

ratio

n,

subj

ectiv

e te

st p

roce

sses

/qu

estio

nnai

res

Supe

riorit

y of

CPA

P tr

eatm

ent

only

in re

latio

n to

AHI

and

O2

satu

ratio

n, re

com

men

datio

n fo

r pos

ition

-dep

ende

nt O

SA

with

CPA

P no

n-co

mpl

ianc

e/in

tole

ranc

e

1b

Holty

and

Gui

llem

inau

lt et

al.

[194

]20

10In

tern

atio

nal

Met

a-an

alys

isO

SA22

MM

A vs

. CPA

P an

d ca

se

serie

sAH

I, lo

ng-t

erm

effe

cts

MM

A re

liabl

y re

duce

s deg

ree

of

seve

rity,

in co

hort

stud

ies w

ith

vent

ilatio

n tr

eatm

ent,

incr

ease

in

max

illar

y pr

e-po

sitio

ning

an

d lo

wer

pre

oper

ativ

e BM

I w

ith p

ositi

ve p

redi

ctio

n.

Tran

sient

faci

al p

ares

thes

ia

in 1

00%

, per

siste

nt a

fter

12 m

onth

s in

14.2

%

1a

lp e

t al.

[201

]20

12In

tern

atio

nal

Revi

ew

met

a-an

alys

isO

SA24

Auto

-CPA

P vs

. CPA

PCo

mpl

ianc

eAu

to-C

PAP

vs. C

PAP

Co

mpl

ianc

e

(per

iod

of u

se/

nigh

t): 1

1 m

in.

ES

S

(0.5

pt.)

–CP

AP v

s. au

to-C

PAP

Sa

O2m

in.

1b–2

c

Kaw

et a

l. [2

29]

2012

Inte

rnat

iona

lM

eta-

anal

ysis

OSA

13 R

CTs

Non

epo

stop

. com

plic

atio

ns in

O

SAS

patie

nts:

–ca

rdia

l –

acut

e pu

lmon

ary

failu

re

desa

tura

tion

ICU

Effec

ts o

n st

udy

end

poin

ts1



Tab.

B.1

0 Cu

rrent

syst

emat

ic re

view

s (SR

) and

met

a-an

alys

es (M

A) fo

r the

trea

tmen

t of o

bstr

uctiv

e sle

ep a

pnea

(OSA

) (co

ntin

ued)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

stud

ies

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Li e

t al.

[261

]20

11In

tern

atio

nal

Revi

ewO

SA13

Nas

al su

rger

y vs

. Pla

cebo

AHI,

ESS,

snor

ing

No

influ

ence

on

AHI,

ESS

and

snor

ing

decr

ease

1b–4

Li e

t al.

[262

]20

13In

tern

atio

nal

Revi

ew/

met

a-an

alys

isO

SA14

OA

vs. C

PAP

AHI,

ESS,

HR

QoL

, CP,

BP,

AI, R

EM, m

in. S

pO2,

SE,

com

plia

nce,

pre

fere

nce,

dr

opou

ts

CPAP

with

rega

rd to

AHI

, AI,

min

. SpO

2, RE

M co

nsid

erat

ions

O

A an

d CP

AP w

ith re

gard

to

ESS

, HRQ

oL, C

P, BP

, SE,

co

mpl

ianc

e, p

refe

renc

e an

d dr

opou

t com

para

ble

1

Lin

et a

l. [2

64]

2008

Inte

rnat

iona

lRe

view

OSA

49M

ulti-

leve

l sur

gery

AHI,

O2 s

atur

atio

n, R

EM

cont

ent,

snor

ing

(VAS

) da

y-tim

e sle

epin

ess,

qual

ity o

f life

Sign

ifica

nt im

prov

emen

t of

AHI (

AHI r

educ

tion

> 50

% to

a

valu

e of

<20

) in

66.4

% o

f all

patie

nts.

Succ

ess r

ate

high

er

with

AHI

> 4

0 (6

9.3%

) tha

n if

AHI <

40

(56.

5%).

No

wor

seni

ng

3–8

year

s pos

tope

rativ

ely.

Sign

ifica

nt im

prov

emen

t of a

ll ot

her p

aram

eter

s inv

estig

ated

1b–4

Mad

boul

y et

al.

[272

]20

14In

tern

atio

nal

Met

a-an

alys

isO

SA12

CPAP

OSA

S de

gree

of s

ever

ity

(AHI

) and

CPA

P co

mpl

ianc

eSi

gn. C

orre

latio

n be

twee

n O

SAS

degr

ee o

f sev

erity

and

co

mpl

ianc

e

2a

Mar

klun

d et

al.

[277

]20

12In

tern

atio

nal

Revi

ewO

SA55

OA

vs. P

lace

boO

A vs

. OA

OA

vs. C

PAP

OA

vs. s

urge

ry

AHI,

RDI,

PSG,

da

y-tim

e tir

edne

ss, Q

oL,

card

iova

scul

ar p

aram

eter

s, lo

ng-t

erm

effe

cts

OA

mor

e eff

ectiv

e th

an

plac

ebo,

deg

ree

of p

rotr

usio

n co

rrela

tes w

ith e

ffect

iven

ess

CPAP

is su

perio

r to

OA

in it

s AHI

re

duct

ion.

Day

-tim

e tir

edne

ss,

QoL

, car

diov

ascu

lar p

aram

eter

s ar

e co

mpa

rabl

e Lo

ng-t

erm

effe

ct is

less

than

in

itial

impr

ovem

ent

1-5


Tab.

B.1

0 Cu

rrent

syst

emat

ic re

view

s (SR

) and

met

a-an

alys

es (M

A) fo

r the

trea

tmen

t of o

bstr

uctiv

e sle

ep a

pnea

(OSA

) (co

ntin

ued)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

stud

ies

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

McD

aid

et a

l. [2

87]

2009

Inte

rnat

iona

lRe

view

OSA

48/2

9CP

APBe

st su

ppor

tive

care

plac

ebo

MAD

ESS

MW

TM

SLT

QAL

Y

CPAP

vs.

cons

erva

tive

ES

S

(sig

n.)

M

WT

–CP

AP v

s.MAD

ES

S: n

o di

ffere

nces

–CP

AP v

s.MAD

Be

nefit

s

Cost

s

2c

Met

ha e

t al.

[295

]20

13In

tern

atio

nal

Met

a-an

alys

isO

SA14

O2 v

ersu

s am

bien

t air

O2 v

ersu

s CPA

PAH

I, O

2 sat

urat

ion

AHI,

O2

satu

ratio

nO

2 is s

uper

ior t

o am

bien

t air

with

rega

rd to

nig

ht-t

ime

O2

satu

ratio

n CP

AP is

supe

rior t

o O

2 with

re

gard

to re

duct

ion

of A

HI

1-4

Qur

eshi

et a

l. [3

69]

2015

Inte

rnat

iona

lM

eta-

anal

ysis

OSA

8CP

AP v

s. no

CPA

PCP

AP tr

eatm

ent a

nd V

HF

frequ

ency

CPAP

: sig

nific

ant r

educ

tion

of

risk

for V

HF2c

Pirk

lbau

er e

t al.

[359

]20

11In

tern

atio

nal

Revi

ewO

SA28

MM

A vs

. CPA

P an

d ca

se

serie

sAH

I, lo

ng-t

erm

effe

cts,

da

y-tim

e sle

epin

ess

MM

A is

com

para

ble

with

ve

ntila

tion

trea

tmen

t, po

sitiv

e eff

ects

on

day-

time

sleep

ines

s, qu

ality

of l

ife, n

o ne

gativ

e eff

ect o

n fa

cial

est

hetic

s

1b–4

Sark

hosh

et a

l. [3

98]

2013

Inte

rnat

iona

lSR

OSA

69Ba

riatr

ic su

rger

yBM

I, AH

IBa

riatr

ic su

rger

y im

prov

es B

MI

and

AHI

1-4

Smith

et a

l. [4

22]

2006

Inte

rnat

iona

lRe

view

OSA

26M

edic

atio

nAH

I, sle

epin

ess

Med

icat

ion

cann

ot b

e re

com

men

ded

1-4

Smith

et a

l. [4

23]

2009

Inte

rnat

iona

lRe

view

(C

ochr

ane)

OSA

45CP

APCo

mpl

ianc

e in

crea

se

thro

ugh

pres

sure

m

odifi

catio

n

–Au

to-C

PAP

vs.C

PAP

Pe

riod

of u

se

(n. s

.)

ES

S

(n. s

.) –

Bi-le

vel

Pe

riod

of u

se (n

. s.)

–Ai

r hum

idifi

catio

n (n

. s.)

1a

Sun

et a

l. [4

38]

2013

Inte

rnat

iona

lM

eta-

anal

ysis

OSA

10CP

APLV

-EF

–CP

AP w

ith O

SA a

nd LV

-EF

LV

-EF

(sig

n.)

–sig

nific

ant c

orre

latio

n be

twee

n LV

-EF

and

AHI

1a



Tab.

B.1

0 Cu

rrent

syst

emat

ic re

view

s (SR

) and

met

a-an

alys

es (M

A) fo

r the

trea

tmen

t of o

bstr

uctiv

e sle

ep a

pnea

(OSA

) (co

ntin

ued)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

stud

ies

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Deg

ree

of

evid

ence

of

indi

vidu

al

stud

ies

Sund

aram

et a

l. [4

39]

2005

Inte

rnat

iona

lRe

view

OSA

7Su

rger

yAH

I, sn

orin

g, ti

redn

ess

No

effec

t, la

ck o

f lon

g-te

rm

data

1 u.

2

Treg

ear e

t al.

[445

]20

10In

tern

atio

nal

Revi

ew

met

a-an

alys

isO

SA9

CPAP

Fr

eque

ncy

of a

ccid

ents

pr

ior t

o an

d du

ring

CPAP

Tr

eatm

ent p

erio

d un

til

fall

in a

ccid

ent f

requ

ency

Day

-tim

e sle

epin

ess

(sig

n.)

afte

r a C

PAP

nigh

tFr

eque

ncy

of a

ccid

ents

with

O

SAS

unde

r CPA

P sig

nific

ant

Tim

e pe

riod

until

fall

in

acci

dent

freq

uenc

y: 2

–7 d

ays

(driv

ing

simul

atio

n)

2c

Woz

niak

et a

l. [4

84]

2014

Inte

rnat

iona

lRe

view

(C

ochr

ane)

OSA

30CP

AP p

lus

–Tr

aini

ng –

Supp

ort

–Be

havi

or th

erap

y

Com

plia

nce

Com

plia

nce

incr

ease

thro

ugh

all f

orm

s of i

nter

vent

ion,

al

thou

gh e

ffect

is sm

all

2c

Yang

et a

l. [4

90]

2013

Inte

rnat

iona

lM

eta-

anal

ysis

OSA

S15

Non

eCP

AP e

ffect

on

–BZ

cont

rol

–in

sulin

resis

tanc

e

Effec

ts o

n st

udy

end

poin

ts13

obs

erva

-tio

nal

2 (L

evel

4)

obse

rva-

tiona

l, co

ntro

lled

(Lev

el 4

) 2

ran-

dom

ized

, co

ntro

lled

(Lev

el 1

)


Tab.

B.1

1 Su

mm

ary

of L

evel

-1 st

udie

s for

the

trea

tmen

t (di

ffere

nt tr

eatm

ent p

roce

sses

) of o

bstr

uctiv

e sle

ep a

pnea

(OSA

). In

clus

ion

crite

ria: S

tudy

pop

ulat

ion

>20,

obs

erva

tion

perio

d ≥

4 w

eeks

Auth

orYe

arCo

untr

ySt

udy

type

Popu

la-

tion

Num

ber o

f pat

ient

s (n

)In

terv

entio

nSt

udy

endp

oint

Effec

t on

stud

y en

d po

int (p

valu

e)Le

vels

of

evid

ence

Baba

dem

ez e

t al.

[30]

2011

Turk

eyRC

TO

SA45

Ope

n tr

anso

ral r

adio

fre

quen

cy b

ase

of

tong

ue re

sect

ion

vs.

subm

ucou

sal m

inim

ally

in

vasiv

e to

ngue

exc

ision

w

ith ra

dio

frequ

ency

vs

. with

ultr

asou

nd

blad

e (a

ll in

com

bina

tion

with

UPP

P)

AHI,

ESS,

tong

ue

volu

me

(MRI

), pa

inN

o re

leva

nt d

iffer

ence

be

twee

n th

e gr

oups

1b

Bäck

et a

l. [3

2]20

09Fi

nlan

dRC

TO

SA32

RFTA

of t

he so

ft pa

late

vs

. pla

cebo

surg

ery

Prim

ary:

AHI

, ESS

, SF

-36

Seco

ndar

y:

Snor

ing,

ce

phal

omet

ric

para

met

ers,

unde

sired

eve

nts

No

diffe

renc

e be

twee

n th

e gr

oups

, alth

ough

ju

st o

ne tr

eatm

ent

com

pare

d to

the

stan

dard

of 2

or m

ore

trea

tmen

ts

1b

Brow

aldh

et a

l. [7

0]20

13Sw

eden

RCT

OSA

65 (BM

I < 3

6, F

riedm

an

stag

e 1

or II

)

UPPP

vs.

7 m

onth

s wai

tPr

imar

y: A

HI

seco

ndar

y: fu

rthe

r PS

G pa

ram

eter

s

UPPP

vas

tly su

perio

r to

wai

ting

with

re

gard

to A

HI a

nd a

ll re

spira

tory

par

amet

ers

irres

pect

ive

of

BMI,

tons

il siz

e an

d Fr

iedm

an st

age.

Of

all s

leep

par

amet

ers

only

aro

usal

inde

x sig

nific

antly

redu

ced

1b

Dix

on e

t al.

[124

]20

12Au

stra

liaPa

ralle

l ove

r 2

year

sO

SA60

Cons

erva

tive

(die

t, ad

vice

) vs.

oper

ativ

e w

eigh

t red

uctio

n (la

paro

scop

. gas

tric

ba

nd)

BMI A

HIBe

tter

in O

P gr

oup

(p <

0.0

01)

Tend

ency

tow

ards

be

tter

in O

P gr

oup

(p =

0.1

8)

1b

Fost

er e

t al.

[147

]20

09US

APa

ralle

l ove

r 1

year

OSA

with

ty

pe 2

di

abet

es

264

Redu

ced-

calo

rie d

iet

vs. a

dvic

eAH

Ip

< 0.

011b

Guim

arae

s et a

l. [1

74]

2009

Braz

ilPa

ralle

l ove

r 3

mon

ths

OSA

31O

roph

aryn

geal

exe

rcise

s ve

rsus

“sha

m” t

hera

pyAH

I ES

S

Sign

ifica

ntly

bet

ter

than

pla

cebo

Sign

ifica

ntly

bet

ter

than

pla

cebo

1b

Joha

nsso

n et

al.

[218

]20

09Sw

eden

Para

llel o

ver 9

w

eeks

OSA

63D

iet v

s. us

ual n

utrit

ion

AHI

ESS

p <

0.01

p

< 0.

011b



Tab.

B.1

1 Su

mm

ary

of L

evel

-1 st

udie

s for

the

treat

men

t (di

ffere

nt tr

eatm

ent p

roce

sses

) of o

bstr

uctiv

e sle

ep a

pnea

(OSA

). In

clus

ion

crite

ria: S

tudy

pop

ulat

ion

> 20

, obs

erva

tion

perio

d ≥

4 w

eeks

(con

tinue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

la-

tion

Num

ber o

f pat

ient

s (n

)In

terv

entio

nSt

udy

endp

oint

Effec

t on

stud

y en

d po

int (p

valu

e)Le

vels

of

evid

ence

Mau

rer e

t al.

[285

]20

13Ge

rman

yRC

TO

SA22

Pilla

r vs.

Plac

ebo

surg

ery

AHI,

Al, H

l, av

er.

Sa0 2

, min

. Sa0

2, ES

S, sn

orin

g

HI, A

HI, m

in. S

aO2,

and

snor

ing

in v

erum

gr

oup

signi

fican

tly

redu

ced,

but

no

signi

fican

t gro

up

diffe

renc

e

1b

Phill

ips e

t al.

[358

]20

13Au

stra

liaRC

TO

SA12

6 (1

08)

OA

vs.C

PAP

(cro

ssov

er)

AHI,2

4 h

BP,

com

plia

nce,

da

y-tim

e tir

edne

ss,

fitne

ss to

driv

e,

QoL

CPAP

redu

ces t

he

AHI m

ore

effec

tivel

y (0

.01)

OA

Com

plia

nce

supe

rior t

o CP

AP

(0.0

0001

). N

o eff

ects

on

the

BP Q

oL,

day-

time

tired

ness

an

d fit

ness

to d

rive

com

para

ble

MAD

in

4 Q

oL su

perio

r to

para

met

ers

1b

Puha

n et

al.

[363

]20

06Sw

itzer

land

Para

llel o

ver

4 m

onth

sO

SA25

Did

gerid

oo g

ame

vers

us

cont

rol g

roup

(wai

ting

list)

AHI

ESS

Sign

ifica

ntly

bet

ter

than

cont

rol

Sign

ifica

ntly

bet

ter

than

cont

rol

1b

Rand

erat

h et

al.

[373

]20

04Ge

rman

yPa

ralle

l ove

r 8

wee

ksO

SA67

Intr

aora

l ele

ctric

st

imul

atio

n ve

rsus

pl

aceb

o

AHI

ESS

No

supe

riorit

y co

mpa

red

to th

e pl

aceb

o N

o su

perio

rity

com

pare

d to

the

plac

ebo

1b

Skin

ner e

t al.

[420

]20

08N

ew Z

eala

ndPa

ralle

l ove

r 4

mon

ths

OSA

20“T

hora

cic

anti-

supi

ne

band

” (m

odifi

ed “t

enni

s ba

ll” m

etho

d) v

ersu

s CP

AP

AHI (

mea

ns

and

succ

essf

ul

redu

ctio

n) a

nd

aver

age

O2

satu

ratio

n ES

S,

FOSQ

, SF-

35

com

plia

nce,

side

eff

ects

CPAP

> p

ositi

on

ther

apy

signi

fican

tly

bett

er th

an co

ntro

l n.

s.Po

sitio

n th

erap

y > C

PAP

1b


Tab.

B.1

1 Su

mm

ary

of L

evel

-1 st

udie

s for

the

treat

men

t (di

ffere

nt tr

eatm

ent p

roce

sses

) of o

bstr

uctiv

e sle

ep a

pnea

(OSA

). In

clus

ion

crite

ria: S

tudy

pop

ulat

ion

> 20

, obs

erva

tion

perio

d ≥

4 w

eeks

(con

tinue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

la-

tion

Num

ber o

f pa-

tient

s (n)

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

end

poin

t (p

valu

e)Le

vels

of

evid

ence

Stro

llo e

t al.

[434

]20

14In

tern

atio

nal

Rand

omiz

ed

trea

tmen

t w

ithdr

awal

OSA

126

(46

in

rand

omiz

ed a

rm)

Stim

ulat

ion

activ

e vs

. ina

ctiv

ePr

im.:

AHI,

OD

I Se

c.: T

90, E

SS,

FOSQ

All t

arge

t par

amet

ers

signi

fican

tly im

prov

ed,

inac

tive

stim

ulat

ion

with

out e

ffect

. 12

mon

ths f

ollo

w-u

p

1b

Tuom

ileht

o et

al.

[447

]20

09Fi

nlan

dPa

ralle

l ove

r 1

year

OSA

72D

iet v

s. di

abet

es

man

agem

ent

AHI

p <

0.05

1b

Vici

ni e

t al.

[453

]20

10Ita

lyRC

TO

SA50

MM

A vs

. APA

PAH

I, ES

SAH

I and

ESS

iden

tical

, ov

eral

l sat

isfac

tion

is gr

eate

r with

MM

A,

12 m

onth

s fol

low

-up

1b

Win

slow

et a

l. [4

81]

2012

USA

Para

llel o

ver

28 w

eeks

OSA

45Ph

ente

rmin

e 15

mg

plus

Topi

ram

at 9

2 m

g vs

. pla

cebo

BMI A

HISu

perio

rity

over

pl

aceb

o (b

oth

p <

0.00

1)

1b



Tab.

B.1

2 Ra

ndom

ized

cont

rolle

d st

udie

s (rK

S), o

utco

me

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or ce

ntra

l sle

ep a

pnea

with

Che

yne-

Stok

es re

spira

tion

and

card

iac

insu

ffici

ency

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

n (n

)In

terv

entio

nO

bser

vatio

n pe

riod

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Leve

ls o

f ev

iden

ce

Andr

eas e

t al.

[16]

1996

Germ

any

rKS

22O

2 (4

l)1

wee

kAH

I (h–1

) VO

2max

26

10

(–62

%)

835

960

(l/m

in)

2b

Arzt

et a

l. [2

5]20

13Ge

rman

y, UK

, Fr

ance

, Can

ada

rKS

72AS

V co

ntro

l3

mon

ths

Cent

ral A

HI

Ntp

ro B

NP

LVEF

20

5/h

(p <

0.0

01)

1039

9

40 p

g/m

L (p

= 0

.06)

30

33%

(ns)

2b

Auro

ra e

t al.

[27]

2012

USA

Met

a-an

alys

isCP

AP:

165

(tran

spla

nt-fr

ee

surv

ival

)37

7 (L

VEF)

282

(AHI

)Bi

-leve

l HF:

28 (A

HI)

ASV:

127

(AHI

)95

(LVE

F

CPAP

Bi-le

vel H

FAS

V

1 ni

ght t

o 24

mon

ths

CPAP

:Tr

ansp

lant

-free

Surv

ival

LVEF

AHI

Bi-le

vel H

F:AH

IAS

V:LV

EFAH

I

9–33

% e

vent

rate

for C

PAP

vs. 2

4–56

% e

vent

rate

for

cont

rols

MD

6.4

hig

her

(2.4

–10.

5 hi

gher

)M

D 2

1 lo

wer

(25–

17 lo

wer

)M

D 4

4 lo

wer

(40–

49 lo

wer

)M

D 6

.1 h

ighe

r(3

.9–8

.4 h

ighe

r)M

D 3

1 lo

wer

(2

5–36

low

er)

2a

Bitt

er e

t al.

[53]

2011

Germ

any

OUS

255

–48

mon

ths

Adeq

uate

trig

gerin

g of

the

impl

ante

d de

fibril

lato

rZS

A (A

HI ≥

15/

h)

inde

pend

ent r

isk fa

ctor

: HR

(95%

CI):

3.4

1 (2

.10–

5.54

), p

< 0.

001

2c

Brad

ley

et a

l. [6

6]20

05Ca

nada

, Ger

-m

any

rKS

258

CPAP

24 m

onth

sAH

I (h–1

) Q

oLLV

EFTo

d/HT

X

40

19

(53%

) 24

.2

26.

4%

1b

Cow

ie e

t al.

[110

]20

15Ge

rman

y, Fr

ance

, Sw

eden

, UK,

Au

stra

lia

Den

mar

k,

Nor

way

, Cz

echi

a,

Finl

and,

Sw

itzer

land

, N

ethe

rland

s

rKS

1325

ASV

31 m

onth

sCo

mbi

ned

end

poin

t:

Dea

th, l

ife-s

avin

g ca

rdio

vasc

ular

in

terv

entio

n or

unp

lann

ed

hosp

italiz

atio

n du

e to

a

wor

seni

ng o

f car

diac

in

suffi

cien

cy

Dea

th o

f all

caus

es

Card

iova

scul

ar m

orta

lity

ASV

vs co

ntro

l: 54

.1 v

s 50.

8%, H

R 1.

13;

95%

Cl 0

.97

to 1

.31;

P

= 0.

10

HR 1

.28;

95%

Cl 1

.06

to

1.55

; P =

0.0

1 HR

1.3

4; 9

5% C

l 1.0

9 to

1.

65; P

= 0

.006

1a


Tab.

B.1

2 Ra

ndom

ized

cont

rolle

d st

udie

s (rK

S), o

utco

me

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or ce

ntra

l sle

ep a

pnea

with

Che

yne-

Stok

es re

spira

tion

and

card

iac

insu

ffici

ency

(con

tinue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

n (n

)In

terv

entio

nO

bser

vatio

n pe

riod

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Leve

ls o

f ev

iden

ce

Dam

y et

al.

[113

]20

12Fr

ance

OUS

384

–47

mon

ths

Com

bine

d en

d po

int f

rom

de

ath,

HTx

and

impl

ant

of a

left

vent

ricul

ar a

ssist

sy

stem

Seve

re Z

SA (A

HI ≥

20/

h)

vers

us n

o/ li

ght Z

SA (A

HI

< 20

h):

HR 1

.61,

95%

Cl

1.16

–2.2

5 (p

= 0

.018

ad

just

ed fo

r sig

nific

ant

inte

rfere

nce

varia

bles

)

2c

Dav

ies e

t al.

[116

]19

93UK

rKS

7CP

AP2

wee

ksD

esat

urat

ion

inde

x LV

EF

2b

Fiet

ze e

t al.

[140

]20

07Ge

rman

yrK

S37

Bi-le

vel P

APHF AS

V

6 w

eeks

AHI (

h–1)

LVEF

Bi-le

vel A

F: 3

5

16

(54%

) AS

V: 3

2

11

(66%

) Bi

-leve

l AF:

26

31%

ASV:

25

27%

2b

Hanl

y et

al.

[180

]19

89Ca

nada

rKS

9O

2 (2–

3 l)

1 ni

ght

AHI (

h–1)

30

19

(–37

%)

2b

Java

heri

et a

l. [2

10]

2007

USA

OUS

88–

51 m

onth

sM

orta

lity

rate

AHI ≥

5/h

ver

sus A

HI

< 5/

h: H

azar

d ra

tio, 2

.1;

P =

0.02

, (ad

just

ed)

2c

Jilek

et a

l. [2

16]

2011

Germ

any

OUS

296

–49

mon

ths

Mor

talit

y ra

teSe

vere

ZSA

(AHI

≥ 2

2.5/

h)

vers

us n

o/ li

ght Z

SA (A

HI

<22.

5/h)

: 38

vs 1

6%,

unad

just

ed p

= 0

.002

, ad

just

ed fo

r age

and

NY

HA c

lass

p =

0.0

35

2c

Kasa

i et a

l. [2

28]

2010

Japa

nrK

S31

ASV

CPAP

3 m

onth

sLV

EF

Plas

ma

BNP

6 m

in w

alk

test

Q

OL

(SF3

6)

ASV

vs. C

PAP

+ 9.

1 vs

. + 1

(p <

0.0

5)–3

6 vs

. –4

(p =

0.0

06)

+35

vers

us –

9 m

(p

= 0

.008

)Si

gnifi

cant

impr

ovem

ent

in 4

of 8

dom

ains

2b

Köhn

lein

et a

l. [2

35]

2002

UKrK

S16

CPAP

Bi-le

vel P

AP2

wee

ksAH

I (h–1

)CP

AP: 2

7

8 (7

0%)

Bi-le

vel:

27

7 (7

4%)

2b

Koya

ma

et a

l. [2

38]

2010

Japa

nrK

S17

ASV

Chec

ks3

mon

ths

LVEF

Plas

ma

BNP

ASV:

44

53

(p =

0.0

02)

Chec

ks: 4

6

46

(p =

0.9

0)AS

V: 2

12

77

(p =

0.0

4)Ch

ecks

: 293

1

49

(p =

0.3

3)

2b

Krac

hman

et a

l. [2

40]

1999

USA

rKS

14O

2 (2

l)1

nigh

tAH

I (h–1

)44

1

8 (–

59%

)2b



Tab.

B.1

2 Ra

ndom

ized

cont

rolle

d st

udie

s (rK

S), o

utco

me

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or ce

ntra

l sle

ep a

pnea

with

Che

yne-

Stok

es re

spira

tion

and

card

iac

insu

ffici

ency

(con

tinue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

n (n

)In

terv

entio

nO

bser

vatio

n pe

riod

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Leve

ls o

f ev

iden

ce

Lanf

ranc

hi e

t al.

[252

]19

99Ita

lyO

US62

–28

mon

ths

Cum

ulat

ive

1 an

d 2

year

m

orta

lity

AHI ≥

30/

h: 2

1 an

d 50

%AH

I < 3

0/h:

5 a

nd 2

6%(P

< 0

.01;

adj

uste

d)

2c

Mor

gent

hale

r et a

l. [3

06]

2007

USA

rKS

15Bi

-leve

l PAP

HF ASV

<1 w

eek

AHI (

h–1)

Resp

irato

ry a

rous

al in

dex

Bi-le

vel P

AP-H

F 34

6

h–1

AS

V 34

1

h–1

Bi-le

vel-H

F 32

6

h–1

ASV

32

2 h

–1

2b

Nau

ghto

n et

al.

[312

]19

95Ca

nada

rKS

29CP

AP3

mon

ths

AHI (

h–1)

QoL

LVEF

39

11

(72%

) 20

2

8%

2b

Nöd

a et

al.

[319

]20

07Ja

pan

rKS

21Bi

-leve

l PAP

1 ni

ght

3 m

onth

sAH

I (h–1

)LV

EF28

5

(74%

)+2

0% (b

i-lev

el P

AP)

+3%

(con

trol

gro

up)

2b

Pepp

erel

l et a

l. [3

52]

2003

UKrK

S30

ASV

1 m

onth

Day

time

sleep

ines

sLV

EFBN

PM

etad

rena

line

(urin

e)

Met

nora

dren

alin

e (u

rine)

26

34

min

(Osle

r tes

t)37

3

8%36

3

278

pg/

ml

61

45

nmol

/mm

ol

crea

tinin

e19

0

153

nm

ol/m

mol

cr

eatin

ine

2b

Phill

ipe

et a

l. [3

56]

2006

Fran

cerK

S25

CPAP

AS

V6

mon

ths

AHI (

h–1)

QoL

(Min

neso

ta q

u.)

Trea

tmen

t com

plia

nce

(6 m

o)

CPAP

: ,

ASV

:

CPAP

: , A

SV:

4.3

h/da

y, CP

AP <

ASV

2b


Tab.

B.1

2 Ra

ndom

ized

cont

rolle

d st

udie

s (rK

S), o

utco

me

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or ce

ntra

l sle

ep a

pnea

with

Che

yne-

Stok

es re

spira

tion

and

card

iac

insu

ffici

ency

(con

tinue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

n (n

)In

terv

entio

nO

bser

vatio

n pe

riod

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Leve

ls o

f ev

iden

ce

Poni

kow

ski e

t al.

[361

]20

12Po

land

, USA

, Ge

rman

yHF

16Un

ilate

ral

stim

ulat

ion

of N

. Phr

e-ni

cus

1 ni

ght

AHI,

cent

ral a

pnea

in

dex,

aro

usal

inde

x,

desa

tura

tion

inde

x

AHI:

45 (3

9–59

) vs.

23

(12–

27) e

vent

s/h,

P

= 0.

002

cent

ral a

pnea

inde

x:27

(11–

38) v

s. 1

(0–5

)ev

ents

/h, P

≤ 0

.001

Arou

sal i

ndex

:32

(20–

42) v

s. 12

(9–2

7)ev

ents

/h, P

= 0

.001

D

esat

urat

ion

inde

x:31

(22–

36) v

s. 14

(7–2

0)ev

ents

/h, P

= 0

.002

4

Rand

erat

h et

al.

[376

]20

12Ge

rman

yrK

S70

ASV

CPAP

12 m

onth

sCe

ntra

l AHI

Ntp

ro B

NP

LVEF

23

6/h

(p <

0.0

01

vs b

ase

line,

p <

0.0

5 vs

CPA

P)53

8

230

pg/

mL

(p <

0.0

5 vs

CPA

P)47

4

5% (n

s)

2b

Roeb

uck

et a

l. [3

87]

2004

Aust

ralia

OUS

78–

52 m

onth

sM

orta

lity

rate

M

orta

lity/

HTX

rate

No

signi

fican

t diff

eren

ce

betw

een

CSA,

OSA

gro

ups

and

the

grou

p w

ithou

t sle

ep a

pnea

2c

Rutt

anau

mpa

wan

et a

l. [3

93]

2009

Cana

da,

Germ

any

rKS

205

CPAP

3 m

onth

sAH

IAr

ousa

l ind

ex39

1

8 (5

4%)

No

signi

fican

t cha

nge

1b

Sasa

yam

a et

al.

[399

]20

09Ja

pan

rKS

5102

(31)

12 w

eeks

AHI (

h–1),

LVEF

, act

ivity

sc

ale

AHI:

19/h

9

/hLV

EF: 3

3%

38%

BNP:

493

5

56 p

g/m

(p

> 0

.05)

QO

L: 3

.9 ±

1.2

to 4

.7 ±

1.6

sp

ecifi

c ac

tivity

scal

e,

p <

0.01

2b

Shar

ma

et a

l. [4

08]

2012

USA

Met

a-an

alys

is53

8AS

V1-

12 m

onth

sAH

I

LVEF

Wei

ght a

vera

ged

effec

ts

of A

SV v

ersu

s con

trol

in

terv

entio

n: –

15 e

vent

s/ho

ur, 9

5%

(CI –

21 to

–8)

0.40

, 95%

(CI 0

.08

to

0.71

) bot

h sig

nific

antly

fa

vour

ed A

SV

2a



Tab.

B.1

2 Ra

ndom

ized

cont

rolle

d st

udie

s (rK

S), o

utco

me

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or ce

ntra

l sle

ep a

pnea

with

Che

yne-

Stok

es re

spira

tion

and

card

iac

insu

ffici

ency

(con

tinue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

n (n

)In

terv

entio

nO

bser

vatio

n pe

riod

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Leve

ls o

f ev

iden

ce

Sin

et a

l. [4

17]

2000

Cana

daO

US66

26 m

onth

sM

orta

lity/

HTX

rate

AHI ≥

15/

h ve

rsus

AHI <

15/

h: H

azar

d ra

tio,

2.5;

95%

(CI,

1.1

to 5

.9;

P =

0.03

2, a

djus

ted)

2c

Sin

et a

l. [4

17]

2000

Cana

darK

S29

CPAP

3/26

mon

ths

LVEF

dea

th/H

TX20

2

8%56

% ri

sk re

duct

ion,

P

= 0.

059

2b

Stan

ifort

h et

al.

[429

]19

98UK

rKS

1102

(21)

4 w

eeks

All c

entr

al fh

f 1)

Nor

epin

ephr

ine

(urin

e)18

4

(78%

)8.

3

4.1

nm

ol/m

mol

cr

eatin

ine

2b

Tesc

hler

et a

l. [4

42]

2001

Germ

any

rKS

1402

(21)

1 ni

ght

AHI (

h–1)

45

28

(–38

%)

2b

Tesc

hler

et a

l. [4

42]

2001

Germ

any

rKS

14CP

APBi

-leve

l PAP

HF ASV

1 ni

ght

AHI (

h–1)

CPAP

: 45

27

(40%

)Bi

-leve

l AF:

45

15

(67%

)AS

V: 4

5

6 (8

7%)

2b

Zhan

g et

al.

[502

]20

12Ch

ina

HF19

Unila

tera

l st

imul

a-tio

n of

the

N. P

hren

icus

1 ni

ght

AHI,

med

ium

and

min

imal

ox

ygen

satu

ratio

n, e

nd

tidal

CO

2, sle

ep e

ffici

ency

de

satu

ratio

n in

dex

AHI:

33.8

± 9

.3 v

s 8.1

± 2

.3,

P <

0.00

1m

ediu

m a

nd m

inim

al

oxyg

en sa

tura

tion:

89.7

% ±

1.6

% v

s 94.

3%

± 0.

9% a

nd 8

0.3%

± 3

.7%

vs 8

8.5%

± 3

.3%

, eac

h P

< 0.

001

End

tidal

CO

2:8.

0 ±

4.3

mm

Hg

vs 4

0.3

± 3.

1 m

m H

g, (P

= 0

.02)

Slee

p effi

cien

cy d

esat

ura-

tion

inde

x:74

.6%

± 4

.1%

vs 7

3.7%

±

5.4%

, P =

0.3

6

–

AHI A

pnea

hyp

opne

a in

dex,

ASV

adap

tive

serv

oven

tilat

ion,

bi-l

evel

PAP

HF “

bi-le

vel p

ositi

ve a

irway

pre

ssur

e” w

ith b

ackg

roun

d fre

quen

cy, B

NP

“bra

in n

atriu

retic

pep

tide,”

CI c

onfid

ence

inte

rval

, CSA

cen

tral s

leep

ap

nea,

HTX

hea

rt tra

nspl

ant,

LVEF

left

vent

ricul

ar e

ject

ion

fract

ion,

OSA

obs

truct

ive

sleep

apn

ea, Q

ol q

ualit

y of

life

, VO

2max

max

imum

oxy

gen

abso

rptio

n


Tab.

B.1

3 O

utco

me

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or ce

ntra

l sle

ep a

pnea

with

Che

yne-

Stok

es re

spira

tion

in st

roke

pat

ient

s

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

n (n

)In

terv

en-

tion

Obs

erva

tion

perio

dSt

udy

endp

oint

Effec

t on

stud

y en

dpoi

ntLe

vels

of

evid

ence

Bonn

in-V

illap

lana

et a

l. [6

1]20

12Sp

ain

OUS

68 (a

fter l

acun

ar

stro

ke)

–<

48 h

Type

of s

leep

ap

nea

CSR

in 2

1% p

f pa

tient

s (>

10%

of

slee

ping

tim

e).

Patie

nts w

ith C

SR:

Cent

ral A

HI 1

3/h,

ob

stru

ctiv

e AH

I 22

/h

3

John

son

and

John

son

[221

]20

10US

AO

US29

Pub

licat

ions

23

43 p

atie

nts

with

isch

emic

or

hem

orrh

egic

st

roke

or t

rans

itory

isc

hem

ic a

ttac

k

––

17 P

ublic

atio

ns

repo

rted

the

prev

alen

ce o

f the

ZS

A (A

HI ≥

10/

h)

with

CSR

7% (C

l 4.5

–12%

)1

Parr

a et

al.

[340

]20

00Sp

ain

Case

serie

s11

6(n

= 4

2.28

% C

SA,

48–7

2 h

afte

r a

stro

ke)

–3

mon

ths

AHI

(0

3 m

onth

s)Ce

ntra

l Al

(0

mon

ths)

22

17

(P <

0.0

5)

6

3 (P

< 0

.05)

4

Sahl

in e

t al.

[394

]20

08Sw

eden

OUS

132

(23

OSA

, 28

CSA

)–

10 y

ears

Mor

talit

yAH

I ≥10

/h (C

SA)

vers

us A

HI <

10/h

: Ha

zard

ratio

, 1.3

1;

95%

Cl,

0.80

to

2.16

; P =

0.2

9,

(adj

uste

d)

2c

Sicc

oli e

t al.

[411

]20

08Sw

itzer

-la

ndCa

se se

ries

74 (n =

30.

41%

CSR

- C

SA, 5

day

s afte

r a

stro

ke)

––

––

4



Tab.

B.1

4 Co

ntro

lled

stud

ies (

KS),

outc

ome

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or ce

ntra

l sle

ep a

pnea

with

hei

ght-

depe

nden

t per

iodi

c re

spira

tion

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nIn

terv

entio

nSt

udy

endp

oint

Effec

t on

stud

y en

dpoi

ntLe

vels

of

evid

ence

Fisc

her e

t al.

[142

]20

04Ge

rman

yrK

S30

hea

lthy

men

Theo

phyl

line

vers

us

acet

azol

amid

e ve

rsus

pl

aceb

o

HAPB

Theo

phyl

line

and

acet

azol

amid

e-re

duce

d HA

PB.

Acet

azol

amid

e al

so

impr

oved

the

oxyg

en

satu

ratio

n

2b

Lats

hang

et a

l. [2

53]

2012

Switz

erla

ndrK

S51

Pat

ient

with

OSA

tr

eate

d w

ith A

utoC

PAP

Acet

azol

amid

e +

Auto

CPAP

ver

sus

plac

ebo

+ Au

toCP

AP

HAPB

, AHI

, oxy

gen

satu

ratio

nAd

ditio

nal

adm

inist

ratio

n of

ac

etaz

olam

ide

to A

u to

CPA

P tr

eatm

ent

less

ened

HAP

B,

redu

ced

the

AHI a

nd

incr

ease

d th

e ox

ygen

sa

tura

tion

at 1

630

and

2590

m h

eigh

t

2b

Nus

sbau

mer

-Och

sner

et a

l. [3

24]

2010

Switz

erla

ndrK

S34

Pat

ient

s with

un

trea

ted

OSA

490

m (b

ase

line)

, 18

60 a

nd 2

590

m

heig

ht

HAPB

, AHI

Incr

ease

of A

HI d

ue to

HA

PB w

ith in

crea

sing

heig

ht

2b

Nus

sbau

mer

-Och

sner

et a

l. [3

25]

2012

Switz

erla

ndrK

S21

Par

ticip

ants

with

a

hist

ory

of a

ltitu

de

pulm

onar

y ed

ema

Dex

amet

haso

neHA

PB, A

HI, m

ediu

m

oxyg

en sa

tura

tion

Dex

amet

haso

ne

less

ens h

ypox

ia a

nd

HAPB

in 1

. and

3. n

ight

at

499

5 m

hei

ght

2b

Przy

bylo

wsk

i et a

l. [3

65]

2003

Pola

ndCa

se se

ries

-20

00 m

des

cent

HAPB

Redu

ctio

n is

HAPB

fo

llow

ing

desc

ent

4


Tab. B.15 Controlled studies (KS), outcome research studies (OUS) and case series (FS) for central sleep apnea through drugs, medication or substances

Author Year Country Study type

Popula-tion

Interven-tion

Study endpoint Effect on study endpoint

Levels of evidence

Alattar et al. [7] 2009 USA FKS 6 Morphine SaO2 Bi-level respiration corrects hypoxemia through CSA

3b

Farney et al. [134] 2003 USA HF 3 patients Opioid medication

Description of sleep-related respiratory dysfunction

– 4

Mogri et al. [302] 2008 USA HF 3 Opioid CSA AHI Short-term opioid administration increases AHI

4

Walker et al. [458] 2007 USA FKS 60 Opioid AHI CSA-AHI correlated dose-dependent with opioid intake

3b

Wang et al. [462] 2008 Australia ORS 50 Methadone Daytime sleepiness

CSA and methadone concentration do not cause daytime sleepiness

3b

Webster et al. [469] 2008 USA ORS 392 Methadone AHI AHI is directly correlated with methadone dosage

2c

Tab. B. 16 Controlled studies (KS), outcome research studies (OUS) and case series (FS) for primary central sleep apnea

Author Year Country Study type

Popula-tion

Interven-tion

Study endpoint Effect on study endpoint

Levels of evidence

Bradley et al. [64] 1986 USA Case series 18 None Clinical description

None 4

Guilleminault and Robinson [173] 1996 USA Overview – None Clinical description

None 5



Tab.

B. 1

7 Co

ntro

lled

stud

ies (

KS),

outc

ome

rese

arch

stud

ies (

OU

S) a

nd ca

se se

ries (

FS) f

or tr

eatm

ent-

rela

ted

cent

ral s

leep

apn

ea

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nRe

sults

Com

men

tsLe

vels

of

evid

ence

Alla

m e

t al.

[8]

2007

USA

Retr

ospe

ctiv

e, R

evie

w,

PSG

N =

100,

Com

pSAS

(63%

), CS

A (2

2%),

CSA/

CSR

(15%

), AH

I 48

(24–

62),

age

72

(60–

79),

BMI 3

1 (2

8–33

) kg

/m2 , E

SS 1

1 (7

–14)

CPAP

AHI

31

(17–

47) (

p =

0.02

vs

. bas

elin

e), p

rimar

ily C

SA.

Bile

vel S

AHI

75

(46–

111)

(p

= 0

.055

). Bi

leve

l ST

AHI 1

5 (1

1–31

) (p

= 0.

002)

. ASV

AHI

5

(1–1

1) (p

< 0

.000

1 vs

. bas

elin

e an

d CP

AP).

ASV

raise

d RE

M

vs. b

asel

ine

and

CPAP

Retr

ospe

ctiv

e,

hete

roge

neou

s po

pula

tion

4

Brow

n SE

et a

l. [7

1]20

11US

ARe

tros

pect

ive

coho

rt

stud

y , A

SVN

= 25

cons

ecut

ive

patie

nts

with

PAP

refra

ctor

y CS

A,

aged

60

± 17

, BM

I 30.

4 ±

6.1

kg/m

2 , AHI

49

± 30

, (CA

I 11

± 1

6). 1

8 Co

mpS

AS

No

signi

fican

t cha

nges

of t

he

AHI w

ith P

AP w

hen

com

pare

d to

the

base

line.

CAI

raise

d 35

±

24, (

p <

0.00

1). A

SV: A

HI fe

ll to

4 ±

4 (p

< 0

.001

). AH

I < 1

0 in

92%

of p

atie

nts,

CAI 1

± 2

, (p

< 0

.001

). Re

spira

tory

aro

usal

s im

prov

e in

par

alle

l with

ASV

–4

Cass

el e

t al.

[90]

2011

Germ

any

Pros

pect

ive

stud

y, PS

G ba

selin

e, fi

rst n

ight

and

af

ter 3

cyc

les o

f CPA

P

N =

675

(86%

mal

e) O

SA

patie

nts,

aged

56

± 12

, BM

I 32.

2 ±

5.7

kg/m

2 . ES

S 11

± 5

. N

= 82

(86.

6% m

ale)

with

Co

mpS

A, 6

0 ±

10 y

ears

, BM

I 31.

8 ±

5.3

kg/m

2 , AH

I 36

(22–

55).

N =

593

(86%

mal

e) n

o Co

mpS

A, a

ged

55 ±

12,

BM

I 32.

3 ±5

.8 k

g/m

2 , AH

I 26

(15–

44)

12.2

% C

ompS

A ba

selin

e. 2

8 no

fo

llow

-up.

Com

pSA

in fo

llow

-up

for 1

4/54

pat

ient

s. Co

mpS

A in

fo

llow

-up

for 1

6/38

2 pa

tient

s, no

t ini

tially

dia

gnos

ed w

ith

com

pSA.

Com

pSA

in fo

llow

-up

6.9%

. Ind

ivid

uals

with

Com

pSA

wer

e 5

year

s old

er, 4

0% C

AD

–3

Del

lweg

et a

l. [1

20]

2013

Germ

any

RCT,

ASV

vs. b

ileve

l ST

(NIV

), PS

G af

ter 6

wee

ksN

= 30

(21

mal

e) C

ompS

AS,

base

line

data

und

er C

PAP

befo

re ra

ndom

izat

ion

(NIV

vs

. ASV

): 64

± 1

1 ye

ars,

61 ±

11,

mal

e 10

vs.

11,

BMI 2

9.7

± 4.

2 kg

/m2 v

s. 30

.3 ±

4.3

, AHI

29

± 6

vs. 2

8 ±

10, A

l 19

± 6

vs. 2

1 ±

9,

CAI,

17 ±

5 v

s. 18

± 7

NIV

vs.

ASV

noct

urna

l titr

atio

n:

AHI (

9 ±

4 vs

. 9 ±

6),

CAI (

2 ±

3 vs

. 3 ±

4).

Afte

r 6 w

eeks

: AH1

17

± 8

vs. 7

± 4

, p =

0.0

27, C

A110

±

5 vs

. 2 ±

2, p

< 0

.000

1.

No

othe

r sle

ep p

aram

eter

s wer

e us

ed

–1b


Tab.

B. 1

7 Co

ntro

lled

stud

ies (

KS),

outc

ome

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or tr

eatm

ent-

rela

ted

cent

ral s

leep

apn

ea (c

ontin

uatio

n)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nRe

sults

Com

men

tsLe

vels

of

evid

ence

Der

naik

a et

al.

[121

]20

07US

ACr

oss-

sect

ion

anal

ysis,

sp

lit-n

ight

PSG

N =

42 O

SA p

atie

nts w

ith

(21)

and

with

out (

21)

CPAP

-rela

ted

CSA.

With

CSA

: age

d 59

± 1

2,

BMI 3

5.9

± 6.

1 kg

/m2 .

With

out C

SA: a

ged

59 ±

12,

BM

I 36.

8 ±

5.9

kg/m

2 .Ec

hoca

rdio

grap

hy

pulm

onar

y fu

nctio

n bl

ood

gas a

naly

sis. P

SG a

fter 2

–3

cycl

es o

f CPA

P in

the

CSA

patie

nt g

roup

No

diffe

renc

es in

the

dem

ogra

phic

dat

a, LV

EF. C

SA:

decr

ease

d sle

ep e

ffici

ency

, S1

stag

e in

crea

sed,

shift

in

the

sleep

stag

es, W

ASO,

tota

l ar

ousa

ls. 9

2% o

f CSA

pat

ient

s: co

mpl

ete

or a

lmos

t com

plet

e el

imin

atio

n of

CSA

in th

e fo

llow

-up

PSG,

impr

ovem

ent o

f sle

ep p

aram

eter

s

–3

Java

heri

et a

l. [2

12]

2009

USA

Retr

ospe

ctiv

e st

udy,

PSG,

CPA

P tit

ratio

n.

4-w

eek

follo

w-u

p. C

PAP

adhe

renc

e

N =

1286

OSA

pat

ient

s with

PA

P tit

ratio

nN

= 84

(70

mal

e) p

atie

nts

CSA

≥ 5,

age

d 53

± 1

3,

BMI 3

3 ±

4 kg

/m2 .

Ove

rall

inci

denc

e 6.

5%.

Seco

nd P

SG in

42

patie

nts:

Elim

inat

ion

of C

SA in

33/

42.

CSA

rem

aine

d in

9/4

2: b

asel

ine

for s

ever

e ca

ses o

f OSA

; 5

patie

nts C

AI ≥

5 b

asel

ine;

2/

9 du

e to

use

of o

pioi

ds

–4

Kuzn

iar e

t al.

[249

]20

11US

AN

on-ra

ndom

ized

, pa

ralle

l coh

orts

, re

tros

pect

ive,

4–

6 w

eeks

N =

76

(61

mal

e)

cons

ecut

ive

patie

nts,

aged

65

(54–

78),

ESS

11 (8

–14)

w

ith C

ompS

AS, P

SG, C

PAP

follo

wed

by V

PAP

Adap

tSV®

or

bile

vel A

utoS

V®.

N =

35 (2

8 m

ale)

VPA

P Ad

aptS

V® p

atie

nts,

aged

66

(59–

78),

ESS

11 (8

–13)

.N

= 41

(33

mal

e) b

ileve

l Au

toSV

®, a

ged

64 (5

3–78

), ES

S 12

(9–1

6)

35 V

PAP

Adap

tSV®

, 41

bile

vel

Auto

SV®.

73.

7% a

dher

ence

, no

ctur

nal u

se 5

h (3

–6) f

or

VPAP

Ada

ptSV

® vs

. 6 h

(4–7

) fo

r bile

vel A

utoS

V® (p

= 0

.081

); ra

ised

base

line

AHI a

nd

impr

oved

ESS

dev

elop

men

t w

ith b

ileve

l Aut

oSV®

4 (1

–9)

vs. 3

(0–5

), p

= 0.

02

Non-

hom

ogen

eous

po

pula

tion,

no

subs

tant

ial

diffe

renc

es

betw

een

the

tech

nica

l eq

uipm

ent u

sed

4

Kuzn

iar e

t al.

[250

]20

13US

ARe

tros

pect

ive

anal

ysis

of p

atie

nt d

ata

N =

150

Com

pSAS

pat

ient

s97

pat

ient

s, (6

4.7%

) ≥ 1

risk

fa

ctor

for C

SA.

Low

pre

vale

nce

of d

ecre

ased

LV

EF a

nd h

ypoc

apni

a PA

P tr

eat-

men

t adh

eren

ce 7

3.3%

–4



Tab.

B. 1

7 Co

ntro

lled

stud

ies (

KS),

outc

ome

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or tr

eatm

ent-

rela

ted

cent

ral s

leep

apn

ea (c

ontin

uatio

n)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nRe

sults

Com

men

tsLe

vels

of

evid

ence

Lehm

an e

t al.

[256

]20

07Au

stra

liaRe

tros

pect

ive,

PSG

; cl

inic

al d

ata

N =

99 co

nsec

utiv

e O

SAS,

N

= 13

(12

mal

e.) C

SA-C

PAP

patie

nts,

aged

55

± 16

, BM

I 33

.4 ±

7.9

kg/

m2 : C

AI ≥

5/h

at

± 1

cm

H 2O

CPA

P.

N =

86 (6

8% m

ale)

not

CS

A-CP

AP p

atie

nts,

aged

57

± 1

1, B

MI 3

3.1

± 5.

8 kg

/m2

CSA-

CPAP

: 13

patie

nts.

(13.

1%),

46%

CSA

bas

elin

e (v

s. 8%

p <

0.0

1). B

asel

ine

raise

d AH

I (72

vs.

53, p

= 0

.02)

, ra

ised

AI (4

3 vs

. 29,

p <

0.0

1),

raise

d m

ixed

AI (

7 vs

. 1,

p =

0.03

), ra

ised

CPAP

in o

rder

to

elim

inat

e O

SA (1

1 vs

. 9,

p =

0.08

), of

ten

from

CAD

or H

F.N

o di

ffere

nces

in a

ge o

r BM

I

–4

Mor

gent

hale

r et a

l. [3

06]

2007

USA

Pros

pect

ive,

ra

ndom

ized

, cro

ssov

er,

NIV

vs.

ASV,

in C

SA/C

SR,

prim

arily

mix

ed a

pnea

s an

d Co

mpS

AS, a

cute

se

ttin

g

N =

21 (2

0 m

ale)

pat

ient

s, ag

ed 6

5 ±

12, B

MI 3

1 ±

5 kg

/m2 , A

HI 5

2 ±

23 (6

CSA

/CS

R, 6

prim

arily

mix

ed a

p-ne

as, 9

Com

pSAS

), ba

selin

e AH

I 52

± 23

, RAI

46

± 27

15 p

atie

nts w

ith in

itial

CPA

P an

d pe

rsist

ent r

espi

rato

ry

even

ts (A

HI 3

4 ±

26,

RAI 3

2 ±

30).

NIV

(n =

21)

: AHI

6 ±

8 a

nd R

AI

6 ±

8.AS

V: A

HI 1

± 2

and

RAI

2 ±

5.

AHI a

nd R

AI si

gnifi

cant

ly lo

wer

w

ith A

SV (p

< 0

.01)

–1b

Mor

gent

hale

r et a

l. [3

08]

2014

USA

RCT,

CPAP

vs.

ASV,

90

day

sN

= 66

pat

ient

s, 33

in e

ach

arm

, age

d 59

± 1

3, B

MI

35.0

± 8

.0, E

SS 1

0 ±

5, A

HI

38 ±

28,

CAI

3 ±

6

Initi

al A

HI w

ith A

SV 5

± 8

(CAI

1

± 4)

, with

CPA

P 14

± 2

1 (C

AI

9 ±

16) (

p ≤

0.00

03).

Afte

r 90

days

, ASV

AHI

4 ±

10,

CPA

P 10

± 1

1 (p

= 0

.002

4). A

HI

< 10

: ASV

89.

7%, C

PAP

64.5

%

(p =

0.0

214)

. No

diffe

renc

es in

co

mpl

ianc

e, E

SS, S

AQLI

–1b

Nak

azak

i et a

l. [3

11]

2012

Japa

nCa

se se

ries

Endp

oint

s: PS

G, LV

EF,

nasa

l res

istan

ce

N =

52 p

atie

nts w

ith

susp

ecte

d O

SA, a

ged

51 ±

13:

OSA

: N =

38

(90%

mal

e), a

ged

50 ±

14

, BM

I 30.

3 ±

5.3

kg/m

2 , Co

mpS

AS: N

= 5

(100

%

mal

e), 4

5 ±

10 y

ears

, BM

I 28

.7 ±

7.1

kg/

m2

CSA:

N =

9

Com

pSAS

: Nas

al re

sista

nce

high

er in

Com

pSAS

vs.

OSA

S (0

.30

± 0.

10 v

s. 0.

19 ±

0.0

7 Pa

/cm

3 /s, p

= 0

.004

), no

rmal

LVEF

.O

SAS:

ArI,

S1,

SaO

2 sig

nific

antly

de

crea

sed,

REM

sign

ifica

ntly

in

crea

sed

usin

g CP

AP

–3


Tab.

B. 1

7 Co

ntro

lled

stud

ies (

KS),

outc

ome

rese

arch

stud

ies (

OUS

) and

cas

e se

ries (

FS) f

or tr

eatm

ent-

rela

ted

cent

ral s

leep

apn

ea (c

ontin

uatio

n)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nRe

sults

Com

men

tsLe

vels

of

evid

ence

Pusa

lavi

dyas

agar

et a

l. [3

66]

2006

USA

Retr

ospe

ctiv

e, re

view

N =

133

(64%

mal

e) O

SAS,

ag

ed 5

8 ±

12 a

nd

N =

34 (8

2% m

ale)

co

mpS

AS, a

ged

54 ±

16

CPAP

pre

scrib

ed in

94

and

88%

of O

SAS

and

Com

pSAS

, (P

= 0

.284

), no

sign

ifica

nt

diffe

renc

e in

CPA

P pr

essu

re

(P =

0.1

12) a

nd in

the

frequ

ency

of

oth

er p

resc

ribed

trea

tmen

ts.

Firs

t USA

follo

w-u

p ea

rlier

fo

r Com

pSAS

(46

± 47

vs.

54 ±

37

days

; p =

0.0

22).

No

diffe

renc

es in

CPA

P co

mpl

ianc

e an

d ES

S. In

terf

ace

prob

lem

s m

ore

frequ

ent w

ith C

ompS

AS

shor

tnes

s of b

reat

h/dy

spne

a (0

.8 v

s. 8.

8%) a

nd u

nint

entio

nal

rem

oval

of t

he m

ask

(2.6

vs.

17.7

%) (

all p

< 0

.050

)

4

Ram

ar e

t al.

[372

]20

13US

ARe

tros

pect

ive

stud

y. AS

V tit

ratio

n w

ith P

SG

signa

ls ac

cess

ible

to

“car

diop

ulm

onar

y co

uplin

g (C

PC)”

anal

ysis

N =

106

(89

mal

e)

cons

ecut

ive

Com

pSAS

pa

tient

s, ag

ed 6

3. B

asel

ine

AHI 3

8 (2

1–56

), AH

I usin

g CP

AP 3

7 (2

3–58

), CA

I 23

(13–

39)

ASV:

AHI

11

± 13

, AHI

< 1

0:

81.1

%.

Incr

ease

d na

rrow

ban

d lo

w

frequ

ency

“cou

plin

g” 4

5.3%

.N

o co

rrela

tion

of e

NB-

LFC

with

AS

V su

cces

s

4

Yaeg

ashi

et a

l. [4

88]

2009

Japa

nRe

tros

pect

ive,

revi

ewN

= 29

7 O

SAS

patie

nts

usin

g CP

AP ti

trat

ion,

AHI

≥

20.

N =

280

(84%

mal

e) O

SAS

patie

nts,

59 ±

15

year

s, BM

I 25.

7 ±

3.9

kg/m

2 , AH

I 48

± 20

.N

= 17

Com

pSAS

pat

ient

s, 55

± 1

6 ye

ars,

BMI 2

8.8

± 6.

1 kg

/m2 , A

HI 5

6 ±

24

17 p

atie

nts (

5.7%

) with

Co

mpS

AS. “

Mul

tiple

, ste

pwise

, an

d lo

gist

ic re

gres

sion

anal

yses

”: Si

gnifi

cant

di

ffere

nces

in th

e su

pine

po

sitio

n re

latin

g to

CAI

dur

ing

NRE

M (p

= 0

.026

) Com

pSAS

vs

. OSA

S (2

.5 ±

3.1

vs.

0.9

± 2.

3),

devi

atio

ns w

ithin

the

norm

al

rang

e

4



Tab. B.18 Sleep-related hypoventilation/hypoxemia (pursuant to ICSD-3)

1. Sleep-related hypoventilation

1.1. Obesity hypoventilation syndrome

1.2. Congenital central alveolar hypoventilation syndrome

1.3. Late-onset central hypoventilation with hypothalamic dysfunction

1.4. Idiopathic central alveolar hypoventilation

1.5. Sleep-related hypoventilation caused by medication or substances

1.6. Sleep-related hypoventilation caused by a physical illness – by parenchymal pulmonary disease – by vascular pulmonary disease – by obstruction of the lower respiratory tract – by neuromuscular diseases or diseases of the chest wall

2. Sleep-related hypoxemia


Tab.

B.1

9 St

udie

s of N

IV tr

eatm

ent f

or a

lveo

lar h

ypov

entil

atio

n w

hen

awak

e or

whi

le sl

eepi

ng in

the

fram

ewor

k of

neu

rom

uscu

lar d

iseas

es (N

ME)

, tho

rax

rest

rictiv

e di

seas

es a

d ob

esity

hyp

oven

tilat

ion

synd

rom

e (O

HS)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

patie

nts

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

end-

poin

tLe

vels

of

evid

ence

Anna

ne [1

7]20

14Fr

ance

Met

a-an

alys

isN

ME

8 RC

TsN

IV v

s. st

anda

rd

trea

tmen

tSu

rviv

al, B

GA,

sym

ptom

sAl

l bet

ter w

ith N

IV1a

Bour

ke e

t al.

[63]

2006

Unite

d Ki

ngdo

mRC

TO

rtho

pnea

or

hype

rcap

nia

with

AL

S

22 v

s 19

NIV

vs.

stan

dard

LQ, s

urvi

val

Both

impr

oved

in

patie

nts t

hat s

how

ed n

o sy

mpt

oms o

f bul

bar

1b

Budw

eise

r [74

]20

07Ge

rman

yCo

hort

s, hi

stor

ical

co

ntro

ls

Stab

le re

spira

tory

in

suffi

cien

cy w

ith

OHS

126

NIV

BGA,

LUFU

, su

rviv

al in

co

mpa

rison

to

hist

oric

al co

ntro

l gr

oup

All p

aram

eter

s im

prov

ed d

urin

g th

e co

urse

of t

reat

men

t. Su

rviv

al ra

tes b

ette

r th

an in

the

hist

oric

al

cont

rol g

roup

4

Buys

e [7

7]20

03Be

lgiu

mCa

se se

ries

Stab

le re

spira

tory

in

suffi

cien

cy w

ith

KS

18 v

s. 15

pa

tient

sN

IV v

s. O

2BG

A, su

rviv

alBo

th im

prov

ed w

ith

NIV

; alth

ough

the

base

line

valu

es w

ere

wor

se

4

Gust

afso

n et

al.

[176

]20

06Sw

eden

FKS

Stab

le re

spira

tory

in

suffi

cien

cy

with

KS

100

NIV

, 144

O2

NIV

or O

2Su

rviv

alIm

prov

ed w

ith N

IV2c

Jäge

r et a

l. [2

04]

2008

Swed

enFK

SSt

able

resp

irato

ry

insu

ffici

ency

with

po

st-t

bc

85 N

IV, 1

03 O

2N

IV o

r O2

Surv

ival

Impr

oved

with

NIV

2c

Pipe

r et a

l. [3

54]

2008

Aust

ralia

RCT

Stab

le re

spira

tory

in

suffi

cien

cy w

ith

OHS

2 ×

18Bi

leve

l vs.

CPAP

PaCO

2 tag

sD

ecre

ased

with

bot

h ty

pes o

f tre

atm

ent

1b

Schö

nhof

er e

t al.

[401

]20

01Ge

rman

yFK

SSt

able

resp

irato

ry

insu

ffici

ency

per 1

0 pa

tient

sN

IV v

s. st

anda

rd

trea

tmen

tM

uscl

e fu

nctio

n,

BGA

Mus

cle

func

tion

and

BGA

impr

oved

with

NIV

1b

Sim

onds

and

Elli

ott [

414]

1995

Unite

d Ki

ngdo

mCa

se se

ries

NM

E, K

S,

PPS,

CO

PD,

bron

chie

ctas

is

180

NIV

NIV

usa

ge (n

ot

usin

g N

IV re

sulte

d in

dea

th)

Bett

er su

rviv

al ra

tes

than

bef

ore

the

NIV

era

, ex

cept

for C

OPD

and

br

onch

iect

asis

4

Sim

onds

et a

l. [4

15]

1998

Unite

d Ki

ngdo

mCa

se se

ries

DM

D w

ith

resp

irato

ry

insu

ffici

ency

23N

IVBG

A, su

rviv

al1y

- les

s tha

n 5y

surv

ival

ra

te o

f 85

and

73%

re

spec

tivel

y, im

prov

ed

BGA.

In th

e hi

stor

ical

co

ntro

l, su

rviv

al ra

tes

wer

e >1

yea

r with

re

spira

tory

insu

ffici

ency

4



Tab.

B.1

9 St

udie

s of N

IV tr

eatm

ent f

or a

lveo

lar h

ypov

entil

atio

n w

hen

awak

e or

whi

le sl

eepi

ng in

the

cont

ext o

f neu

rom

uscu

lar d

iseas

es (N

ME)

, tho

rax

rest

rictiv

e di

seas

es a

nd o

besit

y hy

pove

ntila

tion

synd

rom

e (O

HS) (

cont

inue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

patie

nts

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Leve

ls o

f ev

iden

ce

Vian

ello

et a

l. [4

52]

1994

Italy

FKS

Duc

henn

e m

uscu

lar

dyst

roph

y

2 ×

5N

IV v

s. st

anda

rd

trea

tmen

t ove

r a

time

perio

d of

2

year

s

Dea

th0/

5 N

IV p

atie

nts d

ied;

4/

5 co

ntro

l pat

ient

s di

ed

3b

War

d et

al.

[466

]20

05Un

ited

King

dom

RCT

Neu

rom

uscu

lar

dise

ases

, no

rmoc

apni

a du

ring

day,

hypo

vent

ilatio

n w

hile

slee

ping

12 in

eac

h gr

oup

NIV

vs.

stan

dard

tr

eatm

ent o

ver

a tim

e pe

riod

of

2 ye

ars

ptc

CO2 a

t nig

ht

SaO

2 at n

ight

N

IV re

quire

d fo

r co

ntro

l gro

up

ptc

CO2 a

t nig

ht S

aO2

at n

ight

resp

irato

ry

insu

ffici

ency

dur

ing

the

day

with

NIV

requ

ired

for 1

1/12

of t

he co

ntro

l pa

tient

s

1b

ALS

amyo

troph

ic la

tera

l scl

eros

is, B

GA

bloo

d ga

s ana

lysis

, Bile

vel B

ileve

l pos

itive

airw

ay p

ress

ure,

CO

PD c

hron

ic o

bstru

ctiv

e pu

lmon

ary

dise

ase,

CPA

P co

ntin

uous

pos

itive

airw

ay p

ress

ure,

DM

D D

uche

nne

mus

cula

r dy

stro

phy,

FKS

case

-con

trol s

tudy

, ICU

day

snum

ber o

f day

s spe

nt in

inte

nsiv

e ca

re, K

S Ky

phos

colio

sis, L

UFU

pul

mon

ary

func

tion

test

, LQ

qua

lity

of li

fe, N

IV n

on-in

vasiv

e ve

ntila

tion,

NM

E ne

urom

uscu

lar d

iseas

es,

PaCO

2 arte

rial c

arbo

n di

oxid

e pa

rtial

pre

ssur

e, P

aO2 a

rteria

l oxy

gen

parti

al p

ress

ure,

pos

t-Tbc

Pos

t-tbc

synd

rom

e, P

PS P

ost-p

olio

synd

rom

e, P

atcC

O2 c

arbo

n di

oxid

e pa

rtial

pre

ssur

e m

easu

red

trans

cuta

neou

sly, R

CT

rand

omize

d co

ntro

l stu

dy


Tab.

B.2

0 St

udy

of N

IV tr

eatm

ent f

or a

lveo

lar h

ypov

entil

atio

n w

hile

aw

ake

or w

hile

slee

ping

in th

e co

ntex

t of C

OPD

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

patie

nts

(n)

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Leve

ls o

f ev

iden

ce

Budw

eise

r [73

]20

07Ge

rman

yPr

ospe

ctiv

e ob

serv

atio

nal

stud

y (P

OS)

Stab

le h

yper

cap-

nic

COPD

99 v

s. 41

NIV

vs.

stan

dard

tr

eatm

ent o

ver

a tim

e pe

riod

of u

p to

4 y

ears

Surv

ival

Incr

ease

d su

rviv

al

rate

usin

g N

IV2c

Casa

nova

et a

l. [8

9]20

00Ita

lyRC

TSt

able

hyp

erca

p-ni

c CO

PD52

NIV

vs.

stan

dard

tr

eatm

ent o

ver

a tim

e pe

riod

of

1 ye

ar

Exac

erba

tion

rate

s, ho

spita

lizat

ion,

in

tuba

tion,

mor

talit

y, dy

spne

a, B

GA

Dys

pnea

dec

reas

ed

with

NIV

1b

Clin

i et a

l. [1

03]

2002

Italy

RCT

Stab

le h

yper

cap-

nic

COPD

43 v

s. 47

NIV

vs.

stan

dard

tr

eatm

ent o

ver

a tim

e pe

riod

of

2 ye

ars

BGA,

LQ,

hosp

italiz

atio

n, d

ays

spen

t in

ICU,

surv

ival

Dec

reas

e of

PaC

O2

durin

g th

e da

y, im

prov

emen

t of L

Q

and

dysp

nea

1b

Garro

d et

al.

[156

]20

00Un

ited

King

dom

RCT

Stab

le h

yper

cap-

nic

COPD

23 v

s 22

NIV

+ tr

aini

ng

vs. t

rain

ing

6 m

in. w

alki

ng te

st,

sym

ptom

s, pO

2

All s

igni

fican

tly

impr

oved

with

NIV

1b

Gay

et a

l. [1

60]

1996

USA

RCT

Stab

le h

yper

cap-

nic

COPD

7 vs

6N

IV v

s. pl

aceb

o N

IV

over

a p

erio

d of

3

mon

ths

BGA,

LUFU

ns1b

Köhn

lein

et a

l. [2

36]

2014

Germ

any

RCT

Stab

le h

yper

cap-

nic

COPD

102

vs. 9

3N

IV v

s. st

anda

rd1

year

mor

talit

yUs

e of

NIV

sig

nific

antly

ex

tend

ed su

rviv

al

1a

Kolo

dzie

j [23

7]20

07Ca

nada

Met

a-an

alys

is of

15

stud

ies

Stab

le h

yper

cap-

nic

COPD

–N

IV v

s. st

anda

rdM

ultip

leIm

prov

ed LQ

us

ing

NIV

, BGA

in

unc

ontr

olle

d st

udie

s im

prov

ed

with

NIV

1a

McE

voy

et a

l. [2

88]

2009

Aust

ralia

RCT

Stab

le h

yper

cap-

nic

COPD

72 v

s. 72

NIV

+ LT

OT v

s. LT

OTSu

rviv

al, l

ufu,

BGA

, qu

ality

of l

ifeN

IV +

LTOT

im

prov

ed c

hanc

e of

surv

ival

, but

de

crea

sed

qual

ity

of li

fe

1a

Mee

cham

Jone

s et a

l. [2

93]

1995

Unite

d Ki

ngdo

mRC

T, cr

oss-

over

Stab

le h

yper

cap-

nic

COPD

14N

IV v

s. st

anda

rd

trea

tmen

t eac

h ov

er a

per

iod

of

3 m

onth

s

PaCO

2 and

PaO

2 du

ring

the

day,

sleep

, LQ

Sign

ifica

nt

impr

ovem

ent o

f all

targ

et p

aram

eter

s w

ith N

IV

1b

Stru

ik e

t al.

[436

]20

13N

ethe

rland

sM

eta-

anal

ysis

of 7

stud

ies

Stab

le h

yper

cap-

nic

COPD

245

NIV

vs.

stan

dard

Mul

tiple

No

diffe

renc

e in

BG

A; lu

fu, q

ualit

y of

life

1a



Tab.

B.2

0 St

udy

of N

IV tr

eatm

ent f

or a

lveo

lar h

ypov

entil

atio

n w

hile

aw

ake

or w

hile

slee

ping

in th

e co

ntex

t of C

OPD

(con

tinue

d)

Auth

orYe

arCo

untr

ySt

udy

type

Popu

latio

nN

umbe

r of

patie

nts

(n)

Inte

rven

tion

Stud

y en

dpoi

ntEff

ect o

n st

udy

endp

oint

Leve

ls o

f ev

iden

ce

Stru

mpf

et a

l. [4

37]

1991

USA

RCT,

cros

s-ov

erSt

able

hyp

erca

p-ni

c CO

PD7

NIV

vs.

stan

dard

tr

eatm

ent o

ver

a tim

e pe

riod

of

3 m

onth

s

BGA,

LQ, s

leep

ns1b

Tsol

aki e

t al.

[446

]20

08Gr

eece

FKS

Stab

le h

yper

cap-

nic

COPD

27 v

s 22

NIV

vs.

stan

dard

(p

atie

nts w

ho

decl

ined

NIV

)

LQ, B

GA, d

yspn

eaAl

l sig

nific

antly

im

prov

ed w

ith N

IV3b

Wijk

stra

et a

l. [4

78]

2003

Cana

daM

eta-

anal

ysis

of 4

stud

ies

Stab

le h

yper

cap-

nic

COPD

86N

IV v

s. st

anda

rd

>3 w

eeks

LUFU

, BGA

, sle

epns

1a

ALSa

myo

troph

ic la

tera

l scl

eros

is, B

GA

bloo

d ga

s ana

lysis

, Bile

vel b

ileve

l pos

itive

airw

ay p

ress

ure,

CO

PD c

hron

ic o

bstru

ctiv

e pu

lmon

ary

dise

ase,

CPA

P co

ntin

uous

pos

itive

airw

ay p

ress

ure,

DM

D D

uche

nne

mus

cula

r dy

stro

phy,

FKS

case

-con

trol s

tudy

, ICU

day

s num

ber o

f day

s spe

nt in

inte

nsiv

e ca

re, K

H h

ospi

tal, K

S Ky

phos

colio

sis, L

UFU

pul

mon

ary

func

tion

test

, LQ

qua

lity

of li

fe, N

IV n

on-in

vasiv

e ve

ntila

tion,

NM

E ne

urom

uscu

lar

dise

ases

, PaC

O2 a

rteria

l car

bon

diox

ide

parti

al p

ress

ure,

PaO

2 arte

rial o

xyge

n pa

rtial

pre

ssur

e, p

ost-

tbc

Post

-tbc

synd

rom

e, P

atcC

O2 c

arbo

n di

oxid

e pa

rtial

pre

ssur

e m

easu

red

trans

cuta

neou

sly, R

CT ra

ndom

ized

cont

rolle

d st

udy


10.3 Annex C: Algorithms

Suspected upper respiratory tract obstruction or impairment

of vigilance

Determination of the pre-test probability of obstructive

sleep apnea (daytime sleepiness, pauses during breathing and snoring)?

Check the speci�c treatment options

Causal organic, psychiatric or mental illness or one that

requires optimization?Yes

No

No

No

No NoNo

No

Yes

Yes

Yes

Yes

Yes

No

YesYes

Pre-test prob. high?

OSA?

PSG for di�. diagn.

Central sleep apnea?

Polygraphy of the cardioresp. parameters

Obstructive AHI > 15 h?

Risk of night-time hypoventilation?

Treatment of OSA and hypoventilation OSA treatment

Hypercapnia when the patient is awake or asleep? (blood gas analysis during the day and

night-time capnometry and PSG)

For more, see CSA

Other sleep medicine disease? Sleep medicine consultation

Spec. treatment

0

1

2

3

4

5

6

7

8

9 10

1416

171513

12

11

Fig. C.1 Algorithms for treating patients with suspected obstruction of the upper respiratory tract After excluding organic or psychological illnesses that still require optimization, a polygraphy of cardio-respiratory parameters can be sufficient as a diagnostic tool for patients with a high pretest probability, i.e patients that present with daytime sleepiness plus lapses in breathing plus snoring. If pretest probability is low, a polysomnography is used in such cases as a tool for providing a differential diagnosis



Underlying disease: Arterial hypertension, heart failure, absolute arrhythmia, CNS

disease

0

31

10

1214 16

1315

8

9

11

2

4

6

7

Symptoms of SRRD? Monitoring for SRRD reduced systems with

1-3 channels

Suspected SRRD?

Polysomnography for di�erential diagnosis

Treatment of the underlying disease and where necessary repetition of

the sleep-related diagnosis

Other somnological disease?

No somnological disease

OSA? CSA?

Treatment of CSA Speci�c

treatment

High pre-test prob. Snoring AND respiratory disorders noticed by external parties

AND daytime sleepiness

6-channel polygraphy

OSA con�rmation?

OSA treatment

Yes

YesYes

YesNo

No

No

No

No No No

Yes

Yes

Yes

Fig. C.2 Algorithms for handling patients with cardiovascular diseases and sleep-related respiratory disorders.Approximately 50% of patients with cardiovascular diseases and sleep-related respiratory disorders suffer from sleep-related respiratory disorders. That is why monitoring for sleep-related respiratory disorders, using reduced systems with 1–3 channels, can also be used for asymptomatic cardiovascular patients. The use of a polygraph or polysomnography is justified if the patients is already showing symptoms of a sleep-related respiratory disorder.


OSAS that requires treatment

Sus. dysmorphia and pathogenically relevant

anatomical abnormalities of the upper respiratory tract?

0

1

4

5

7

98

CPAP/APAP116

10

14

Yes

Yes

No

No

No

No

CPAP/APAP or attempt at LJB

AHI <= 30 h?

E�ective?

E�ective?

E�ective?

CPAP/APAP or LJB

Treatment optimization** Treatment optimization**

Treatment control

Residual daytime sleepiness?

If necessary Moda�nil o�-label**

Yes

Yes

Yes

Yes

3219

12

13

CPAP/APAP attempt

No

No

Bilevel/auto-bilevel attempt**

Bilevel/auto-bilevel

15

16

17

18

Yes

No

If necessary sleep medicine consultation, individual treatment

recommendation on di�erent methods of treatment

If necessary correction(e.g., surgical measures)

OSAS that still requires treatment? *

Fig. C.3 Algorithms for treating patients with obstructive sleep apnea.*Patient training, behavioral recommendations, sleep medicine consultation; for patients who are overweight it is also recommended that treatment is accompanied by supported weight loss. ** If other forms of treatment are not possible or were not tolerated by the patient, positional therapy can also be considered for an AHI ≤ 30h and positional OSA. Lower jaw brace (LJB) can also be considered for patients with serious sleep apnea who do not tolerate or refuse CPAP treatment, or for those patients where CPAP cannot be used despite having tried all available supporting measures. If PAP or LJB do not work, there are no anatomical abnormalities and an AHI of 15–50h, hypoglossal nerve stimulation (HGNS) can be used for overweight patients up to severity grade 1. A prerequisite of this treatment is that there is no concentric obstruction of the respiratory tracts



0Suspected CSA

Polygraphy or polysomnography

Evidence of SRRD? Consultation

Obstructive sleep apnea? Further OSA algorithm

Heart failure?

Guideline-compliant treatment of heart failure

EF <= 45%?

Sleep medicine Consultation, in exceptional cases where there are clear symptoms

attempt at CPAP

Optimization of treatment of the underlying disease

Kidney failure, CNS disease, other comorbidities?

Idiopathic CSA

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

YesYes

Yes

Yes

No

No

No

No

No

No No

No

No

No

No

No

Polysomnography for di�erential diagnosis*

CSA?

Opioid-induced sleep apnea?

Consider discontinuation or dose reduction

Further CSA? Further CSA?

Further CSA?

CPAP

E�ective?

E�ective?

CPAP

ASV

ASV

Sleep medicine consultation

Sleep medicine consultation

1

27

25 26

16

17

15

10

13

14

11

12

18

19

20

23

22

2124

2

3

4

5

6

7

8

9

Fig. C.4 Algorithms for treating patients with suspected central sleep apnea.*If there are any doubts following polygraphic diagnosis then a polysomnography can be used for differential diagnosis


10.4 Annex D: Addendum

The scientific journal was published after the conclusion of the consensual process (McEvoy RD, Antic NA, Heeley E et al. (2016)). CPAP for Prevention of Car-diovascular Events in Obstructive Sleep Apnea. NEJM 375:919-931) couldn’t be incorporated for formal reasons.

The results of the study show that CPAP treatment used alongside stan-dard treatment with a short CPAP cycle (on average only 3.3 hours each night) for patients with obstructive sleep ap-nea and coronary artery disease or cere-brovascular disease does not improve a patient’s chance of survival. Improved quality of life can be achieved for pa-tients with CAD and sleep apnea with-out obvious symptoms.

The results of the study have no effect on the recommendations specified in these guidelines.

Link to the ESC Guideline for the diagnosis and treatment of acute and chronic heart failure: http://leitlinien.dgk.org/2016/2016-esc-guidelines-for-the-diagnosis-and-treatment-of-acute-and-chronic-heart-failure/

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