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Somnologie 2017 · 20 (Suppl s2): p97–p180
DOI 10.1007/s11818-016-0093-1
Published online: November 29, 2016
© Springer Medizin Verlag Berlin 2016
S3-Guideline on Nonrestorative
Sleep/Sleep Disorders - Chapter
on “Sleep-Related Respiratory
Disorders”
German Sleep Society (Deutsche
Gesellschaft für Schlafforschung und
Schlafmedizin, DGSM)
Table of Contents
5.6
1.2.1
1.2.2
1.2.3
1.2.4
5.7
5.8
5.9
5.10
5.11
5.12
5.13
5.14
5.15
5.15.1
1.
1.1
1.2
2.
3.
3.1
3.2
3.2.1
3.2.2
3.2.3
3.2.4
3.2.5
3.2.6
4.
5.
5.1
5.2
5.3
5.4
5.5
Summary
What’s new?
New recommendations
regarding the Guideline
on “Nonrestorative Sleep,”
Chapter on “Sleep-Related
Breathing Disorders” of 2009
Perioperative management
Obstructive sleep apnea
Central sleep apnea
Sleep-related hypoventilation/
hypoxemia
Introduction
Diagnosis
General
Non-instrument-based
diagnosis
Questionnaires and
performance and vigilance
tests
Clinical examination
Instrument-based diagnosis
Polysomnography
Polygraphy for Sleep-Related
Respiratory Disorders
Monitoring for sleep-relates
respiratory disorders with
reduced systems.
Principles of the creation
of the indication for the
treatment of sleep-related
respiratory disorders
Obstructive sleep apnea
syndrome
Obstructive sleep apnea
Clinical symptoms
Epidemiology
Predisposing and triggering
factors
Family history, genetics
5.15.2
5.15.3
5.16
5.17
5.18
5.19
5.19.1
5.20
5.20.1
5.20.2
5.20.3
5.20.4
5.20.5
5.20.6
5.20.7
5.20.8
5.20.9
5.20.10
Start, progression,
complications
Daytime sleepiness
Cardiovascular risk
Arterial hypertension
Stroke
Heart failure
Diabetes mellitus
Malignant diseases
Perioperative complications
PAP treatment methods
Nighttime positive pressure
breathing
Modified positive pressure
treatment methods
Compliance
Telemonitoring of sleep-related
respiratory disorders
OSA in pregnancy
OSA in elderly people
Obstructive sleep apnea and
dementia
Treatment of obstructive sleep
apnea in people with dementia
Non-CPAP methods of treating
obstructive sleep apnea
Weight reduction
Non-operative weight
reduction
Operative weight reduction
Lower jaw braces
Treatment with medication
Treatment with medication in
patients with residual daytime
sleepiness receiving CPAP
treatment
Method to increase muscle
tone
Treatment with oxygen
Positional therapy
Surgical treatment
Central sleep apnea
syndrome
6.1
Central sleep apnea with
Cheyne-Stokes respiration
6.1.1 Main findings
6.1.2 Epidemiology
6.1.3 Diagnosis
6.1.4 Treatment
6.1.5 Respiratory stimulants
and CO2
6.1.6 Unilateral stimulation of the
phrenic nerve
6.1.7 Oxygen
6.1.8 Continuous Positive Airway
Pressure
6.1.9 Bilevel Positive Airway
Pressure
6.1.10 Adaptive servo ventilation
6.2
Central sleep apnea without
Cheyne-Stokes respiration
6.2.1 Main findings
6.2.2 Diagnosis
6.2.3 Treatment
6.3
Central sleep apnea with
periodic breathing at a high
altitude
6.3.1 Main findings
6.3.2 Treatment
6.4
Centrals sleep apnea caused
by medication, drugs or
substances
6.4.1 Main findings
6.4.2 Treatment
6.5
Primary central sleep apnea
6.5.1 Main findings
6.5.2 Epidemiology
6.5.3 Treatment
6.6
Central sleep apnea as
a consequence of treatment
6.6.1 Main findings
6.6.2 Epidemiology
6.
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S3-Guideline on Sleep-Related Respiratory Disorders
6.6.3
6.6.4
7.
7.1
7.1.1
7.1.2
7.1.3
7.2
7.2.1
7.2.2
7.2.3
7.2.4
8.
9.
10.
10.1
10.2
10.3
10.4
11.
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Diagnosis
Treatment
Sleep-related
hypoventilation/sleep-related
hypoxemia
Obesity hypoventilation
syndrome (OHS)
Main findings
Diagnosis
Treatment
Sleep-related hypoventilation
caused by a physical illness
Main findings
Start, progression,
complications
Diagnosis
Treatment
Legal consequences
Glossary
Appendices
Annex A: Guideline report
Annex B: Tables
Annex C: Algorithms
Annex D: Addendum
Bibliography
Somnologie · Suppl s2 · 2017
Composition of the guideline
group, involvement of
stakeholders
Steering committee and published
–– 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 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 MusterBerufsordnung 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 sleeprelated 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. Diagnosis
a. The STOP-BANG questionnaire
was included in the diagnostic
spectrum.
2. Clinical examination
a. Examination of the oral cavity,
tooth status, if applicable
a teleradiograph should be
carried out to evaluate the
cranial morphology.
3. Polygraphy
a. 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 management
a. 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 apnea
1. 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
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S3-Guideline on Sleep-Related Respiratory Disorders
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 positiondependent 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
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Somnologie · Suppl s2 · 2017
(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 apnea
1. Diagnosis
a. In patients with central
sleep apnea, where possible
the internal medicine,
pharmacological and
neurological causes should be
clarified (A).
2. Treatment
a. Guideline-compliant treatment
of the heart failure should be
carried out to treat central
sleep apnea in patients with
heart failure and reduced leftventricular 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/hypoxemia
1. 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 sleeprelated 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. Treatment
a. 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 hypoventilation. Depending on the type of respiratory disorder the patient has, it may
be associated with hypoxemia or cause
hypercapnia and acidosis.
ICSD-3 [9, 10] distinguishes 5 diagnostic 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 respiratory disorders is based on central
nervous and/or neuromuscular processes 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, individual sleep-related respiratory disorders
are also characterized by further disease
features which are based on predisposition-related or triggering factors in combination with the changes which occur
as a result of breathing events and consequential damages. This can be different
aspects such as symptoms of insomnia,
somnolence during the day or long-term
metabolic, endocrine, neurological, psychiatric, cardiovascular or pulmonary
consequences. The combination of the
factors triggered in each case, the change
in sleep during the night and the shortterm and long-term consequences result
in typical symptoms and results for the
respective diagnosis. These can range
from nonrestorative sleep and somnolence during the day with an increased
risk of accident to cor pulmonale, cardiac arrhythmias, arterial hypertension, 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 distorted but rather the secondary diseases
and their symptoms which justify a suspected diagnosis of sleep-related respiratory 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 comorbid diseases also have to be taken
into account.
The prompt detection and treatment of
for example obstructive SRRDs decreases the risk of accidents, improves the
quality of life and reduces the morbidity and mortality of the person affected
considerably. Nowadays, the assumption
is made that for example untreated obstructive 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 perspective [29, 143, 274, 440, 467].
3. Diagnosis
3.1 General
The diagnosis of sleep-related respiratory 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-related respiratory disorders. They are used
to determine the severity and any con-
comitant disorders, and are intended to
estimate the extent of the consequences. They comprise the patient history,
questionnaires for self-assessment, outpatient and in-patient multi-channel
devices, video recordings, clinical laboratory diagnostics and both non-instrument-based and instrument-based
performance diagnostics. They are all or
in combination used for making a diagnosis and controlling treatment; they are
also necessary for a social medicine evaluation and assessment.
The diagnosis procedures are combined, used simultaneously or one after
the other, as a supplement or exclusively 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 algorithm 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 significance in patients with cardiovascular
diseases [330].
Evaluations and examinations to provide evidence of questionnaires, sensitivity 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 findings (e.g., patient history questions).
Some have been validated for special
groups of patients (e.g., Epworth Sleepiness Scale, Berlin Questionnaire, MSLT/
MWT, STOP, STOP-BANG).
In accordance with the ICSD-3 published in 2014, a distinction is made between five main groups of sleep-related
respiratory disorders (see Tab. B.1).
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S3-Guideline on Sleep-Related Respiratory Disorders
An overview of sleep medicine diagnosis 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 tests
Sleep medicine symptoms are primarily
determined through the patient history, but also via self-assessment questionnaires 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 STOPBANG questionnaire [333] are used in
major international studies. The diagnostic value of these questionnaires in
the sense of a prediction compared to
each other and in comparison with polysomnography is currently being investigated ([133, 413]; see Tab. B.4).
The neck circumference and hip
circumference are recorded as a highly simplified examination to predict
sleep-related obstructive respiratory
disorders. Further anthropometric procedures 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. Under 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 studies (n = 1484 patients), what are known
as “STOP” studies (snoring, tiredness,
observed apneas and high blood pressure) in combination with the BMI, age
and neck circumference (“BANG” questionnaires) showed the highest methodS102
Somnologie · Suppl s2 · 2017
ological quality for screening in patients
with OSAS [1].
Quantitative attention and vigilance
tests in order to gain an objective overview of the somnolence during the day
and of the reaction time include the psychomotor vigilance test (PVT), the Osler Test, the Divided Attention Steering
Test (DASS) and other procedures [417].
Various investigations have been carried
out on PVT [40]. Fewer have been carried out on the other procedures. The
use of these procedures is possible to
record sleepiness under certain conditions, 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 evaluation, the management and the longterm care of adults OSAS patients as
follows:
Questions on OSAS and on cardiovascular concomitant diseases (e.g., arterial
hypertension, cardiac arrhythmias, etc.)
should be part of each clinical patient history. 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 diagnosis. 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 examination
The 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 diagnosis
The need for an instrument-based diagnosis 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 likeliness 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. Validated questionnaires e.g., STOP, STOPBANG, and the Epworth Sleepiness
Scale are used to determine the pre-test
likelihood [413].
3.2.4 Polysomnography
The basic tool and the reference for sleep
medicine diagnostics in the sleep laboratory is monitored cardiorespiratory
polysomnography, by common agreement now known as polysomnography
(PSG) for short. In this procedure records the physiological signals which
are needed for a quantitative evaluation
of sleep, sleep disorders and diseases associated 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 reliability is increased [115]. A chapter on
central nervous activation (arousal) uses
the definitions from a previous recommendation paper [60]. Further chapters
set out the recording and the evaluation of parameters of the EKG [87] and
of leg movements. The motor patterns
such as periodic leg movements, bruxism and REM sleep behavioral disorders
are precisely defined [460]. There are
definitions of apneas and hypopneas of
various kinds in nightly respiratory disorders. The reference method to record
the obstructive respiratory activity is the
esophageal pressure measurement. Induction plethysmography is recognized
as a non-invasive method with comparable results [384]. In order to recognize 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 pressure (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 polysomnography, sleep disorders with changes in
the physiological parameters can be investigated and indicated quantitatively
with a severity. With current computer-aided technology, polysomnography
represents a manageable instrumental
effort. It requires staff specifically trained
in sleep medicine to carry out the measurement and evaluate the biosignals.
Sleep medicine training and qualifications have been established for medical
technical staff, psychologists and natural
scientists and for doctors at an additional 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 respiratory 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 somnologist.
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 laboratories 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 corresponds to the current requirements in
terms of the quality of a visual evaluation 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 criteria [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 Disorders
Simplified, portable systems are available 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 processing can reduce the number of false positive diagnoses [104, 105]. A preliminary
selection of the patients using a targeted
patient history can increase pre-test likelihood significantly and also reduce the
number of false-positive diagnoses.
Using polygraphy, it is fundamentally 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 diagnosis 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]. Using the SCOPER system method, the
number of channels is insignificant and
the recording of the functions is the focus (S = sleep, C = cardiovascular, O =
oximetry, P = position, E = effort, R = respiratory; [105]). There are several classes 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 system is now used for classification in the
polygraphy systems.
The evaluation of the polygraphy
must be carried out in accordance with
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Prognostic
benefits
Side effects
e.g., sleep disorders,
psychosocial
consequences, costs,
“inconvenience” to the
patient, etc.
e.g., reduction in
cardiovascular risk
factors, reduction in
metabolic risks, 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]
the current rules of polysomnography
[49] and enable a visual evaluation and
processing of artefacts. The implementation 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 p
­ re-test
likelihood, the symptoms and the comorbidities to diagnose sleep-related
respiratory disorders. In Germany, in accordance with the BUB-Richtline [388]
(Guideline on Methods for Ambulatory
Care), sleep medicine training is a requirement to charge for polygraphy in
accordance with EBM. Polygraphy systems can be used to diagnose obstructive 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 disorder), 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
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primarily has hypopneas, polygraphy
systems do not always enable a definitive
differentiation to be made between central 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 polysomnography 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 irregularities of the breathing rhythm in the transition 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 channels (pulse oximetry, long-term EKG, actigraphy, 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 definitive diagnosis or to rule out sleep-related
respiratory disorders is not recommended (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 corresponding to a 4-6 channel polygraphy [489].
Some systems increase pre-test likelihood of sleep-related respiratory disorders [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).
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 sleeprelated 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 sleeprelated 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 options to treat them. These are set out in
detail and discusses in other parts of this
guideline. The results of studies on diagnosis and treatment are critically evaluated and systematically assessed in the
relevant chapters. These evidence-based
recommendations form the basic framework of medical decisions on the treatment 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 knowledge and the correct application of evidence-based recommendations of this
type. The intention is therefore to set out
the individual indication for the treatment of sleep-related respiratory disorders in principle below.
The indication for treatment (but also
for no treatment!) of an SRRD always relates 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 psychological 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 apnea 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 recommendations 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 comorbidities. It can be the case that a wide range
of further symptoms and restrictions
in terms of performance occur in mulSomnologie · Suppl s2 · 2017
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timorbid and/or elderly patients in addition 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 diagnosis is not possible.
The indication is significantly more
difficult in individual cases of oligosymptomatic or asymptomatic patients
in whom the treatment of a sleep-related
respiratory disorder would not lead to
a short-term or medium-term alleviation 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 effects of treatment of the SRRD and the
“stress” for the patient associated with
any treatment must be weighed up carefully against the expected future benefits
( Fig. 1).
The possible benefits of treatment of
SRRD in patients with pronounced cardiovascular 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 taking into account possible side effects of
treatment and the subjective experience
of the “inconvenience” caused by treatment, 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 example, an insomniac patient is meant to
receive treatment with CPAP which increases their insomnia symptoms.
The treatment effects of the treatment of sleep-related respiratory disorders 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
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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 individual 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 Volume V of the Social Insurance Code
“needs-oriented and uniform care corresponding to the generally recognized level
of medical knowledge” is required (Section 70 of Volume V of the Social Insurance 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 Committee). When interpreting legal specifications regarding the application in a specific individual case, this guideline and
the above-mentioned statement can be
used for the indication.
5. Obstructive sleep apnea
syndrome
Obstructive sleep apnea syndrome comprises two diagnoses. Obstructive sleep
apnea in adults will be described in the
following section. Obstructive sleep apnea 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 substances 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 explicitly notice it. Day sleepiness causes
a defective performance an impairs cognitive performance and social compatibility and quality of life over the course
of the disease (see Signs and Symptoms)
Other people report a history of the patient stopping breathing. The main diagnostic result is the Apnea Hypopnea
Index (AHI) which indicates the number 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, memory impairment, impotence, personality
changes, depressive disorders and the
occurrence of automatic behavior are
possible symptoms during the day or
while awake. Viewed in isolation, however, these symptoms only have a low
specificity [118, 192, 246, 258, 270,
454, 495].
5.3 Epidemiology
5.5 Family history, genetics
There are relatively few population-based
sleep laboratory studies. The prevalence
data have not been corrected to reflect
the clinical symptoms as relevant components for the evaluation of the severity
of the disease as the resulting requirement for treatment.
In the Wisconsin study, obstructive
sleep apnea with clinical symptoms was
identified in 2% to 4% of adults aged between 30 and 60 [494]. 58% of the patients were obese. In Great Britain, 0.5%
to 1% the middle-aged men had moderate to severe sleep apnea [316]. Today in the USA these figures are 13% of
men and 6% of women [350]. We identified 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. Independently of this, the prevalence is
twice to three times higher in patients
with cardiovascular diseases than in the
normal population. Men are more commonly affected than women [364, 497].
The prevalence increases in older people [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].
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 suspicions that the disease can be inherited.
Approximately 35% of the variability of
OSA can be traced back to genetic factors [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].
5.4 Predisposing and triggering
factors
Factors which determine the occurrence
of obstructive sleep apnea are primarily BMI, age, gender and craniofacial
features. Other factors are smoking, alcohol, pregnancy, chemoreceptor sensitivity in the region of the breathing
regulation and existing diseases such as
rheumatism, acromegaly, hypothyroidism, and polycystic ovary syndrome
[292, 497].
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 responsible 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 other diseases and circumstances, so it has
a low specificity as a symptom [465].
5.8 Cardiovascular risk
Obstructive sleep apnea has been associated with coronary heart disease and
atrial fibrillation [126, 153, 154, 225, 294,
369, 400, 430]. The link to other cardiac arrhythmias is as yet unclear [371].
These links have been proven for both
OSA patients in the general population
[364] and OSA patients with cardiovascular diseases [425]. Links to pulmonary
hypertension [202], diabetes mellitus
[139, 199], kidney failure [2] and atherosclerosis [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 obstructive sleep apnea and arterial hypertension, particularly resistant hypertension [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 mortality [84, 185, 275, 276, 278, 280, 425, 498].
The effects of CPAP treatment on arterial 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 pressure both the systolic and the diastolic
blood pressure were able to be reduced
significantly (p < 0.001), although the
values were clinically negligible (systolic 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 incidence of the development of hypertension decreases [38]. Additional weight
reduction is also sensible [98].
Sleep apnea increases the risk of cardiac and cerebrovascular diseases. Various
studies also show a reduction in the cardiac and cerebrovascular risk as a result
of the treatment of SRRD, although there
are as yet no randomized, controlled
studies [167, 258]. In multimodal treatment concepts in patients with cardiovascular diseases, treatment of a nighttime respiratory disorder should always
be considered.
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5.10 Stroke
5.12 Diabetes mellitus
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 recommend the implementation of a polysomnography 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-refractory arterial hypertension (class 1, evidence grade A). A multicenter, randomized, controlled treatment study with
a follow-up period of five years showed
an improvement in the functional consequences of stroke and a reduction
in mortality in patients with ischemic
stroke and moderate to severe sleep apnea being treated with CPAP [341, 342].
A current meta-analysis confirms the
link between moderate to severe sleep
apnea and stroke [126]. However, insufficient evidence has been provided to
show that the treatment of sleep apnea
reduces the risk of a stroke.
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-analysis 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 improved 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 metabolism 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].
5.11 Heart failure
Sleep-related respiratory disorders that
occur frequently in patients with heart
failure, obstructive and central sleep apnea (see CSA) are also associated with
increased morbidity and mortality in
patients who subjectively do not experience hypersomnia [95, 210, 252, 463].
Patients with heart failure with particularly obstructive sleep apnea should be
directed to treatment depending on the
AHI, as should comparable OSA patients without heart failure.
The effects of CPAP on left ventricular
function in patients with OSAS was examined in a meta-analysis of 10 randomized, controlled studies. Patients with
OSAS and an existing disorder of left
ventricular function experienced a significant improvement in the left ventricular ejection fraction during treatment
with CPAP, those OSAS patients who
did not have a disorder of left ventricular function only improved marginally.
A significant correlation was identified
between the initial AHI and the left ventricular ejection fraction [438].
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5.13 Malignant diseases
There is a link between OSA and malignant diseases and their progression.
­Evidence has, however, yet to be provided on the impact of CPAP treatment
[85, 257, 317, 338].
5.14 Perioperative complications
In addition to the risks caused by associated 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 management is carried out for these patients
[266, 303, 304]. However, there are numerous indications that OSA patients
have an increased risk of various perioperative complications of systemic analgesia with opioids and sedation or a general 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 catecholamine 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 significantly 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 identifying and treating an OSA before
an operation the increased risk of the
above-mentioned complications occurring can be reduced at least in part [175,
310].
A particular challenge for the perioperative treatment team is that OSA is not
diagnosed before treatment in the majority of surgical patients [141, 381].
There are currently only few guidelines and recommendations from medical specialist associations regarding
the optimal perioperative management
of patients with (suspected) OSA [172,
224]. In 2015, the German Anesthesiology and Intensive Medicine Association 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 American Society of Ambulatory Anesthesia
recommends the following procedure:
patients with diagnosed OSA and optimal treatment of the concomitant diseases can have operations in an ambulatory 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 optimal manner can receive operations in
an ambulatory environment on condition that the pain which occurs after the
operation is not treated with opioids. Patients in whom the concomitant diseases
are not being treated sufficiently well are
not suitable for operations in an ambulatory environment [224].
There are currently insufficient data
on the risk of perioperative complications in patients with other non-obstructive SRRDs such as CSA [108]. The
perioperative management of these patients should therefore take into account
the individual situation with a consideration 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, obstructive, hypoventilation) and the clinical symptoms, primarily daytime sleepiness 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 isolated manner and in combination with one
another.
5.15.1 Nighttime positive pressure
breathing
The most common form of treatment
for all severities of obstructive sleep apnea 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 indications for the introduction of CPAP
treatment arise from the synopsis of the
patient history, polysomnograph and instrument-based results and the concomitant 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 mentioned 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 diseases. The initial application of positive
pressure ventilation should be carried
out in a sleep laboratory under continuous monitoring, and the possibility
of immediate intervention by a doctor.
Two nights of polysomnograph procedures are generally sufficient to determine the settings. Initiation of PAP
using a polysomnograph is sensible in
order to cover other masked sleep disorders such as insomnia, PLMD (periodic 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 reactions, improve or normalize the ventilation 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 polysomnographical control in a sleep laboratory.
This procedure is effective in terms of
respiratory disorders [144, 244] and daytime sleepiness [93, 100], but no better
than the levels being set in the sleep laboratory [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 longSomnologie · Suppl s2 · 2017
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term success. Patients with a suspected
additional sleep disorder in addition to
the OSA or with an increased comorbidity 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 therapy should be made be a doctor qualified
in sleep medicine.
Automatic (APAP, auto-bilevel, ASV)
procedures can be used to set the positive pressure treatment, but many titration 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, hypopneas, 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 Difference: 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, particularly 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
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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 disorders 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 approximately 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 increase 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 reduction 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 device 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 pressure in OSA patients decreased by approximately 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-refractory hypertension [281]. Predictors
for an even clearer treatment effect include 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 studies indicate that good use of CPAP has
a positive impact on survival [83, 275].
CPAP decreases the burden of cardiac
arrhythmias, particularly atrial fibrillation [369] and the LVEF in patients with
severe OSA [396]. Further positive effects caused by CPAP can be seen in the
markers for inflammation and oxidative
stress [21, 106, 396].
5.15.2 Modified positive pressure
treatment methods
Modified long-term treatment methods include automatic APAP treatment
[305, 396], bilevel S/T treatment [247,
396], pressure-delayed treatment (pressure 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 general [179]. Automatic PAP procedures
in particular showed themselves to be
equal to standard CPAP treatment in
long-term use and [111] and are therefore 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 calculate the effective continuous minimum
pressure in advance [396]. The Canadian
Thoracic Society, for example, recommends CPAP as the primary treatment
of OSAS (recommendation level IB).
APAP is an alternative effective form of
treatment in OSAS patients with no comorbidities [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 provided 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 recommendations for clinical practice [3].
The current general recommendations
for the use of APAP devices are as follows:
1. diagnoses should not be made
using APAP.
2. it should not be used in patients
with severe cardiopulmonary
diseases, nighttime decreases in
­ xygen which are not due to an
o
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) polysomnography.
4. For check-up examinations in
patients whose diseases are already
being controlled with CPAP [307].
Patients in whom a higher CPAP pressure is no longer tolerated or cannot be
applied (e.g., COPD patients) who have
central apneas or in whom these develop 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 servo 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 comorbid diseases and the patient’s compliance are all key elements when selecting 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 always be tried first in patients with severe
sleep apnea (see also Tab. B10 and B.11).
5.15.3 Compliance
The Cochrane Analysis of 2009 on CPAP
compliance used as an endpoint the impact on CPAP compliance, the influence
of mechanical interventions (air humidification) (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 patient training, support provided to the
patient and behavioral therapy measures 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 patients) and to a lower rate of discontinuation. 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 treatment 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 improvement in daytime sleepiness, performance, 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 support are necessary [247, 248]. Ultimately, 5-50% of patients who have started on
CPAP discontinue their treatment in the
first seven days. Annual long-term controls 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 inclusion of the partner, the careful selection
and adjustment of the mask, the efforts
to get used to the treatment the day before the first night on CPAP and the recognition and treatment of claustrophobia, 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 treatment 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 effects 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 international compliance is approximately
40-60%. Between 29-83% of OSA patients 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 compliance information are the above-mentioned influence factors, which are taken
into account and controlled in a country-specific manner, including depending on the quality of sleep medicine care.
Deficiencies to date: The definition
of compliance is based on the doctor’s
perspective. User sensitivity and specific 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 checkup examinations are not yet clearly defined [484].
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An official statement by the American
Thoracic Society (ATS) on the control of
CPAP adherence determined the following, among other things [403] (expert
opinion):
1. The measurement of CPAP use
through nighttime ventilation pressure is sensible. although the effect
on compliance is not clear.
2. Pressure monitoring should routinely be read.
3. A uniform technical standard for
pressure monitoring for the identification of apneas, hypopneas and
mask leakages is required.
4. Documentation on CPAP adherence 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 adherence must be standardized by the
manufacturer. The AHI flow is the
parameter for the remaining respiratory events (see also Tab. B.9).
5.16 Telemonitoring of sleeprelated respiratory disorders
The technical options made available by
telemonitoring have developed significantly in the past few years. For example,
it is now possible to transfer the patient’s
usage data from the PAP device to a central server night by night and there to record 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 example to train them, advise them or motivate them in a targeted manner via the
telephone or using internet-based measures, or to arrange an on-site intervention. The effects of telemonitoring have
not yet been the subject of much scientific investigation. A number of studies
show entirely positive effects on nighttime 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].
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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 telemedicinal scenarios cannot be directly
compared with one another. Other telemedicine applications such as teletherapy, teleconsultation and telediagnostics
have not yet been evaluated sufficiently
and should not be used in the routine
care of patients with sleep-related respiratory disorders.
To date, telemonitoring has only been
developed for positive pressure (PAP
treatment) of patients with obstructive
sleep apneas. An application in ventilation 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 recording and determination of data in coordination 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 medicine physician.
The legal limits of admissible and inadmissible 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. [76].
5.17 OSA in pregnancy
According to an American morbidity/
mortality study (1998-2008), the prevalence of sleep-related respiratory disorders 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 generally given as 0.7-7%, and in pregnant
women as 11-20%, in other words significantly higher. It is known that OSA
is associated with a higher risk of pre-eclampsia, eclampsia, cardiomyopathies,
diabetes mellitus and pulmonary embolisms [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 apnea increases with age [14]. The values
given, however, fluctuate wildly (20 to
40%) and are among other things dependent on the sub-group of patients
being investigated and the AHI limit
used [13, 497]. A conservative estimation assumes a doubling of the prevalence in old age [13]. Prevalence figures
of up to 70% are given for residents of
homes. In principle, diagnostic and therapeutic 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 reason 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 women all without cognitive impairment at
the start of the study investigate the effect
of obstructive sleep apnea on brain performance. In men, there was a significantly greater loss in brain performance
after an average of 3.4 years if they had
obstructive sleep apnea with additional hypoxemia [57]. In the women with
obstructive sleep apnea and hypoxemia
the risk of developing a mild cognitive
impairment (MCI) or dementia was increased by a factor of 1.85 (95% CI 1.113.08) over the course of 4.7 years after
adjusting for other risk factors [487].
Furthermore, evidence was provided of
a significant reduction in the instrumental 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
dementia
In 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 discontinued the study after randomization [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 deterioration in both men and women. CPAP
treatment decreases daytime sleepiness
in people with mild and moderate dementia and improves global brain performance.
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 reduction
A risk factor for OSA is being overweight. 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
reduction
A 10-15% weight reduction leads to an
approximately 50% reduction in the AHI
in male patients who are moderately
overweight [497]. Reference has therefore 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 interventions (e.g., intensive diet-based measures with low calorie liquid food with or
without a program for increased physical activity or to modify the lifestyle)
with control treatment [147, 219, 447].
These intensive weight reduction programs 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 evidence of the positive effects of successful
weight reduction, the fundamental limitations in terms of treatment remain.
The unclear prospects of the success of
long-term, stable weight reduction, the
fact that substantial conservative weight
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S3-Guideline on Sleep-Related Respiratory Disorders
reduction requires a high degree of personal effort and commitment which cannot be provided with any degree of regularity 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 problematic elements.
Intensive measures to ensure conservative reduction of the body weight
should however be recommended to all
patients with excess weight as a concomitant treatment measure. This is consistent with the recommendations of other specialist associations and societies
[131, 367, 375].
5.20.3 Operative weight reduction
Bariatric surgery has become increasingly 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 reduction associated with bariatric surgery 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 bariatric surgery on OSA [72, 171, 398].
Despite the documented effect on AHI,
for example, many patients still have an
OSA which requires treatment even after bariatric surgery, so corresponding
polysomnographic controls are necessary [171]. In a randomized study, the
superiority of operative weight reduction 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 basis of the OSA and requires a differentiated assessment of the obesity and
the individual comorbid disorders.
Specialized facilities are therefore the
only ones qualified to identify the indication. A recommendation for bariatric
surgery in general or specific operative
techniques can therefore not form part
of this guideline. If a morbidly obese patient has an OSA as a concomitant disorder, this should be taken into account
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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 braces
Treatment with lower jaw braces (Synonyms: oral appliance [OA], mandibular
advancement device [MAD], mandibular repositioning device [MRD]) improves night-time respiratory disorders
and reduces the associated health and
social impairments [131, 262, 358]. Intraoral lower jaw braces and non-invasive, 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 compared to CPAP was able to be demonstrated [358].
Lower jaw braces can be used as an
alternative in patients with mild to moderate OSAs. They can also be considered
for use in by patients with severe sleep
apnea who do not tolerate CPAP or refuse it or in whom CPAP treatment cannot be used despite all supportive measures 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 depends 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 indication 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 increments 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 individually determined on the basis of a preliminary 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 polysomnograph [131, 375, 247]. LJB can be used
as permanent treatment. Temporary
discomfort in the teeth and the muscles and increased salivation may occur
[375]. The clinical examination and adjustment of LJB should be carried out by
a person with expertise in dentistry and
sleep medicine [131, 158, 378, 379]. Possible side effects on the stomatognathic 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 examinations 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 medication
The data on treatment of OSA with medication 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 medication, regardless of the existence of other 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 allergic rhinitis with fluticasone propionate nasal spray [232].
However, there is no convincing evidence 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 applies 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 specialist 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
treatment
There are only very few, mostly retrospective investigations of the prevalence
of this clinical picture. An average of
around 10% of all CPAP patients suffer 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, clinically relevant yet moderate improvement
in daytime sleepiness in subjective and
objective parameters compared to a placebo. 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 residual daytime sleepiness in patients with
OSA, despite effective CPAP treatment,
because there was a lack of large, placebo-controlled studies and sufficient
pharmacovigilance data and there
were doubts about residual sleepiness
as a clinical entity. The inverse histamine-3 receptor agonists pitolisant and
MK-0249 have not yet been investigated
in terms of their ability to decrease residual sleepiness in patients with OSA, or
at least have not been investigated sufficiently [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
tone
Several 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 methods, however, there are also randomized, controlled clinical trials, including the method for intraoral electrical
stimulation [373], regularly playing
a didgeridoo [363] and the use of myofunctional exercises [174]. For intraoral
electrical stimulation, superiority in
the RCT mentioned was only able to be
proven in terms of a reduction in snoring, 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 myofunctional exercises, however, a significant
superiority of the intervention group
over the control group was able to be
demonstrated both in terms of respiratory 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 approximately 50% can be achieved through the exercises [81]. However, the reliability of
the data is often limited because of the
often small treatment groups and the
short follow-up periods. Electrical surface stimulation to increase muscle tone
is therefore not able to be recommended.
Non-electrical methods such as the playing 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.
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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 oxygen
The use of night-time treatment with oxygen to prevent or improve desaturation
associated with the respiratory events
has been investigated in numerous controlled and uncontrolled treatment studies. 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 cohort studies, in all cases a higher average
oxygen saturation was able to be determined, and in the majority of the studies, a minimally lower number of respiratory 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 administration 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 superiority of treatment with O2 compared to
ambient air in terms of the parameters
mentioned and CPAP treatment compared to the administration of O2 was
able to be confirmed in a meta-analysis
[295].
Treatment with oxygen alone in patients with obstructive sleep apnea can
therefore improve the night-time oxygen saturation significantly, but is inferior to CPAP treatment because of the
lack of or minimal effect on the number
of respiratory events. The administration of oxygen alone at night furthermore potentially brings with it the right
of prolonging respiratory events and increasing hypercapnias. To date, no convincing effects in terms of the daytime
symptoms were able to be demonstrated
in OSA patients.
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Recommendation
––Night-time oxygen treatment alone
should not be used to treat OSA (A).
5.20.9 Positional therapy
The position-dependency of the respiratory events in patients with OSA is
a known phenomenon. Lying in a supine
position appears to be the most vulnerable sleeping position in this group of
patients. Depending on the manifestation, 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 position is more than twice as high as in
other sleeping positions. Preventing the
patient from lying in the supine position has a fundamental therapeutic potential 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 supine position. As with all other tools, the
problem here is that of compliance. The
success of any measures to treat the position of patients with OSA should fundamentally be examined objectively.
Three randomized studies and a meta-analysis which builds on these are
available for a comparison between position-based and CPAP treatment. The
study by [420] compared one-month
treatment using a modified “tennis ball”
method with CPAP treatment. A reduction in the AHI was able to be achieved
in both groups. CPAP treatment was
found to be superior in terms of reduction in the AHI and improvement in
average oxygen saturation, while compliance and the side effect profile were
more favorable in the positional therapy
group. There was no significant difference in terms of the parameters of daytime 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 objective target parameters in both treatment
arms using a similar tool [222]. CPAP
treatment proved to be superior to positional therapy in terms of reduction
in AHI and improvement in the minimum 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 plastic block that was strapped to the back
using a belt, the aim of which was to
prevent the patient from lying in a supine position in a more reliable manner
than the “tennis ball” method [355]. In
their collective they were able to identify 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 reduced 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 relevance 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 treatment
In surgical treatment, a distinction is
made between resective and non-resective 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 improve general acceptance of CPAP treatment [261].
Resective procedures include all surgical measures which aim to remedy
or correct obstructions or obstacles to
the airflow through resection in the region of the upper respiratory tract. In
a randomized study with a high-quality method uvulopalatopharyngoplasty
(UPPP) was highly significantly superior 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 increases as the side of the tonsils increases and
the size of the tongue decreases [260]. In
the case of patients with very large tonsils, simply removing the tonsils can be
sensible in individual cases.
Overall, there is an increase perioperative and postoperative risk associated
with resective procedures, which however 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 uvulopalatopharyngoplasty can be recommended to patients with mild to moderate 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 modifications of the UPPP (e.g., uvula flap, z palatoplasty, relocation pharyngoplasty, hanUPPP, lateral pharyngoplasty, expansion
sphincteroplasty) is as yet unclear and
corresponding studies should be carried
out [439]. Laser-assisted uvulopalatoplasty (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 results 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 reduce 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 suspension and stimulation therapy of the
upper respiratory tract.
As minimally invasive operations, radio frequency ablation (RFA) and soft
palate implants are more tolerable than
the resective operations [99, 136]. To
date, evidence has only been provided of a 31%, short-term reduction in
sleepiness in patients receiving RFA using 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 session 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 individual studies [482]. A change in taste
was not able to be identified either subjectively or objectively [132]. For soft
palate implants, considerable evidence
has been provided of a slight to moderate 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 stimulation of the hypoglossal nerve, resulting in the genioglossus nerve being
activated in a manner in which the respiratory tract is considerably more open.
The aim of this is to remedy a functional
disorder of the muscles in the respiratory 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 treatment after 12 months was recently published. In this study, the stimulation of
the hypoglossal nerve synchronously
with breathing had a lasting treatment effect in patients with moderate to severe
OSA and the respiratory disorder reappeared to the original extent after treatment was withdrawn [434]. The morbidity 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 confirmed 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 response rates do not differ if tongue suspension is used for the retrolingual operation 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 significant differences between the groups in
three different tongue resections each in
combination with a UPPP [30]. The response 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 apnea which requires treatment: Laser-assisted soft palate surgery, uvula capping,
“cautery-assisted palatal stiffening operation,” “injection snoreplasty,” radio frequency surgery in the tonsils, “transpalatal advancement pharyngoplasty” and
isolated genioglossus advancement.
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Osteotomies to enable a preliminary
displacement of the upper and lower
jaw (maxillo-mandibular advancement)
enlarge the pharyngeal respiratory tract,
thereby increasing the pharyngeal muscle tone. Both effects reduce the collapsibility of the pharynx synergistically.
They can be a highly effective form of
treatment for OSA in patients with congenital abnormalities (including Pierre
Robin sequence, Crouzon syndrome,
Apert syndrome) or in patients with anatomical abnormalities of the upper respiratory 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 sagittal 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 patients 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 therapy was seen in either cohort studies or
in a randomized study [359, 453]. Transient paresthesias (changes in sense) of
the second and/or third trigeminal nerve
branches are often indicated as undesirable effects [194], although evidence of
these was only still able to be found in
14% of patients after 12 months. Aesthetic effects are classified as either positive of neutral by more than 90% of patients [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 depending on the anatomy and function
of the upper respiratory tract and are
correspondingly difficult to standardize 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 increasing numbers of controlled and randomized studies which compare the surgical
treatment methods with CPAP, placebo or simply waiting. However, to date
there have only been a small number
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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 surgical procedures. The effect of operative
treatment methods on cardiovascular
parameters and daytime symptoms has
not yet been tested in qualitative studies. However, cohort studies have shown
a positive effect. In comparison to a control 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 monoxide values and the endothelium-dependent vasodilation was successfully able
to be achieved three months after successful UPPP [255, 265]; TNF-a and IL-6
as inflammatory markers were significantly reduced three months after UPPP
with a septoplasty compared to a healthy
control group [107]. In an epidemiological cohort study of 444 patients, the
mortality in patients with OSA was able
to be reduced significantly and comparably 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 diagnostics procedure. The predictors for
the success of an operation and therefore
the selection criteria when choosing appropriate surgical treatment in patients
with OSA have to be developed separately for each intervention. They sometimes
vary considerably and are not present
for all operations. Only obesity is a negative predictor, but with different and in
some cases unknown threshold values
depending on the intervention. It is not
possible to predict the complete removal of an OSA by means of an operation
on an individual basis. The resective and
non-resective procedures are in principle not without risk [150, 264]. In general, therefore, with the exception of oste-
otomies and where the patient’s anatomy
is suitable tonsillectomy and uvulopalatopharyngoplasty, 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 anatomical 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 necessary 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 abovementioned 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
syndrome
This group of sleep-related respiratory
disorders is characterized by a disorder
of breathing regulation and/or the transfer of the impulses to the thoracic skeleton 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 breathing effort for the entire duration of the
suspended airflow [48, 198]. In patients
with central hypopneas, there is a decrease in breathing effort and breathing
flow. In contrast to obstructive respiratory disorders, there are no signs of paradoxical breathing [377].
There is no agreement in the literature about the number of central events
which are still considered to be normal.
In uninterrupted sleep, central apneas can occur in the transition between
being asleep and awake without having
a pathological significance. This fact
must be taken into account when diagnosing central events.
In CSA, a distinction is made between
hypercapnic and non-hypercapnic
forms. Hypercapnic respiratory disorders are characterized by a decrease in
the breathing impetus or the transfer
or implementation of the impulses on
the breathing muscles (neuromuscular 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 patients with cardiovascular/cerebrovascular diseases and kidney failure). In this
group, CSAs in patients with heart failure, 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 epidemiological 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 characterized 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/hyperventilation phase) is at least 40 s (typically 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 duration of at least two hours [48, 198]. This
alternative occurrence of hyperventilation and hypoventilation causes fluctuations in the arterial oxygen and carbon
dioxide levels. The hypoxemias caused
by apnea and hypoventilation in combination 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 fragmented sleep [65].
6.1.2 Epidemiology
In patients with heart failure and a reduced 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 affected 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 ventricular function (HFpEF) have CSA
with CSR [52, 94, 189, 405]. The percentage of central apneas and hypopneas as
a ratio to obstructive apneas and hypopneas increases as the restriction of the
diastolic function increases [457].
6.1.1 Main findings
Most 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 patients in the early phase after a stroke
[320, 411]. Consequences of CSA in
combination with CSR can include daytime sleepiness, tiredness, night-time
dyspnea, nycturia and insomnia [25, 55,
205]. These symptoms can be further enhanced by the underlying disease.
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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 extent of the stroke the CSA with CSR also
depends on an underlying heart failure
[320, 411]. These diseases are often combined respiratory disorder with phases of
central breathing events during NREM
sleep alternating with obstructive events
during REM sleep or in the supine position.
6.1.3 Diagnosis
CSA with CSR is diagnosed if the diagnosis criteria A or B, C and D and met
(ICSD-3): Occurrence of one or more of
the following symptoms: Daytime sleepiness, 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 semiquantitative measurement of the
airflow using an oronasal thermistor
is much less sensitive [321].
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6.1.4 Treatment
The treatment of the underlying disease,
for example heart failure, is an important 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 theophylline [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 breathing 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 nerve
Treatment 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 reaction in some patients [361, 502]. The
literature research did not show any randomized studies of cardiovascular endpoints.
6.1.7 Oxygen
A 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 administration of oxygen is associated with
an increase in the PCO2 and persistent
periodic breathing [268]. Without an
oxygen saturation, these persistent respiratory events are often not classified
as hypopnea [48]. Both randomized and
non-randomized studies show no significant influence on left ventricular ejection fraction [16, 22, 501].
6.1.8 Continuous Positive Airway
Pressure
Continuous Positive Airway Pressure
can lead to a variable reduction in central apneas and hypopneas of approximately 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 sympathicus activation and biomarkers of
heart failure (e.g., Brain Natriuretic Petide, 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 significant 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 posthoc analysis of the study, patients with
HFrEF whose central apneas and hypopneas were suppressed to less than 15/h
showed a significant increase in left ventricular ejection fraction and improved
transplant-free survival [23]. HFrEF
patients with persistent CSA with CSR
receiving CPAP treatment have an elevated mortality rate [23]. CPAP treatment 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 significant reduction in the apneas and hypopneas with CPAP.
6.1.9 Bilevel Positive Airway
Pressure
Treatment with Bilevel Positive Airway
Pressure (Bilevel-PAP) with no background 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 pressure-controlled ventilation procedures
with a background frequency (Bilevel-PAP ST treatment; [125, 140, 226,
442, 475, 476]). While CPAP and adaptive 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 continuation of the hyperventilation [442].
In a randomized study with HFrEF patients 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 adaptive servo ventilation (25–27%) [140].
6.1.10 Adaptive servo ventilation
Adaptive servo ventilation (ASV) suppresses central apnea and hypopneas
more effectively than oxygen, CPAP or
Bilevel-PAP ST [27, 408, 442]. In a meta-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 normalizes the PCO2 in patients with HFrEF
with hypocapnic CSA [442]. Adaptive
ventilation procedures are also effective
in patients with the combination of central sleep apnea and obstructive sleep
apnea [8, 374].
A meta-analysis investigated the effects of treatment with ASV on heart
function in patients with HFrEF and
CSA with CSR [408]. Six non-randomized [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 randomized studies showed that ASV treatment
did not improve the left ventricular ejection fraction compared to a control intervention (treatment with medication
and treatment using a device of the heart
failure, CPAP or Bilevel-PAP ST) [25,
140, 228, 352, 376]. Randomized studies 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 without CSA indicate that CSA with/without
CSR is an independent predictor of increased mortality [95, 113, 181, 210, 216,
252, 330, 387, 417, 499]. One cause of the
mortality risk could be the increased frequency 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 patients with severe, chronic HFrEF (predominantly 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 contraindicated 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 ventricular ejection fraction must be determined 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 occurs 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 autonomous nervous system such as diabetes mellitus and heart and kidney failure can cause this type of central sleep
­apnea.
6.2.1 Main findings
The symptoms of the respective underlying disease and the consequences of
sleep fragmentation can be identified.
These may be both daytime sleepiness
and insomnia.
6.2.2 Diagnosis
Central apneas occur in light and REM
sleep; the increased occurrence of arousals can lead to sleep fragmentation.
6.2.3 Treatment
The focus is on treatment of the underlying 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 alternation between hyperventilation and
hypoventilation leading to apnea. An
increase in hypoxia and a worsening of
existing central sleep apnea at high altitude can occur in patients with existing
sleep apnea.
6.3.1 Main findings
Tiredness, exhaustion, and shortness of
breath.
Periodic breathing occurs from a clinical perspective. Diagnosis using instruments is mostly not possible.
6.3.2 Treatment
Safe treatment involves immediate
descent [324, 365], with heights of less
than 2500 o 4000 meters needing to be
reached. In healthy patients, acetazolamide can reduce HAPB [142]. There are
also positive reports of dexamethasone
in patients who are sensitive to high-altitude pulmonary edema [326]. These can
be avoided in part through the use of acetazolamide and predominantly avoided
using a combination of acetazolamide
and auto-CPAP [253]. Tab. B.14 provides information about studies on high
altitude periodic breathing.
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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 regulation, muscle activity in the upper respiratory tract and chemosensitivity [251].
In addition to the characteristic type of
atactic breathing, opiates and other substances which have a depressive effect
on breathing (e.g., sodium oxybate) can
lead to obstructive hypopneas, a decrease in breathing rate, central apneas,
prolonged hypoxias or periodic breathing even in the case of chronic use [134,
161, 302, 441, 461, 462, 469]. This applies
in particular to the combination of sedative substances and those with a depressive effect on breathing [161].
6.4.1 Main findings
The consequences of sleep fragmentation can be both daytime sleepiness and
insomnia.
6.4.2 Treatment
To date there are minimal data on optimal treatment. In any case, it is necessary to check whether discontinuation
or reduction of the opiates is medically
possible and reasonable [117]. If the respiratory disorders continued, positive
pressure methods can be used. There
are different results from case series and
non-randomized studies. CPAP treatment can only be promising in individual cases where there are obstructions
in the upper respiratory tract. Adaptive
servo ventilation and non-invasive ventilation 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 respiration (ICSD-3).
6.5.1 Main findings
The main element is repeatedly waking
up at night as a result of the cessation of
breathing, often accompanied by shortness of breath. The consequences of
sleep fragmentation can be both daytime
sleepiness and insomnia [64].
6.5.2 Epidemiology
The rare clinical picture mostly occurs in
middle-aged people, possibly more commonly in men than in women [389]. No
statements on prevalence are available.
6.5.3 Treatment
Clinical case descriptions report the successful 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 persists when PAP treatment is used.
Furthermore, the avoidable causes of
CSA should be ruled out during treatment with PAP. This includes elevated
treatment pressure, apneas following hyperventilation, apneas following arousal,
incorrect classification of obstructive
and central hypopneas, impaired respiratory breathing [311]. Incorrect diagnoses can also occur as a result of the
different division of obstructive and central 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 sensitivity and apnea limit have to be gradually
adjusted to the new situation [121, 250,
256, 377]. The pathophysiology, the significance in terms of quality of life and
the prognosis of CSA as a consequence
of treatment have not yet been the subject of scientific investigation.
6.6.1 Main findings
No specific symptoms are known. Nighttime shortness of breath and unintentional removal of the mask can occur
more frequently than in OSA [366].
6.6.2 Epidemiology
CSA as a consequence of treatment
occurs rarely in patients with healthy
hearts with OSA in the night of diagnosis during treatment with PAP (1%)
[473]. Where patients have underlying
heart failure CSA occurs more commonly as a consequence of treatment (18%)
[54].
6.6.3 Diagnosis
Polysomnography
with PAP.
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during
treatment
6.6.4 Treatment
To date there are date from a small number of randomized and some retrospective and non-randomized investigations.
In these, adaptive servo ventilation
was significantly superior to continued
CPAP treatment or non-invasive ventilation with Bilevel ST in suppressing the
central respiratory disorders [71, 120,
249]. Like CPAP and APAP, Bilevel can
even increase central respiratory disorders [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 leftventricular 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 opiateinduced 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 algorithm is set out in Appendix C.
7. Sleep-related
hypoventilation/sleep-related
hypoxemia
In contrast to ICSD-2, ICSD-3 [10]
differentiates between sleep-related
hypoventilation and sleep-related hypoxemia. Within sleep-related hypoventilation 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 nighttime pulse oximetry document an oxygen saturation of ≤ 88% over a period of
≥ 5 minute and the patient is not experiencing sleep-related hypoventilation.
Sleep-related hypoxemia is generally
the result of an internal or neurological 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 hypoventilation syndrome and sleep-related hypoventilation caused by a physical
disease.
7.1 Obesity hypoventilation
syndrome (OHS)
The following are used as diagnostic criteria:
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 respiratory disorder must also be present,
most commonly (in 90% of cases) this is
obstructive sleep apnea (OSA).
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Depending on the study, the prevalence 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 frequency of 10-50%.
7.1.1 Main findings
Since 90% of patients have obstructive 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 hypertension 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 elevated need for invasive ventilation in the
hospital, cardiovascular sequelae such as
arterial hypertension, heart failure, pulmonary heart disease and angina pectoris contribute to the elevated morbidity.
As a result, the quality of life in patients
with OHS is reduced considerably.
7.1.2 Diagnosis
A 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 nighttime determination of the PCO2 (arterial, 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 Treatment
CPAP treatment alone is not sufficient
in some OHS patients, so only a shortterm attempt to carry out CPAP treatment with simultaneous transcutaneous
measurement of the CO2 monitored in
a sleep laboratory or a ventilation unit is
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justified. If the CO2 measured transcutaneously 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-invasive ventilation (NIV). Otherwise there
should be a re-evaluation of the CPAP
treatment after three months. If the patient has experienced a clinical improvement and normocapnia, the CPAP treatment 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 treatment with O2 cannot be recommended.
In contrast to this, non-invasive ventilation (NIV) improves the respiratory
response, the blood gases, the microstructure and macrostructure of sleep,
the quality of life, hemodynamic parameters and the survival of OHS patients.
This treatment should therefore be used
primarily or if CPAP treatment is ineffective. NIV with fixed pressure support
and with a specification of target volume
have proven to be effective. Comparison
studies show various results. Weight reduction is to be seen as a key causal measure in patients with OHS, although ventilation 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 bariatric 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 findings
The patient’s symptoms are uncharacteristic and often overshadowed by those
of the underlying disease. Since the focus is on the impairment of ventilation,
patients typically complain of dyspnea
when exercising, decreased physical performance, commonly leg edemas and
also headaches as a result of hypercapnia. 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,
complications
The underlying disease causes a decreased capacity and/or increased burden on the breath pumping apparatus
which was not able to be compensated
for in earlier stages of the disease. As the
underlying disease advances, hypoventilation with phases of hypercapnia initially 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 progresses, hypoventilation/hypercapnia occur
in NREM sleep too, and ultimately the
full picture of hypercapnic respiratory
failure while awake develops.
7.2.3 Diagnosis
By 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, laboratory tests and chest x-rays and where applicable an echocardiography test should
be carried out depending on the patient’s
history and the clinical findings. Regardless of the underlying disease, hypercapnias 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 underlying disease, there is a risk of overlooking
the early phases of chronic ventilation
insufficiently with hypoventilation solely at night, thereby delaying sufficient
treatment. It is therefore necessary to
carry out a measurement of the respiration at night in patients with corresponding risks of the occurrence of secondary 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 sufficient to provide evidence of sleep-related hypoventilation. Night-time arterial
PaCO2 measurements are not practicable. A transcutaneous or end tidal pCO2
measurement in combination with the
polygraph is therefore required to provide evidence of sleep-related hypoventilation.
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 hypoventilation is therefore good, but it is not suitable to rule this out. A polysomnography
is therefore indicated in patients with
night-time symptoms with no evidence
of hypoventilation.
7.2.4 Treatment
In the case of both chronic underlying
diseases, treatment is mostly not sufficient to remedy the hypoventilation.
From a treatment perspective, non-invasive ventilation (NIV) is therefore
carried out during the sleep using a mast
with the aim of increasing the alveolar
ventilation and avoiding hypoventilation. The main criteria for the start of
long-term NIV treatment in a patient
with sleep-related hypoventilation
caused by a physical disease are symptoms and consequences of the ventilation insufficiency such as dyspnea and
edema and limitation in quality of life
caused by non-restorative sleep as a result of disorders sleeping throughout the
night and furthermore
––in patients with sleep-related
hypoventilation as part of an
obstruction of the lower respiratory
tract:
ƒƒ repeated, severe (i.e. associated with
respiratory acidosis) exacerbations
which require hospitalization or
ƒƒ a day PaCO2 ≥ 50 mm Hg or
ƒƒ a night-time PaCO2 ≥ 55 mm Hg
or an increase in the CO2 measured transcutaneously at night
≥ 10 mmHg
ƒƒ 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:
ƒƒ a day PaCO2 ≥ 45 mm Hg or
ƒƒ a night-time PaCO2 ≥ 50 mm Hg
or an increase in the CO2 measured transcutaneously at night
≥ 10 mmHg
The aim of the ventilation is normocapnia achieved by the remedying of
the hypoventilation through ventilation
while the patient is sleeping and the reduction in PaCO2 through to normocapnia 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 ventilation and it must be amended to include 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 polysomnography is indicated in the case of uncertainty regarding the night-time hypoventilation during REM sleep.
The NIV can be given as assisted, assisted-controlled or purely controlled
ventilation. There are no data regarding
the superiority of one method. Patients
with neuromuscular diseases and diseases of the thoracic skeleton often tolerate
the controlled mode subjectively very
well while patients with COPD mostly
prefer the assisted mode. Optimal, individually adjusted settings are key to the
good acceptance and success of treatment.
There are only a few controlled studies of the effects of NIV with high-quality methods (see Tab. B.19 and B.20). In
the case of slowly progressing muscle
diseases, kyphoscoliosis and post-tuberculosis conditions, NIV achieves a dramatic 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 reduced [9, 63]. In some cases, the physiological 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 neuromuscular 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 underlying disease restricts the positive effects
of NIV. An individual indication for
ventilation treatment is required in these
patients. The ethical discussion of the acceptance of invasive ventilation that may
eventually necessary should therefore be
had as early as possible.
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Patients with COPD represent the
largest group of patients who meet the
indication criteria for NIV. Shorter, controlled investigations in patients receiving 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 substantial reduction in the PaCO2 as a result of
NIV treatment. In a randomized, controlled study, however, the life expectancy 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 ventilation 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
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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 sleeprelated 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 sleepiness 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, abnormal 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 examination is instructed to ask about diseases
with elevated levels of daytime sleepiness
(e.g., sleep disorders) and if he has a specific 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 carried out where the doctor has significant
doubts about the patient’s ability to drive.
A statement on this was written in November 2015 by the DGSM.
On July 1, 2014, the “European Parliament and the Council on Driving Licences” 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. People 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 vigilance when on medication.
In accordance with the “principles of
medical case” valid since 2009 (previously “guide to expert medical activities”), 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, pulmonary hypertension) should also be
taken into account.
In patients with obstructive sleep apnea, an inability to work is an exception
as there are suitable treatment methods
as a result of which as a minimum a reduction in symptoms can be expected
[123].
Somnologie · Suppl s2 · 2017
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S3-Guideline on Sleep-Related Respiratory Disorders
Glossary
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 Medizinischen Fachgesellschaften
(Working Group of Scientific
Medical Societies)
BdP
Bundesverband der Pneumologen (Federal Association
of Pneumonologists)
BMI
Body mass index
BUB
Richtlinie zu Untersuchungsund Behandlungsmethoden
der vertragsärztlichen
Versorgung (Guideline on
Investigation and Treatment
in Contract Medical Care)
COPD
DGMKG
Continuous positive airway
pressure
CSR
Glossary
Deutsche Gesellschaft für
Mund-Kiefer-Gesichtschirurgie (German Society of Oral,
Jaw and Facial Surgery)
DGN
Deutsche Gesellschaft für
Neurologie (German Neurology Society)
DGP
Deutsche Gesellschaft für
Pneumologie und Beatmungsmedizin (German
Society of Pneumonology
and Respiratory Medicine)
DGPPN
Deutsche Gesellschaft für
Psychiatrie, Psychotherapie und Nervenheilkunde
(German Society of Psychiatry, Psychotherapy and
Neurology)
DGSM
Deutsche Gesellschaft
für Schlafforschung und
Schlafmedizin (German Sleep
Society)
DGZS
Deutsche Gesellschaft
Zahnärztliche Schlafmedizin
(German Dental Sleep Medicine Society)
Chronic obstructive pulmonary disease
CPAP
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)
EBM
Evidence-based medicine
Cheyne-Stokes respiration
EEG
Electroencephalogram
DASS
Divided Attention Steering
Test
EOG
Electrooculogram
ERJ
European Respiratory Journal
Sham
Feigning
DEGAM
Deutsche Gesellschaft für Allgemein-und Familienmedizin
(German Society of General
and Family Medicine)
ERS
European Respiratory Society
SRS
Sleep Research Society
ESC
European Society of Cardiology
STOP
Snoring, tiredness, observed
apneas, high blood pressure
ESRS
European Society of Sleep
Research
STOP-BANG
FRS
Fernröntgenbild (teleradiograph)
Snoring, tiredness, observed
apneas, high blood
pressure + BMI, age, neck
circumference
GOLD
Global Initiative for Chronic
Obstructive Lung Disease
TcpCO2
Transcutaneous carbon
dioxide
HFrEF
Heart failure with reduced
ejection fraction
LJB
Lower Jaw Brace
UPPP
Uvulopalatopharyngoplasty
International Classification of
Sleep Disorders
Sus.
Suspected
WASM
World Association of Sleep
Medicine
WFSRS
World Federation of Sleep
Research Societies
St. P.
Status post
CSA
Central sleep apnea
DGAI
DGAV
DGHNOKHC
DGIM
DGK
DGKFO
S128
Glossary
AASM
Deutsche Gesellschaft
für Anästhesiologie und
Intensivmedizin (German
Society of Anesthesiology
and Intensive Medicine)
Deutsche Gesellschaft für
Allgemein- und Viszeralchirurgie (German Society of
General and Visceral Surgery)
Deutsche Gesellschaft für
Hals-, Nasen- und Ohrenheilkunde, Kopf- und
Halschirurgie (German Society for ENT Medicine, Head
and Neck Surgery)
ICSD
LAUP
Laser-assisted uvulopalatoplasty
LVEF
Left ventricular ejection
fraction
Deutsche Gesellschaft für
Innere Medizin (German Society of Internal Medicine)
MAD
Mandibular advancement
device
MCI
Mild cognitive impairment
Deutsche Gesellschaft für
Kardiologie (German Cardiology Society)
MRD
Mandibular reposition device
MSLT
Multiple sleep latency test
MWT
Multipler Wachbleibetest
(multiple staying awake test)
NIV
Non-invasive ventilation
Deutsche Gesellschaft für
Kieferorthopädie (German
Jaw Orthopedics Society)
Somnologie · Suppl s2 · 2017
9. Glossary
10. Appendices
Tab. A.1 Elements of the systematic
development of the guideline
Tab. A.2 Elements of the systematic
development of the guideline
Logic (clinical algorithm)
Levels of evidence
Consensus
Degree of
recommendation
Evidence
A
1a, 1b, 1c
Decision analysis
B
2a–c, 3a, 3b
C
4.5
Different degrees of evidence may be
applied as part of the consensus process in
justified cases
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”
Clinical condition
Decision:
Activity
1
Logical numbering
sequence
10.1 Annex
A: Guideline report
1
10.1.1 Scope and purpose
This guideline on sleep-related respiratory 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 studies have been added which all need to
be taken into account. The scope of the
scientific knowledge has increased sig-
nificantly, so “sleep-related respiratory disorders” will appear as a separate
guideline.
Sleep-related respiratory disorders
include obstructive sleep apnea, central
sleep apnea and sleep-related hypoventilation/sleep-related hypoxemia.
This guideline is aimed at medical and
non-medical professionals (e.g., psychologists, natural scientists), nursing
staff, self-help groups and interested laymen.
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.
Somnologie · Suppl s2 · 2017
S129
S3-Guideline on Sleep-Related Respiratory Disorders
Medical expert associations
––Bundesverband der Pneumologen
(BdP, representative C. Franke)
––Deutsche Gesellschaft für Allgemeinund Familienmedizin (DEGAM1,
comment by E. Baum with no formal
mandate)
––Deutsche Gesellschaft für Allgemeinund 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
Note: For staffing reasons, the expert association was not able to take part in the consensus conferences, so there are only comments in
the ongoing correspondence.
1
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Somnologie · Suppl s2 · 2017
10.1.3 Methodical procedure
The AWMF provided support throughout the guideline development process.
The coordination of the consensus conferences was carried out in accordance
with the nominal group process by moderated by PD. Dr. Helmus Sitter.
As it is an S3 guideline, the consensus program includes the following elements:
Logical analysis (clinical algorithm),
formal consensus finding, evidence-based
results, decision analysis For an S3 guideline, a clearly defined question is used to
bring about a solution with conditional 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 understandable.
10.1.4 Drawing up the guideline/
gaining consent
The first version of the guideline was
drafted under the guidance of the people 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 November 27, 2015 in Frankfurt. The following
people were present:
Michael Arzt, Martina Bögel, Hendrik Bonnemeier, Bert Braumann, Ingo
Fietze, Christian Franke, Helmut Frohnhofen, Wolfgang Galetke, Peter Geisler,
Michael Herzog, Joachim T. Maurer, Geert Mayer, Maritta Orth, Thomas Penzel, 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 Frohnhofen, 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
research
General search criteria: The literature research was carried out for all studies that
had been published up to April 2014 in
the Pub-Med database and Cochrane Library. Current literature up to December
2015 was also taken into account provided it met the criteria set out below and
was deemed to be important. The update
to the AASM Manual, which was published in 2016, was the only exception.
The following were defined as inclusion
criteria:
publications in German or English,
prospective or retrospective clinical trials, randomized controlled trials, controlled 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: Original works, published in a language other
than English or German, animal experiments, 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 literature 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 Controlled ­Trial, Review, Controlled Clinical
Trial, Guideline, English, German. Snoring 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.” Additional search terms for published guidelines of SRRD were: Practical guidelines,
standard of practice papers, practice
parameters, consensus papers, position
papers and/or sleep apnea, sleep related
breathing disorders, snoring, Homepages 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 Society, ERJ, ESC, AWMF Leitlinien anderer
Gesellschaften, Cochrane, HTA reports.
There was a total of 502 relevant entries.
10.1.6 Evaluation
The evaluation of literature has been
carried out by two independent experts
in line with the Oxford Centre for evidence-based medicine levels of evidence
(2001).
10.1.7 Clinical algorithms
A total of 4 clinical algorithms were created (s. Appendix C):
––the diagnostic approach for
obstructive sleep apnea,
––the diagnostic approach for central
sleep apnea,
––the diagnostic approach for sleeprelated breathing difficulties and
a presence of cardiovascular
comorbidities,
––the therapeutic approach for
obstructive sleep apnea.
of interest has been critically examined
by 2 members of the Steering Committee. 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 Participants abstained from voting on the
subject of neurostimulation processes;
1 participant on the subject of APAP.
10.1.10 Preparation and
implementation
The guideline is distributed via the professional journal Somnologie and can be
inspected online on the website of the
AWMF (http://www.awmf.org/ awmfonline-das-portal-der-wissen-schaftlichen-medizin/awmf-aktuell. html).
10.1.11 Period of validity and
updating process
The guideline will remain valid for
3 years from its date of publication
The algorithms were created by the
Steering Committee and approved together with the specialist companies.
10.1.8 External assessment and
approval
The guideline has been discussed and
approved by the chairmen of participating medical specialist companies.
10.1.9 Editorial independence
Financing 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 potential conflicts of interest has been documented with the aid of standardized
forms issued by the AWMF. All participants have answered the necessary questions. Information regarding conflicts
Somnologie · Suppl s2 · 2017
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S3-Guideline on Sleep-Related Respiratory Disorders
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 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
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
Central sleep apnea syndrome
Sleep-related hypoventilation
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
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Somnologie · Suppl s2 · 2017
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
Sensitivity
Specificity
Positive
predicative
value
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
Sleep
Breathing
Parameters
Technology
Optimal scanning rate (Hz)
Filter (Hz)
EEC, EOC
Electrodes
500
0.3-35
EMG
Electrodes
500
10-100
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
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S3-Guideline on Sleep-Related Respiratory Disorders
Tab.B.7 Studies for polygraphy for sleep apnea
S134
Study title
Author
Year
Country Study type
Pat.
Outcome
number
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 under
certain 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 meta-analysis, as studies 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 Collop et al. [105]
devices for out-of-center
(OOC) testing: technology evaluation
2011
USA
Polygraphy equipment evaluation
with systematic
literature review
–
–
1
Home diagnosis of sleep
apnea: a systematic
review of the literature
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
Ross et al. [392]
meta-analysis of the
literature regarding the
diagnosis of sleep apnea
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
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
Flemmons et al. [145]
Yalamanchali et al. [489]
Somnologie · Suppl s2 · 2017
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Year
2015
2014
2009
2001
2012
2012
2006
2013
2013
2013
Author
Correa et al. [108]
Gross et al. [172]
Finkel et al. [141]
Gupta et al. [175]
Joshi et al. [224]
Kaw et al. [229]
Kim and Lee [233]
Lockhart et al. [266]
Mokhlesi et al. [303]
Mokhlesi et al. [304]
USA
USA
USA
South Korea
USA
USA
USA
USA
USA
USA
Country
Tab. B.8 Perioperative complications
Orthopedic patients with or
without OSA
Retrospective cohort
study
Retrospective cohort
study
Prospective cohort
study
Retrospective
case-control study
Retrospective
case-control study
14,962
180
471
Elective surgery patients
1,058,710
Adult bariatric surgery patients 91,028
Adult surgical patients
OSA pat. with uvulopalatopharyngoplasty
Adult non-cardiosurgical
patients with PSG
–
202
2877
–
–
Adult surgical patients
Number of studies: 8
Number of
patients (n)
ZSA patients
Population
consensus statement –
of the Society for Ambulatory Anesthesia
Retrospective
case-control study
Prospective observational study
Guidelines of the
American Society of
Anesthesiologists
Systematic review
Study type
–
–
–
–
–
–
Preoperative
CPAP treatment
–
–
–
Intervention
Hospital mortality
Ambulatory period
Cardial complications
Respiratory complications
Hospital mortality
Ambulatory period
Cardial complications
Respiratory complications
Postoperative mortality after 20
days/1 year
Incidences of difficult intubation
Postoperative complications
Ambulatory period
–
Postoperative complications
Ambulatory period
Prevalence OSA
Postoperative complications
–
Prevalence, mechanisms, perioperative management
Design/end points
2b
2b
2b
3b
3b
–
3b
2b
–
3a
Levels of
evidence
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Year
2014
2012
2015
2002
2010
2012
Author
Mutter et al. [310]
Ravesloot et al. [381]
Rösslein et al. [390]
Siyam and Benhamo [419]
Stierer et al. [431]
Vasu et al. [451]
USA
USA
France
Germany
Netherlands
USA
Country
Tab. B.8 Perioperative complications (continued)
Systematic review
Prospective observational cohort study
Retrospective
case-control study
Position paper
DGHNOKHC/DGAI
Prospective,
multi-disciplinary,
single-center observational study
Matched cohort
analysis
Study type
17,842
Number of
patients (n)
Surgical OSA patients
Ambulatory surgical patients
Surgical patients
–
Number of studies: 11
2139
113
–
Adult bariatric surgery patients 279
Pat. with known OSA with/
without CPAP treatment vs.
pat. with unknown OSA
Population
–
–
–
–
–
CPAP
Intervention
Postoperative complications
OSA prevalence
Postoperative complications
Incidences of difficult intubation
–
OSA prevalence OSA predictors
Cardial complications respiratory
complications
Design/end points
2a
(Degree of
evidence of
individual
studies: 2b–3b)
2b
3b
–
2b
2b
Levels of
evidence
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Year
2009
2009
2010
Author
Antic et al. [18]
Damjanovic et al. [112]
Dellaca et al. [119]
International
International
International
Country
OSA
Population
Monitoring study
OSA
Placebo controlled, OSA
parallel, randomized
Randomized,
controlled
Study type
10
n = 100
n = 195
Patients
Tab. B.9 Studies for the improvement of CPAP compliance, Cochrane analysis 2011, studies from 2009
CPAP, titration
in residential
environment
CPAP/APAP
new set-up,
follow-up
3 months,
9 months
CPAP new
set-up,
follow-up:
3 months
Intervention
2. after 1 week of
polysomnographic control in
the sleep laboratory
1. Telemetry:
–– based on conventional
GPRS cellphone – related
observation and titration of
CPAP pressure
Intervention 1:
EDUCATION: Standard
instruction plus CPAP/APAP
Intervention 2: Training,
monthly visits at home
(6 months)
1. Polysomnographic
diagnostics (1 night) and CPAP
set-up (1 night), monitoring
by sleep physician
Intervention:
Auto CPAP set-up, pulse
oximetry, monitoring through
sleep medicine trained nurse
Design/end points
lb
ESS: no differences
Compliance: no differences
compared with placebo?
Intervention 1: Costs lower
than placebo?
Ambulatory polysomnography:
–– no relevant change of
telemetrically adjusted CPAP
parameters
Telemetric pressure titration:
–– Significant improvement/
normalization of ventilatory
parameters
llc
lb
Re-examination:
Intervention 1: 68%
Intervention 2: 88%, p < 0.05
Period of use:
Intervention 1:
4.6 ± 0.4 h/night
Intervention 2:
5.7 ± 0.2 h/night, p < 0.05
Days of use (%):
Intervention 1: 57.0 ± 5.9
Intervention 2:
80.4 ± 2.8, p < 0.0
–– No differences in period of
use between CPAP and APAP
Degree of
evidence of
individual
studies
Effect on CPAP compliance
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Year
2010
2014
Author
Holmdahl et al. [193]
Mendelson et al. [296]
International
International
Country
Multi-center,
randomized,
controlled
Randomized,
controlled
Study type
OSA
OSA
Population
107
200
Patients
OSA
Regular visits,
follow-up
2 years
Intervention
Tab. B.9 Studies for improving CPAP compliance, Cochrane analysis 2011, studies from 2009 (continued)
Standard instruction:
Mask adjustment
Auto-CPAP
After 2 days questioning
regarding adherence, side
effects by sleep specialist
4 weeks: Read-out of data,
personal discussion with sleep
specialist
2. Telemonitoring
Smartphone (input of blood
pressure, CPAP adherence,
quality of life) + telemetric
feedback
3rd End point:
RR set-up
Intervention
1. Annual visits from sleep
medicine nursing specialist
2. Annual visits from physician
+ pulse oximetry
Design/end points
Degree of
evidence of
individual
studies
lb
lb
Effect on CPAP compliance
Both groups:
99% highly satisfied with CPAP
Quality of life:
idem in 1 and 2
–– Blood pressure
characteristics same for
both groups
–– no improvement in blood
pressure set-up through
telemedicine
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Year
2009
2010
Author
Smith et al. [423]
Sparrow et al. [426]
International
International
Country
Randomized,
controlled
Randomized,
placebo controlled,
follow-up: 6 months
Study type
OSA
OSA, new
set-up
Population
CPAP
MAD
97
250
Intervention
Patients
Tab. B.9 Studies for improving CPAP compliance, Cochrane analysis 2011, studies from 2009 (continued)
Compliance improvement
Intervention 1: n = 124
Interactive answer machine
with feedback
2. n = 126
Placebo:
General health information,
via the telephone
Intervention:
EDUCATION
1. Instruction regarding CPAP
use
2. Diary:
Period of use, side effects,
positive effects
3rd Audio tape, mask
adjustment instruction,
breathing pattern, relaxation
through music
Placebo:
Audio tape with information
Design/end points
lb
lb
1 month:
Higher adherence in
intervention group (p < 0.01)
376 months:
No differences in compliance
between both intervention
groups
CPAP use:
Intervention 1 vs.
intervention 2
6 months:
CPAP use 1 h longer per night
12 months:
CPAP use 2 h
Degree of
evidence of
individual
studies
Effect on CPAP compliance
S140
2011 International
2013 International
2009 International
2011 International
2015 International
2015 International
Ahrens et al. [4]
Anandam et al. [12]
Bäck et al. [32]
Bakker and Marshall [33]
Bratton et al. [67]
Bratton et al. [67]
Country
Year
Author
Somnologie · Suppl s2 · 2017
Review
meta-analysis
Meta-analysis
Review
meta-analysis
Review
Meta-analysis
Review
Study type
OSA
OSA
OSA
Snoring
OSA
OSA
Population
67
51
7
30
9
14
Number of
studies
CPAP vs. MAD
CPAP vs. no CPAP
MAD vs. no MAD
CPAP + MAD vs. no
CPAP, no MAD
CPAP vs. flexible CPAP,
air humidification
RFTA soft palate vs.
placebo
Conservative weight
reduction
OA vs. OA
OA vs. Placebo
Intervention
Tab. B.10 Current systematic reviews (SR) and meta-analyses (MA) for the treatment of obstructive sleep apnea (OSA)
CPAP vs. MAD: more effective
Day-time sleepiness more
effective

MAD: meaningful treatment
alternative for CPAP intolerance
CPAP vs. no CPAP
RR systol./diastol. significant

MAD vs. no MAD
RR systol./diastol. significant
CPAP vs. MAD
no differences
in RR reduction
Blood pressure (RR)
changes systol., diastol.
prior to and during
treatment
Sleepiness
ESS
No compliance improvement
through flexible CPAP
Snoring becomes moderate,
although significantly reduced
with lower morbidity than
LAUP or injection snoreplasty.
Effect falls after more than
12 months
Weight reduction improves BMI
and AHI
OAs more effective than
placebo protrusion is crucial
Vertical opening has no
influence
Effect on study endpoint
Compliance
Snoring, undesired effects
BMI, AHI
AHI, RDI
Study endpoint
1a
1a
1a
1b–4
1-4
1-5
Degree of
evidence of
individual
studies
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2014 International
2010 International
2013 International
2013 International
Camacho et al. [80]
Caples et al. [82]
Choi et al. [99]
Dong et al. [126]
Country
Year
Author
OSA
Population
Meta-analysis
Meta-analysis
OSA
OSA
(snoring
without
OSA)
Review,
OSA
(meta-analysis)
Review
Study type
17
OSAS (medium severity)
and
^CAD
^stroke -^general heart
conditions
Pillar soft palate implant AHI, ESS, (snoring),
vs. placebo
extrusion rate for all
14 studies
7 OSA
(7 snoring)
AHI, day-time sleepiness,
undesired effects
AI, CAI, AHI, ODI, day-time
sleepiness
Study endpoint
MMA (9), UPPP (15),
LAUP (2), RFTA (8),
Pillar (2)
Tracheostomy
Intervention
36
18
Number of
studies
Tab. B.10 Current systematic reviews (SR) and meta-analyses (MA) for the treatment of obstructive sleep apnea (OSA) (continued)
3a
–– OSAS and general heart
conditions:
OR 1.37, 95% CI 0.95–1.98
OR 1.37, 95% CI
–– OSAS and stroke:
OR 2.48, 95% CI 1.98–3.1
–– OSAS and CAD
1b–4
1b–4
4 and 5
Degree of
evidence of
individual
studies
Pillar implants reduce AHI, ESS
(for OSA) and snoring with
moderate effect over a period
of 3 to 29 months maximum.
Extrusions are described in
9.3% of patients
Moderate evidence: LAUP
without effect. Low evidence:
MMA with pronounced effect,
UPPP, RFTA and Pillar with
moderate effect. Complication
rates have decreased in later
studies
TT reliably rectifies OSA with
regard to beating disorders and
day-time sleepiness; central
apnea > no longer detectable
14 weeks after TT; from BMI
45 obesity hypoventilation
syndrome possible reason for
persistently increased ODI
Effect on study endpoint
S142
2015 International
2008 International
2014 International
2009 International
2009 International
Drager et al. [129]
Farrar et al. [136]
Fava et al. [138]
Franklin et al. [150]
Greenburg et al. [171]
Country
Year
Author
Somnologie · Suppl s2 · 2017
Meta-analysis
Meta-analysis
Review and
meta-analysis
Meta-analysis
Meta-analysis
Study type
OSA
OSA and
snoring
OSA
OSA
OSA
Population
12
4
31
RCTs
16
25
Number of
studies
Bariatric surgery
LAUP (2), RFTA base
of tongue (1) or soft
palate (1) vs. waiting or
placebo
CPAP vs. active/passive
treatment
RFTA soft palate, base
of tongue or both vs.
placebo or case series
CPAP vs. no CPAP
Intervention
BMI, AHI
Day-time sleepiness, AHI,
snoring, undesired effects
(also uvulopalatoplasty
and uvulopalatopharyngalplasty)
RR lowering
AHI, ESS, undesired effects
BMI prior to and during
CPAP
Study endpoint
Tab. B.10 Current systematic reviews (SR) and meta-analyses (MA) for the treatment of obstructive sleep apnea (OSA) (continued)
Bariatric surgery improves BMI
and AHI
LAUP and RFTA base of tongue
without effect in day-time
sleepiness and AHI, RFTA
sift palate reduced snoring.
No randomized studies are
available for all other surgical
procedures, therefore not
included in the analysis.
Difficulty swallowing after
uvulopalatopharyngalplasty
or uvulopalatoplasty surgery
in 31% or 27% of cases,
respectively. Complication rates
have decreased in later studies
Effect on study end point CPAP:
significant RR lowering
Moderate reduction of AHI and
ESS, continued over 24 months
in case series. Controlled study
with comparable effect on
quality of life and day-time
sleepiness as for CPAP and
better than placebo
BMI increase during CPAP
Effect on study endpoint
1-4
1b (effectiveness) and 4
(UW)
1
1b–4
2a
Degree of
evidence of
individual
studies
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2010 International
2010 International
2012 International
Hirai et al. [190]
Holty and Guilleminault
et al. [194]
lp et al. [201]
2012 International
2011 International
Hecht et al. [186]
Kaw et al. [229]
2014 International
Handler et al. [178]
Country
Year
Author
Meta-analysis
Review
meta-analysis
Meta-analysis
Meta-analysis
Review and
meta-analysis
Review
Study type
OSA
OSA
OSA
OSA
OSAS
OSA
Population
13 RCTs
24
22
3
6 (3 parallel,
2 cross-over,
1 controlled)
27
Number of
studies
None
Auto-CPAP vs. CPAP
MMA vs. CPAP and case
series
Position treatment
vs. CPAP
CPAP, randomized and
non-randomized
Tongue suspension (6),
all other work with
UPPP
Intervention
desaturation
ICU
postop. complications in
OSAS patients:
–– cardial
–– acute pulmonary failure
Compliance
AHI, long-term effects
AHI, ESS, 02 saturation,
subjective test processes/
questionnaires
CPAP effect on
–– glucose metabolism
–– insulin resistance
AHI
Study endpoint
Tab. B.10 Current systematic reviews (SR) and meta-analyses (MA) for the treatment of obstructive sleep apnea (OSA) (continued)
Effects on study end points
SaO2min. 
Auto-CPAP vs. CPAP
Compliance  (period of use/
night): 11 min.
ESS  (0.5 pt.)
–– CPAP vs. auto-CPAP
MMA reliably reduces degree of
severity, in cohort studies with
ventilation treatment, increase
in maxillary pre-positioning
and lower preoperative BMI
with positive prediction.
Transient facial paresthesia
in 100%, persistent after
12 months in 14.2%
Superiority of CPAP treatment
only in relation to AHI and O2
saturation, recommendation
for position-dependent OSA
with CPAP non-compliance/
intolerance
No effect on study end points
Tongue suspension alone
with response rate of 36.6%,
in combination with UPPP
as good as genioglossus
advancement and hyoid
suspension (62.1% vs. 61.6%)
Effect on study endpoint
1
1b–2c
1a
1b
5 Level 1 1
1 Level 3
Degree of
evidence of
individual
studies
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2011 International
2013 International
2008 International
2014 International
2012 International
Li et al. [261]
Li et al. [262]
Lin et al. [264]
Madbouly et al. [272]
Marklund et al. [277]
Country
Year
Author
Somnologie · Suppl s2 · 2017
Review
Meta-analysis
Review
Review/
meta-analysis
Review
Study type
OSA
OSA
OSA
OSA
OSA
Population
55
12
49
14
13
Number of
studies
OA vs. Placebo
OA vs. OA
OA vs. CPAP
OA vs. surgery
CPAP
Multi-level surgery
OA vs. CPAP
Nasal surgery
vs. Placebo
Intervention
1
1b–4
Degree of
evidence of
individual
studies
Sign. Correlation between
OSAS degree of severity and
compliance
OA more effective than
placebo, degree of protrusion
correlates with effectiveness
CPAP is superior to OA in its AHI
reduction. Day-time tiredness,
QoL, cardiovascular parameters
are comparable
Long-term effect is less than
initial improvement
AHI, RDI, PSG,
day-time tiredness, QoL,
cardiovascular parameters,
long-term effects
1-5
2a
Significant improvement of
1b–4
AHI (AHI reduction > 50% to
a value of <20) in 66.4% of all
patients. Success rate higher
with AHI > 40 (69.3%) than if
AHI < 40 (56.5%). No worsening
3–8 years postoperatively.
Significant improvement of all
other parameters investigated
CPAP with regard to AHI, AI,
min. SpO2, REM considerations
OA and CPAP with regard
to ESS, HRQoL, CP, BP, SE,
compliance, preference and
dropout comparable
No influence on AHI, ESS and
snoring decrease
Effect on study endpoint
OSAS degree of severity
(AHI) and CPAP compliance
AHI, O2 saturation, REM
content, snoring (VAS)
day-time sleepiness,
quality of life
AHI, ESS, HR QoL, CP, BP,
AI, REM, min. SpO2, SE,
compliance, preference,
dropouts
AHI, ESS, snoring
Study endpoint
Tab. B.10 Current systematic reviews (SR) and meta-analyses (MA) for the treatment of obstructive sleep apnea (OSA) (continued)
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2015 International
2011 International
2013 International
2006 International
2009 International
Qureshi et al. [369]
Pirklbauer et al. [359]
Sarkhosh et al. [398]
Smith et al. [422]
Smith et al. [423]
2013 International
2013 International
Metha et al. [295]
Sun et al. [438]
2009 International
McDaid et al. [287]
Country
Year
Author
Meta-analysis
Review
(Cochrane)
Review
SR
Review
Meta-analysis
Meta-analysis
Review
Study type
OSA
OSA
OSA
OSA
OSA
OSA
OSA
OSA
Population
10
45
26
69
28
8
14
48/29
Number of
studies
CPAP
CPAP
Medication
Bariatric surgery
MMA vs. CPAP and case
series
CPAP vs. no CPAP
O2 versus ambient air
O2 versus CPAP
CPAP
Best supportive care
placebo
MAD
Intervention
LV-EF
Compliance increase
through pressure
modification
AHI, sleepiness
BMI, AHI
AHI, long-term effects,
day-time sleepiness
CPAP treatment and VHF
frequency
AHI, O2 saturation AHI, O2
saturation
ESS
MWT
MSLT
QALY
Study endpoint
Tab. B.10 Current systematic reviews (SR) and meta-analyses (MA) for the treatment of obstructive sleep apnea (OSA) (continued)
LV-EF  (sign.)
–– significant correlation
between LV-EF and AHI
–– CPAP with OSA and LV-EF 
Period of use (n. s.)
–– Air humidification (n. s.)
1a
1a
–– Auto-CPAP vs.CPAP
Period of use  (n. s.)
ESS  (n. s.)
–– Bi-level
1-4
1-4
1b–4
2c
Medication cannot be
recommended
Bariatric surgery improves BMI
and AHI
MMA is comparable with
ventilation treatment, positive
effects on day-time sleepiness,
quality of life, no negative
effect on facial esthetics
CPAP: significant reduction of
risk for VHF
O2 is superior to ambient air
with regard to night-time O2
saturation
CPAP is superior to O2 with
regard to reduction of AHI
Benefits 
Costs 
1-4
2c
CPAP vs. conservative
ESS  (sign.)
MWT 
–– CPAP vs.MAD
ESS: no differences
–– CPAP vs.MAD
Degree of
evidence of
individual
studies
Effect on study endpoint
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2005 International
2010 International
2014 International
2013 International
Sundaram et al. [439]
Tregear et al. [445]
Wozniak et al. [484]
Yang et al. [490]
Country
Year
Author
Meta-analysis
Review
(Cochrane)
Review
meta-analysis
Review
Study type
OSAS
OSA
OSA
OSA
Population
15
30
9
7
Number of
studies
None
CPAP plus
–– Training
–– Support
–– Behavior therapy
CPAP
Surgery
Intervention
Effects on study end points
Compliance increase through
all forms of intervention,
although effect is small
Compliance
CPAP effect on
–– BZ control
–– insulin resistance
Day-time sleepiness  (sign.)
after a CPAP night
Frequency of accidents with
OSAS under CPAP significant 
Time period until fall in
accident frequency: 2–7 days
(driving simulation)
No effect, lack of long-term
data
Effect on study endpoint
Frequency of accidents
prior to and during CPAP
Treatment period until
fall in accident frequency
AHI, snoring, tiredness
Study endpoint
Tab. B.10 Current systematic reviews (SR) and meta-analyses (MA) for the treatment of obstructive sleep apnea (OSA) (continued)
13 observational
2 (Level 4)
observa­
tional,
controlled
(Level 4)
2 randomized,
controlled
(Level 1)
2c
2c
1 u. 2
Degree of
evidence of
individual
studies
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2012
2009
Dixon et al. [124]
Foster et al. [147]
2009
2013
Browaldh et al. [70]
Johansson et al. [218]
2009
Bäck et al. [32]
2009
2011
Babademez et al. [30]
Guimaraes et al. [174]
Year
Author
Sweden
Brazil
USA
Australia
Sweden
Finland
Turkey
Country
Parallel over 9
weeks
Parallel over 3
months
Parallel over 1
year
Parallel over 2
years
RCT
RCT
RCT
Study type
OSA
OSA
OSA with
type 2
diabetes
OSA
OSA
OSA
OSA
Population
63
31
264
60
65
(BMI < 36, Friedman
stage 1 or II)
32
45
Study endpoint
Diet vs. usual nutrition
Oropharyngeal exercises
versus “sham” therapy
Reduced-calorie diet
vs. advice
Conservative (diet,
advice) vs. operative
weight reduction
(laparoscop. gastric
band)
UPPP vs. 7 months wait
RFTA of the soft palate
vs. placebo surgery
AHI
ESS
ESS
AHI
AHI
BMI AHI
Primary: AHI
secondary: further
PSG parameters
Primary: AHI, ESS,
SF-36
Secondary:
Snoring,
cephalometric
parameters,
undesired events
AHI, ESS, tongue
Open transoral radio
volume (MRI), pain
frequency base of
tongue resection vs.
submucousal minimally
invasive tongue excision
with radio frequency
vs. with ultrasound
blade (all in combination
with UPPP)
Number of patients Intervention
(n)
1b
Levels of
evidence
p < 0.01
p < 0.01
Significantly better
than placebo
Significantly better
than placebo
p < 0.01
Better in OP group
(p < 0.001)
Tendency towards
better in OP group
(p = 0.18)
1b
1b
1b
1b
UPPP vastly superior
1b
to waiting with
regard to AHI and all
respiratory parameters
irrespective of
BMI, tonsil size and
Friedman stage. Of
all sleep parameters
only arousal index
significantly reduced
No difference between 1b
the groups, although
just one treatment
compared to the
standard of 2 or more
treatments
No relevant difference
between the groups
Effect on study end
point (p value)
Tab. B.11 Summary of Level-1 studies for the treatment (different treatment processes) of obstructive sleep apnea (OSA). Inclusion criteria: Study population >20, observation period ≥ 4 weeks
S148
Year
2013
2013
2006
2004
2008
Author
Maurer et al. [285]
Phillips et al. [358]
Somnologie · Suppl s2 · 2017
Puhan et al. [363]
Randerath et al. [373]
Skinner et al. [420]
New Zealand
Germany
Switzerland
Australia
Germany
Country
Parallel over
4 months
Parallel over
8 weeks
Parallel over
4 months
RCT
RCT
Study type
OSA
OSA
OSA
OSA
OSA
Population
20
67
25
126 (108)
22
“Thoracic anti-supine
band” (modified “tennis
ball” method) versus
CPAP
Intraoral electric
stimulation versus
placebo
Didgeridoo game versus
control group (waiting
list)
OA vs.CPAP (crossover)
Pillar vs. Placebo surgery
Number of patients Intervention
(n)
AHI (means
and successful
reduction) and
average O2
saturation ESS,
FOSQ, SF-35
compliance, side
effects
AHI
ESS
AHI
ESS
AHI,24 h BP,
compliance,
day-time tiredness,
fitness to drive,
QoL
AHI, Al, Hl, aver.
Sa02, min. Sa02,
ESS, snoring
Study endpoint
1b
CPAP > position
1b
therapy significantly
better than control
n. s.
Position therapy > CPAP
No superiority
compared to the
placebo
No superiority
compared to the
placebo
1b
1b
CPAP reduces the
AHI more effectively
(0.01) OA Compliance
superior to CPAP
(0.00001). No effects
on the BP QoL,
day-time tiredness
and fitness to drive
comparable MAD
in 4 QoL superior to
parameters
Significantly better
than control
Significantly better
than control
1b
Levels of
evidence
HI, AHI, min. SaO2,
and snoring in verum
group significantly
reduced, but no
significant group
difference
Effect on study end
point (p value)
Tab. B.11 Summary of Level-1 studies for the treatment (different treatment processes) of obstructive sleep apnea (OSA). Inclusion criteria: Study population > 20, observation period ≥ 4 weeks (continued)
S3-Guideline on Sleep-Related Respiratory Disorders
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S149
Year
2014
2009
2010
2012
Author
Strollo et al. [434]
Tuomilehto et al. [447]
Vicini et al. [453]
Winslow et al. [481]
USA
Italy
Finland
International
Country
Parallel over
28 weeks
RCT
Parallel over
1 year
Randomized
treatment
withdrawal
Study type
OSA
OSA
OSA
OSA
Population
45
50
72
126 (46 in
randomized arm)
Number of patients (n)
Phentermine 15 mg
plus Topiramat 92 mg
vs. placebo
MMA vs. APAP
Diet vs. diabetes
management
Stimulation active
vs. inactive
Intervention
BMI AHI
AHI, ESS
AHI
Prim.: AHI, ODI
Sec.: T90, ESS,
FOSQ
Study endpoint
Levels of
evidence
Superiority over
placebo (both
p < 0.001)
AHI and ESS identical,
overall satisfaction
is greater with MMA,
12 months follow-up
p < 0.05
1b
1b
1b
All target parameters
1b
significantly improved,
inactive stimulation
without effect.
12 months follow-up
Effect on study end
point (p value)
Tab. B.11 Summary of Level-1 studies for the treatment (different treatment processes) of obstructive sleep apnea (OSA). Inclusion criteria: Study population > 20, observation period ≥ 4 weeks (continued)
S150
Year
1996
2013
2012
2011
2005
2015
Author
Andreas et al. [16]
Arzt et al. [25]
Aurora et al. [27]
Somnologie · Suppl s2 · 2017
Bitter et al. [53]
Bradley et al. [66]
Cowie et al. [110]
Germany,
France,
Sweden, UK,
Australia
Denmark,
Norway,
Czechia,
Finland,
Switzerland,
Netherlands
Canada, Germany
Germany
USA
Germany, UK,
France, Canada
Germany
Country
72
22
Population (n)
258
1325
rKS
255
rKS
OUS
Meta-analysis CPAP:
165 (transplant-free
survival)
377 (LVEF)
282 (AHI)
Bi-level HF:
28 (AHI)
ASV:
127 (AHI)
95 (LVEF
rKS
rKS
Study type
ASV
CPAP
31 months
24 months
48 months
1 night to
24 months
CPAP
Bi-level HF
ASV
–
3 months
1 week
ASV control
O2 (4 l)
Intervention Observation
period
9–33% event rate for CPAP
vs. 24–56% event rate for
controls
MD 6.4 higher
(2.4–10.5 higher)
MD 21 lower
(25–17 lower)
MD 44 lower
(40–49 lower)
MD 6.1 higher
(3.9–8.4 higher)
MD 31 lower
(25–36 lower)
20  5/h (p < 0.001)
1039  940 pg/mL
(p = 0.06)
30  33% (ns)
26  10 (–62%)
835  960 (l/min)
Effect on study endpoint
Cardiovascular mortality
Death, life-saving
cardiovascular
intervention or unplanned
hospitalization due to
a worsening of cardiac
insufficiency
Death of all causes
Combined end point:
AHI (h–1)
QoL
LVEF
Tod/HTX
HR 1.28; 95% Cl 1.06 to
1.55; P = 0.01
HR 1.34; 95% Cl 1.09 to
1.65; P = 0.006
ASV vs control:
54.1 vs 50.8%, HR 1.13;
95% Cl 0.97 to 1.31;
P = 0.10
40  19 (53%)

24.2  26.4%

Adequate triggering of the ZSA (AHI ≥ 15/h)
implanted defibrillator
independent risk factor:
HR (95% CI): 3.41
(2.10–5.54), p < 0.001
Bi-level HF:
AHI
ASV:
LVEF
AHI
AHI
CPAP:
Transplant-free
Survival
LVEF
LVEF
Central AHI
Ntpro BNP
AHI (h–1)
VO2max
Study endpoint
Tab. B.12 Randomized controlled studies (rKS), outcome research studies (OUS) and case series (FS) for central sleep apnea with Cheyne-Stokes respiration and cardiac insufficiency
1a
1b
2c
2a
2b
2b
Levels of
evidence
S3-Guideline on Sleep-Related Respiratory Disorders
Somnologie · Suppl s2 · 2017
S151
1989
2007
2011
2010
2002
Hanly et al. [180]
Javaheri et al. [210]
Jilek et al. [216]
Kasai et al. [228]
Köhnlein et al. [235]
1999
2007
Fietze et al. [140]
Krachman et al. [240]
1993
Davies et al. [116]
2010
2012
Damy et al. [113]
Koyama et al. [238]
Year
Author
USA
Japan
UK
Japan
Germany
USA
Canada
Germany
UK
France
Country
rKS
rKS
rKS
rKS
OUS
OUS
rKS
rKS
rKS
OUS
Study type
14
17
16
31
296
88
9
37
7
384
Population (n)
O2 (2 l)
ASV
Checks
CPAP
Bi-level PAP
ASV
CPAP
–
–
O2 (2–3 l)
Bi-level PAP
HF
ASV
CPAP
–
1 night
3 months
2 weeks
3 months
49 months
51 months
1 night
6 weeks
2 weeks
47 months
Intervention Observation
period
AHI (h–1)
LVEF
Plasma BNP
AHI (h–1)
Plasma BNP
6 min walk test
QOL (SF36)
LVEF
Mortality rate
Mortality rate
AHI (h–1)
LVEF
AHI (h–1)
Desaturation index LVEF
Combined end point from
death, HTx and implant
of a left ventricular assist
system
Study endpoint
44  18 (–59%)
ASV: 44  53 (p = 0.002)
Checks: 46  46 (p = 0.90)
ASV: 212  77 (p = 0.04)
Checks: 293  149
(p = 0.33)
2b
2b
2b
2b
ASV vs. CPAP
+ 9.1 vs. + 1 (p < 0.05)
–36 vs. –4 (p = 0.006)
+35 versus –9 m
(p = 0.008)
Significant improvement
in 4 of 8 domains
CPAP: 27  8 (70%)
Bi-level: 27  7 (74%)
2c
2c
2b
2b
2b
2c
Levels of
evidence
Severe ZSA (AHI ≥ 22.5/h)
versus no/ light ZSA (AHI
<22.5/h): 38 vs 16%,
unadjusted p = 0.002,
adjusted for age and
NYHA class p = 0.035
AHI ≥ 5/h versus AHI
< 5/h: Hazard ratio, 2.1;
P = 0.02, (adjusted)
30  19 (–37%)
Bi-level AF: 35  16 (54%)
ASV: 32  11 (66%)
Bi-level AF: 26  31%
ASV: 25  27%


Severe ZSA (AHI ≥ 20/h)
versus no/ light ZSA (AHI
< 20 h): HR 1.61, 95% Cl
1.16–2.25 (p = 0.018
adjusted for significant
interference variables)
Effect on study endpoint
Tab. B.12 Randomized controlled studies (rKS), outcome research studies (OUS) and case series (FS) for central sleep apnea with Cheyne-Stokes respiration and cardiac insufficiency (continued)
S152
Somnologie · Suppl s2 · 2017
Year
1999
2007
1995
2007
2003
2006
Author
Lanfranchi et al. [252]
Morgenthaler et al. [306]
Naughton et al. [312]
Nöda et al. [319]
Pepperell et al. [352]
Phillipe et al. [356]
France
UK
Japan
Canada
USA
Italy
Country
rKS
rKS
rKS
rKS
rKS
OUS
Study type
25
30
21
29
15
62
Population (n)
CPAP
ASV
ASV
Bi-level PAP
CPAP
Bi-level PAP
HF
ASV
–
6 months
1 month
1 night
3 months
AHI (h–1)
QoL (Minnesota qu.)
Treatment compliance
(6 mo)
Metnoradrenaline (urine)
Daytime sleepiness
LVEF
BNP
Metadrenaline (urine)
AHI (h–1)
LVEF
AHI (h–1)
QoL
LVEF
AHI (h–1)
Respiratory arousal index
<1 week
3 months
Cumulative 1 and 2 year
mortality
Study endpoint
28 months
Intervention Observation
period
CPAP: , ASV: 
CPAP: , ASV: 
4.3 h/day, CPAP < ASV
26  34 min (Osler test)
37  38%
363  278 pg/ml
61  45 nmol/mmol
creatinine
190  153 nmol/mmol
creatinine
28  5 (74%)
+20% (bi-level PAP)
+3% (control group)
39  11 (72%)

20  28%
Bi-level PAP-HF 34  6 h–1
ASV 34  1 h–1
Bi-level-HF 32  6 h–1
ASV 32  2 h–1
AHI ≥ 30/h: 21 and 50%
AHI < 30/h: 5 and 26%
(P < 0.01; adjusted)
Effect on study endpoint
2b
2b
2b
2b
2b
2c
Levels of
evidence
Tab. B.12 Randomized controlled studies (rKS), outcome research studies (OUS) and case series (FS) for central sleep apnea with Cheyne-Stokes respiration and cardiac insufficiency (continued)
S3-Guideline on Sleep-Related Respiratory Disorders
Somnologie · Suppl s2 · 2017
S153
Year
2012
2012
2004
2009
2009
2012
Author
Ponikowski et al. [361]
Randerath et al. [376]
Roebuck et al. [387]
Ruttanaumpawan et al.
[393]
Sasayama et al. [399]
Sharma et al. [408]
USA
Japan
Canada,
Germany
Australia
Germany
Poland, USA,
Germany
Country
51
205
78
70
16
Population (n)
Meta-analysis 538
rKS
rKS
OUS
rKS
HF
Study type
ASV
02 (31)
CPAP
–
ASV
CPAP
Unilateral
stimulation
of N. Phrenicus
1-12 months
12 weeks
3 months
52 months
12 months
1 night
Intervention Observation
period
LVEF
AHI
AHI (h–1), LVEF, activity
scale
AHI
Arousal index
Mortality rate
Mortality/ HTX rate
Ntpro BNP
LVEF
Central AHI
AHI, central apnea
index, arousal index,
desaturation index
Study endpoint
0.40, 95% (CI 0.08 to
0.71) both significantly
favoured ASV
Weight averaged effects
of ASV versus control
intervention:
–– 15 events/hour, 95%
(CI –21 to –8)
AHI: 19/h  9/h
LVEF: 33%  38%
BNP: 493  556 pg/m
(p > 0.05)
QOL: 3.9 ± 1.2 to 4.7 ± 1.6
specific activity scale,
p < 0.01
39  18 (54%)
No significant change
No significant difference
between CSA, OSA groups
and the group without
sleep apnea
23  6/h (p < 0.001
vs base line, p < 0.05
vs CPAP)
538  230 pg/mL
(p < 0.05 vs CPAP)
47  45% (ns)
AHI: 45 (39–59) vs. 23
(12–27) events/h,
P = 0.002
central apnea index:
27 (11–38) vs. 1 (0–5)
events/h, P ≤ 0.001
Arousal index:
32 (20–42) vs. 12 (9–27)
events/h, P = 0.001
Desaturation index:
31 (22–36) vs. 14 (7–20)
events/h, P = 0.002
Effect on study endpoint
2a
2b
1b
2c
2b
4
Levels of
evidence
Tab. B.12 Randomized controlled studies (rKS), outcome research studies (OUS) and case series (FS) for central sleep apnea with Cheyne-Stokes respiration and cardiac insufficiency (continued)
S154
Somnologie · Suppl s2 · 2017
2000
2000
1998
2001
2001
2012
Sin et al. [417]
Sin et al. [417]
Staniforth et al. [429]
Teschler et al. [442]
Teschler et al. [442]
Zhang et al. [502]
China
Germany
Germany
UK
Canada
Canada
Country
HF
rKS
rKS
rKS
rKS
OUS
Study type
19
14
14
11
29
66
Population (n)
Unilateral
stimulation of the
N. Phrenicus
CPAP
Bi-level PAP
HF
ASV
02 (21)
02 (21)
CPAP
1 night
1 night
1 night
4 weeks
3/26 months
26 months
Intervention Observation
period
AHI, medium and minimal
oxygen saturation, end
tidal CO2, sleep efficiency
desaturation index
AHI:
33.8 ± 9.3 vs 8.1 ± 2.3,
P < 0.001
medium and minimal
oxygen saturation:
89.7% ± 1.6% vs 94.3%
± 0.9% and 80.3% ± 3.7%
vs 88.5% ± 3.3%, each
P < 0.001
End tidal CO2:
8.0 ± 4.3 mm Hg vs 40.3
± 3.1 mm Hg, (P = 0.02)
Sleep efficiency desaturation index:
74.6% ± 4.1% vs 73.7%
± 5.4%, P = 0.36
CPAP: 45  27 (40%)
Bi-level AF: 45  15 (67%)
ASV: 45  6 (87%)
AHI (h )
–1
45  28 (–38%)
18  4 (78%)
8.3  4.1 nmol/mmol
creatinine
20  28%
56% risk reduction,
P = 0.059
AHI ≥ 15/h versus
AHI < 15/h: Hazard ratio,
2.5; 95% (CI, 1.1 to 5.9;
P = 0.032, adjusted)
Effect on study endpoint
AHI (h–1)
All central fhf 1)
Norepinephrine (urine)
LVEF death/HTX
Mortality/ HTX rate
Study endpoint
–
2b
2b
2b
2b
2c
Levels of
evidence
AHI Apnea hypopnea index, ASV adaptive servoventilation, bi-level PAP HF “bi-level positive airway pressure” with background frequency, BNP “brain natriuretic peptide,” CI confidence interval, CSA central sleep
apnea, HTX heart transplant, LVEF left ventricular ejection fraction, OSA obstructive sleep apnea, Qol quality of life, VO2max maximum oxygen absorption
Year
Author
Tab. B.12 Randomized controlled studies (rKS), outcome research studies (OUS) and case series (FS) for central sleep apnea with Cheyne-Stokes respiration and cardiac insufficiency (continued)
S3-Guideline on Sleep-Related Respiratory Disorders
Somnologie · Suppl s2 · 2017
S155
Year
2012
2010
2000
2008
2008
Author
Bonnin-Villaplana et al. [61]
Johnson and Johnson [221]
Parra et al. [340]
Sahlin et al. [394]
Siccoli et al. [411]
Switzerland
Sweden
Spain
USA
Spain
Country
Case series
OUS
Case series
OUS
OUS
Study type
74
(n = 30.41% CSR
- CSA, 5 days after
a stroke)
132 (23 OSA,
28 CSA)
116
(n = 42.28% CSA,
48–72 h after
a stroke)
29 Publications
2343 patients
with ischemic
or hemorrhegic
stroke or transitory
ischemic attack
68 (after lacunar
stroke)
Population (n)
3 months
–
–
–
10 years
–
–
–
< 48 h
Observation period
–
Intervention
Tab. B.13 Outcome research studies (OUS) and case series (FS) for central sleep apnea with Cheyne-Stokes respiration in stroke patients
–
Mortality
AHI
(0  3 months)
Central Al
(0  months)
17 Publications
reported the
prevalence of the
ZSA (AHI ≥ 10/h)
with CSR
Type of sleep
apnea
Study endpoint
–
AHI ≥10/h (CSA)
versus AHI <10/h:
Hazard ratio, 1.31;
95% Cl, 0.80 to
2.16; P = 0.29,
(adjusted)
4
2c
4
1
7% (Cl 4.5–12%)
22  17 (P < 0.05)
6  3 (P < 0.05)
3
Levels of
evidence
CSR in 21% pf
patients (> 10%
of sleeping time).
Patients with CSR:
Central AHI 13/h,
obstructive AHI
22/h
Effect on study
endpoint
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Year
2004
2012
2010
2012
2003
Author
Fischer et al. [142]
Latshang et al. [253]
Nussbaumer-Ochsner et al. [324]
Nussbaumer-Ochsner et al. [325]
Przybylowski et al. [365]
Poland
Switzerland
Switzerland
Switzerland
Germany
Country
Case series
rKS
rKS
rKS
rKS
Study type
-
21 Participants with
a history of altitude
pulmonary edema
34 Patients with
untreated OSA
51 Patient with OSA
treated with AutoCPAP
30 healthy men
Population
2000 m descent
Dexamethasone
490 m (base line),
1860 and 2590 m
height
Acetazolamide +
AutoCPAP versus
placebo + AutoCPAP
Theophylline versus
acetazolamide versus
placebo
Intervention
HAPB
HAPB, AHI, medium
oxygen saturation
Reduction is HAPB
following descent
Dexamethasone
lessens hypoxia and
HAPB in 1. and 3. night
at 4995 m height
Increase of AHI due to
HAPB with increasing
height
Additional
administration of
acetazolamide to Au
to CPAP treatment
lessened HAPB,
reduced the AHI and
increased the oxygen
saturation at 1630 and
2590 m height
HAPB, AHI, oxygen
saturation
HAPB, AHI
Theophylline and
acetazolamidereduced HAPB.
Acetazolamide also
improved the oxygen
saturation
Effect on study
endpoint
HAPB
Study endpoint
Tab. B.14 Controlled studies (KS), outcome research studies (OUS) and case series (FS) for central sleep apnea with height-dependent periodic respiration
4
2b
2b
2b
2b
Levels of
evidence
S3-Guideline on Sleep-Related Respiratory Disorders
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
Population
Intervention
Study endpoint
Effect on study
endpoint
Levels of
evidence
Alattar et al. [7]
2009
USA
FKS
6
Morphine
SaO2
Bi-level respiration 3b
corrects hypoxemia
through CSA
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
2c
correlated with
methadone dosage
Tab. B. 16 Controlled studies (KS), outcome research studies (OUS) and case series (FS) for primary central sleep apnea
Author
Year
Country Study
type
Population
Intervention
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
Somnologie · Suppl s2 · 2017
S157
S158
Year
2007
2011
2011
2013
Author
Allam et al. [8]
Brown SE et al. [71]
Somnologie · Suppl s2 · 2017
Cassel et al. [90]
Dellweg et al. [120]
Germany
Germany
USA
USA
Country
RCT, ASV vs. bilevel ST
(NIV), PSG after 6 weeks
Prospective study, PSG
baseline, first night and
after 3 cycles of CPAP
Retrospective cohort
study , ASV
Retrospective, Review,
PSG
Study type
N = 30 (21 male) CompSAS,
baseline data under CPAP
before randomization (NIV
vs. ASV): 64 ± 11 years,
61 ± 11, male 10 vs. 11,
BMI 29.7 ± 4.2 kg/m2 vs.
30.3 ± 4.3, AHI 29 ± 6 vs. 28
± 10, Al 19 ± 6 vs. 21 ± 9,
CAI, 17 ± 5 vs. 18 ± 7
N = 675 (86% male) OSA
patients, aged 56 ± 12,
BMI 32.2 ± 5.7 kg/m2.
ESS 11 ± 5.
N = 82 (86.6% male) with
CompSA, 60 ± 10 years,
BMI 31.8 ± 5.3 kg/m2,
AHI 36 (22–55).
N = 593 (86% male) no
CompSA, aged 55 ± 12,
BMI 32.3 ±5.8 kg/m2,
AHI 26 (15–44)
N = 25 consecutive patients
with PAP refractory CSA,
aged 60 ± 17, BMI 30.4 ±
6.1 kg/m2, AHI 49 ± 30, (CAI
11 ± 16). 18 CompSAS
N = 100, CompSAS (63%),
CSA (22%), CSA/CSR (15%),
AHI 48 (24–62), age 72
(60–79), BMI 31 (28–33)
kg/m2, ESS 11 (7–14)
Population
Retrospective,
heterogeneous
population
Comments
NIV vs. ASV nocturnal titration:
–
AHI (9 ± 4 vs. 9 ± 6), CAI (2 ± 3
vs. 3 ± 4). After 6 weeks: AH117
± 8 vs. 7 ± 4, p = 0.027, CA110
± 5 vs. 2 ± 2, p < 0.0001.
No other sleep parameters were
used
12.2% CompSA baseline. 28 no –
follow-up. CompSA in follow-up
for 14/54 patients. CompSA in
follow-up for 16/382 patients,
not initially diagnosed with
compSA. CompSA in follow-up
6.9%. Individuals with CompSA
were 5 years older, 40% CAD
No significant changes of the
–
AHI with PAP when compared
to the baseline. CAI raised 35
± 24, (p < 0.001). ASV: AHI fell
to 4 ± 4 (p < 0.001). AHI < 10
in 92% of patients, CAI 1 ± 2,
(p < 0.001). Respiratory arousals
improve in parallel with ASV
CPAP AHI 31 (17–47) (p = 0.02
vs. baseline), primarily CSA.
Bilevel S AHI 75 (46–111)
(p = 0.055). Bilevel ST AHI 15
(11–31) (p = 0.002). ASV AHI 5
(1–11) (p < 0.0001 vs. baseline
and CPAP). ASV raised REM
vs. baseline and CPAP
Results
Tab. B. 17 Controlled studies (KS), outcome research studies (OUS) and case series (FS) for treatment-related central sleep apnea
1b
3
4
4
Levels of
evidence
S3-Guideline on Sleep-Related Respiratory Disorders
Somnologie · Suppl s2 · 2017
S159
2009
2011
Javaheri et al. [212]
Kuzniar et al. [249]
2013
2007
Dernaika et al. [121]
Kuzniar et al. [250]
Year
Author
USA
USA
USA
USA
Country
Retrospective analysis
of patient data
Non-randomized,
parallel cohorts,
retrospective,
4–6 weeks
Retrospective study,
PSG, CPAP titration.
4-week follow-up. CPAP
adherence
Cross-section analysis,
split-night PSG
Study type
N = 150 CompSAS patients
N = 76 (61 male)
consecutive patients, aged
65 (54–78), ESS 11 (8–14)
with CompSAS, PSG, CPAP
followed by VPAP AdaptSV®
or bilevel AutoSV®.
N = 35 (28 male) VPAP
AdaptSV® patients, aged 66
(59–78), ESS 11 (8–13).
N = 41 (33 male) bilevel
AutoSV®, aged 64 (53–78),
ESS 12 (9–16)
97 patients, (64.7%) ≥ 1 risk
factor for CSA.
Low prevalence of decreased
LVEF and hypocapnia PAP treatment adherence 73.3%
35 VPAP AdaptSV®, 41 bilevel
AutoSV®. 73.7% adherence,
nocturnal use 5 h (3–6) for
VPAP AdaptSV® vs. 6 h (4–7)
for bilevel AutoSV® (p = 0.081);
raised baseline AHI and
improved ESS development
with bilevel AutoSV®4 (1–9)
vs. 3 (0–5), p = 0.02
4
3
Levels of
evidence
–
4
Non-homogeneous 4
population,
no substantial
differences
between the
technical
equipment used
–
N = 1286 OSA patients with N = 84 (70 male) patients
PAP titration
CSA ≥ 5, aged 53 ± 13,
BMI 33 ± 4 kg/m2.
Overall incidence 6.5%.
Second PSG in 42 patients:
Elimination of CSA in 33/42.
CSA remained in 9/42: baseline
for severe cases of OSA;
5 patients CAI ≥ 5 baseline;
2/9 due to use of opioids
Comments
–
Results
No differences in the
demographic data, LVEF. CSA:
decreased sleep efficiency,
S1 stage increased, shift in
the sleep stages, WASO, total
arousals. 92% of CSA patients:
complete or almost complete
elimination of CSA in the
follow-up PSG, improvement of
sleep parameters
N = 42 OSA patients with
(21) and without (21)
CPAP-related CSA.
With CSA: aged 59 ± 12,
BMI 35.9 ± 6.1 kg/m2.
Without CSA: aged 59 ± 12,
BMI 36.8 ± 5.9 kg/m2.
Echocardiography
­pulmonary function blood
gas analysis. PSG after 2–3
cycles of CPAP in the CSA
patient group
Population
Tab. B. 17 Controlled studies (KS), outcome research studies (OUS) and case series (FS) for treatment-related central sleep apnea (continuation)
S160
Year
2007
2007
2014
2012
Author
Lehman et al. [256]
Morgenthaler et al. [306]
Somnologie · Suppl s2 · 2017
Morgenthaler et al. [308]
Nakazaki et al. [311]
Japan
USA
USA
Australia
Country
Case series
Endpoints: PSG, LVEF,
nasal resistance
RCT, CPAP vs. ASV,
90 days
Prospective,
randomized, crossover,
NIV vs. ASV, in CSA/CSR,
primarily mixed apneas
and CompSAS, acute
setting
Retrospective, PSG;
clinical data
Study type
N = 52 patients with
suspected OSA, aged
51 ± 13: OSA: N = 38
(90% male), aged 50 ±
14, BMI 30.3 ± 5.3 kg/m2,
CompSAS: N = 5 (100%
male), 45 ± 10 years, BMI
28.7 ± 7.1 kg/m2
CSA: N = 9
N = 66 patients, 33 in each
arm, aged 59 ± 13, BMI
35.0 ± 8.0, ESS 10 ± 5, AHI
38 ± 28, CAI 3 ± 6
N = 21 (20 male) patients,
aged 65 ± 12, BMI 31 ± 5
kg/m2, AHI 52 ± 23 (6 CSA/
CSR, 6 primarily mixed apneas, 9 CompSAS), baseline
AHI 52 ± 23, RAI 46 ± 27
N = 86 (68% male) not
CSA-CPAP patients, aged
57 ± 11, BMI 33.1 ± 5.8
kg/m2
N = 99 consecutive OSAS,
N = 13 (12 male.) CSA-CPAP
patients, aged 55 ± 16, BMI
33.4 ± 7.9 kg/m2: CAI ≥ 5/h
at ± 1 cmH2O CPAP.
Population
CompSAS: Nasal resistance
higher in CompSAS vs. OSAS
(0.30 ± 0.10 vs. 0.19 ± 0.07 Pa/
cm3/s, p = 0.004), normal LVEF.
OSAS: ArI, S1, SaO2 significantly
decreased, REM significantly
increased using CPAP
Initial AHI with ASV 5 ± 8 (CAI
1 ± 4), with CPAP 14 ± 21 (CAI
9 ± 16) (p ≤ 0.0003). After 90
days, ASV AHI 4 ± 10, CPAP
10 ± 11 (p = 0.0024). AHI
< 10: ASV 89.7%, CPAP 64.5%
(p = 0.0214). No differences in
compliance, ESS, SAQLI
15 patients with initial CPAP
and persistent respiratory
events (AHI 34 ± 26,
RAI 32 ± 30).
NIV (n = 21): AHI 6 ± 8 and RAI
6 ± 8.
ASV: AHI 1 ± 2 and RAI 2 ± 5.
AHI and RAI significantly lower
with ASV (p < 0.01)
CSA-CPAP: 13 patients.
(13.1%), 46% CSA baseline
(vs. 8% p < 0.01). Baseline
raised AHI (72 vs. 53, p = 0.02),
raised AI (43 vs. 29, p < 0.01),
raised mixed AI (7 vs. 1,
p = 0.03), raised CPAP in order
to eliminate OSA (11 vs. 9,
p = 0.08), often from CAD or HF.
No differences in age or BMI
Results
Tab. B. 17 Controlled studies (KS), outcome research studies (OUS) and case series (FS) for treatment-related central sleep apnea (continuation)
–
–
–
–
Comments
3
1b
1b
4
Levels of
evidence
S3-Guideline on Sleep-Related Respiratory Disorders
Somnologie · Suppl s2 · 2017
S161
Year
2006
2013
2009
Author
Pusalavidyasagar et al. [366]
Ramar et al. [372]
Yaegashi et al. [488]
Japan
USA
USA
Country
Retrospective, review
Retrospective study.
ASV titration with PSG
signals accessible to
“cardiopulmonary
coupling (CPC)” analysis
Retrospective, review
Study type
17 patients (5.7%) with
CompSAS. “Multiple, stepwise,
and logistic regression
analyses”: Significant
differences in the supine
position relating to CAI during
NREM (p = 0.026) CompSAS
vs. OSAS (2.5 ± 3.1 vs. 0.9 ± 2.3),
deviations within the normal
range
ASV: AHI 11 ± 13, AHI < 10:
81.1%.
Increased narrow band low
frequency “coupling” 45.3%.
No correlation of eNB-LFC with
ASV success
N = 106 (89 male)
consecutive CompSAS
patients, aged 63. Baseline
AHI 38 (21–56), AHI using
CPAP 37 (23–58), CAI 23
(13–39)
N = 297 OSAS patients
using CPAP titration, AHI
≥ 20.
N = 280 (84% male) OSAS
patients, 59 ± 15 years,
BMI 25.7 ± 3.9 kg/m2,
AHI 48 ± 20.
N = 17 CompSAS patients,
55 ± 16 years, BMI 28.8 ±
6.1 kg/m2, AHI 56 ± 24
CPAP prescribed in 94 and
88% of OSAS and CompSAS,
(P = 0.284), no significant
difference in CPAP pressure
(P = 0.112) and in the frequency
of other prescribed treatments.
First USA follow-up earlier
for CompSAS (46 ± 47 vs.
54 ± 37 days; p = 0.022). No
differences in CPAP compliance
and ESS. Interface problems
more frequent with CompSAS
shortness of breath/dyspnea
(0.8 vs. 8.8%) and unintentional
removal of the mask (2.6 vs.
17.7%) (all p < 0.050)
Results
N = 133 (64% male) OSAS,
aged 58 ± 12 and
N = 34 (82% male)
compSAS, aged 54 ± 16
Population
Tab. B. 17 Controlled studies (KS), outcome research studies (OUS) and case series (FS) for treatment-related central sleep apnea (continuation)
Comments
4
4
4
Levels of
evidence
S3-Guideline on Sleep-Related Respiratory Disorders
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
S162
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S163
2006
2007
2003
2006
2008
2008
2001
1995
Bourke et al. [63]
Budweiser [74]
Buyse [77]
Gustafson et al. [176]
Jäger et al. [204]
Piper et al. [354]
Schönhofer et al. [401]
Simonds and Elliott [414]
1998
2014
Annane [17]
Simonds et al. [415]
Year
Author
United
Kingdom
United
Kingdom
Germany
Australia
Sweden
Sweden
Belgium
Germany
United
Kingdom
France
Country
Case series
Case series
FKS
RCT
FKS
FKS
Case series
Cohorts,
historical
controls
RCT
Meta-analysis
Study type
DMD with
respiratory
insufficiency
NME, KS,
PPS, COPD,
bronchiectasis
Stable respiratory
insufficiency
Stable respiratory
insufficiency with
OHS
Stable respiratory
insufficiency with
post-tbc
Stable respiratory
insufficiency
with KS
Stable respiratory
insufficiency with
KS
Stable respiratory
insufficiency with
OHS
Orthopnea or
hypercapnia with
ALS
NME
Population
23
180
per 10 patients
2 × 18
85 NIV, 103 O2
NIV
NIV
NIV vs. standard
treatment
Bilevel vs. CPAP
NIV or O2
100 NIV, 144 O2 NIV or O2
NIV vs. O2
NIV
126
18 vs. 15
patients
NIV vs. standard
NIV vs. standard
treatment
Intervention
22 vs 19
8 RCTs
Number of
patients
BGA, survival
NIV usage (not
using NIV resulted
in death)
Muscle function,
BGA
PaCO2 tags
Survival
Survival
BGA, survival
BGA, LUFU,
survival in
comparison to
historical control
group
LQ, survival
Survival, BGA,
symptoms
Study endpoint
1a
Levels of
evidence
1y- less than 5y survival
rate of 85 and 73%
respectively, improved
BGA. In the historical
control, survival rates
were >1 year with
respiratory insufficiency
Better survival rates
than before the NIV era,
except for COPD and
bronchiectasis
Muscle function and
BGA improved with NIV
Decreased with both
types of treatment
Improved with NIV
Improved with NIV
Both improved with
NIV; although the
baseline values were
worse
All parameters
improved during the
course of treatment.
Survival rates better
than in the historical
control group
4
4
1b
1b
2c
2c
4
4
1b
Both improved in
patients that showed no
symptoms of bulbar
All better with NIV
Effect on study endpoint
Tab. B.19 Studies of NIV treatment for alveolar hypoventilation when awake or while sleeping in the framework of neuromuscular diseases (NME), thorax restrictive diseases ad obesity hypoventilation
syndrome (OHS)
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1994
2005
Vianello et al. [452]
Ward et al. [466]
United
Kingdom
Italy
Country
RCT
FKS
Study type
Neuromuscular
diseases,
normocapnia
during day,
hypoventilation
while sleeping
Duchenne
muscular
dystrophy
Population
NIV vs. standard
treatment over
a time period of
2 years
NIV vs. standard
treatment over
a time period of
2 years
12 in each
group
Intervention
2×5
Number of
patients
ptc CO2 at night
SaO2 at night
NIV required for
control group
Death
Study endpoint
ptc CO2 at night SaO2
at night respiratory
insufficiency during the
day with NIV required
for 11/12 of the control
patients
0/5 NIV patients died;
4/5 control patients
died
Effect on study
endpoint
1b
3b
Levels of
evidence
ALS amyotrophic lateral sclerosis, BGA blood gas analysis, Bilevel Bilevel positive airway pressure, COPD chronic obstructive pulmonary disease, CPAP continuous positive airway pressure, DMD Duchenne muscular
dystrophy, FKS case-control study, ICU daysnumber of days spent in intensive care, KS Kyphoscoliosis, LUFU pulmonary function test, LQ quality of life, NIV non-invasive ventilation, NME neuromuscular diseases,
PaCO2 arterial carbon dioxide partial pressure, PaO2 arterial oxygen partial pressure, post-Tbc Post-tbc syndrome, PPS Post-polio syndrome, PatcCO2 carbon dioxide partial pressure measured transcutaneously, RCT
randomized control study
Year
Author
Tab. B.19 Studies of NIV treatment for alveolar hypoventilation when awake or while sleeping in the context of neuromuscular diseases (NME), thorax restrictive diseases and obesity hypoventilation
syndrome (OHS) (continued)
S3-Guideline on Sleep-Related Respiratory Disorders
Somnologie · Suppl s2 · 2017
S165
2000
1996
2014
2007
2009
Garrod et al. [156]
Gay et al. [160]
Köhnlein et al. [236]
Kolodziej [237]
McEvoy et al. [288]
2013
2002
Clini et al. [103]
Struik et al. [436]
2000
Casanova et al. [89]
1995
2007
Budweiser [73]
Meecham Jones et al. [293]
Year
Author
Netherlands
United Kingdom
Australia
Canada
Germany
USA
United Kingdom
Italy
Italy
Germany
Country
Stable hypercapnic COPD
Stable hypercapnic COPD
Stable hypercapnic COPD
Stable hypercapnic COPD
Stable hypercapnic COPD
Stable hypercapnic COPD
Stable hypercapnic COPD
Stable hypercapnic COPD
Population
Meta-analysis
of 7 studies
Stable hypercapnic COPD
RCT, cross-over Stable hypercapnic COPD
RCT
Meta-analysis
of 15 studies
RCT
RCT
RCT
RCT
RCT
Prospective
observational
study (POS)
Study type
245
14
72 vs. 72
–
102 vs. 93
Multiple
1 year mortality
NIV vs. standard
NIV vs. standard
treatment each
over a period of
3 months
Multiple
PaCO2 and PaO2
during the day,
sleep, LQ
NIV + LTOT vs. LTOT Survival, lufu, BGA,
quality of life
NIV vs. standard
NIV vs. standard
NIV vs. placebo NIV BGA, LUFU
over a period of
3 months
7 vs 6
Decrease of PaCO2
during the day,
improvement of LQ
and dyspnea
BGA, LQ,
hospitalization, days
spent in ICU, survival
No difference in
BGA; lufu, quality
of life
Significant
improvement of all
target parameters
with NIV
NIV + LTOT
improved chance
of survival, but
decreased quality
of life
Improved LQ
using NIV, BGA
in uncontrolled
studies improved
with NIV
Use of NIV
significantly
extended survival
ns
All significantly
improved with NIV
Dyspnea decreased
with NIV
Exacerbation rates,
hospitalization,
intubation, mortality,
dyspnea, BGA
6 min. walking test,
symptoms, pO2
Increased survival
rate using NIV
Effect on study
endpoint
Survival
Study endpoint
NIV + training
vs. training
NIV vs. standard
treatment over
a time period of
2 years
NIV vs. standard
treatment over
a time period of
1 year
NIV vs. standard
treatment over
a time period of up
to 4 years
Intervention
23 vs 22
43 vs. 47
52
99 vs. 41
Number of
patients
(n)
Tab. B.20 Study of NIV treatment for alveolar hypoventilation while awake or while sleeping in the context of COPD
1a
1b
1a
1a
1a
1b
1b
1b
1b
2c
Levels of
evidence
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1991
2008
2003
Strumpf et al. [437]
Tsolaki et al. [446]
Wijkstra et al. [478]
Canada
Greece
USA
Country
Population
Meta-analysis
of 4 studies
FKS
Stable hypercapnic COPD
Stable hypercapnic COPD
RCT, cross-over Stable hypercapnic COPD
Study type
86
27 vs 22
7
Number of
patients
(n)
NIV vs. standard
>3 weeks
NIV vs. standard
(patients who
declined NIV)
NIV vs. standard
treatment over
a time period of
3 months
Intervention
LUFU, BGA, sleep
LQ, BGA, dyspnea
BGA, LQ, sleep
Study endpoint
ns
All significantly
improved with NIV
ns
Effect on study
endpoint
1a
3b
1b
Levels of
evidence
ALSamyotrophic lateral sclerosis, BGA blood gas analysis, Bilevel bilevel positive airway pressure, COPD chronic obstructive pulmonary disease, CPAP continuous positive airway pressure, DMD Duchenne muscular
dystrophy, FKS case-control study, ICU days number of days spent in intensive care, KH hospital, KS Kyphoscoliosis, LUFU pulmonary function test, LQ quality of life, NIV non-invasive ventilation, NME neuromuscular
diseases, PaCO2 arterial carbon dioxide partial pressure, PaO2 arterial oxygen partial pressure, post-tbc Post-tbc syndrome, PatcCO2 carbon dioxide partial pressure measured transcutaneously, RCT randomized
controlled study
Year
Author
Tab. B.20 Study of NIV treatment for alveolar hypoventilation while awake or while sleeping in the context of COPD (continued)
S3-Guideline on Sleep-Related Respiratory Disorders
10.3 Annex C: Algorithms
0
Suspected upper respiratory
tract obstruction or impairment
of vigilance
1
2
Causal organic, psychiatric or
mental illness or one that
requires optimization?
Check the specific
treatment options
Yes
No
3
Determination of the pre-test
probability of obstructive
sleep apnea (daytime
sleepiness, pauses during
breathing and snoring)?
4
No
Pre-test prob. high?
Yes
5
Polygraphy of the
cardioresp. parameters
6
No
Obstructive AHI > 15 h?
PSG for diff. diagn.
Yes
12
Yes
OSA?
No
7
Risk of night-time
hypoventilation?
11
Central sleep apnea?
Yes
Yes
8
Hypercapnia when the patient is
awake or asleep? (blood gas
analysis during the day and
night-time capnometry and PSG)
15
13
No
No
Other sleep medicine
disease?
For more, see CSA
Sleep medicine consultation
Yes
14
No
17
No
16
Spec. treatment
Yes
9
Treatment of OSA and hypoventilation
10
OSA treatment
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
Somnologie · Suppl s2 · 2017
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S3-Guideline on Sleep-Related Respiratory Disorders
0
Underlying disease: Arterial
hypertension, heart failure,
absolute arrhythmia, CNS
disease
1
3
Symptoms of SRRD?
No
Monitoring for SRRD
reduced systems with
1-3 channels
Yes
10
8
Suspected SRRD?
No
Treatment of the underlying disease
and where necessary repetition of
the sleep-related diagnosis
Yes
2
9
High pre-test prob. Snoring
AND respiratory disorders
noticed by external parties
AND daytime sleepiness
No
Polysomnography for
differential diagnosis
11
Yes
OSA?
4
6-channel polygraphy
No
CSA?
Yes
OSA confirmation?
No
Treatment
of CSA
Yes
Other somnological
disease?
16
No
No somnological
disease
Yes
13
6
14
12
No
15
Specific
treatment
Yes
7
OSA treatment
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.
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0
OSAS that requires treatment
1
19
2
Sus. dysmorphia and
pathogenically relevant
anatomical abnormalities of the
upper respiratory tract?
3
If necessary correction
(e.g., surgical measures)
Yes
OSAS that still requires
treatment? *
Yes
No
If necessary sleep medicine
consultation, individual treatment
recommendation on different
methods of treatment
No
4
No
AHI <= 30 h?
12
CPAP/APAP
attempt
Yes
5
13
Effective?
CPAP/APAP or
attempt at LJB
15
No
Bilevel/auto-bilevel
attempt**
Yes
6
Effective?
No
11
Treatment optimization**
Yes
14
CPAP/APAP
16
Effective?
18
Treatment optimization**
Yes
7
17
CPAP/APAP or LJB
Bilevel/auto-bilevel
8
Residual daytime
sleepiness?
No
Yes
9
If necessary
Modafinil off-label**
No
10
Treatment control
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
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S3-Guideline on Sleep-Related Respiratory Disorders
0
Suspected CSA
1
Polygraphy or
polysomnography
2
No
Evidence of SRRD?
27
Consultation
Yes
3
Polysomnography for
differential diagnosis*
No
25
4
No
CSA?
Obstructive sleep apnea?
26
Yes
Further OSA algorithm
Yes
16
5
No
Opioid-induced sleep apnea?
No
Heart failure?
Yes
21
Kidney failure, CNS disease, other
comorbidities?
Yes
17
Guideline-compliant treatment
of heart failure
6
Consider discontinuation or dose
reduction
7
Further CSA?
No
15
Sleep medicine consultation
Yes
No
Yes
22
Optimization of treatment of the
underlying disease
18
Further CSA?
Yes
8
No
CPAP
19
EF <= 45%?
Yes
9
Effective?
Yes
10
CPAP
No
11
ASV
12
Effective?
20
Sleep medicine Consultation,
in exceptional cases where
there are clear symptoms
attempt at CPAP
No
23
Further CSA?
Yes
Yes
13
ASV
No
14
Sleep medicine consultation
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
S170
Somnologie · Suppl s2 · 2017
24
No
Idiopathic CSA
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 Cardiovascular 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 standard treatment with a short CPAP cycle
(on average only 3.3 hours each night)
for patients with obstructive sleep apnea and coronary artery disease or cerebrovascular disease does not improve
a patient’s chance of survival. Improved
quality of life can be achieved for patients with CAD and sleep apnea without 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-forthe-diagnosis-and-treatment-of-acuteand-chronic-heart-failure/
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