Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4566_Библиотеки_им_академика_М_И_Перельмана
.pdf
Neurobiology and physiology
https://t.me/medicina_free
• Saper CB, et al. (2017). Wake-sleep circuitry: an overview. Curr Opin Neurobiol; 44: 186–192.
• Scheer FA, et al. (2014). Human circadian system causes a morning peak in prothrombotic
plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle. Blood; 123:
590–593.
• Silvani A, et al. (2013). Central control of cardiovascular function during sleep. Am J Physiol
Heart Circ Physiol; 305: H1683–H1692.
• Tarbichi AG, et al. (2003). Lack of gender dierence in ventilatory chemoresponsiveness and
post-hypoxic ventilatory decline. Respir Physiol Neurobiol; 137: 41–50.
• White DP, et al. (1982). Hypoxic ventilatory response during sleep in normal premenopausal
women. Am Rev Respir Dis; 126: 530–533.
14
ERS Handbook: Respiratory Sleep Medicine
Definitions of sleep
https://t.me/medicina_free
disordered breathing
Johan Verbraecken
The term “sleep disordered breathing” is used to describe a spectrum of respiratory
disturbances that occur during sleep. In the 3rd edition of the ICSD (ICSD-3), five
major categories of SDB were defined: OSAS, CSA syndrome, sleep-related alveolar
hypoventilation, sleep-related hypoxaemia disorder, and isolated symptoms and
normal variants (American Academy of Sleep Medicine, 2014). The fundamental
dierence between the first two categories is the pathophysiological mechanism
that causes the respiratory abnormality (Verbraecken et al., 2009). Upper airway
obstruction in OSA is generally caused by abnormal anatomical structures and/or
abnormal control of the muscles that maintain the upper airway’s patency, resulting
in insucient ventilation. In CSA, dysfunction of respiratory control in the central
neurons is involved, resulting in a cyclical pattern of reduced or absent respiratory
eort. A distinction is made between idiopathic syndrome types and the type resulting
from pathological or environmental factors. Obstructive apnoea/hypopnoea can be
defined as a respiratory event that lasts for ≥10 s and is characterised by a transient
reduction (hypopnoea) in, or complete cessation (apnoea) of, breathing (figures 1
and 2). According to the American Academy of Sleep Medicine (AASM) criteria from
2012 (Berry et al., 2012), hypopnoea can be defined as a decrease from baseline in
the amplitude of flow, based on a peak signal excursion drop of ≥30% of pre-event
baseline using a nasal canula, with a duration of ≥10 s, and an oxygen desaturation of
≥3% from pre-event baseline or an event that is associated with an arousal (Iber et al.,
2007) (figure 2). CSA refers to a cessation of ventilation lasting for ≥10 s (in adults)
due to transient loss of neural output to the ventilatory muscles (figure 1). The degree
of severity is defined according to the number of apnoeas and hypopnoeas per hour of
sleep (AHI) and the severity of daytime symptoms.
Key points
• OSA is characterised by recurrent episodes of partial or complete upper airway
collapse during sleep.
• Minimal diagnostic criteria exist for OSA and CSA.
• OHS is also part of the spectrum of SDB.
• Hypoventilation syndromes can occur independently of obesity.
15ERS Handbook: Respiratory Sleep Medicine
Definitions of sleep disordered breathing
Oronasal flow
Thoracic
movements
O
https://t.me/medicina_free
a)
Oronasal flow
Thoracic
movements
saturation
O
2
b)
Oronasal flow
Thoracic
movements
O
saturation
2
c)
Obstructive
Arousal
100%
0%
Arousal
Mixed
100%
0%
Arousal
Central
100%
saturation
2
Figure 1. Dierent presentations of apnoeas.
The ICSD-3 divides central apnoeas into eight subgroups. These dierent subgroups
will be discussed below. A distinction can be made between hypercapnic and nonhypercapnic CSA. Hypercapnic CSA is usually seen in neurological disorders with
reduced central drive to the respiratory musculature or diminished muscle strength.
It can be found in brainstem disorders, OHS, cerebrovascular accidents, encephalitis
and neuromuscular diseases. Patients also tend to remain hypercapnic in the wake
state. Men are aected as oen as women. Hypercapnic CSA is also present in
opioid users and thoracic malformations, such as (kypho)scoliosis. Non-hypercapnic
CSA occurs in connection with chronic HF (CSR), high altitude, and acromegaly,
hypothyroidism, and the idiopathic form of CSA.
16
0%
Apnoea ≥10 s
ERS Handbook: Respiratory Sleep Medicine
a)
Oronasal flow
Thoracic
movements
O
saturation
b)
Oronasal flow
Thoracic
movements
O
https://t.me/medicina_free
2
saturation
2
Definitions of sleep disordered breathing
100%
0%
Arousal
100%
0%
Hypopnoea ≥10 s
Figure 2. Dierent presentations of hypopnoeas. A hypopnoea can be defined as a) a decrease
from baseline in the amplitude of flow, based on a peak signal excursion drop of ≥30% of preevent baseline using a nasal canula, with a duration of ≥10 s, and ≥3% oxygen desaturation
from pre-event baseline, or b) an event associated with an arousal.
A third patient group in the spectrum of SDB is sleep-related hypoventilation disorders.
Sleep-induced hypoventilation is characterised by increased P
(>45 mmHg) while asleep or levels that are disproportionately increased in relation to
those during wakefulness (American Sleep Disorders Association, 1999). An elevated
P
when waking is very suggestive, as is an elevated bicarbonate (HCO
aCO
2
blood gas analysis (without any other evident explanation, such as use of diuretics).
To find these patients, a series of daytime tests is useful: FVC <50% and venous HCO
>27 mmol·L−1. This group includes six subcategories, which will be discussed below
(ICSD-3). Among these categories, OHS is the most common clinical presentation of
this syndrome.
When brainstem anomalies are ruled out (preferably via MRI), the term “idiopathic
central hypoventilation syndrome” is used.
Finally, sleep-related hypoxaemia disorder, and isolated symptoms and normal
variants constitute two smaller categories, which will not be further discussed here.
The definition of OSA
OSA can be considered if A and B or C satisfy the criteria (ICSD-3):
A. The presence of one or more of the following:
1. The patient complains of sleepiness, non-restorative sleep, fatigue or insomnia
symptoms.
levels of >6.0 kPa
aCO
2
−
3
) in the
3
−
17ERS Handbook: Respiratory Sleep Medicine
Definitions of sleep disordered breathing
https://t.me/medicina_free
2. The patient wakes with breath-holding, gasping or choking.
3. The bed partner or other observer reports habitual snoring, breathing
interruptions or both during the patient’s sleep.
4. The patient has been diagnosed with hypertension, a mood disorder, cognitive
dysfunction, coronary artery disease, stroke, CHF, atrial fibrillation (AF) or type 2
diabetes mellitus.
B. PSG or out-of-centre sleep testing (OCST) demonstrates:
1. Five or more predominantly obstructive respiratory events (obstructive and
mixed apnoeas, hypopnoeas or respiratory eort-related arousals (RERAs)) per
hour of sleep during PSG or per hour of monitoring (OCST).
OR
C. PSG or OCST demonstrates:
1. ≥15 predominantly obstructive respiratory events (apnoeas, hypopnoeas or
RERAs) per hour of sleep during a PSG or per hour of monitoring (OCST).
Obstructive breathing events may include not only apnoeas or hypopnoeas but
also RERAs. A RERA is a series of breaths characterised by increasing respiratory
eort, leading to microarousal from sleep, but not meeting the criteria for an
apnoea or hypopnoea. These events present with a pattern of increasingly
negative oesophageal pressures, ending with an abrupt change in pressure
to a less negative level and a microarousal. Oesophageal pressure has been
proposed as the recommended sensor (American Sleep Disorders Association,
1999); the suggested feasible alternative is a flattening of the flow curve via
nasal pressure, together with induction plethysmography. In daily practice, nasal
pressure is the method of choice for the majority of sleep laboratories. These
events last ≥10 s.
The definition of CSA
Diagnosis of CSA can also be made using criteria recommended by the ICSD-3.
CSA with CSR
CSR is a form of unstable breathing in which the same mechanisms apply as in primary
CSA, alone or in combination with central apnoea. A periodic pattern of waxing and
waning ventilation with episodes of hyperventilation, alternating with central apnoeas
and hypopnoeas, is defined as CSR. CSR can be considered if A or B+C+D satisfy the
criteria (ICSD-3):
A. The presence of one or more of the following:
1. Sleepiness.
2. Diculty initiating or maintaining sleep, frequent awakenings or non-restorative
sleep.
3. Awakening short of breath.
4. Snoring.
5. Witnessed apnoeas.
B. The presence of AF/flutter, CHF or a neurological disorder.
C. PSG (during diagnostic or PAP titration) shows all of the following:
1. Five or more central apnoeas and/or central hypopnoeas per hour of sleep.
2. The total number of central apnoeas and/or central hypopnoeas is >50% of the
total number of apnoeas and hypopnoeas.
3. The pattern of ventilation meets criteria for CSR.
D. The disorder is not explained more clearly by another current sleep disorder,
medication use (e.g. opioids) or substance use disorder.
18
ERS Handbook: Respiratory Sleep Medicine
Definitions of sleep disordered breathing
https://t.me/medicina_free
The pattern of ventilation meets the criteria for CSR (crescendo–decrescendo of
≥10 min, with at least three cycles, a minimum sleep registration time of 2 h and a
cycle length of ≥40 s) (Berry et al., 2012).
CSR occurs in patients with (acute or chronic) HF and aer stroke. It is characterised
by an unstable breathing pattern with a relatively long cycle time of 40–90 s, with an
observable arousal at the peak of the hyperpnoea phase. In CSR, oxygen desaturations
are characteristically long and recover slowly. An underlying cardiopulmonary disease
is present in ∼70% of patients with CSR.
CSA due to a medical disorder without CSR
This subcategory is used for CSA that is attributed to a medical or neurological
condition (and does not have the pattern of CSR). The majority of the patients in this
category have brainstem anomalies. Criteria A–C must be met (ICSD-3):
A. The presence of one or more of the following:
1. Sleepiness.
2. Diculty initiating or maintaining sleep, frequent awakenings or non-restorative
sleep.
3. Awakening short of breath.
4. Snoring.
5. Witnessed apnoeas.
B. PSG shows all of the following:
1. Five or more central apnoeas and/or central hypopnoeas per hour of sleep.
2. The number of central apnoeas and/or central hypopnoeas is >50% of the total
number of apnoeas and hypopnoeas.
3. Absence of CSR.
C. The disorders occurs as a consequence of a medical or neurological disorder but is
not due to medication use or substance abuse.
CSA due to high-altitude periodic breathing
This condition occurs typically at >2500 m high. Criteria A–D must be met (ICSD-3):
A. Recent ascent to a high altitude
B. The presence of one or more of the following:
1. Sleepiness.
2. Diculty initiating or maintaining sleep, frequent awakenings or non-restorative
sleep.
3. Awakening short of breath or morning headache.
4. Witnessed apnoeas.
C. The symptoms are clinically attributable to high-altitude periodic breathing, or PSG,
if performed, demonstrates recurrent central apnoeas or hypopnoeas primarily
during NREM sleep at a frequency of ≥5 events·h−1.
D. The disorder is not better explained by another current sleep disorder, medical or
neurological disorder, medication use (e.g. opioids), or substance use disorders.
CSA due to medication or a substance
CSA is found with acute as well as chronic opioid intake, depending on the dosage.
Criteria A–E must be met (ICSD-3):
A. The patient is taking an opioid or other respiratory depressant.
B. The presence of one or more of the following:
1. Sleepiness.
19ERS Handbook: Respiratory Sleep Medicine
Definitions of sleep disordered breathing
https://t.me/medicina_free
2. Diculty initiating or maintaining sleep, frequent awakenings or non-restorative
sleep.
3. Awakening short of breath.
4. Snoring.
5. Witnessed apnoeas.
C. PSG (diagnostic or on PAP) shows all of the following:
1. Five or more central apnoeas and/or central hypopnoeas per hour of sleep (PSG).
2. The number of central apnoeas and/or central hypopnoeas is >50% of the total
number of apnoeas and hypopnoeas.
3. Absence of CSR.
D. The disorder occurs as a consequence of an opioid or other respiratory depressant.
E. The disorder is not better explained by another current sleep disorder.
Primary CSA
In the majority of patients with CSA, no underlying disease has been ascertained. This
variant is called primary CSA. Patients do not display any typical respiratory pattern
during sleep (CSR), and central apnoeas can either be isolated or occur in cycles of
∼40 s. There are arousals at the end of the apnoea, which fragment sleep. The main
symptoms are daytime sleepiness or even sleeplessness.
Criteria A–D must be met (ICSD-3):
A. The presence of at least one of the following:
1. Sleepiness.
2. Diculty initiating or maintaining sleep, frequent awakenings or non-restorative
sleep.
3. Awakening short of breath.
4. Snoring.
5. Witnessed apnoeas.
B. PSG demonstrated all of the following:
1. Five or more central apnoeas and/or central hypopnoeas per hour of sleep (PSG).
2. The number of central apnoeas and/or central hypopnoeas is >50% of the total
number of apnoeas and hypopnoeas.
3. Absence of CSR.
C. There is no evidence of daytime or nocturnal hypoventilation.
D. The disorder is not explained more clearly by another current sleep disorder,
medical or neurological disorder, medication use or substance use disorder.
Primary CSA of infancy
For further information on this topic, we refer the interested reader to chapter 17 on
paediatric respiratory sleep medicine.
Primary CSA of prematurity
For further information on this topic, we refer the interested reader to chapter 17 on
paediatric respiratory sleep medicine.
Treatment-emergent CSA
Treatment-emergent CSA (TECSA) should be used in patients with predominantly
obstructive events during the diagnostic set-up, who exhibit central apnoeas or
hypopnoeas when applying CPAP/PAP as a treatment for OSA. CSA associated with
other identifiable aetiologies, such as CSR or substance-induced CSA, cannot be
classified as treatment-emergent.
20
ERS Handbook: Respiratory Sleep Medicine
Definitions of sleep disordered breathing
https://t.me/medicina_free
Criteria A–C must be met (ICSD-3):
A. Diagnostic PSG shows five or more predominantly obstructive respiratory events
(obstructive or mixed apnoeas, hypopnoeas or RERAs) per hour of sleep.
B. PSG during use of PAP without a back-up rate shows significant resolution of
obstructive events and emergence or persistence of central apnoea or central
hypopnoea with both of the following:
1. Central AHI ≥5 events·h−1.
2. Number of central apnoeas and central hypopnoeas is ≥50% of total number of
apnoeas and hypopnoeas.
C. The CSA is not better explained by another CSA disorder (e.g. CSA with CSR or CSA
due to a medication or substance).
Definition of hypoventilation syndromes
OHS
OHS is probably the most common clinical presentation of hypoventilation. Criteria
A–C must be met (ICSD-3):
A. The presence of hypoventilation during wakefulness (P
as measured by P
B. The presence of obesity (BMI >30 kg·m−2; >95th percentile for age and sex for children).
, end-tidal carbon dioxide tension or P
aCO
2
>6.0 kPa (>45 mmHg)),
aCO
2
.
tcCO
2
C. Hypoventilation is not primarily due to lung parenchymal or airway disease,
pulmonary vascular pathology, chest wall disorder (other than mass loading from
obesity), medication use, a neurological disorder, muscle weakness, or a known
congenital or idiopathic central alveolar hypoventilation syndrome.
A new classification of patients with OHS has been proposed by the European
Respiratory Society (ERS) (Randerath et al., 2017).
Congenital central hypoventilation syndrome
Nocturnal hypoventilation is characteristic of congenital central hypoventilation
syndrome, oen with severe hypercapnia (P
oxygen desaturation, immediately aer falling asleep. There is oen a certain degree
of hypoventilation when awake. Primary cardiac or pulmonary diseases must be ruled
out, as well as neuromuscular diseases, brainstem abnormalities (by neuroimaging)
and congenital metabolic disorders. The cause of congenital central hypoventilation
syndrome is a mutation in the PHOX2B gene (mostly the novo), which is present in
100% of cases.
Criteria A and B must be met (ICSD-3):
A. Sleep-related hypoventilation is present.
B. Mutation of the PHOX2B gene is present.
Late-onset central hypoventilation with hypothalamic dysfunction
For the specific criteria, we refer the interested reader to the ICSD-3, as this is a very
rare condition.
Idiopathic central alveolar hypoventilation
Criteria A and B must be met (ICSD-3):
A. Sleep-related hypoventilation is present.
>8.0 kPa (>60 mmHg)) and prolonged
aCO
2
21ERS Handbook: Respiratory Sleep Medicine
Definitions of sleep disordered breathing
https://t.me/medicina_free
B. Hypoventilation is not primarily due to lung parenchymal or airway disease,
pulmonary vascular pathology, a chest wall disorder, medication use, a neurological
disorder, muscle weakness, or obesity of congenital hypoventilation syndromes.
Sleep-related hypoventilation due to medication or a substance
Criteria A–C must be met (ICSD-3):
A. Sleep-related hypoventilation is present.
B. A medication or substance known to inhibit respiration and/or ventilator drive is
believed to be the primary cause of sleep-related hypoventilation.
C. Hypoventilation is not primarily due to lung parenchymal or airway disease,
pulmonary vascular pathology, chest wall disorder, neurological disorder, muscle
weakness, OHS, or a known congenital central alveolar hypoventilation syndrome.
Hypoventilation may be present during wakefulness but is not required for the
diagnosis.
Sleep-related hypoventilation due to a medical disorder
Criteria A–C must be met (ICSD-3):
A. Sleep-related hypoventilation is present.
B. A lung parenchymal or airway disease, pulmonary vascular pathology, chest wall
disorder, neurological disorder or muscle weakness is believed to be the primary
cause of hypoventilation.
C. Hypoventilation is not primarily due to OHS, medication use or a known congenital
central alveolar hypoventilation syndrome.
Hypoventilation may be present during wakefulness but is not required for the
diagnosis.
Further reading
• American Academy of Sleep Medicine (2014). International Classification of Sleep Disorders.
3rd Edn. Darien, American Academy of Sleep Medicine.
• American Sleep Disorders Association (1999). Sleep-related breathing disorders in adults:
recommendations for syndrome definition and measurement techniques in clinical research.
Sleep; 22: 667–689.
• Berry RB, et al. (2012). Rules for scoring respiratory events in sleep: update of the 2007 AASM
manual for scoring of sleep and associated events. J Clin Sleep Med; 8: 597–618.
• Iber C, et al. (2007). The AASM Manual for the Scoring of Sleep and Associated Events: Rules,
Terminology and Technical Specifications. Darien, American Academy of Sleep Medicine.
• Randerath W, et al. (2017). Definition, discrimination, diagnosis and treatment of central
breathing disturbances during sleep. Eur Respir J; 49: 1600959.
• Verbraecken J, et al. (2009). Upper airway mechanics. Respiration; 78: 121–133.
22
ERS Handbook: Respiratory Sleep Medicine
More specific grading
https://t.me/medicina_free
of sleep disordered
breathing
Steven Vits, Frederik Massie and Johan Verbraecken
The AHI calculates the frequency of apnoea–hypopnoea events but does not take into
account the amount of hypoxaemia provoked by obstructive respiratory events, the
length of events, or other pathophysiological consequences. Moreover, in patients with
rather low AHIs, a therapeutic dilemma can occur. These patients are oen susceptible
to being part of dierent SDB severity categories, depending on the hypopnoea scoring
criteria used to score their PSGs. There is now growing evidence that characterising OSA
by a frequency-oriented metric is not sucient as a singular assessment parameter
for classifying and rating the severity of OSA. The Baveno classification is a valuable
multicomponent grading system for OSA severity beyond the AHI and will be discussed
in chapter 2.3 of this Handbook, ‘Evaluation of obstructive sleep apnoea severity’. New
metrics have been proposed and validated based on advanced signal processing and
complex analyses, and appear useful for risk stratification, tailored sleep medicine (or
precision medicine) and patient selection for clinical trials. This chapter summarises
a number of these emerging alternative metrics that more accurately quantify the
respiratory event-specific hypoxaemia, arousal intensity, and autonomic response. The
emerging role of genetics and biomarkers will also be highlighted.
Event duration
The idea of taking apnoea and hypopnoea event duration into account in the severity
estimation of OSA was introduced by Kulkas et al. (2013). Its relevance was later
confirmed in the Sleep Heart Health Study (SHHS), where an important relationship
was observed between the duration of the respiratory events and the overall mortality
seen in the SHHS. Short respiratory events could reflect a low arousal threshold, but
Key points
• Characterising OSA by frequency-oriented metrics is not sucient for
classifying the severity of OSA and risk stratification.
• New metrics better quantify the respiratory event-specific hypoxaemia,
arousal intensity and autonomic response.
• Sophisticated algorithms are mandatory to perform in-depth analyses beyond
the AHI.
• The applicability of genetics and biomarkers is limited by costs, reproducibility,
significant delays for results, and lack of specificity.
23ERS Handbook: Respiratory Sleep Medicine
Соседние файлы в папке Библиотека им академика М.И. Перельмана