Ergebnisse der Inneren Medizin und Kinderheilkunde/Advances in Internal Medicine and Pediatrics

209 Pages·1984·9.76 MB·English

by  P. Frick, K. Kochsiek, G. A. Martini, A. Prader (eds.), G.-A. von Harnack, Ch. Guilleminault (auth.)

Ergebnisse der
Inneren Medizin und
Kinderheilkunde
52
Advances in
Internal Medicine and
Pediatrics
Neue Foige
Herausgegeben von
P. Frick G.-A. von Harnack K. Kochsiek
G. A. Martini A. Prader
Mit 26 Abbildungen und 50Tabellen
Springer-Verlag
Berlin Heidelberg New York Tokyo 1984
ISBN-13: 978-3-642-69766-1 e-ISBN-13: 978-3-642-69765-4
DOl: 10.1007/978-3-642-69765-4
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Inhalt/Contents
Diagnosis, Pathogenesis, and Treatment of the Sleep Apnea Syndromes.
Ch. Guilleminault (With 8 Figures) . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1
Asthma bronchiale im Kindesalter.
D. Reinhardt (Mit 13 Abbildungen) . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 59
Das Prune-Belly-Syndrom.
B.H. Belohradsky und C. Henkel (Mit 5 Abbildungen) ................. 157
Diagnosis, Pathogenesis, and Treatment
of the Sleep Apnea Syndromes
CR. GUILLEMINAULTI
1 Introduction and Brief Historical Overview of the Sleep Apnea Syndromes. • . . . . • • . . 2
2 Epidemiological Data .•..•................. . • . • • : • . . . . . . . . . . . 6
3 Key Tests in the Sleep Apnea Syndromes . . . • • . . . . . . . . . . . . . . . . . . . . . • . . 7
3.1 The Polysomnogram .....................••.......•....... 7
3.1.1 Indices Derived from the Polysomnogram ...•.•...•.......•.... 7
3.1.2 Calculation ofindices and Their Normative Values in Adults .....•••.•• 8
3.2 Radiologic and Imaging Testing. • . . . • . . . . . . . . . . • . . . . . . . . . . . . . .. 8
3.3 Flow Volume Loops. • . . . . . • • . . • . . . . . . . . . . . • . • . . . . • . . . . . .. 9
3.4 How Much Pulmonary Testing Should be Performed? . . • . . . . . . . . . . . . . . .. 10
3.5 Obstructive Sleep Apnea Syndrome and Neurological Tests. . . • . . . . . . . . . . .. 10
3.6 Autonomic Nervous System and R-R Intervals as a Screening Tool. . . . . . . • . • .. 12
4 Obstructive Sleep Apnea Syndrome • . . • . . . . . . . • . . . . . . • . . . . . . • . . . . •. 12
4.1 Clinical Symptoms. . . . . . . • . . • . • . . . . . • . . . . . . . . . . . . . . . • . . .. 12
4.2 Examination of the Patient with Obstructive Sleep Apnea. . . . . . . . . . . . . . . •. 13
4.2.1 Evaluation of Obesity . . • . • . • • . . . . . . . . . . . . . . . . . . . . . . . .• 13
4.2.2 Evaluation of the Oronasomaxillofacial Region. . . . . . . . . . . . . . . . . .. 13
4.2.3 Aggravating Factors .• . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . •. 14
5 Central Sleep Apnea Syndrome. . • . . . . . . . . . . . . . . . . . . . . . . . . . . • • . • .. 14
5.1 Clinical Symptoms. . . . . . . . . . . . . . . . . . . • . . . • . . . . . . . . . . . . . •. 14
5.2 Examination of Patient with Central Sleep Apnea .................... '. 14
6 Risks Associated with the Sleep Apnea Syndromes. . . . . . • • . . . . • . . . . . . . . . .. 15
6.1 Hemodynamic Changes. . . . . . . . . . • . . . . . . . . . . . • . . . • . • . . . . • . .. 15
6.2 Cardiac Arrhythmia. •.............••.....•.....•......... '. 15
6.3 Anoxic Seizure. . . . . . . . . . . • . . . . . . . . . . . . . . . . . . . . . . . . . • . .. 15
6.4 Overwhelming Sleepiness and Confusion. . . . . . . • . . . . . . . . . • . . . • . . • •. 17
6.5 Sudden Death During Sleep. . . . . . . . . . . . . • . . . . • • . . . . . . • . . . . . .. 17
7 How Does Obstructive Sleep Apnea Syndrome Develop? . . . . . . . . . . . . . . • . . . .. 17
7.1 Case Vignettes. . . . . . . . . . . . . . . . . . . . . . . . . • . . . . . . . . . . . . . . .. 17
7.1.1 OSAS and NMSIDS Infants. . • • . • . • . . • . . . • . . • . . . • . . . • . • .. 18
7.1.2 Pierre Robin Syndrome, Crouzon's Disease, Retrognathia, and Apnea in
Infants and Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
7.1.3 Development of Apnea After Surgery for Qeft Palate. . . . . . . . . . . . . .. 19
7.1.4 Reappearance of Apnea After Removal of Tracheostomy . . . . . . . • . . . .. 20
7.2 Studies on the Pathogenesis of OSAS. . . . . . . . . • . . • . . • . • . . . . . . • . . .. 20
7.3 REM Sleep and the Pathogenesis of Sleep Apnea. . . . . . . • . • . . . . • • . • . . .. 22
8 Why Does an Apneic Episode Terminate? . . . . . . . . . . . . . . . . . . . . . . . . . • . .. 24
8.1 Hypoxemia and Termination of Apnea. . . . . . . . . . . . . • . . • . . . . . . . . • .. 25
8.2 Could It be Hypercapnia? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 26
8.3 Other FactQrs Leading to Arousal. . . . . . . . . . . . . • . . . . • . . . • . . . . . • .. 26
1 Sleep Disorders Center, TD-114, Stanford University School of Medicine, Stanford, CA 94305,
USA
2 Ch. Guilleminault
9 Therapeutic Approaches in Adults. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 28
9.1 Behavioral Approaches and Toxicological Avoidance. . . . . . . . . . . . . . . . .. 28
9.1.1 The Issue of Weight. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29
9.1.2 Role of Low-Flow Oxygen During Sleep. . . . . . . . . . . . . . . . . . . .. 30
9.2 Mechanical Devices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 31
9.2.1 Orthodontic Approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 31
9.2.2 The Tongue-Retaining Device .......................... , 31
9.2.3 Continuous Positive Airway Pressure. . . . . . . . . . . . . . . . . . . . . .. 32
9.3 Surgical Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 32
9.3.1 Tracheostomy.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 32
9.3.2 Palatopharyngoplasty. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 33
9.3.3 Palatopharyngoplasty with Nasal Reconstruction. . . . . . . . . . . . . . .. 35
9.3.4 Palatopharyngoplasty with Geniotubercle Advancement. . . . . . . . . . .. 36
9.3.5 Surgical Mandibular Advancement, Retrognathia, and OSAS . . . . . . . .. 37
9.3.6 Surgery on the Gastrointestinal Tract and OSAS . . . . . . . . . . . . . . .. 38
9.3.7 An Experimental Procedure: Resection of the Hyoid Bone. . . . . . . . .. 40
9.4 Pharmacological Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 40
9.4.1 Naloxone. ................. ; ................... , 40
9.4.2 Theophylline and Aminophylline ........................ , 41
9.4.3 Medoxyprogesterone.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 41
9.4.4 Tricyclic Medications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 42
9.4.5 Acetazolamide.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 44
9.4.6 L-Tryptophan and SAS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 45
10 Sleep Apnea Syndromes in Children. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 45
10.1 Nocturnal Symptoms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 46
10.2 Sleep and Sleep States .................................. , 47
10.3 Breathing Patterns During Sleep. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 47
10.4 Therapeutic Approaches ................................. , 48
10.5 The Problem of Sleep Apnea in Infancy ........................ , 48
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 49
Key words: Sleep apnea - cephalometrics - imaging - palatopharyngoplasty -
maxillofacial surgery - gastric stapling - drug treatment of sleep apnea - polygra-
phic recording - central apnea - obstructive apnea.
1 Introduction and Brief Historical Overview of
the Sleep Apnea Syndromes
For many years respiration during sleep was thought to follow patterns similar to
those observed during wakefulness, but the dicoveryof two different states of sleep -
rapid eye movement (REM) and non-rapid eye movement (NREM) - led to a reap-
praisal of respiration and ventilation during sleep in humans and other mammals [6].
It is difficult to study the central control of breathing, and for a number of years
investigators have used convenient anesthetic preparations. Recent studies have clearly
demonstrated, however, that multiple efferent pathways are eliminated in such prepa-
rations, so that results of these experiments are valid only for anesthetized animals,
not for understanding ventilation during wakefulness, NREM sleep, and REM sleep.
Future studies on respiration and ventilation during sleep will have to use the chroni-
cally implanted preparations used in studying the basic phenomena of sleep physiology.
Diagnosis, Pathogenesis, and Treatment of the Sleep Apnea Syndromes 3
Sleep and sleep states have an effect on respiration. It has been shown that during
REM sleep the atonia observed in the antigravidic muscles also involves the intercostal
and accessory respiratory muscles [52, 53]. There is a measurable increase in the dia-
phragmatic workload during REM sleep. In association with sleep, other biological
variables are modified, from increases in airway pressure to changes in the Hering-
Breuer reflex [158]. It also appears that, depending on the state of alertness (wake,
REM sleep, or NREM sleep), the importance of peripheral input (amount of oxygen
desaturation, etc.) on the central control of ventilation will vary. The behavioral
control of ventilation is dominant during wakefulness and very active during REM
sleep; the chemical control of ventilation is the major controlling element during
NREM sleep [158]. In people with normal sleep patterns, REM sleep can be divided into
"phasic" and "tonic" phases on the basis of polygraphically monitored neurophysiolo-
gical events [114]. A "REM-sleep system" superseding peripheral input is in effect in
respiration during this sleep state. In this system, CO2 has little influence during phaSic
REM sleep but is still in effect, for example, during tonic REM sleep. These different
physiological findings explain why the study of ventilation and respiration during sleep
and the different sleep states is critical, both in individuals with normal respiration and
diseased individuals. Physiological changes may cause substantial and unsuspected
changes in air exchange that may, in tum, lead to life-threatening situations involving
the cardiorespiratory system during sleep, and to daytime complaints that have no
obvious relationship to respiration.
The basic abnormal breathing event during sleep is an "apnea," the cessation of
airflow at the nostrils and mouth leasting at least 10 s [81]. There are several subdivi-
sions of apneas: a sleep-related apnea may be secondary to a sleep-induced obstruction
of the airway (obstructive or upper airway apnea) or to decreased respiratory muscle
activity (central or diaphragmatic apnea) or it may be mixed (combining upper airway
and diaphragmatic phenomena) [200]. Some patients have sleep-related "hypopneas"
where air exchange is reduced but does not cease. Hypopneas can also be obstructive,
central, or mixed [88]. Each of these abnormal breathing events during sleep has been
defined by polygraphically monitoring respiration using thermistors or expired CO2
monitors to measure air flow, and a variety of devices such as thoracoabdominal strain
gauges, end oesophageal balloons, transducers, or respiratory inductive plethysmography
and intercostal muscle electromyograms (EMG) to measure respiratory "effort." Such
recording frequently includes continuous monitoring of arterial oxygen saturation. In
selected cases, fiberoptic studies and ftlming (Fig. 1), can visually confirm the data
obtained by polysomnography [85, 88].
These abnormal breathing patterns during sleep can lead to decreased arterial
blood oxygen saturation (and in some patients to complex cardiovascular changes
during sleep) and to daytime complaints. The impact of these abnormal events during
sleep varies according to the duration of the event, its type, the level of oxygen satura-
tion prior to the event, and probably the sleep state. Abnormal breathing patterns with
impaired arterial oxygenation during sleep are seen in various pathological states, but
they can appear also as independent, isolated syndromes. In a given patient the three
types of apneic patterns are usually seen during long-term (nocturnal or 24-h) poly-
graphic monitoring, but one type generally predominates. Based on the predominant
type of abnormality, two basic sleep apnea syndromes have been identified: the pre-
4 Ch. Guilleminault
Diagnosis, Pathogenesis, and Treatment of the Sleep Apnea Syndromes 5
dominantly obstructive - or upper airway - sleep apnea syndrome and the predominant-
ly diaphragmatic - or central- sleep apnea syndrome. The distinction can be artificial,
as some patients begin with a predominantly central syndrome that evolves into an
obstructive form. However, it is traditional to distinguish between the two because the
underlying physiopathological mechanisms are not always necessarily the same [73].
In 1837, in the Posthumous Papers of the Pickwick Club, Charles Dickens [48]
described an incredibly fat boy named JOE with persistent somnolence. Dickens'
nearly clinical description may have been influenced by Doctor W. Wadd's presenta-
tion of a short report entitled "Cursory remarks on corpulence - by a member of the
Royal College of Surgeons" in 1810 in London [207]. In 1918, Sir William Osler [156]
coined the term "pickwickian," referring to obese, hypersomnolent patients; in 1936,
Kerr and Lagen [117] noted that a significant cardiocirculatory problem could develop
in such patients. In 1956, Burwell et al. [26] reviewed the clinical symptoms of the
"pickwickian syndrome." Because this clinical description had not been based on an
understanding of the underlying mechanisms responsible for the clinical picture, ambi-
guities quickly became obvious. In 1955,Auchinc/oss et al. [8] had attracted the atten-
tion of internists to differences existing in the physiopathology of syndromes leading
to obeSity, hypersomnolence, and polycythemia. Alexander et al. [1,2] in 1959-1962
identified a JOE type of the pickwickian syndrome characterized only by obesity and
hypersomnolence. It appeared to neurologists and internists that the pickwickian syn-
drome was not a single entity, but ways and means to break this "wastebasket" syn-
drome down were not clear.
Neurologists have played a major role in deciphering the sleep apnea syndromes,
particularly between 1960 and 1975. The neurologist Gelineau [65], in 1880, was the
first to describe "narcolepsy," which he defined with very clear delimiters. Unfortu-
nately the word became common medical jargon, a catchall phrase denoting "excessive
daytime sleepiness," and Gelineau's [65] and later Daniels' [47] precise descriptions
were ignored. In the early 1960s, Sieker et al. [181] reported on the hypersomnolent
state [12, 181] and narcolepsy. They had found that blood gases, particularly oxygen
saturation, could decrease during sleep; they published a photograph of their narcolep-
tic; he was a massively obese gentleman. In 1965, two different teams published sim-
ilar findings: Gastaut et al. [63] reported on the presence of repetitive obstructive
apnea during sleep in the obese pickwickian patient; lung and Kuhlo [115] also
reported a case study with similar sleep-related respiratory pauses.!
In 1969-1969 Doll et al. [49] reported that tracheostomy was beneficial to pick-
wickians. Their initial hypothesis had been based on two observations made in the late
19th century by the British physician Caton [33] and the French physician Lamaco
[125], who had noted that "narcoleptics" may suffer from obstructed airways during
sleep that lead to "periodic states of suffocation." In 1967, Schwartz and Escande
[177] performed the first cinematographic study of obstructive apnea in pickwickians.
They demonstrated that an oropharyngeal collapse occurs, which has been confirmed
1 Actually, lung and Kuhlo's [1151 case attracted my personal attention for another reason. They
reported a rarely cited point: that their case had had sleep apneic episodes for 10 years before
the pickwickian syndrome appeared. In 1969 I began a systematic search for nonobese patients
with apnea during sleep
6 Ch. Guilleminault
by every fiberoptic study since. The existence of this "collapse" was challenged in
1978 [211] and the hypothesis of an active closure at the velopharyngeal sphincter
presented in its place, but electromyographic studies performed on oropharyngeal
muscles in conjuction with fiberoptic scope and cinematography studies [85] supported
the collapse hypothesis.
In 1972, Sadoul and Lugaresi [169] organized the first international meeting on
hypersomnia with periodic breathing. In his foreword to the conference volume,
Sadoul [68] noted the abuse of terms such as pickwickian syndrome, Ondine's curse,
and others. Nosological difficulties were obvious: Londsdorfer et al. [130] used terms
such as "pickwickian-Joe's type" and "pickwickian-Burwell's type," while Carrol [28]
had a pickwickian syndrome (a) Alexander's type (b) Auchincloss' type, (c) Sieker's
type, and (d) Gastaut's type. The terms "sleep apnea" [78] and "sleep apnea syn-
dromes" (1974-1978) were chosen as alternatives. The change in terminology did not
resolve all problems, but now the terms referred to a specific pathological problem
that explained some specific clinical symptoms.
In 1972, several groups reported on systematic hemodynamic studies during sleep
in obese [39, 121, 130] and nonobese [78] patients with sleep apnea, and the impact
of these apneas on the cardiovascular system during sleep. Monobese patients with
micrognathia, hypersomnolence, cardiocirculatory failure, and apnea during sleep were
also discussed [16, 199, 205]. In 1972-1973, two articles raised the issue of sleep
apnea in the sudden infant death syndrome (SIDS), near miss SIDS, and children [79,
186]. Finally, the first textbook on physiology during sleep, with a chapter on sleep
and breathing, was published in 1980 [152].
This brief historical sketch demonstrates that although sleep apnea syndromes
have been recognized for at least 100 years, our lack of knowledge about the physiolo-
gical effects of sleep and sleep states on ventilation has hindered our understanding of
specific breathing problems during sleep.
2 Epidemiological Data
A recent survey performed by the Association of Sleep Disorders Centers (ASDC),
encompassing ten Sleep Disorders Centers with different orientations, tabulated the
different diagnoses of adult patients seen in the centers during the first 6 months of
1980. All patients had been given complete evaluations, including polygraphic moni-
toring. A total of 4192 patients were studied: 29% complained of a disorder of initiat-
ing or maintaining sleep (DIMS), and 2% were diagnosed as having sleep apnea insom-
nia (6% of the total DIMS); 51% complained of a disorder of excessive sleepiness
(DOES), and 20% suffered from sleep apnea hypersomnia (42% of the total DOES)
[43].
Lavie [126] studied 1502 industrial workers in Israel, 84% of whom were male
and 16% of whom were female. The population distribution with respect to age and
country of origin was identical to that for civilian industrial workers obtained from the
National Statistical Bureau. Lavie [126] found that 1.26% of industrial workers had an
apnea index (see Sect. 3.1.1) above 5 (lowest estimate) and that an additional 1.03%
Diagnosis, Pathogenesis, and Treatment of the Sleep Apnea Syndromes 7
of industrial workers had an apnea index above 5 and subjective complaints (lowest
estimate). These statistics are moderate estimates of the pervasiveness of the problem
in Israel. The following review of the two syndromes, obstructive sleep apnea and
central sleep apnea, is based primarily on our experience with over 1000 sleep apneic
patients.
3 Key Tests in the Sleep Apnea Syndromes
3.1 The Polysomnogram
Because sleep apnea syndromes are the result of abnormal events occurring during
sleep, it is mandatory that patients be studied during sleep. There are various tech-
niques that document the number and predominant type of apneic episodes, the level
of oxygen saturation, and the severity of the syndrome [69]. With microprocessors,
a patient's breathing and other biological variables can be monitored at home. Regard-
less of the technique, the sleep-related test must monitor enough information to
appreciate the severity of the sleep-related disturbance and the eventual risks to the
patient. It is important to recognize the two sleep states, NREM and REM sleep, and
to correlate them with the abnormal breathing events during sleep. Oxygen saturation
and cardiac arrhythmia are also systematically monitored with accurate noninvasive
techniques. The nocturnal sleep period, rather than daytime naps, should be monitored,
usually for a minimum of one night. Without nocturnal monitoring, the 24-h distribu-
tion of REM sleep, which most frequently occurs between 3 a.m. and 6 a.m. in normal
individuals, cannot be determined. There may be no REM sleep at all during daytime
naps. Recent studies have shown that apnea may be related to circadian rhythms,
particularly in children, whose apneas peak between 3 a.m. and 6 a.m. [109]. Finally,
in children with intermittent apneic episodes, the number of apneas may increase
with the length of sleep [90]. It may be easy to diagnose sleep apnea in severe cases,
but evaluating its potential risk to the patient is difficult without all-night monitoring.
3.1.1 Indices Derived from the Polysornnogram
Several indices can be obtained from the polysomnogram. The most common is the
Apnea + Hypopnea Index (A+H)I [86, 88], which is similar to the Respiratory Distur-
bance Index (RDI) [13]. To obtain the (A+H)I, the total number of abnormal respira-
tory events during sleep is divided by total sleep time in minutes and multiplied by 60.
Thus the (A +H)I gives the number of abnormal respiratory events per sleep hour. This
index indicates the severity of the syndrome but may not be sufficient to describe the
entire disorder. Several indices have been derived from oxygen saturation measure-
ments. One measures the number of events associated with desaturation under a
certain oxygen level, i.e., < 90%, < 80%. Another one, more complex, measures the
amount of sleep time spent below a certain amount of oxygen saturation. In conjunc-
tion with these oxygen saturation indices, a Cardiac Arrhythmia Index has also been
used that notes the number of cardiac arrhythmias per hour of sleep. These indices