TITLE: Health Related Consequences of Obstructive Sleep Apnea and

Response to Therapy
SORCE: !rand Rounds "resentation# T$%# &ept' of Otolaryn(olo(y
&ATE: $ay )*# +,-
RESI&E.T "H/SICIA.: Sarah Rodri(ue0# $&
1ACLT/ "H/SICIA.: To2o3o $a3ishi2a# $&
SERIES E&ITORS: 1rancis %' 4uinn# 5r'# $& and $atthe6 7' Ryan# $&
"This material was prepared by resident physicians in partial fulfillment of educational requirements established for
the Postgraduate Training Program of the UTMB Department of Otolaryngology/ead and !ec" #urgery and was
not intended for clinical use in its present form$ %t was prepared for the purpose of stimulating group discussion in a
conference setting$ !o warranties& either e'press or implied& are made with respect to its accuracy& completeness& or
timeliness$ The material does not necessarily reflect the current or past opinions of members of the UTMB faculty
and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and
informed professional opinion$"
Introduction
In the last thirty years there has been a blossoming body of knowledge regarding the
diagnosis and treatment of sleep disorders. The otolaryngologist is frequently involved in the
management of these patients. A thorough understanding of sleep disorders and their treatment
is key for the practicing otolaryngologist. Specifically, one must be familiar with the health-
related consequences of obstructive sleep apnea !SA" such as neuropsychological sequelae,
metabolic derangements, hypertension, heart and vascular disease. The otolaryngologist must
also be able to counsel patients on available treatments for !SA and the relative ability of these
treatments to impact the health-related consequences of !SA.
Definitions
To understand the specific disorders one must understand some of the definitions. An
apnea is defined as cessation of airflow for ten seconds which results in an arousal. If the chest
wall continues to mechanically move during this time, then it is an obstructive apnea. If the
chest wall does not attempt to ventilate, then it is presumably due to a neurologic etiology and is
termed a central apnea. Sometimes there are characteristics of both an obstructive and a central
apnea, and this is termed a mixed apnea. The number of apneas per hour is termed the apnea
index.
A hypopnea is a less well-defined entity, but usually is considered a diminution in airflow
which results in hypo#emia and results in an arousal. The number of hypopneas per hour is
termed the hypopnea index.
$unctionally, there is little difference between apneas and hypopneas, and the sum of
these vents per hour is termed the apnea-hypopnea index %A&I'. This is also referred to as the
respiratory disturbance index %()I'. !ccasionally a lab will also report the arousal index,
which is the number of arousal per hour. This may be different than the ()I due to limb
movement or other causes of arousal.
*enerally the obstructive sleep apnea syndrome %!SAS' is considered to be an ()I + ,.
Also described is the obstructive sleep hypopnea syndrome %!S&S' which is a hypopnea inde#
of greater than -,, but as mentioned there is little clinical utility in differentiating this from
!SAS. Severity of !SAS is also stratified by the ()I, with mild being considered ,-./,
moderate ./-0/, moderate-severe 0/-1/, and severe + 1/.
As the field of sleep medicine progressed there arose an awareness of certain patients
who report e#cessive daytime sleepiness but do not have !SAS %e.g. ()I 2 ,'. 3y esophageal
manometry some of these patients have been shown to have increased negative thoracic pressure
during inspiration. Thus, their increased work of breathing is thought to be responsible for their
symptoms. This syndrome has been termed the upper airway resistance syndrome %4A(S'.
Together with !SAS these are 5ointly referred to as sleep-disordered breathing %S)3'. Those
patients who snore but have an ()I 2 , and who do not have increased intrathoracic pressure
upon inspiration simply have primary snoring. !ne hypothesis is that these disorders represent
a spectrum of disease with primary snoring being the mildest, followed by 4A(S, and finally
!SAS as the full manifestation of the disease.
Pathophysiology
Although incompletely understood, the pathophysiology of !SAS relates to airway
collapse. This may occur at various levels, including the palate, the base of tongue, and the
hypopharyn#. 6asal obstruction appears to facilitate or e#acerbate the syndrome although it
does not appear to be primarily responsible. 4nfavorable anatomy appears to be the most
important cause. This can be due to a narrow palate, an elongated uvula, redundant tissue at the
base of tongue, micro7retrognathia, a retrodisplaced hyoid, and so on. Adenotonsillar
hypertrophy may be a cause as well, particularly in the pediatric population. 8#perimental
evidence shows that in the pharyn# the collapse occurs predominantly from the lateral walls, not
merely from anteroposterior collapse as might seem likely in patients with elongated palates.
This also may e#plain the way in which obesity increases the prevalence of !SAS, as the lateral
pharyngeal fat pads may narrow the airway in the lateral dimension.
Although unfavorable anatomy is important etiologically, there also appears to be a
physiologic defect in the pharyngeal dilators. There is also e#perimental evidence that
longitudinal tension appears to be inversely related to airway collapse. Additionally, e#trinsic
factors such as sedating medications may e#acerbate the physiologic defects.
Rationale for treating OSAS
4ntreated, !SAS has a rather impressive list of deleterious consequences9
I' .europsycholo(ical Sequelae:
a. .Sleepiness7tendency to fall asleep. :atients with severe !SA often have mean
sleep onset latencies in the pathological range of , minutes or less, some .
standard deviations below normal mean values of -.. Improvements in both
sub5ective and ob5ective tests of sleepiness are seen with ;:A: therapy for
!SA. These improvements are moderate to large.
b. b.Attention. There is a si<able effect of !SA on the ability to sustain attention
over time, particularly on the quality of the performance rather than simple
reaction time. In terms of attention-based cognitive outcomes, there is a
modest improvement of functioning with ;:A:.
c. ;ognitive function. =oderate to severe !SA negatively impacts memory and
e#ecutive performance>although presence and degree of deficit in these
categories is controversial
d. ?uality of life. Studies indicate that patients with !SA have significantly
impaired ?!@ and social functioning and a high prevalence of minor
psychiatric morbidity. The large impairments in sleepiness and energy related
?!@ scores show substantial improvement with ;:A:>those with the most
severe !SA reap the most benefit.
II. $etabolic Effects8Insulin Resistance
a. $eslier et al +,,9
,A, male patients referred for polysomnography underwent a . hour
oral glucose tolerance test.
0A0 pts had !SAS %A&I + -/'
$asting and postload blood glucose increased with severity of sleep
apnea
Insulin sensitivity decreased with increasing severity of sleep apnea
3=I, age and A&I are all have an independent effect on blood glucose
and insulin sensitivity
Ip et al +,,+
-B, pts with !SAS %A&I+,'
Insulin resistance increased with age obesity %main determinant'
Independent determinants of !SA were A&I and min /. sat
"un:abi et al +,,9 ;Revie6<
&abitual snoring is associated with abnormal fasting glucose and
insulin values independent of age and 3=I
:rospective data from two separate studies indicate that habitual
snoring is associated with more than a .-fold risk of developing
)= type II over a ten year period independent of 3=I and
other confounders
Several studies have suggested that the minimum o#ygen saturation
and A&I are predictive of glucose intolerance and insulin
resistance independent of 3=I, age and waist to hip ratio
%abu et al +,,*
., pts with )= type II, obesity %mean 3=I 0..C', and !SA %mean
A&I ,1' were evaluated before and after a A/ day trial of ;:A:
There were significant reductions in postprandial glucose values
;oncluded that !SA is pathophysiologically related to impaired
glucose homeostasis and that ;:A: is an important therapy for pts
with )= type II and !SA
Harsch et al +,,9
$orty patients with A&I+./ were evaluated for insulin sensitivity
before, . d after and D mos after treatment with ;:A:. Insulin
sensitivity significantly increased after two days and remained stable
after three months of treatment.
:atients with 3=I 2 D/ had a much greater improvement in insulin
sensitivity.
III. &ypertension
a. 7isconsin Sleep Cohort Study' )emonstrated an increased risk for
development of hypertension in patients with !SA over a 0 to B year follow
up period. The severity of !SA increased risk for development of
hypertension independent of baseline blood pressure status, age, gender, 3=I,
alcohol and cigarette use.
b. Sleep Heart Health Study' There is an elevated risk for hypertension found
in sub5ects with sleep disordered breathing after ad5usting for demographics,
3=I, alcohol consumption and smoking.Association between S)3 and &T6
was seen regardless of age, gender, ethnicity, 3=I.
c. $echanis29 Individual episodes of sleep apnea cause acute surges in &( and
3: at apnea termination driven by hypo#ia ' 8pidemiologic evidence and
physiologic studies in humans and animals support the idea that chronic
e#posure to repeated apneas may lead to a sustained diurnal &T6 via
increased sympathetic tone and activation of the renin-angiotensis system.
d. Treatment of !SAS does appear to lower blood pressure although the
literature is inconsistent.
I=' Cardiovascular effects
$arin et al published results of -/ year observational study of DCC primary
snorers, 0/D pt with untreated mild to moderate !SA, .D, pts with severe !SA
who refused treatment, DC. pts with !SA treated with ;:A:, .10 healthy pts. The
endpoints myocardial infarction, stroke, or acute coronary insufficiency requiring
invasive management, death of myocardial infarction or stroke" were D times as
high in pts with untreated severe apnea as in the healthy control individuals.
$illeron et al prospectively monitored ,0 patients with both ;A) %+EC/F
coronary artery stenosis' and !SA %A&I +E-,', ., of whom were treated with
;:A: or upper airway surgery and .A who declined treatment for !SA, for a
median of B1., G DA months. The endpoint %cardiovascular death, acute coronary
syndrome, hospitali<ation for heart failure, or need for coronary revasculari<ation'
was reached in only .0F of the treated patients compared with ,BF of those who
declined !SA treatment.
Conclusion
Sleep medicine is an e#citing, relatively new field that has emerged. The
otolaryngologist has become a key figure in the diagnosis and management of sleep disorders
due to his or her familiarity with the airway and the ability to intervene surgically. An
understanding of the medical and surgical issues involved is necessary for the otolaryngologist to
deal with this field which is rapidly evolving.
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