Obstructive Sleep Apnoea Syndrome

Obstructive Sleep Apnoea
Syndrome
Dr Tom Mackay
Consultant Respiratory Physician
Royal Infirmary & Spire Edinburgh Hospitals
Outline of talk
• Excessive Daytime Sleepiness
Consequences
Causes
• OSAS
Epidemiology
Causes
Diagnosis
Treatment
Consequences
Associated Conditions
• Summary
New Patient Referrals to Sleep Centre
Main Symptom: Excessive Daytime Sleepiness
New Referrals in Year
2800
2400
2000
1600
1200
800
400
0
1984 1988 1992 1996 2000 2004 2008 2012 2016
Year
Excessive Daytime Sleepiness
• The effects of sleep loss / deprivation are
cumulative
• The danger of an error due to sudden
overwhelming sleepiness increases progressively
with increasing sleep loss (“sleep debt”)
• Individuals can cope temporarily with sleepiness
by increasing physical activity or taking dietary
supplements (caffeine / carbohydrate)
→ inactivity / “autopilot” behaviour can lead to
overwhelming sleepiness (“microsleeps”)
Three Mile Island
1979
Chernobyl
1986
Bhopal
1984
Exxon Valdez
1989
Sleepiness and Catastrophies
• Three Mile Island Nuclear Power Plant disaster (USA)
occurred at 4am
• Chernobyl Disaster occurred at 1.23am
• Columbia Shuttle Launch 1986 at 6 am
aborted 31 seconds before lift off after 18,000
pounds of liquid oxygen had been accidentally
drained from external fuel tanks
• Space Shuttle Challenger Disaster
blamed on human error / poor judgement
flight managers worked irregular hours and had
less than 2 hours sleep the night before the
launch
• Exxon Valdez disaster : crew apparently fell asleep
on the bridge
Steering error
SLEEPY PATIENTS ARE DANGEROUS DRIVERS
Control
OSAHS
George AJRCCM
1996;154:175-81
Steering error
SLEEPY PATIENTS ARE DANGEROUS DRIVERS
Control Ethanol
OSAHS
George AJRCCM
1996;154:175-81
Factors which can produce
Excessive Daytime Sleepiness
• Inadequate sleep time / Sleep deprivation
• Misalignment of the body’s circadian rhythm with the
environment
Shift work
Advanced or Delayed Sleep Phase Syndrome (Circadian
Rhythm
Disorders)
• Qualitative Sleep Deficiency
OSAHS
Periodic Limb Movement Disorder (PLMD) / RLS
• CNS abnormalities
Narcolepsy
Depression
• Drugs
Opioids
Sedatives
Obstructive Sleep Apnoea
Hypopnoea Syndrome
Epidemiology of OSAS
• Common problem
• Prevalence of 2 – 4% in middle aged men
0.5 - 1% in middle aged women
(similar to that of Type 1 diabetes and twice that of
severe asthma)
• 50,000 adults affected in Scotland (10,000 currently
receiving treatment) ? 500,000 adults in UK
• Referral for suspected OSAS is now the fastest
growing source of new outpatient respiratory referrals
in Scotland exceeding asthma, COPD and lung cancer
combined
• Driven by increased awareness of sleep issues and
increasing level of obesity in the population
• Increasing levels of obesity worldwide
Obesity trends in the USA
Prevalence of obesity in different countries
35
30
USA
Europe
China
Brazil
Kuwait
Australia
25
20
Percent
15
10
5
0
Europe 16%
Source: World Health Organization
Obesity trends in the UK
• The percentage of adults who are obese
has doubled since the mid 1980’s
• Weight increases with age
2007
Overweight
Obese
Total
Males
46%
17%
63%
Females
32%
21%
53%
Mechanism of Obstruction in OSAS
Retrognathia
Low set uvula
Visceral Obesity
Collar > 17”
Pharyngeal
Obstruction
Sleep Stage
Sleep Position
Alcohol / Sedatives
Activity of airway
dilating muscles
PHARYNGEAL
SIZE
Describing Abnormalities of the Upper
Airway
• Abnormalities of the upper airway can be
categorised using the Mallampati score
originally devised for anaesthetic practice
(Mallampati 1983)
10
AIRWAY MRIs
CONTROL
OSAS
A normal night’s sleep
Non REM Stage 1 + 2 Sleep
Non REM Stage 3 + 4 Sleep (SWS)
REM sleep
23.00
07.00
Sleep architecture is well structured and refreshing
= a good night’s sleep REM cycles occur approximately
every 90 minutes
Sleep in OSAS
Non-REM Sleep stage 1 + 2 sleep
Non-REM Sleep stage 3 + 4 sleep
REM Sleep
Awake
23.00
Unrefreshing light sleeping pattern
Very little stage 3 + 4 sleep
Brief awakenings
07.00
OSAHS: CLINICAL FEATURES
• * Excessive Daytime Sleepiness
ESS > 11
• Unrefreshing sleep
• Poor concentration / Depression
• Snoring / Apnoeic Episodes
• Nocturia
• 80% obese (BMI > 30)
*
Cardinal symptom
Diagnosis of OSAS
• Clinical Features
• Subjective Assessment of Sleepiness
(Epworth Sleepiness Score)
• Objective Sleep Study
Oximetry
Limited (Respiratory) Study
PSG
Subjective Assessment of Sleepiness
Epworth Score
• 8 Questions
• Rated 0-3, Maximum Score = 24
•
•
•
•
•
•
•
•
Sitting and reading
Watching TV
Sitting inactive in a public place
As a car passenger for one hour
Lying down to rest in the afternoon
Sitting and talking to somebody
Sitting quietly after lunch without alcohol
In a car, while stopped for a few minutes in traffic
Epworth Score
• Various degrees of sleepiness
•
•
•
•
ESS < 11
ESS 11-14
ESS 15-18
ESS >18
Normal
Mild Sleepiness
Moderate Sleepiness
Severe Sleepiness
Objective Sleep Studies
• Training of personnel is vital
• Location : Hospital v Home
• Varying degrees of complexity
Simple: pulse / oximetry
Limited: oximetry / pulse / thoracoabdominal respiratory movement / airflow
Complicated (PSG): brain waves, breathing
pattern, airflow, movement, snoring,
video
Oximetry
• May miss up to 1/3 cases of OSAS
• Younger and thinner patients may not
desaturate despite having significant
OSAHS
• > 25 x 4% dips / hour is the usual cut off
for diagnosis of OSAS (occasionally go as
low as 15 / hour in PSG)
Limited Sleep Studies
• Usually measure 4 variables
Airflow
Thoraco-abdominal movement
Oximetry
Pulse
+/- Snoring
• Usually focus on respiratory signals
Limited Sleep Study
•
•
•
•
•
Often performed at home
Edinburgh: 50 mile radius if transport is available
Written instruction sheet provided
Cheaper than hospital study (25-30% saving)
AH > 25 / hr in bed = AHI > 15 / hr slept (PSG)
(Whittle et al Thorax 1997;52:1068-73)
• Speeds up the diagnosis
• Possible decrease in diagnostic accuracy
• Does not measure sleep
(ie may give a normal result if the subject doesn’t
sleep)
Diagnosis of OSAS
*
• Presence of suggestive symptoms
Snoring , apnoeic episodes
• Subjective Assessment of Sleepiness
High Epworth Score (self rated or partner’s assessment) > 11
PLUS
• Abnormal Objective Sleep Study result
Oximetry : > 25 x 4% desaturation dips per hour
Limited Study : AH score > 25 /events per hour in bed
PSG : AHI > 15 events per hour asleep
* You cannot make a diagnosis of OSAS unless there is
excessive daytime sleepiness present
TREATMENT OF OSAHS
• General (always give advice about life
style, sleep hygiene and weight loss if
BMI > 30)
• CPAP
• Mandibular splints (MRS)
• Surgery
• Drugs
CPAP
CPAP is cheap and effective : cost per QALY = £3200
Mandibular Repositioning Splint
MRS/CPAP EFFECTIVENESS
 CPAP
MRS 
Treatment use
***p<0.001
Acceptability
A+H/hr
***
Symptom score
***
-0.5
-0.25
0
0.25
0.5
Effect size (SD units)
Engleman.
0.75
AJRCCM 2002;166:855-9
SURGERY FOR OSAHS
•
No controlled trial evidence that palatal
surgery improves OSAHS
•
Controlled trial evidence that maxillomandibular advancement improves AHI
and vigilance to a similar extent as
CPAP
Conradt JSR 1998;7:217-23
Drugs for OSAS
• There are no drug treatments for the
primary treatment of OSAS
• Modafanil (a non amphetamine based
stimulant) may have a role in the
adjuvant treatment of OSAS if objective
sleepiness remains after good CPAP
compliance is demonstrated
Morbidity Associated With OSAS
• OSAS may contribute directly to a number
of co-morbidities
• These include:
– Increased rate of road traffic and
occupational accidents (Sleepiness)
– Neuropsychological impairment
– Metabolic Syndrome / Hypertension
– Cardiovascular / Cerebrovascular risk
Consequences of OSAS
Effect
Magnitude
(Odds Ratio)
Reference
Neurocognitive
Motor vehicle accidents 7
Occupational accidents
2.2
Cardiovascular
Overall
Teran-Santos (1999)
Hypertension
2.9
Marin (2005)
Coronary disease
1.3
Peppard (2000)
Stroke
1.6
Shahar (2001)
2.4
Shahar (2001)
Lindberg (2001)
What is the link between OSAS
and these conditions ?
Central Obesity
Types of Obesity
•
•
•
•
•
Central
“apple” shaped
Visceral obesity
Metabolically more
active brown fat
Increased waist-tohip girth ratio
WHR > 1.0
Increased collar size
> 17” (42.5 cm)
Peripheral
• “pear” shaped
• Less metabolically
active white fat
• Normal waist-to-hip
girth ratio
WHR < 1.0
Central Obesity
Why should central obesity
carry additional health risks?
• Associated with OSAS → recurrent transient hypoxic
episodes
• Increased leptin / TNF production
• Increased FFA production
• Reduction in peripheral insulin sensitivity
→ insulin resistance → diabetes mellitus
hyperlipidaemia
endothelial dysfunction
→ hypertension, atherosclerotic heart
disease
= METABOLIC SYNDROME
Metabolic Syndrome
Impaired glucose tolerance and / or insulin
resistance → hyperinsulinaemia
PLUS two or more of:
• Hypertension
• Elevated triglyceride and / or reduced HDL
cholesterol
• Visceral (central) obesity
• Microalbuminuria
Expert Panel of WHO (1998)
WHO Consultation , 1999: 31-33
Metabolic Syndrome
Other Associated Features
• Hyperuricaemia / gout
• Increased LDL cholesterol
• Fibrinolysis activation
(this suggests an inflammatory link)
Central Obesity and OSAHS
Vgontzas AN et al J Int Med 2003; 254: 32-44
Prospective study
Snoring is a risk factor for diabetes
in male general population
Incidence of new diabetics,
from 1984 to 1994, in four
sub-populations based on
combinations of habitual
snoring and obesity.
•Younger group, men aged 3049 years at baseline
•Older group, men aged 50-69
years at baseline.
independently of BMI and other
confounding factors
Elmasry et al. J Intern Med 2000; 248: 13-20
Obesity and OSAHS: a cumulative
risk for NIDDM
Obesity and DM
Visceral obesity ( WHR > 1.0)
and DM
RR=11.8
RR=5.7
RR=3.6
(n=150)
Elmasry et al, J Intern Med 2001; 249: 153-161
OSAHS / Metabolic Syndrome
and Mediators
 Untreated OSAS is associated with repeated episodes of
hypoxia
 Increased levels of
Leptin
IL-6
TNF
in OSAHS compared to age and BMI matched subjects
(14 OSA, 11 obese and 12 normal weight men)
 Plasma inflammatory cytokines follow a circadian rhythm
peak 01.00 - 02.00
Vgontzas AN et al J Clin Endocrinol Metab 2000: 85; 1151-58
Effect of CPAP treatment on
Inflammatory Mediators
CPAP Treatment and Leptin
• Leptin levels fall in OSAHS patients
following CPAP treatment
After 3 days
Chin et al Circulation 1999: 100: 706-12
After 6 months
Ip et al Chest 2000: 118;580-586
Comparison of serum leptin, insulin, and cortisol levels in OSAS patients
before and after 3 to 4 days of NCPAP treatment
Chin, K. et al. Circulation 1999;100:706-712
Copyright ©1999 American Heart Association
Reduced Mortality After
Treatment For OSAS
• Survival for OSAS
pts treated with
CPAP n=346)
( _ ) or nontreated (n=98)
(----)
• Hazard ratio after
treatment ~0.22
Marti. ERJ 2002;20 (6):1511-18
Summary
• Excessive daytime sleepiness (EDS) is
common
• OSAS is the commonest medical cause of
EDS and is a significant public health issue
• OSAS is associated with a wide variety of
common conditions causing significant
morbidity and mortality
• OSAS can be treated cheaply and
effectively