FRACP Teaching 2014

Sleep For Exams

Abnormal sleep disordersAbnormal sleep disorders

DIMSDIMS (disorder of initiation and maintenance of (disorder of initiation and maintenance of sleep)sleep)

DOESDOES (disorders of excessive sleepiness) (disorders of excessive sleepiness) - not enough sleep - not enough sleep - OSA- OSA - Narcolepsy- Narcolepsy - PLMS/RLS- PLMS/RLS

ParasomniasParasomnias (Abnormal behavior during sleep) (Abnormal behavior during sleep) - NREM (sleep walking/ night terrors)- NREM (sleep walking/ night terrors) - REM (nightmares, REM sleep behavior disorders)- REM (nightmares, REM sleep behavior disorders)

Sleep Wake CycleSleep Wake Cycle

NREM NREM Relatively inactive yet Relatively inactive yet actively regulating brain in a actively regulating brain in a movablemovable body body

Stage 1(drowsiness)Stage 1(drowsiness) 5% 5% Slowing of alpha to thetaSlowing of alpha to theta Slow rolling eye movementsSlow rolling eye movements

Stage 2 (light sleepStage 2 (light sleep)) 50% 50% Sleep Spindles and K ComplexesSleep Spindles and K Complexes

Stage 3 and 4 (deepStage 3 and 4 (deep sleep) sleep) 20%20% Delta waves Delta waves

Sleep- Wake CycleSleep- Wake CycleWhat is normal ?What is normal ?

Sleep enters through NREM (slow wave sleep)

Alternates with REM about every 90 minutes

SWS in first 1/3 rd of night and REM in last 1/3rd

REM peaks in early hours of morning which coincides

with trough of body temperature

REM Sleep REM Sleep

REM sleepREM sleep : : Highly activated brain in a paralyzed Highly activated brain in a paralyzed bodybody

Saw tooth EEGSaw tooth EEG DreamingDreaming AtoniaAtonia Phasic events (irregularities in HR and respiration)Phasic events (irregularities in HR and respiration)

Hallmark:

Hypo-tonic, Hypo-ventilation, Hypo-tension

REM Sleep

Important neuro-transmittersImportant neuro-transmitters

NENE AchAch

WakingWaking

NREMNREM

Tonic REMTonic REM

Phasic REMPhasic REM

Respiratory Changes in REM sleepRespiratory Changes in REM sleep

Withdrawal of noradrenergic excitation on upper Withdrawal of noradrenergic excitation on upper airwaysairways

Suppression of activity of hypoglossal motor neuronsSuppression of activity of hypoglossal motor neurons

Reduced activity of geniohyoid and genoglossusReduced activity of geniohyoid and genoglossus - Increased upper airway resistance- Increased upper airway resistance

Atonia of intercostal musclesAtonia of intercostal muscles - paradoxical chest collapse during inspiration- paradoxical chest collapse during inspiration

Decreased diaphragmatic activityDecreased diaphragmatic activity

Changes in sleep with AGEChanges in sleep with AGE

SWS decreases with age after age 20--- biomarker ageing CNSSWS decreases with age after age 20--- biomarker ageing CNS REM constant after infancyREM constant after infancy WASO increases with ageWASO increases with age REM latency reduces with age (early onset REM)REM latency reduces with age (early onset REM)

Factors modifying sleep stages ct..Factors modifying sleep stages ct..

Recovery from sleep loss ( e.g. OSA started on CPAP)Recovery from sleep loss ( e.g. OSA started on CPAP)

11stst night SWS recovers night SWS recovers 22ndnd night REM recovers with REM rebound night REM recovers with REM rebound SOREMS if chronic sleep restriction (mimic narcolepsy)SOREMS if chronic sleep restriction (mimic narcolepsy)

Drugs and drug withdrawalsDrugs and drug withdrawals

Benzo’s suppress SWSBenzo’s suppress SWS TCA/MAOI’s suppress REM (withdrawal causes SOREMS)TCA/MAOI’s suppress REM (withdrawal causes SOREMS) Alcohol REM suppression followed by REM reboundAlcohol REM suppression followed by REM rebound Chronic THC – long term suppression of SWS (“ageing”)Chronic THC – long term suppression of SWS (“ageing”)

Sleep in OSASleep in OSAbefore and after CPAPbefore and after CPAP

Before:

Lots of SWS / Arousals

Minimal REM

2nd night of CPAP:

REM rebound

Patho-physiology of OSAPatho-physiology of OSA

What happens in OSAWhat happens in OSA

Narrowing of airways + Airway Collapse (Beronill’e Narrowing of airways + Airway Collapse (Beronill’e principle)principle)

Increased effortIncreased effort

Sympathetic outpouring (‘cause for most harm’)Sympathetic outpouring (‘cause for most harm’)

De-saturationsDe-saturations

ArousalArousal

Poor sleep (effort of breathing and arousals disturbs Poor sleep (effort of breathing and arousals disturbs sleep not the hypoxia )sleep not the hypoxia )

TerminologyTerminology

Obstructive sleep apnoea (OSA) AHI: Apnoea and hypopnoea per hour RDI: Respiratory disturbance index (AHI + RERA) 5-15 mild, 15-30 moderate, > 30 severe

Obstructive sleep apnoea syndrome (OSAS) OSA + Excessive somnolence and its squeal (Impaired concentration/ irritability, snoring with witnessed apnoea, nocturia)

Repetitive partial /complete closure of pharynx during sleep

Recurrent Arousals

Day time drowsiness…..

Recurrent nocturnal hypoxemia

Fragmented sleep

“Floppy airway”

Reduced neural output

Nocturnal sympathetic

surges

Who gets OSAS

Middle aged men (2-4% men and 1% women) Overweight Snorers Collar size > 43 cm Craniofacial abnormalities, retrognathia. Large tonsils (large adenoids in chidhood) Hypothyroidism Alcohol…..

Neuromuscular disease Rare: Acromegaly, Cushing's syndrome, Down's

syndrome.

Consequences of OSA

Excessive sleepiness - QOL, cognition, accidents Loud snoring, witnessed apnoea and chocking Feeling un-refreshed waking Poor concentration/ irritability/ depression Nocturia Reduced libido Hypertension ? Cardiovascular disease ? Metabolic syndrome

Signs in OSASigns in OSA

Sleepiness ( Epworth sleepiness score)Sleepiness ( Epworth sleepiness score)

ObesityObesity

Crowed Pharynx (Malapatti Score)Crowed Pharynx (Malapatti Score)

ReterognathiaReterognathia

Congested noseCongested nose

HypertensionHypertension

Epworth sleepiness Score

Best available tool to guide clinicians to patient

perception of sleepiness

Predicts level of compliance with CPAP

Guides to urgency of assessment

Thorax 2011; 66(2):97-100

Normal < 11

Mild 11- 14

Moderate 15-18

Severe > 18

Treatment options

Improve upper airway: Weight reduction, tonsillar surgery, Bariatic surgery

CPAP: acts as a pneumatic splint (Compliance !!!)

Dental devices (‘MAD’): As good as CPAP in mild-moderate OSA, better tolerated

Surgery: UPPP, RF tissue reduction, Tracheotomy

Others: Avoid alcohol, sleep on side (‘tennis balls’, postural

alarm, special pillows)

Adherence to CPAP

Adherences during the first week…

Severity of OSA (a weak relationship)

Degree of day time sleepiness (strong relationship)

Level of education….

Psychological traits: optimism, motivation to engage in

healthy behaviour ( ‘healthy user effect’)

Non-compliance: use < 4 hours a night (30% - 80%)

What about OSA, CPAP and The heart ?

Association of OSA with Hypertension

JAMA:2012;307:2169

37% developed HT at 12 years Dose response effect

Is CPAP useful in Hypertension ?.....Yes

BUT….. Reduction in mean BP is only small (- 2.5mm vs. + 0.8mm) at 4 weeks

Greater decrease among severe OSA (- 3.3mm)

Reduction in BP less than with anti-hypertensive (Lorstatan vs. CPAP: -9mm vs. -2.1mm)

Reduction in BP is less in non-sleepy than in sleepy patients

Lancet 2002:359;204

AJRCCM 2010:182:954

SBP reduced by -1.8 mm at 1 year DBP reduced by – 2.1mm

Effects of CPAP in HT with non-sleepy OSA

CPAP more useful in reducing BP in sleepy than in non- sleepy OSA

In most studies patients who did not have excessive day

time drowsiness had NO reduction in the BP with CPAP

In sleepy patients benefits with CPAP seen even within 4

weeks of treatment, whereas non-sleepy patients need

CPAP for longer to achieve a smaller reduction in BP

OSA and Coronary heart disease:The Sleep Heart Health study:

10 years follow up

Circulation 2010:122:352-360

1927 males 2495 females

OSA was predictor of incident CHD only in men, BUT after adjustment for diabetes, lipids, hypertension and anti-hypertensive medication use, the association was not statistically significant in any group.

OSA and CHD

Association of OSA with incident CHD (Myocardial infarction, re-vascularisation

and coronary heart disease death) is equivocal

OSA and cardiovascular events:Observational 10 years study in 1651

men

Lancet 2005: 365;1046-53

Stroke, MI, re-vascularisation, CABG

? Independent risk factor

? Just an association

Therapeutic CPAP itself reduces adiposity

OSA and Cardiovascular disease

CPAP in severe OSA may reduce cardiovascular events BUT…

No RCT that prove that CPAP improves mortality

No clinical trials to support routine use of CPAP in OSA for sole purpose of reducing cardiovascular events

‘Healthy User effect’ could effect outcomes in studies

Chest 2010; Study of the healthy user effect in OSA

OSA and Heart failure:The Sleep Heart Health study:

10 years follow up

Circulation 2010:122:352-360

1927 males 2495 females

OSA predicted incident heart failure in men but not in women

Does CPAP improve heart function ?

All had AHI > 15 and day time drowsiness (ESS >11)

All had excessive day time drowsiness (ESS > 11)

No control group---- diet, exercise, changes in medications and medication adherence could be effected by close monitoring in the study

Natural history of CMRI in OSA is not known

CPAP adherence was 100% ( 52/52) ( “Healthy user effect”)

Does CPAP improve heart function ?

OSA and arrhythmia

Recurrence of AF (at 1 year) after cardio version

Non OSA patients------- 52 % recurrence Untreated OSA------ 82% Treated with CPAP---- 42%

CPAP most useful for abolishing nocturnal ventricular asystole and bradycardia ( ? effect on mortality)

If observed nocturnal arrhythmia– think OSA !!

OSA and Pulmonary HT Risk only if co-existent day time hypoxemia (i.e.

associated chronic lung disease)

Treatment with CPAP causes only very modest reduction in PASP (from 29 mm to 24mm)

Eur Heart J 2006:27:1106

Evidence of improved mortality is lacking

Pulmonary HT alone is NOT an indication for diagnostic evaluation of OSA

Benefits of CPAP in OSAThe evidence !!

Decreased day time sleepiness Improved quality of life Improves cognitive function Improves resistant

hypertension Improves heart function in heart

failure

Reduces cardiovascular events Improves metabolic

abnormalities Reduces mortality

?????

With regards to Cheyne –Stokes respirationWith regards to Cheyne –Stokes respiration

Can occur at sleep onset in 40-80% normal subjectsCan occur at sleep onset in 40-80% normal subjects(Set point of ventilation different in sleep vs. wakefulness)(Set point of ventilation different in sleep vs. wakefulness)

Can be seen in cerebro-vascular disease and heart Can be seen in cerebro-vascular disease and heart failurefailure

(enhanced ventilatory response to C02)(enhanced ventilatory response to C02)

Increased circulation time not importantIncreased circulation time not important

Is not always improved with cardiac transplant and Is not always improved with cardiac transplant and normalization of cardiac functionnormalization of cardiac function

A 54 year old morbidly obese man was referred to the Sleep A 54 year old morbidly obese man was referred to the Sleep Disorders Clinic because of hypersomnolence and suspicion of Disorders Clinic because of hypersomnolence and suspicion of obstructive sleep apnea. He complained of habitual loud and obstructive sleep apnea. He complained of habitual loud and disruptive snoring, frequent nocturnal choking episodes and disruptive snoring, frequent nocturnal choking episodes and witnessed apneas for the past 8 years. He had gained witnessed apneas for the past 8 years. He had gained approximately 45 kg in the last 10 years. The Epworth Sleepiness approximately 45 kg in the last 10 years. The Epworth Sleepiness Score was 16/24. Score was 16/24.

Past medical history: hypertension and type 2 diabetes. Past medical history: hypertension and type 2 diabetes.

Medications include metformin, hydrochlorothiazide and lisinopril Medications include metformin, hydrochlorothiazide and lisinopril 40 mg daily. 40 mg daily.

BMI of 45.4 kg/m2. Oral examination demonstrated Mallampati BMI of 45.4 kg/m2. Oral examination demonstrated Mallampati class 4 airway. The neck circumference was 51 cm. Room air class 4 airway. The neck circumference was 51 cm. Room air pulse oximetry was 91% while sitting and resting. pulse oximetry was 91% while sitting and resting.

Lab: Serum bicarbonate noted to be elevated at 36 meqLab: Serum bicarbonate noted to be elevated at 36 meq

Which of the following features has been shown Which of the following features has been shown to be predictive of obesity hypoventilation to be predictive of obesity hypoventilation

syndrome (OHS)?syndrome (OHS)? A.BMI>35 kg/m A.BMI>35 kg/m

B. Peripheral edema B. Peripheral edema

C. Neck circumference of 51 cm C. Neck circumference of 51 cm

D. Mallampati class IV airway D. Mallampati class IV airway

E. Serum bicarbonate above the upper limits of E. Serum bicarbonate above the upper limits of normalnormal

Hypercapnic OSA = OHS

Which is the most appropriate next step in the Which is the most appropriate next step in the care of this patient? care of this patient?

A. Nocturnal home oxygen evaluation A. Nocturnal home oxygen evaluation

B. Tracheostomy B. Tracheostomy

C. Polysomnogram with titration of bi-level C. Polysomnogram with titration of bi-level positive airway pressure only positive airway pressure only

D. Polysomnogram with titration of continuous D. Polysomnogram with titration of continuous positive airway pressure, followed by bi-level positive airway pressure, followed by bi-level positive airway pressure, if necessary positive airway pressure, if necessary

E. Gastric bypass surgery E. Gastric bypass surgery

All of the following would also be part of an All of the following would also be part of an appropriate workup in this patient appropriate workup in this patient exceptexcept::

A. Pulmonary function tests A. Pulmonary function tests

B. Complete blood count B. Complete blood count

C. Chest imaging C. Chest imaging

D. Multiple sleep latency test D. Multiple sleep latency test

E. Thyroid stimulating hormoneE. Thyroid stimulating hormone

CPAP treatment is initiated for a patient. She CPAP treatment is initiated for a patient. She returns 1 month after starting treatment but returns 1 month after starting treatment but complains of continued daytime sleepiness. complains of continued daytime sleepiness.

Which of the following initial data would be most Which of the following initial data would be most helpful for determining the next step in her helpful for determining the next step in her

management? management? AA. Repeat MSLT after a PSG on CPAP. Repeat MSLT after a PSG on CPAP

B. Maintenance of wakefulness test B. Maintenance of wakefulness test

C .Sleep log C .Sleep log

D. Compliance report D. Compliance report

E. Repeat CPAP titrationE. Repeat CPAP titration

Which of the following symptoms, if present, Which of the following symptoms, if present, would be most indicative of narcolepsy? would be most indicative of narcolepsy?

AA. Hypnagogic hallucinations . Hypnagogic hallucinations

B. Cataplexy B. Cataplexy

C. Sleep paralysis C. Sleep paralysis

D. Automatic behaviors D. Automatic behaviors

E. Hypnopompic hallucinationsE. Hypnopompic hallucinations

NarcolepsyNarcolepsy

REM intrusions during wakefulness REM intrusions during wakefulness

20-40 times greater risk of family history20-40 times greater risk of family history

10-20% concordances in identical twins10-20% concordances in identical twins

100% have HLADQB1.0602 (but so do 10-20% of 100% have HLADQB1.0602 (but so do 10-20% of normal population)normal population)

Age of onset 60% 11-20 years, 25% 20-40 yearsAge of onset 60% 11-20 years, 25% 20-40 years

Narcolepsy- diagnosisNarcolepsy- diagnosis REM latency of < 8 minutes with 2 REM onset nap REM latency of < 8 minutes with 2 REM onset nap (SOREM’s)(SOREM’s)

Diagnosis by Multiple Sleep latency Test (MSLT)Diagnosis by Multiple Sleep latency Test (MSLT)

Excessive day time drowsiness: 100% (MWT) Excessive day time drowsiness: 100% (MWT)

Cataplexy 70%Cataplexy 70%

Sleep paralysis 25%Sleep paralysis 25%

Hypnogognic and hypnapompic hallucinations 30%Hypnogognic and hypnapompic hallucinations 30%

Multiple Sleep latency Test (MSLT)Multiple Sleep latency Test (MSLT)

MSLT is test for narcolepsyMSLT is test for narcolepsy

Four or five, twenty minute nap opportunities Four or five, twenty minute nap opportunities that are scheduled about two hours apart. that are scheduled about two hours apart.

Positive if mean REM latency of < 8 minutes with Positive if mean REM latency of < 8 minutes with 2 REM onset naps (but just presence of SOREM is 2 REM onset naps (but just presence of SOREM is not diagnostic of narcolepsynot diagnostic of narcolepsy

Test negative if patient cannot sleep Test negative if patient cannot sleep

Maintenance of Wakefulness test (MWT)Maintenance of Wakefulness test (MWT)

To determine if a patient is able to stay awake during To determine if a patient is able to stay awake during soporific conditions.soporific conditions.

To access airline pilots and commercial drivers, To access airline pilots and commercial drivers, narcolepsynarcolepsy

Four sleep trials with breaks lasting for two hours in Four sleep trials with breaks lasting for two hours in between them. You are not allowed to do other things to between them. You are not allowed to do other things to try and keep yourself awake.try and keep yourself awake.

If you fall asleep, then you will be awakened after If you fall asleep, then you will be awakened after sleeping for only about 90 seconds. The test ends if sleeping for only about 90 seconds. The test ends if cannot fall asleep within 40 minutes cannot fall asleep within 40 minutes

97.5% of normal sleepers stay awake for > 8 minutes97.5% of normal sleepers stay awake for > 8 minutes

Falling asleep in < 8 minutes is considered abnormal.Falling asleep in < 8 minutes is considered abnormal.

RBDRBD(REM behavior Disorder)(REM behavior Disorder)

Is associated with lewy body dementiaIs associated with lewy body dementia

Is more prevalent in the elderlyIs more prevalent in the elderly

Is frequently unreported by patientsIs frequently unreported by patients

Is not associated with Shy-Drager syndromeIs not associated with Shy-Drager syndrome

Restless Leg Syndrome (RLS)Restless Leg Syndrome (RLS)

Desire to move legs when sleepy (‘parasthesia’)Desire to move legs when sleepy (‘parasthesia’)

Worst at rest better with activityWorst at rest better with activity

PLMS in repetitive flexion of legs 0.5 to 5 seconds PLMS in repetitive flexion of legs 0.5 to 5 seconds in duration every 20-40 secondsin duration every 20-40 seconds

PLMS is the PSG finding in RLSPLMS is the PSG finding in RLS

80% of RLS have PLMS, 50% of patients with PLMS 80% of RLS have PLMS, 50% of patients with PLMS have RLShave RLS

Epidemiology of RLSEpidemiology of RLS

Most common movement disorderMost common movement disorder

Peak of about 30% in age 50-59 yearsPeak of about 30% in age 50-59 years

15% at age 80 (does not increase linearly 15% at age 80 (does not increase linearly with age)with age)

Twice more common in womenTwice more common in women

Associations Associations

Iron deficiencyIron deficiency From any causeFrom any cause More common in repeat blood donors More common in repeat blood donors

ESRFESRF 15 to 40%15 to 40% ? Due to anemia (EPO helps)? Due to anemia (EPO helps) ? Due to peripheral neuropathy? Due to peripheral neuropathy (improves with dialysis)(improves with dialysis)

OthersOthers Fibromyalgia, Diabetes, drugs (SSRI’s, TCA)Fibromyalgia, Diabetes, drugs (SSRI’s, TCA)

Treatment of RLSTreatment of RLS

L - dopaL - dopa

Efficacy good BUTEfficacy good BUT

2 major side effects2 major side effects

Morning reboundMorning rebound

Augmentation (in 81% )Augmentation (in 81% )- shifting of symptoms earlier during the dayshifting of symptoms earlier during the day- Symptoms affecting previously unaffected partsSymptoms affecting previously unaffected parts

Dopaminergic agonists (ergot derivatives)Dopaminergic agonists (ergot derivatives) All have SE of nausea and postural hypotensionAll have SE of nausea and postural hypotension

Bromocryptine (D2 receptor agonist)Bromocryptine (D2 receptor agonist) Half life 3 to 8 hoursHalf life 3 to 8 hours

PergolidePergolide ( D2 receptor agonist)( D2 receptor agonist) Half life 7-16 hoursHalf life 7-16 hours

Carbegoline:Carbegoline: Half life 65 hoursHalf life 65 hours

Dopaminergic agonists (Non Ergot derivatives)Dopaminergic agonists (Non Ergot derivatives) Less Side effects of nausea, postural Less Side effects of nausea, postural

hypotensionhypotension

Pramipexole( D3 receptor agonist)Pramipexole( D3 receptor agonist) Long term efficacy NOT decreased even after Long term efficacy NOT decreased even after

7.8 months7.8 months Sustained efficacy of > 90% with Sustained efficacy of > 90% with

augmentation in only 30%.augmentation in only 30%.

RopiniroleRopinirole