Respiratory JC016: A Fatigued And Sleepy Patient: Sleep And Breathing: Sleep Apnea

Question 1

Definition of sleep

Answer 1

Complex amalgam of physiological + behavioural process

2 physiological states:
1. Rapid eye movement (REM) sleep
2. Non-rapid eye movement (NREM) sleep
—> Characteristic brain wave activities

Question 2

NREM and REM

Answer 2

• Enter sleep in NREM
• NREM and REM alternate —> 1 cycle 90 mins

NREM:
- 3/4 of sleeping time
- **↓ mental activities
- actively regulatory
- **body movable

Further divided into 4 stages according to EEG waves:
- Stages 1 and 2 (Light sleep)
- Stages 3 and 4 (Deep sleep): Slow wave sleep

REM:
- 1/4 sleep time
- increase in later hours of sleep (2nd phase of sleep)
- **dreaming
- **inhibit brainstem + motor neurons —> body paralysed, flaccid

Question 3

Pattern of sleep

Answer 3

Factors affecting sleep patterns
- Age
- Prior sleep history (e.g. deprived of sleep —> REM rebound)
- Circadian rhythms
- Drug ingestion
- Pathological states

Question 4

Control of breathing during sleep

Answer 4

1. ***Respiratory centres
2. **Chemical (O2, CO2 level), **Mechanical (respiratory muscle), CNS information
3. ***Respiratory muscles (synchronised contraction)
   - upper airway muscles
   - diaphragm
   - others

Question 5

Sleep and Breathing

Answer 5

Sleep: ↓ Ventilation

NREM:
- ***↓ TV
- Similar rate

REM:
- **Unstable pattern
- **More shallow
—> If have lung disease —> even worse breathing pattern —> more hypoxaemia

In normal healthy lungs:
- Mild ↓ in blood O2 tension but still normal with no ↓ in SaO2
- Mild ↑ in blood CO2 tension but still normal

In diseased states e.g. COPD:
- Abnormal baseline —> worsen during sleep

Question 6

Contributors for ↓ Ventilation in sleep

Answer 6

1. ***↓ Muscle contraction from intercostal muscles (diaphragm relatively normal)
2. **↓ Chemosensitivity to O2, CO2 with **↓ Ventilatory response to hypoxia and hypercapnia
3. ***↓ Arousal response
4. Recumbency (***Supine) with ↓ in Functional residual capacity (FRC) (∵ Diaphragm move up)

Question 7

Primary sleep-related breathing disorders vs Respiratory diseases

Answer 7

Primary sleep-related breathing disorders:
- Breathing disorder occurs during sleep
- e.g. Sleep apnea

Respiratory diseases:
- Derangements in breathing pattern and gas exchange during sleep
- Changes in sleep pattern

Question 8

Case:

• 45 male
• chronic smoker, social drinker
• sedentary lifestyle
• excessive fatigue 1-2 years but never dozed off during work
• wife notes he dozes off on buses / watching TV
• drives only on weekends, never dozed off but need loud music to keep awake
• heavy snoring for years
• weight gain 5kg in past few years
• no other systemic symptoms
• BP borderline high

Answer 8

History:
1. Sleep history
- duration
- ***quality

2. Night time symptoms
   - ***sleep choking (sense of suffocation during sleep)
   - unusual body / limb movements
3. Daytime symptoms
   - **sleepiness / fatigue (esp. during passive activity)
   - assessment of sleepiness (subjective report using questionnaires in most daily settings, objective test too expensive)
   —> **Epworth sleepiness scale
   - “Do you think you will doze off in conditions where you should be keeping awake?”
4. Assess occupational / personal risks
   - ***driving
   - operation of mechanical devices
   - home accidents
5. Other diseases
   - ***hypertension
   - stroke
   - DM
6. Ask for medications

Physical examination
1. Body habitus: BMI, waist, neck circumference

2. Craniofacial + Oropharyngeal features
   - **chin structure (e.g. steep **thyromental plane)
   - **enlarged tonsils (e.g. adenoid, palatine tonsils esp. in children)
   - **uvula
3. BP, pulse
4. Others

Question 9

Common causes of Daytime sleepiness other than OSA

Answer 9

Daytime sleepiness: Cardinal symptom of OSA

Other causes:
- Insufficient sleep
- **Medications (e.g. opioids)
- Disturbance of sleep-wake cycle e.g. shift work
- **Central sleep apnea (mainly occur in people with certain disease)
- **Obesity hypoventilation syndrome
- Narcolepsy (cataplexy, sudden sleepiness)
- **Depression
- ***Fibromyalgia (Chronic fatigue syndrome)
- Idiopathic hypersomolence
- Periodic leg movement syndrome?
- Many medical conditions can cause “fatigue”

Question 10

History and Physical examination of OSA

Answer 10

History:
1. Sleep history
- duration
- ***quality

2. Night time symptoms
   - ***sleep choking (sense of suffocation during sleep)
   - unusual body / limb movements
3. Daytime symptoms
   - **sleepiness / fatigue (esp. during passive activity)
   - assessment of sleepiness (subjective report using questionnaires in most daily settings, objective test too expensive)
   —> **Epworth sleepiness scale
   - “Do you think you will doze off in conditions where you should be keeping awake?”
4. Assess occupational / personal risks
   - ***driving
   - operation of mechanical devices
   - home accidents
5. Other diseases
   - ***hypertension
   - stroke
   - DM
6. Ask for medications

Physical examination
1. Body habitus: BMI, waist, neck circumference

2. Craniofacial + Oropharyngeal features
   - **chin structure (e.g. steep **thyromental plane)
   - **enlarged tonsils (e.g. adenoid, palatine tonsils esp. in children)
   - **uvula
3. BP, pulse
4. Others

Question 11

Definitions of events

Answer 11

Apnea
- **complete cessation of airflow at nose and mouth lasting **>= 10 seconds

Hypopnea
- ↓ in airflow, usually needs O2 desaturation criteria (3-4% from baseline)
- ***>10 seconds per episode
- not complete closure of airway

**Apnea-Hypopnea index (AHI) / Respiratory disturbance index
- no. of apnoeic / hypopneic episodes per sleep hour
- normal: **<5 events per sleep hour (different for children / elderly) (some can be as severe as 100 episodes per hour)
- OSA: 5-15 times / hour (mild), 15-30 (moderate), >30 (severe) (from SC071)

Question 12

2 mains types of sleep apnea

Answer 12

1. Obstructive
2. Central

One person may have both
- e.g. HF, Stroke
- NOT called “mixed apnea” —> refers to third type of apneic event

Question 13

Obstructive Sleep Apnea

Answer 13

• Sleep-related breathing disorder
• Recurrent apneic / hypopneic episodes during sleep due to **Functional occlusion of upper airway
  —> otherwise **patent during daytime
• Apneic / hypopneic episodes will terminate eventually
• Wide range of severity
  —> classified by conventional measurement of Apnea-Hyponea index

Categorisation for need of treatment:
- **Symptoms e.g. Daytime sleepiness
- **Sleep parameters e.g. Oxygen desaturation

Question 14

***Mechanisms of obstruction

Answer 14

Anatomical + Non-anatomical factors

Non-anatomical factors:
1. **↓ Neuromuscular tone of upper airway during sleep
2. **Subatmospheric (negative) pressure in upper airway during inspiration (if airway more collapsible —> OSA)
3. Weight of soft tissue of neck

Anatomical abnormalities predisposing to functional obstruction:
1. **Micrognathia (small jaw)
2. **Enlarged tongue (falling back on supine posture)
3. ***Enlarged tonsils, adenoids (important factor in children)
4. Redundant pharyngeal tissue (fatty infiltration)

N.B. Acute infection / tumour can cause obstruction but not OSAS

Question 15

***Investigations: Polysomnography (Sleep study)

Answer 15

• Full vs Limited sleep study
• In-laboratory (usually full study) vs Home study
• Non-invasive with multiple belts / leads

Aim:
1. Confirm presence + Define nature (obstructive / central) of apnea / hypopnea
2. Relation to other physiologic disturbances
—> O2 saturation (Multiple repeated dips: ↓ and then ↑)
—> HR, rhythm (***Tachy-Brady cycle)
—> Sleep architecture (sleep stages)
—> Body position (some only have OSA in supine position)
3. Look for Leg movements

Signs:
1. **Flow: episodic no flow (abdominal, thoracic belt moving in **opposite direction: one expand, one contract)
2. **EEG: disturbance in waveform after apneic episode
3. **Arousals
4. **Sleep fragmentation
5. **Intrathoracic pressure swings (∵ upper airway opening and closing) —> may cause strain on heart as well (worsen LV function)
6. **Intermittent hypoxia —> followed by Hypoxia-reoxygenation
7. **↑ BP during apneic episodes

Question 16

Prevalence of OSA

Answer 16

• may occur in all age groups
• men > women
• ***sleepiness do NOT correlate well with numbers of events on sleep studies (i.e. Apnea-Hyponea index)

OSA syndrome (symptomatic OSA, usually defined as AHI >=5 / hour + Sleepiness):
- 4% men, 2% women
- but can be much higher if not take symptoms into consideration (many are asymptomatic)
- can be as high as 50% men with AHI >5
- updated prevalence expected to be much high due to obesity
- ***non-obese patients can have OSA!!! (esp. chinese ∵ unique cranio-facial features)

Question 17

Symptomatology of OSAS

Answer 17

1. ***Snoring
2. ***Excessive daytime sleepiness
3. Witnessed apneas
4. ***Nocturnal choking (subclinical arousal)
5. Restless sleep
6. Unrefreshing sleep, ***morning headache
7. Irritability, Intellectual deterioration, Poor concentration
8. Decreased libido
9. ***Enuresis / Nocturia

Question 18

Risk factors for OSAS

Answer 18

• OSA patients very heterogenous
• multifactorial, unknown determinants

Risk factors:
- **Obesity / central obesity (major risk factor)
- Receding / **Small chin
- Thick neck
- Other medical diseases (esp. obesity-related)
—> HT
—> DM
—> **Metabolic syndrome etc.
- Predisposing diseases
—> **Acromegaly (∵ enlarged tongue)
—> **Hypothyroidism (∵ ↑ soft tissue)
—> Conditions with fluid retention
- **Adenotonsillar enlargement (esp. in children)

Question 19

Co-morbidity / Consequences of OSA?

Answer 19

Consider:
1. Pathophysiology
2. Epidemiologic / Clinical associations, adjusting for confounding factors
3. Treat OSA —> look for improvement

Potential downstream pathophysiology:
Genetics / Non-genetics (diet, exercise, alcohol, smoking)
—> Fat
—> OSA
—> Intermittent hypoxia, Sleep fragmentation (—> Fat)
—> **Sympathetic activation + **Oxidative stress + ***Inflammation (e.g. adipocytokines)
—> Obesity, Insulin resistance, Glucose intolerance, Dyslipidaemia, NAFLD, Metabolic syndrome

Question 20

***Potential consequences of OSA

Answer 20

1. Excessive sleepiness
   - car accidents
   - other accidents
2. Neurocognitive impairment
   - irritability
   - poor concentration
3. Cardiometabolic diseases (suggested role in initiation / aggravation)
   - **HT
   - Atherosclerosis
   - Ventricular dysfunction
   - **HF
   - Arrhythmia: AF
   - ***DM
4. Chronic respiratory failure / Cor pulmonale
   - uncommon in OSA only
   - seen in ***Obesity-hypoventilation syndrome / presence of other condition e.g. COPD + OSA
   —> very hypoxaemic —> Cor pulmonale

Question 21

Aim of treatment of OSA

Answer 21

1. Control symptoms
2. Reduce long term sequelae
3. Evidence based medicine
   - evidence for long term clinical sequalae (e.g. HT)
   - effects of treatment of OSA on these outcome measures

Question 22

***Treatment of OSA

Answer 22

Consideration:
1. Which patients need treatment
2. Think about pathogenetic factors + pathophysiologic mechanisms
3. What treatment method can modify these pathogenetic factors / reverse pathophysiology

1. Lifestyle modifications
   - ***Weight reduction
   - Avoid alcohol / hypnotics
   - Sleep hygiene
   - Sleep posture
   - Avoid driving if not adequately treated
   - Others: treat Rhinitis, Acromegaly, care after sedation / anaesthesia
   - Must watch out for obesity-related conditions e.g. Metabolic syndrome, DM, HT
2. ***Nasal continuous positive airway pressure (nCPAP)
   - positive pressure through nasal mask during sleep
   - consistently effective but effects depends on compliance
3. Oral appliances
   - advance mandible —> “enlarge” upper airway, modifies muscle collapsibility
   - variable efficacy, usually not for severe OSA
4. Surgery
   - children: removal of hypertrophied tonsils / adenoids
   - adults: uvulopharyngoplasty, other faciomaxillary surgeries (for selected group, variable efficacy)
   - bariatric surgery for reducing obesity
5. Newer devices
   - neurostimulator for upper airway muscle
   - sleep positioner
6. Pharmacological? Targeting:
   - upper airway muscle tone
   - obesity
   - arousal threshold
   - hypersomnolence

Question 23

Obesity Hypoventilation Syndrome (OHS)

Answer 23

• Gross obesity
• Majority of OHS have severe OSA
• Hypoventilation evidenced by ***high daytime pCO2 —> sleepiness may be worsened by elevated blood levels of carbon dioxide, which causes drowsiness (“CO2 narcosis”)
• ***Chronic type 2 respiratory failure (may present as acute on chronic respiratory failure and CO2 narcosis)
• ***Cor pulmonale
• Excessive daytime sleepiness
• Respiratory failure respond well to treatment with nCPAP / Bi-level PAP (i.e. similar to non-invasive ventilatory support)

Question 24

Central Sleep Apnea

Answer 24

Defect in:
- Central control: **lack of respiratory drive
- Efferent limb: **no muscle contraction (e.g. Muscular dystrophy / NMJ problem: Myasthenia gravis)
—> resulting in lack of effort to breathe

Sign:
- **Lack of abdominal / thoracic belt movement in polysomnography
- **Cheynes Stokes Breathing (CSR) (~ HF / LV dysfunction)

Question 25

Cheynes Stokes Breathing

Answer 25

Characteristic form of breathing:
- ***wax and wane pattern
- may have central apnea at end of waning phase

• usually associated with HF / stroke
• CSR associated with worse prognosis in HF
• CSR likely caused by HF with circulatory slowing (may disappear if HF controlled)