Causes and Consequences of Respiratory Centre Depression and

Hypoventilation

Lou Irving Director Respiratory and Sleep Medicine, RMH

louis.irving@mh.org.au

Capacity of the Respiratory System

At rest During exercise supplies 250 ml / min O2 supplies > 4000 ml / min O2 removes 200 ml / min CO2 removes > 4000 ml / min CO2

Inadequate function causes 1. Hypoxaemia 2. Hypercapnoea and respiratory acidosis

Can sustain about 0.1 horse power

Glucose + O2 ® energy + H2O + CO2

Aerobic metabolism RQ = 0.8

Aerobic & anaerobic metabolism

Pyruvate ® Lactate + Energy RQ 1.2 -1.5

Functional Organization of the Respiratory System

Respiratory centre &

peripheral chemoreceptors Maintain blood

PaO2 » 100mHg

PaCO2 = 40mmHg

pH = 7.40

CONTROLLER

PUMP GAS EXCHANGER

Alveolar – capillary membrane Capacity VO2 & VCO2 > 4 L/min

Respiratory muscles, chest wall and airways Capacity VE > 100 L/min

Respiratory Control System

Central controller

Sensors Effectors

1. Chemoreceptors 2. Lung receptors 3. Other receptors

Respiratory muscles

1. Brain stem (pons and medulla) 2. Cortex

Central Controller

• Brainstem – neurones in medulla and pons – automatic rhythmic inspiratory stimuli, and sometimes expiratory stimuli – in-put from peripheral sensors – can be over-ridden by cortex – major output is to the phrenic nerves

• Cortex

– voluntary hyperventilation ® hypocapnoea – to a lesser extent, hypoventilation ® hypercapnoea

Sensors • Central chemoreceptors

– situated on ventral surface of medulla, surrounded by CSF – respond to CSF [H+] – CSF [H+] is a reflection of CO2 in cerebral capillaries – ­ PaCO2 ® ­ CSF [H+] ® ­ ventilation – do not respond to PaO2

• Peripheral chemoreceptors

– situated in carotid bodies at bifurcation of common carotid arteries in neck, and aortic bodies around arch of aorta

– rapid responses – respond to ¯ PaO2, ¯ pH, ­ PaCO2 ® ­ ventilation

• Lung and other receptors

– pulmonary stretch, irritant and J receptors – upper airway receptors, joint and muscle receptors, painful stimuli

Carbon dioxide tension

Ventilation

1.5l/min/mmHg

40 60 80

10

20

30

L/min

mmHg

Ventilatory Response to Carbon Dioxide

Small ­ in CO2 ® rapid ­ in ventilation

Significant individual variability

Large fall in PaO2 before any significant ­ in ventilation

Significant individual variability

Stimuli for Ventilation

• Increased metabolic activity

• VE matched to O2 consumption and CO2 production

VE

Metabolic activity Work

PaO2

PaCO2

pH

40 mmHg

7.40

> 80 mmHg

Other Stimuli for Ventilation

• Metabolic acidosis

• VE excessive for O2 consumption and CO2 production, and is aimed at correcting the acidosis

VE

Metabolic acidosis Acidosis

PaO2

PaCO2 < 40 mmHg

> 100 mmHg

pH returns to just below normal

Ventilatory Response to Exercise

• Ventilation increases with work to maintain PaO2 and PaCO2 at baseline. Beyond the anaerobic threshold, relative increase in VE because of extra H+ production from lactic acid

• VE matched to O2 consumption and CO2 and H+ production

VE

Work Work

PaO2

PaCO2

pH

33 mmHg

7.32

> 80 mmHg

Other Stimuli for Ventilation

• Anxiety

• VE excessive for O2 consumption and CO2 production. • Results in a respiratory alkalosis

VE

Anxiety Anxiety

PaO2

PaCO2 < 40 mmHg

> 100 mmHg

pH > 7.45

Hypoventilation

• Situation where rate of alveolar ventilation is not meeting metabolic requirements for oxygen consumption and carbon dioxide production

® ¯ PaO2 and ­ PaCO2

• If acute causes a respiratory acidosis

• If chronic, there is a compensatory metabolic alkalosis

Causes of Hypoventilation

• Reduced respiratory centre activity – Reduced drive (eg low CO2 or high pH) – Suppression of activity by drugs, trauma, vascular accidents etc

• Neuromuscular disease – nerve paralysis (drugs, polio, Guillian- Barre, trauma etc) – muscle weakness (drugs, motor neurone disease, muscular dystrophy)

• Chest wall deformity (gross) • Obesity (gross)

• Sleep disordered breathing

Sleep Disordered Breathing

1. Obstructive sleep apnoea

2. Central sleep apnoea 3. Obesity hypoventilation syndrome

Obstructive Sleep Apnoea (OSA)

• Transient obstruction of the throat during sleep preventing breathing, and disturbing sleep

• Occurs in people who snore (but not all snorers have OSA)

• Obstruction occurs during sleep because of : – Airway muscles relax (floppy throat - esp REM) – Throat already narrowed (obesity, tonsils etc) – Tongue falls backwards ( esp if supine)

OSA - Cycle of Events

1. Snoring in light sleep 2. Complete obstruction (apnoea) in deep sleep 3. Reduced blood O2, increased CO2, other stimuli 4. Brain “wakes” to lighter sleep (arousal) 5. Muscles contract, airways opens, breathing

recommences 6. Back into deep sleep, obstructs again……. Often more than 60 events every hour throughout sleep Very fragmented sleep ® sleep deprivation Bed partner often makes diagnosis

OSA – When to Suspect

1. Snoring 2. Witnessed apnoeas 3. Arousals 4. Choking 5. Symptoms of disturbed sleep

EDS, mood change, poor memory, ¯ libido 6. Difficult to treat hypertension, unexplained respiratory failure etc

OSA - Respiratory Signals from Polysomnogram

Apnoeas

Desaturation during apnoeas

Chest and abdominal wall movement showing paradoxical movement when upper airway obstruction

Arousals

EEG, EMG, ECG snoring and body position not shown

Management

• Nasal CPAP

• Others - mandibular advancement splint surgery lie on side

4-20 cm H2O pressure

85% compliance

for moderate + OSA

Other Forms of Sleep Disordered Breathing

• Less common than OSA

• Central sleep apnoea – several forms, eg Cheyne Stokes breathing – manage underlying heart failure etc +/- CPAP or BiPAP

• Obesity hypoventilation

– usually presents as ventilatory failure +/- right heart failure – “sensitive” to supplemental oxygen – manage with BiPAP and weight reduction (gastric banding)

• Hypoventilation associated with neuromuscular diseases

– Prolonged and improved life with non-invasive ventilatory support in selected cases

Consequences of Chronic Severe Sleep Apnoea

• “Sleep or die” • Hypoventilation during sleep with consequent re-setting of

the respiratory centre ® day-time hypoventilation

• This can also occur with other conditions, such as severe COPD, severe pulmonary fibrosis and neuromuscular disease in which there is less ventilation during sleep than when awake

• These patients develop chronic hypoxia, chronic hypercapnoea, and a compensated respiratory acidosis

Patients with Chronic Hypercapnoea

Are dependent on hypoxic drive (ie not stimulated by chronic hypercapnoea) What happens if give large amount of supplemental oxygen?

PaO2 = 56 mmHg, PaCO2 = 52 mmHg, pH = 7.36