Medicine – Respiratory Failure

Respiratory failure occurs when the respiratory system is unable to maintain adequate gas exchange. This results in inadequate arterial oxygenation, abnormal carbon dioxide elimination, or both.

Respiratory failure is traditionally divided into Type I (hypoxaemic) respiratory failure and Type II (hypercapnic or ventilatory) respiratory failure.

1. Type I Respiratory Failure

Type I respiratory failure is primarily a failure of oxygenation.

It is characterised by significant hypoxaemia with a normal or low arterial carbon dioxide level.

Definition

The traditional arterial blood gas definition is:

PaO₂ <8 kPa (60 mmHg)

with

PaCO₂ normal or low.

Therefore, the main abnormality is a fall in arterial oxygen rather than carbon dioxide retention.

Pathophysiology

Type I respiratory failure commonly results from ventilation–perfusion (V/Q) mismatch.

This means that some areas of the lung receive adequate blood flow but insufficient ventilation, so blood leaving these regions remains poorly oxygenated.

However, V/Q mismatch is not the only mechanism. Type I respiratory failure can also result from intrapulmonary shunting, diffusion impairment, and severe abnormalities of the alveolar–capillary membrane.

Why PaCO₂ Is Usually Normal or Low

Patients with hypoxaemia frequently respond by increasing their respiratory rate and ventilation.

Carbon dioxide diffuses across the alveolar membrane more readily than oxygen and can therefore often still be eliminated effectively.

As a result, PaCO₂ commonly remains normal or becomes reduced because of hyperventilation.

Causes of Type I Respiratory Failure

2. Severe Acute Asthma – Early Stage

During the earlier stages of a severe acute asthma attack, marked airway obstruction causes V/Q mismatch and hypoxaemia.

The patient responds by hyperventilating, so the PaCO₂ is usually low.

A very important clinical point is that a normal or rising PaCO₂ in severe acute asthma is dangerous, because it may indicate respiratory muscle fatigue and progression toward ventilatory failure.

3. Emphysema

Patients with predominantly emphysematous COPD may initially develop hypoxaemia while maintaining sufficient ventilation to prevent significant carbon dioxide retention.

This corresponds to the historical “pink puffer” pattern.

As COPD becomes advanced, however, some patients can develop hypercapnia and therefore progress to Type II respiratory failure.

4. Pneumonia

Pneumonia can produce Type I respiratory failure because infected alveoli become filled with inflammatory exudate.

These alveoli may continue to receive blood but are poorly ventilated, producing severe V/Q mismatch and intrapulmonary shunting.

The result is hypoxaemia, which can become profound in extensive pneumonia.

5. Pulmonary Embolism

A pulmonary embolism (PE) disrupts pulmonary blood flow and produces major abnormalities in ventilation–perfusion matching.

Patients often hyperventilate in response to hypoxaemia and physiological stress.

Consequently, a typical blood gas pattern is low PaO₂ with low PaCO₂, although blood gases vary and cannot by themselves diagnose or exclude PE.

6. Pulmonary Oedema

Pulmonary oedema causes accumulation of fluid within the pulmonary interstitium and alveoli.

This interferes with oxygen transfer and produces V/Q mismatch and shunting.

Acute pulmonary oedema can therefore cause significant Type I hypoxaemic respiratory failure.

7. Interstitial Lung Disease

Interstitial lung disease (ILD) causes thickening and fibrosis of the alveolar–capillary interface.

This impairs oxygen diffusion and may also produce V/Q abnormalities.

Hypoxaemia is often particularly noticeable during exercise, when blood passes through the pulmonary capillaries more rapidly and there is less time available for oxygen equilibration.

Advanced ILD can eventually cause severe resting hypoxaemia.

8. Type II Respiratory Failure

Type II respiratory failure is primarily a failure of alveolar ventilation.

The lungs cannot eliminate carbon dioxide adequately, resulting in hypercapnia together with hypoxaemia.

It is therefore also called hypercapnic respiratory failure or ventilatory failure.

Definition

Traditionally, Type II respiratory failure is characterised by:

PaO₂ <8 kPa (60 mmHg)

and

PaCO₂ >6.0–6.7 kPa (45–50 mmHg), depending on the definition being used.

The older notes use PaCO₂ >6.7 kPa, which represents definite hypercapnia.

Pathophysiology

The fundamental problem in Type II respiratory failure is inadequate alveolar ventilation.

When ventilation is insufficient, the body cannot eliminate the carbon dioxide generated by metabolism.

Therefore:

↓ Alveolar ventilation → ↑ PaCO₂ + ↓ PaO₂

This can result from severe lung disease, abnormalities of the chest wall, neuromuscular weakness, or suppression of the brain’s respiratory drive.

Respiratory Causes of Type II Respiratory Failure

9. COPD

COPD is one of the most important causes of Type II respiratory failure.

Severe airflow obstruction, V/Q mismatch, respiratory muscle loading, and inadequate alveolar ventilation can eventually cause CO₂ retention.

Some patients with advanced COPD develop chronic hypercapnia, while others develop Type II respiratory failure mainly during acute exacerbations.

10. Severe Asthma

Very severe asthma can progress from an initial Type I pattern to Type II respiratory failure.

Initially:

Hyperventilation → low PaCO₂

As respiratory muscles fatigue:

Ventilation falls → PaCO₂ becomes normal

With further deterioration:

PaCO₂ rises → Type II respiratory failure

Therefore, a rising carbon dioxide level in severe asthma is a major warning sign of impending respiratory failure.

11. Bronchiectasis

Advanced bronchiectasis can cause chronic airflow obstruction, extensive V/Q mismatch, and impaired alveolar ventilation.

Patients with severe disease may eventually develop hypoxaemia and hypercapnia, particularly during infective exacerbations.

Thoracic Cage Causes

12. Kyphoscoliosis

Severe kyphoscoliosis restricts expansion of the chest wall.

This produces a restrictive ventilatory defect and can substantially reduce alveolar ventilation.

Advanced disease may therefore cause chronic Type II respiratory failure.

13. Ankylosing Spondylitis

Severe ankylosing spondylitis may restrict movement of the thoracic cage because of involvement and fusion of spinal and costovertebral structures.

When sufficiently advanced, this restriction can contribute to alveolar hypoventilation and hypercapnic respiratory failure.

14. Chest Trauma and Surgery

Severe chest trauma can interfere with effective ventilation because of pain, rib fractures, flail chest, or mechanical disruption of chest-wall movement.

Following major thoracic or abdominal surgery, pain, sedation, and impaired respiratory mechanics can similarly produce hypoventilation.

If ventilation becomes inadequate, PaCO₂ rises and Type II respiratory failure can develop.

Neuromuscular Causes

15. Muscular Dystrophy

Muscular dystrophies can progressively weaken the diaphragm and other respiratory muscles.

As respiratory muscle strength declines, patients become unable to generate sufficient ventilation, particularly during sleep and eventually while awake.

This can produce chronic hypercapnic respiratory failure.

16. Guillain–Barré Syndrome

Guillain–Barré syndrome can cause rapidly progressive respiratory muscle weakness.

Severe weakness of the diaphragm and accessory respiratory muscles may result in inadequate ventilation and acute Type II respiratory failure.

Respiratory function therefore requires close monitoring in patients with significant Guillain–Barré syndrome.

17. Myasthenia Gravis

Severe myasthenia gravis, particularly during a myasthenic crisis, can weaken the respiratory muscles.

Progressive respiratory muscle fatigue may eventually cause alveolar hypoventilation, CO₂ retention, and respiratory failure.

Drug Causes

18. Opioids

Opioids can suppress the respiratory centres within the brainstem.

Respiratory rate and tidal volume decrease, causing reduced alveolar ventilation.

The characteristic sequence is:

Respiratory depression → hypoventilation → CO₂ retention → hypoxaemia

Severe opioid toxicity can therefore cause acute Type II respiratory failure.

19. Benzodiazepines

Benzodiazepines can also depress central nervous system activity and contribute to respiratory depression.

The risk is particularly important when benzodiazepines are combined with opioids, alcohol, or other sedative drugs, or when used in patients who already have significant respiratory disease.

20. Type I Respiratory Failure – Note Form

Main problem: failure of oxygenation.

PaO₂: <8 kPa.

PaCO₂: normal or low.

Main mechanism: usually V/Q mismatch, although shunting and diffusion impairment may also contribute.

Ventilation: generally preserved or increased.

Typical causes: pneumonia, pulmonary embolism, pulmonary oedema, interstitial lung disease, early severe asthma, and some patients with emphysema.

Asthma: early severe attacks usually produce hypoxaemia with a low PaCO₂ because the patient hyperventilates.

21. Type II Respiratory Failure – Note Form

Main problem: failure of alveolar ventilation.

PaO₂: reduced.

PaCO₂: raised, traditionally >6.0–6.7 kPa.

Main mechanism: inadequate alveolar ventilation causes CO₂ retention.

Respiratory causes: COPD, very severe asthma, and advanced bronchiectasis.

Thoracic cage causes: kyphoscoliosis, severe ankylosing spondylitis, and major chest trauma or surgery.

Neuromuscular causes: muscular dystrophy, Guillain–Barré syndrome, and myasthenia gravis.

Drug causes: opioids and sedative drugs such as benzodiazepines.

22. Acute vs Chronic Type II Respiratory Failure

The pH and bicarbonate concentration help determine whether hypercapnic respiratory failure is acute or chronic.

In acute Type II respiratory failure, PaCO₂ rises rapidly and there has been little time for renal compensation. The patient therefore develops respiratory acidosis with a reduced pH.

In chronic Type II respiratory failure, the kidneys retain bicarbonate to compensate for persistent CO₂ retention. Therefore, the bicarbonate is elevated and the pH may be relatively close to normal despite a high PaCO₂.

This distinction is particularly important in patients with advanced COPD.

Key Clinical Pattern

Type I respiratory failure = oxygenation failure.

↓ PaO₂ + normal/↓ PaCO₂

Think particularly of pneumonia, PE, pulmonary oedema, ILD, and early severe asthma.

Type II respiratory failure = ventilation failure.

↓ PaO₂ + ↑ PaCO₂

Think of COPD, very severe asthma, severe bronchiectasis, chest-wall restriction, neuromuscular weakness, and respiratory-depressant drugs.

A particularly important examination point is the change in PaCO₂ during severe asthma:

Early severe asthma → hyperventilation → ↓ PaCO₂

Deterioration/fatigue → PaCO₂ becomes normal

Respiratory muscle failure → ↑ PaCO₂ → Type II respiratory failure

Therefore, a normal or rising PaCO₂ in a patient with severe acute asthma is an ominous sign rather than evidence of improvement.