Overview
Hypoxia is defined as inadequate oxygen delivery to tissues to meet metabolic demands.
Hypoxaemia is a low arterial oxygen concentration (low PaO2). It is one of the causes of hypoxia.
- Signs and symptoms
- Dyspnoea
- Tachypnoea
- Tachycardia
- Restlessness and anxiety
- Combativeness
- Headache
- Confusion
- Cyanosis
- Altered mental status
- Coma
- Investigations
- Pulse oximetry
- SpO2 ≤ 95% is abnormal
- SpO2 < 90% usually requires oxygen
- Arterial blood gas to determine hypoxaemia, hypercapnia, and acid-base disturbance
- Chest X-ray
- CT pulmonary angiography for pulmonary embolism
- V/Q scan if CTPA is contraindicated
- Pulmonary function tests for COPD, asthma and interstitial lung disease
- Exercise testing
- Pulse oximetry
- Treatment
- Oxygen supplementation
- Treat the underlying cause
- Long-term oxygen therapy (LTOT) may be needed if PaO2 ≤ 55 mmHg and SpO2 ≤ 88% or if PaO2 is 55 – 59 mmHg with cor pulmonale, polycythaemia, and right heart failure
A-a Gradient
The A-a gradient measures the difference between oxygen concentration in the alveoli (PAO2) and arterial blood (PaO2). It is used to determine why a patient is hypoxaemic.
A-a gradient = PAO2 – PaO2.
The alveolar gas equation is used to calculate the PAO2. FiO2 = inspired oxygen fraction. At room air it is 0.21. 760 mmHg = atmospheric pressure at sea level. 47 mmHg = water vapour pressure. 0.8 = respiratory quotient
Normal vs increased A-a gradient
| A-a gradient | Description | Summary of causes |
|---|---|---|
| Normal A-a gradient | The lungs are transferring oxygen normally. The problem is before oxygen reaches the alveoli | Low inspired oxygen and hypoventilation |
| Increased A-a gradient | The alveoli contain oxygen, but oxygen does not reach arterial blood effectively. It is a problem of the alveolar-capillary membrane or pulmonary circulation | V/Q mismatch, diffusion limitation, right-to-left shunt |
Causes of hypoxaemia with normal A-a gradient
| Category | Causes |
|---|---|
| Low inspired oxygen | High altitude and low FiO2 |
| Hypoventilation | Opioids, sedatives, CNS depression, neuromuscular disease, obesity, massive ascites, hypoventilation, and COPD with hypoventilation |
Causes of hypoxaemia with increased A-a gradient
| Category | Causes |
|---|---|
| Low ventilation-perfusion (V/Q) ratio | Pneumonia, pulmonary oedema, COPD, asthma, and atelectasis |
| High ventilation-perfusion (V/Q) ratio | Pulmonary embolism and emphysema |
| Diffusion limitation | Interstitial lung disease, pulmonary fibrosis, and pulmonary oedema |
| Anatomical right-to-left shunts | Congenital heart defects (ASD/VSD) and pulmonary arteriovenous malformations |
| Physiological right-to-left shunts | ARDS, severe pneumonia, and complete atelectasis |
Oxygen response in cases of hypoxaemia
| Cause | A–a Gradient | Response to 100% Oxygen |
|---|---|---|
| Low inspired oxygen | Normal | Improves |
| Hypoventilation | Normal | Improves |
| V/Q mismatch | Increased | Improves |
| Diffusion defect | Increased | Improves |
| Right-to-left shunt | Increased | Little or no improvement |
PaO2/FiO2 Ratio (P/F Ratio)
The PaO2/FiO2 (P/F) ratio is used to measure how oxygen is transferred from the alveoli into the arterial blood. It is commonly used in the ICU for ARDS since it is one of the best indicators of oxygen impairment.
The P/F ratio is used since PaO2 alone is misleading, as it depends on the amount of oxygen the patient is receiving.
PaO2 = arterial oxygen tension (mmHg) from an ABG. FiO2 = fraction of inspired oxygen as a decimal
Normal P/F values
| P/F Ratio | Interpretation |
|---|---|
| 400–500 | Normal oxygenation |
| 300–400 | Mild impairment |
| 200–300 | Moderate impairment |
| <200 | Severe hypoxaemia |
| <100 | Very severe hypoxaemia |
Berlin definition of ARDS (with PEEP/CPAP ≥ 5cm H2O)
| Severity | P/F Ratio |
|---|---|
| Mild ARDS | 201–300 |
| Moderate ARDS | 101–200 |
| Severe ARDS | ≤100 |
Additional criteria
- Acute onset (within 1 week of an inciting event)
- Bilateral pulmonary infiltrates on imaging
- Respiratory failure not fully explainable by cardiac failure or fluid overload
Oxygen Devices
The rule of thumb is that each 1L/min increases FiO2 by approximately 4% above room air
FiO₂ (%) ≈ 21 + (4 × oxygen flow in L/min)
Oxygen devices
| Device | Flow rate | FiO2 |
|---|---|---|
| Nasal Cannula | 1 – 6 L/min | 25 – 45% |
| Face mask | 5 – 10 L/min | 35 – 50% |
| Non-rebreather Mask | 10 – 15 L/min | 85 – 90% |
| High-flow nasal cannula | 10 – 60 L/min | 21 – 100% |
| Venturi mask | 2 – 15 L/min depending on the coloured adapter | Provides a fixed FiO2 depending on the coloured adapter |
Other types of tissue hypoxia
| Type | Description |
|---|---|
| Circulatory hypoxia | Poor tissue perfusion despite normal oxygenation. This includes shock and heart failure |
| Anaemia hypoxia | Reduced oxygen-carrying capacity in anaemia and carbon monoxide poisoning |
| Histotoxic hypoxia | The cells cannot utilize oxygen such as in cyanide poisoning |
Case 1
A 30-year-old man is found drowsy at home. Respiratory rate is 8/min. SpO₂ = 85% on room air.
ABG: pH = 7.28, PaCO₂ = 60 mmHg, PaO₂ = 55 mmHg.
Question: What is the likely cause of hypoxaemia?
- Calculate PAO₂Using room air (FiO₂ = 0.21):PAO₂ = (0.21 × 713) − (60/0.8)= 150 − 75= 75 mmHg
- Calculate A–a gradientA–a gradient = PAO₂ − PaO₂= 75 − 55= 20 mmHg
- Compare with normalAge = 70 yearsNormal A–a = (70/4) + 4 ≈ 22 mmHgResult: Normal A–a gradient
- InterpretationThe lungs are transferring oxygen normally. The problem is insufficient alveolar ventilation.
- DiagnosisHypoventilation secondary to opioid overdose
- ↑ PaCO₂
- Normal A–a gradient
- Improves with supplemental oxygen and reversal of opioid toxicity
Case 2
A 65-year-old man presents with fever, productive cough and worsening shortness of breath. Respiratory rate is 30/min. SpO₂ = 82% on room air. Chest X-ray shows right lower lobe consolidation.
ABG: pH = 7.46, PaCO₂ = 35 mmHg, PaO₂ = 50 mmHg.
Question: What is the likely cause of hypoxaemia?
- Calculate PAO₂Using room air (FiO₂ = 0.21):PAO₂ = (0.21 × 713) − (35/0.8)= 150 − 44= 106 mmHg
- Calculate A–a gradientA–a gradient = PAO₂ − PaO₂= 106 − 50= 56 mmHg
- Compare with normalAge = 65 yearsNormal A–a = (65/4) + 4 ≈ 20 mmHgResult: Increased A–a gradient
- InterpretationOxygen is reaching the alveoli but is not being transferred efficiently into arterial blood, indicating impaired gas exchange.
- DiagnosisV/Q mismatch due to pneumonia
- Normal/low PaCO₂
- Increased A–a gradient
- Improves with supplemental oxygen
- Chest X-ray supports pneumonia as the cause
Case 3
A 40-year-old man with severe ARDS is mechanically ventilated on 100% oxygen (FiO₂ = 1.0). Despite maximal oxygen therapy, SpO₂ remains 86%.
ABG: pH = 7.42, PaCO₂ = 40 mmHg, PaO₂ = 70 mmHg.
Question: What is the likely cause of hypoxaemia?
- Calculate PAO₂FiO₂ = 1.0PAO₂ = (1.0 × 713) − (40/0.8)= 713 − 50= 663 mmHg
- Calculate A–a gradientA–a gradient = PAO₂ − PaO₂= 663 − 70= 593 mmHg
- Compare with normalAge = 40 yearsNormal A–a = (40/4) + 4 = 14 mmHgResult: Massively increased A–a gradient
- InterpretationDespite breathing 100% oxygen, arterial oxygen remains very low. This indicates that blood is bypassing ventilated alveoli, so oxygen cannot enter the circulation effectively.
- DiagnosisRight-to-left intrapulmonary shunt due to ARDS
- Normal PaCO₂
- Massively increased A–a gradient
- Little or no improvement with 100% oxygen
- Requires management of the underlying ARDS and advanced ventilatory support (e.g., adequate PEEP, prone positioning) rather than simply increasing FiO₂.