Hypoxaemia

Hypoxaemia is an abnormally low partial pressure of oxygen in arterial blood (PaO2 under 8 kPa or 60 mmHg), or oxygen saturation under 94% in a patient without chronic lung disease (under 88% to 92% in a patient with chronic hypercapnic disease). It may be silent. Because tissues depend on oxygen delivery (haemoglobin, cardiac output and saturation), hypoxaemia is one of three ways in which oxygen supply fails; the others are anaemia and poor perfusion.

Clinical relevance. Hypoxaemia is common in acute illness and is often missed because cyanosis is an unreliable sign and the patient may feel well. Untreated, it causes confusion, arrhythmia, myocardial ischaemia, pulmonary hypertension, organ failure and death. Both too little and too much oxygen harm: uncontrolled oxygen in a patient with chronic obstructive pulmonary disease can cause life threatening hypercapnia.

Classification.

• By severity: mild (PaO2 8 to 10 kPa; saturation 90% to 94%), moderate (6 to 8 kPa; 85% to 90%), severe (under 6 kPa; under 85%). Saturation under 90% is on the steep part of the dissociation curve, where small PaO2 falls produce large saturation falls.
• By mechanism: ventilation perfusion mismatch (commonest: pneumonia, asthma, chronic obstructive pulmonary disease, embolism), shunt (right to left: consolidation, atelectasis, oedema, acute respiratory distress syndrome, congenital heart disease, hepatopulmonary syndrome, pulmonary arteriovenous malformations; poorly responsive to oxygen), hypoventilation (opioids, neuromuscular disease, obesity, brainstem disease; raised PaCO2 and normal alveolar to arterial gradient), diffusion impairment (interstitial disease, emphysema, exercise), low inspired oxygen (altitude, closed spaces, equipment failure).
• By timeline: acute, subacute, chronic (nocturnal, exertional, continuous).
• Related: hypoxia (tissue level), anaemic hypoxia, stagnant hypoxia, histotoxic hypoxia (cyanide), carbon monoxide poisoning (normal PaO2, falsely normal pulse oximetry).

Mechanism. PaO2 depends on alveolar oxygen tension, ventilation and perfusion matching, diffusion and shunt. The alveolar gas equation (PAO2 = FiO2 x (barometric pressure minus 6.3 kPa) minus PaCO2 / 0.8) with the alveolar to arterial gradient (normal under 2 kPa in young adults, rising with age) separates hypoventilation (normal gradient) from other causes (raised gradient).

History.

• Breathlessness, cough, wheeze, chest pain, haemoptysis, orthopnoea, fever, speed of onset, exertional limitation, positional breathlessness (platypnoea), headache, confusion, drowsiness, snoring, nocturnal waking, morning headaches.
• Recent surgery, immobility, long travel (embolism), trauma, choking, drug or alcohol overdose, opioid use, sedatives, altitude, diving, smoke or fumes, heating faults (carbon monoxide), industrial gases.
• Past history: chronic obstructive pulmonary disease, asthma, interstitial lung disease, heart disease, congenital heart disease, sleep apnoea, neuromuscular disease, sickle cell disease, liver disease, HIV, cancer, thromboembolism, previous intubation.
• Drugs: opioids, benzodiazepines, amiodarone, nitrofurantoin, bleomycin, methotrexate, dapsone, nitrates, local anaesthetics (methaemoglobinaemia).
• Home oxygen use and target range.

Examination.

• Airway, breathing, circulation, disability: respiratory rate and pattern (rapid and shallow, slow, irregular), accessory muscles, ability to speak, tracheal position, chest expansion, percussion, auscultation (wheeze, crackles, bronchial breathing, reduced air entry).
• Central cyanosis (tongue, lips; needs about 5 g/dL of deoxygenated haemoglobin, so absent in anaemia and obvious in polycythaemia), peripheral cyanosis, clubbing, flapping tremor (hypercapnia), bounding pulse (hypercapnia), mental state (agitation, confusion, drowsiness).
• Cardiac: heart rate, rhythm, blood pressure, jugular venous pressure, murmurs (shunt), third heart sound, loud P2, oedema.
• Neurological: bulbar function, respiratory muscle weakness (paradoxical abdominal movement), sedation.
• Skin: cherry red colour (carbon monoxide), chocolate brown blood (methaemoglobinaemia), pallor.

Red flags.

• Saturation under 90% on air, or under 94% on high flow oxygen.
• Confusion, agitation, drowsiness, arrhythmia, chest pain, syncope.
• Rapid or slowed respiratory rate (over 30 or under 8), exhaustion, silent chest.
• Cyanosis not responding to oxygen (shunt, methaemoglobinaemia).
• Normal pulse oximetry with symptoms and risk of carbon monoxide poisoning (fumes, headache, multiple affected household members).
• Platypnoea and orthodeoxia (desaturation upright).
• Suspected pulmonary embolism, pneumothorax, anaphylaxis, aspiration or opioid overdose.
• Known chronic obstructive pulmonary disease with oxygen over 28% or flushed, bounding hypercapnia.
• New hypoxaemia in sickle cell disease (acute chest syndrome) or in HIV (pneumocystis).

Ventilation perfusion mismatch. Pneumonia, asthma, chronic obstructive pulmonary disease, bronchiectasis, pulmonary embolism, interstitial lung disease, pulmonary hypertension, bronchiolitis, atelectasis.

Shunt. Lobar pneumonia, pulmonary oedema (cardiogenic and non cardiogenic), acute respiratory distress syndrome, atelectasis, intracardiac shunt (Eisenmenger syndrome, patent foramen ovale with raised right pressures), pulmonary arteriovenous malformation, hepatopulmonary syndrome, pulmonary haemorrhage, massive effusion, pneumothorax.

Hypoventilation. Opioid and sedative overdose, central sleep apnoea and obesity hypoventilation, neuromuscular disease (Guillain-Barre syndrome, myasthenic crisis, motor neurone disease, muscular dystrophy), chest wall disease (flail chest, kyphoscoliosis), brainstem stroke, severe chronic obstructive pulmonary disease, upper airway obstruction.

Diffusion limitation. Pulmonary fibrosis, emphysema, pulmonary vascular disease, alveolar proteinosis, pneumocystis pneumonia, lymphangitis.

Reduced inspired oxygen. Altitude, confined spaces, equipment error, diving, fire.

Apparent or special causes. Methaemoglobinaemia, sulphaemoglobinaemia, carbon monoxide poisoning (normal PaO2), cyanide poisoning, severe anaemia (normal PaO2 but low delivery), poor peripheral perfusion (false oximetry), nail varnish, motion, abnormal haemoglobin variants, low pulse oximeter signal.

1. Confirm hypoxaemia: pulse oximetry (accurate to plus or minus 2% to 3% when saturation is over 90%, less accurate when under 80% and in dark skin, where occult hypoxaemia is more common), then arterial blood gas for any saturation under 92% or any patient unwell, to check PaO2, PaCO2, pH, bicarbonate, lactate, carboxyhaemoglobin and methaemoglobin by co-oximetry.
2. Rapid review of airway, breathing and circulation; bedside tests: ECG, glucose, temperature, peak flow.
3. Chest radiograph (consolidation, oedema, pneumothorax, effusion, hyperinflation, fibrosis, mass, cardiomegaly); bedside ultrasound of lung, heart and legs.
4. Alveolar to arterial gradient: normal gradient with raised PaCO2 means hypoventilation; raised gradient means mismatch, shunt or diffusion defect. Response to 100% oxygen: PaO2 rises over 60 kPa with mismatch, but little with shunt (over 30% shunt).
5. Blood tests: full blood count (anaemia, polycythaemia), electrolytes, urea, creatinine, liver function, C reactive protein, procalcitonin, troponin, natriuretic peptide, D-dimer, coagulation, lactate, toxicology, thyroid function, creatine kinase, HIV test, cultures.
6. CT pulmonary angiography for embolism; high resolution CT for interstitial and parenchymal disease; V/Q scan if contrast contraindicated; bubble contrast echocardiography for intracardiac shunt (bubbles in left heart within 3 beats suggest intracardiac; after 3 to 5 beats, pulmonary arteriovenous malformation); contrast CT for malformations.
7. Spirometry, lung volumes, transfer factor, maximal inspiratory and expiratory pressures, supine and upright vital capacity.
8. Overnight oximetry and capnography, sleep study for nocturnal hypoxaemia; six minute walk with oximetry or cardiopulmonary exercise test for exertional desaturation.
9. Orthodeoxia test: saturation lying and sitting upright (fall over 5% or PaO2 fall over 0.5 kPa).
10. Assessment for long term oxygen: two arterial blood gases at least 3 weeks apart when stable on optimal treatment.

Limits. Pulse oximetry overestimates saturation in dark skin, is falsely normal in carbon monoxide poisoning, falsely about 85% in methaemoglobinaemia, and unreliable in shock, cold hands, nail polish and movement. Arterial blood gas gives PaO2 but misses oxygen content and delivery. Saturation near 100% may hide a falling PaO2 on high FiO2. Acute hypoxaemia may coexist with normal chest radiograph (embolism, early asthma, early pneumocystis).

Immediate priorities.

• Airway opening and support; call for help for severe hypoxaemia; sit upright unless shocked; monitor saturation, ECG and blood pressure; obtain intravenous access and blood gas.
• Oxygen: for critically ill or unknown patients give 10 to 15 L/min by reservoir (non rebreather) mask, then titrate to 94% to 98%; patients at risk of hypercapnia (chronic obstructive pulmonary disease, obesity hypoventilation, neuromuscular and chest wall disease, cystic fibrosis, previous hypercapnic failure) target 88% to 92% with a Venturi mask 24% (2 to 3 L/min) or 28% (4 L/min) or nasal cannulae 1 to 2 L/min; repeat gas at 30 to 60 minutes and with each change.
• Escalate: high flow nasal oxygen (30 to 60 L/min, FiO2 0.3 to 1.0) for hypoxaemic failure; continuous positive airway pressure 5 to 10 cmH2O (cardiogenic oedema, pneumonia, sleep apnoea); bilevel non invasive ventilation (inspiratory 12 to 20 cmH2O, expiratory 4 to 5 cmH2O) for hypercapnic acidosis (pH under 7.35 with PaCO2 over 6.5 kPa); intubation for exhaustion, refractory hypoxaemia, failing non invasive ventilation, airway risk or reduced consciousness.
• Prone positioning (awake or ventilated) in severe acute respiratory distress syndrome; lung protective ventilation (6 mL/kg ideal body weight, plateau pressure under 30 cmH2O); extracorporeal membrane oxygenation for refractory cases.
• Treat the cause at once.

Cause directed treatment.

• Pneumonia: antibiotics within 1 hour for sepsis (co-amoxiclav 1.2 g intravenously every 8 hours with clarithromycin 500 mg intravenously twice daily, or ceftriaxone 2 g daily with clarithromycin); fluids 500 mL boluses; prednisolone or dexamethasone for severe pneumonia where appropriate (dexamethasone 6 mg daily for hypoxic COVID-19 for up to 10 days).
• Asthma and chronic obstructive pulmonary disease: salbutamol 5 mg nebulised every 15 to 20 minutes, ipratropium 500 micrograms, prednisolone 40 to 50 mg (asthma) or 30 to 40 mg (chronic obstructive pulmonary disease), magnesium sulphate 2 g for severe asthma, controlled oxygen, non invasive ventilation.
• Pulmonary embolism: rivaroxaban 15 mg twice daily for 21 days then 20 mg daily, or apixaban 10 mg twice daily for 7 days then 5 mg twice daily, or enoxaparin 1 mg/kg twice daily; alteplase 100 mg over 2 hours for shock.
• Pulmonary oedema: furosemide 40 to 80 mg intravenously, glyceryl trinitrate infusion 10 to 200 micrograms/minute, continuous positive airway pressure.
• Pneumothorax: needle decompression when tension, then chest drain.
• Opioid overdose: naloxone 400 micrograms intravenously (or 800 micrograms intramuscularly), repeat every 2 to 3 minutes up to 2 mg then infusion of two thirds of the effective dose each hour; ventilate if needed.
• Anaphylaxis: adrenaline 0.5 mg intramuscularly, repeat after 5 minutes if needed, with oxygen, fluids, chlorphenamine 10 mg and hydrocortisone 200 mg.
• Carbon monoxide poisoning: 100% oxygen by tight mask until carboxyhaemoglobin is under 5% (hyperbaric oxygen for coma, pregnancy, carboxyhaemoglobin over 25%, or cardiac ischaemia); disregard oximeter readings.
• Methaemoglobinaemia: methylene blue 1 to 2 mg/kg intravenously over 5 minutes (repeat in 1 hour; avoid in G6PD deficiency), stop the oxidising drug.
• Cyanide poisoning: hydroxocobalamin 5 g intravenously over 15 minutes.
• Neuromuscular failure: forced vital capacity every 4 hours; ventilate when under 15 to 20 mL/kg.
• Acute chest syndrome (sickle cell): oxygen, analgesia, incentive spirometry, antibiotics (ceftriaxone 2 g daily with azithromycin 500 mg), transfusion or exchange transfusion for severe disease.
• Pneumocystis pneumonia: co-trimoxazole 120 mg/kg/day in divided doses for 21 days with prednisolone 40 mg twice daily for 5 days when PaO2 is under 9.3 kPa.
• Hepatopulmonary syndrome: oxygen; liver transplantation assessment.
• Anaemia: transfusion for symptomatic or severe anaemia.

Chronic hypoxaemia (stable).

• Long term oxygen therapy for at least 15 hours daily when PaO2 is 7.3 kPa or under (or 8 kPa with pulmonary hypertension, oedema or polycythaemia with haematocrit over 55%), measured twice 3 weeks apart; flow rate to keep PaO2 over 8 kPa or saturation 90% or more; no smoking and fire safety.
• Ambulatory oxygen for exertional desaturation proven by testing.
• Nocturnal oxygen or continuous positive airway pressure for nocturnal hypoxaemia and sleep apnoea.
• Treat the underlying disease and optimise comorbidities; pulmonary rehabilitation.
• Air travel assessment: patients with resting saturation under 92% need formal testing (hypoxic challenge) and may need 2 L/min of in flight oxygen.
• Altitude illness: descent, oxygen, dexamethasone 4 mg every 6 hours, acetazolamide 250 mg twice daily (prevention 125 mg twice daily), nifedipine 30 mg modified release twice daily for pulmonary oedema.

Oxygen safety. Prescribe a target range; record flow and device; avoid 100% oxygen for long periods in patients not at risk (absorption atelectasis, toxicity); avoid oxygen over 94% in myocardial infarction and stroke when normoxic; wean when stable.

Disposition.

• Critical care or resuscitation room: saturation under 90% on high flow oxygen, need for non invasive or invasive ventilation, shock, exhaustion, confusion.
• Admit: new hypoxaemia with saturation under 92% on air, suspected embolism, pneumonia, heart failure, exacerbation of chronic lung disease needing oxygen, neuromuscular failure, poisoning, acute chest syndrome.
• Discharge: only when saturation is 94% or more on air (or at baseline), cause treated, home oxygen set up where needed.

Monitoring. Continuous oximetry and respiratory rate; gases 30 to 60 minutes after changes and daily in ventilated patients; early warning score; lactate; fluid balance; chest radiograph after procedures; oxygen cylinder duration; carbon dioxide trends.

Referral and escalation. Critical care, respiratory, cardiology, neurology, haematology, toxicology, liver service, long term oxygen and home ventilation services, pulmonary hypertension centre, sleep medicine.

Safety netting. Return urgently for worsening breathlessness, drowsiness, confusion, headache with flushing, blue lips, or oxygen concentrator failure. Home oxygen users: no smoking, no flames within 2 metres, never exceed prescribed flow, carry a steroid and antibiotic plan if prescribed.

Special groups. Children: lower saturation targets are not used; give oxygen for saturation under 92%; look for grunting, nasal flare, recession and poor feeding; bronchiolitis, pneumonia, croup, asthma, foreign body, congenital heart disease. Pregnancy: keep saturation over 95%, left lateral tilt, embolism and amniotic fluid embolism, peripartum cardiomyopathy, asthma, pneumonia and anaemia.

Older adults: reduced reserve, delirium as first sign. Dark skin: oximetry overestimates; use arterial gas when concern persists. Obesity: hypoventilation, atelectasis. High altitude: acute mountain sickness, high altitude pulmonary and cerebral oedema. Endemic regions: severe malaria with respiratory distress, tuberculosis, pneumonia, sickle cell disease and carbon monoxide from indoor cooking fires.