Write a short note on cyanosis.

Definition

Cyanosis is the bluish discoloration of the skin and mucous membranes resulting from an increased absolute concentration of deoxygenated (reduced) haemoglobin — conventionally more than 5 g/dL — in the capillary blood, or from the presence of abnormal haemoglobin pigments.

The critical point is that it depends on the ABSOLUTE amount of deoxygenated haemoglobin, not on the percentage saturation. Two consequences follow, and they are the most examined aspect of the topic:

• In POLYCYTHAEMIA, cyanosis appears EARLY and at a higher oxygen saturation, because 5 g/dL of deoxyhaemoglobin is reached more readily when total haemoglobin is high.
• In SEVERE ANAEMIA, cyanosis may NEVER appear, even with profound hypoxaemia — a patient with a haemoglobin of 5 g/dL cannot generate 5 g/dL of deoxyhaemoglobin. Absence of cyanosis therefore never excludes hypoxia.

Classification

Examine the tongue and buccal mucosa — this is the single most reliable way to distinguish central from peripheral cyanosis, since these are warm, highly vascular and unaffected by peripheral vasoconstriction.

Causes

Central Cyanosis:

1. Reduced inspired oxygen — high altitude

2. Respiratory disease with hypoxaemia:

• Ventilation-perfusion mismatch — COPD, pneumonia, asthma, pulmonary embolism (the commonest mechanism)
• Hypoventilation — respiratory depression, neuromuscular disease, obesity hypoventilation
• Diffusion impairment — interstitial lung disease, pulmonary oedema
• Shunt — ARDS, lobar collapse, pulmonary arteriovenous malformation

3. Cardiac — RIGHT-TO-LEFT SHUNT (characteristically does not improve with 100% oxygen):

• Tetralogy of Fallot (the commonest cyanotic congenital heart disease beyond infancy)
• Transposition of the great arteries, tricuspid atresia, truncus arteriosus, total anomalous pulmonary venous connection
• EISENMENGER SYNDROME — reversal of a left-to-right shunt (VSD, ASD, PDA) once pulmonary hypertension exceeds systemic pressure. In patent ductus arteriosus with Eisenmenger physiology, the cyanosis and clubbing are DIFFERENTIAL — affecting the toes but not the fingers, because desaturated blood enters the aorta distal to the origin of the head and arm vessels

4. Abnormal haemoglobins:

• METHAEMOGLOBINAEMIA — slate-grey cyanosis, unresponsive to oxygen, with a NORMAL PaO2 and a "saturation gap"; chocolate-brown blood. Causes: dapsone, local anaesthetics (prilocaine, benzocaine), nitrates and nitrites, aniline dyes, naphthalene, and contaminated well water in infants
• Sulfhaemoglobinaemia

5. Massive pulmonary embolism; severe pulmonary hypertension

Peripheral Cyanosis:

• Reduced cardiac output — heart failure, shock of any cause
• Cold exposure — physiological vasoconstriction (the commonest cause overall)
• Arterial occlusion — peripheral arterial disease, embolism, Raynaud's phenomenon
• Venous obstruction — deep vein thrombosis, superior vena cava obstruction
• Increased blood viscosity — polycythaemia
• All causes of central cyanosis also produce peripheral cyanosis

Clinical Assessment

History: duration (lifelong suggests congenital heart disease; acute suggests embolism, pneumothorax or methaemoglobinaemia), exertional symptoms, squatting in children (characteristic of tetralogy of Fallot), smoking and occupational exposure, drug and chemical exposure (methaemoglobinaemia), and family history.

Examination:

• distinguish central from peripheral by examining the tongue
• assess clubbing (present in cyanotic congenital heart disease, bronchiectasis, lung abscess, ILD and lung cancer — but NOT in uncomplicated COPD)
• examine for differential cyanosis
• assess respiratory and cardiovascular systems
• look for polycythaemia (plethoric facies, conjunctival suffusion) as a consequence of chronic hypoxia.

Investigations

• Pulse oximetry — a rapid screen. Note that it is falsely NORMAL in methaemoglobinaemia (plateauing around 85%) and falsely HIGH in carbon monoxide poisoning, because it cannot distinguish these pigments from oxyhaemoglobin.
• ARTERIAL BLOOD GAS — essential: measures PaO2 directly. A normal PaO2 with clinical cyanosis and a low measured saturation ("saturation gap") indicates an abnormal haemoglobin — methaemoglobinaemia.
• CO-OXIMETRY — measures methaemoglobin and carboxyhaemoglobin directly; the definitive test.
• CBC — polycythaemia (chronic hypoxia) or anaemia.
• Chest X-ray, ECG and echocardiography — for cardiac and respiratory causes; bubble contrast echocardiography to demonstrate a right-to-left shunt.
• THE HYPEROXIA TEST — administer 100% oxygen: PaO2 rises substantially in respiratory disease, but fails to rise significantly with a fixed right-to-left cardiac shunt. A simple bedside test that separates cardiac from pulmonary cyanosis.
• Pulmonary function tests, CT pulmonary angiography, and cardiac catheterisation as indicated.

Management

Treat the underlying cause — this is the whole of management:

• Oxygen therapy for hypoxaemic respiratory disease (with caution in COPD with CO2 retention — target 88–92%)
• Bronchodilators, antibiotics, ventilatory support as appropriate
• Anticoagulation or thrombolysis for pulmonary embolism
• Surgical or transcatheter correction of congenital heart disease; management of Eisenmenger syndrome with pulmonary vasodilators (and avoidance of pregnancy, which carries very high mortality)
• METHAEMOGLOBINAEMIA: remove the offending agent and give METHYLENE BLUE (contraindicated in G6PD deficiency, where ascorbic acid or exchange transfusion is used instead)
• Peripheral cyanosis: warm the part, improve cardiac output, treat arterial or venous obstruction