What is cyanosis?

The unnatural bluish hue of the skin and mucous membranes known as cyanosis is brought on by high concentrations of reduced or deoxygenated haemoglobin (or its derivatives) flowing through the blood vessels(subpapillary venous plexus and superficial dermal capillaries).¹ The term "cyanosis" originates from the word "cyan", which refers to a blue-green hue. A significant diagnostic problem may arise from the appearance of cyanosis. Determining the reason might be aided by a meticulous assessment with the appropriate diagnostic equipment.²

Understanding cyanosis

There are two types of cyanosis, central and peripheral.¹ 

• The widespread bluish discolouration of the skin and visible mucous membranes is known as central cyanosis. It happens as a result of low oxygenation brought on by circumstances that raise the levels of aberrant or deoxygenated haemoglobin
• The bluish discolouration of the distal extremities (hands, fingertips, and toes) is known as peripheral cyanosis and is rarely a medical emergency that poses a serious risk to life. Mucous membranes are usually not affected, though it might occasionally affect the periorbital and circumoral regions. To avoid any difficulties, it is necessary to identify the underlying reason and address it as soon as possible³

How this condition affects you

When haemoglobin has relatively little oxygen bonded to it, cyanosis usually occurs. The blood contains oxygen in two different physical states. Of these, about 2% dissolves in the plasma and the remaining 98% binds to haemoglobin. A possible sign of insufficient oxygen supply to the peripheral tissues is cyanosis.² 

Different wavelengths of light are absorbed by haemoglobin depending on whether it is deoxygenated or oxygenated. Blood is brilliant red when it is oxygen-saturated, meaning that oxyhaemoglobin is present. Red blood becomes bluish when oxygen is lost from haemoglobin. The quantity of deoxygenated haemoglobin in the blood vessels determines the existence of cyanosis.⁴ The total oxygen dissolved in plasma and bound to haemoglobin, or 1.34 mL of oxygen per gram of haemoglobin and 0.003 mL of oxygen per 100 mL of plasma, is the arterial oxygen content. Cyanosis usually shows up extremely clearly when the haemoglobin level is between 3 and 5 g/dL.²

Symptoms and clinical presentation

Areas with a thin overlying dermis and a rich superficial vasculature are the best spots to observe cyanosis. The mouth cavity, lips, nose, earlobes, hands and feet, fingertips and toes are among them. 

When arterial blood has an excessively low oxygenation concentration (80–85%) or hypoxemia, cyanosis typically becomes visible.³ The colour of your skin, gums, lips, nails, eyes, and tongue can vary depending on your cyanosis type. Cyanosis may seem white or grey on people with darker complexion. 

The usual cause of cyanosis is another illness. Other symptoms you might encounter, contingent on the aetiology of the cyanosis, include hypothermia, tingling or numbness in your legs and arms, coughing, trouble breathing, light-headedness, extreme weariness or fatigue, and weakness.⁶

Common underlying conditions and risk factors

Cardiovascular disorders

Congenital heart abnormalities including congestive heart failure, cardiac arrest, Tetralogy of Fallot, and the right ventricle with two outlets, might show cyanosis as a symptom. A cardiopulmonary condition might cause central cyanosis, particularly if virtual clubbing is involved.² 

If heart failure and shock are severe enough, reduced cardiac output may result in peripheral cyanosis. Low blood pressure hinders the proper flow of blood enriched with oxygen to the extremities. Moreover, the reflex cutaneous vasoconstriction caused by it diverts blood flow from the limbs to the internal organs causing extremity cyanosis.³ 

Tricuspid atresia, Ebstein abnormality, significant pulmonary stenosis, and other abnormalities are among the congenital heart disease conditions that manifest with cyanosis during the first week of life. Truncus arteriosus, transposition of the major arteries, Tetralogy of Fallot, and other disorders typically show symptoms after the first week.³

Respiratory disorders

Suffocation (due to choking), swelling (due to croup) surrounding your vocal cords, epiglottitis, or inflammation of the membrane covering your windpipe, elevated altitude, breathing difficulties, an infection within your breathing system, pneumonia, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and a blood clot in a lung artery (pulmonary embolism) might also show cyanosis. If there is an infectious cause of cyanosis, such as croup, pneumonia, septic shock, etc., fever may be observed. Central cyanosis is more frequently linked to respiratory symptoms.³

Haematologic disorders

Methemoglobinemia-related cyanosis is caused by oxidised haemoglobin rather than decreased haemoglobin. Because the iron in methaemoglobin is in the ferric form and does not bind to oxygen, it is an oxidised form of haemoglobin. Methaemoglobin gives the skin a strong blue tint. Most often, methemoglobinemia is the result of a medication reaction, particularly to drugs that contain nitrite or nitrate, such as nitroglycerin, dapsone, and certain topical anaesthetics. Excess methaemoglobin lowers measured oxygen saturations but does not affect arterial blood's partial pressure of oxygen. When a patient with methemoglobinemia has low arterial partial pressure of oxygen, it is important to look for a concurrent pulmonary problem.⁴

Other conditions

• Vasospasm might result in peripheral cyanosis; the history should be asked about current or recent exposure to cold² 
• Raynaud’s phenomenon is characterised by aberrant vasospasm brought on by emotional events and temperature fluctuations. The extremities turn blue as a result of the reduced blood supply.⁴ The bluish skin tone known as pseudocyanosis is unrelated to peripheral vasoconstriction or hypoxemia. It is especially prevalent in sun-exposed locations and is brought on by metals or medications like lead or silver nitrate
• In regions with less melanotic pigment, hemosiderin deposition is more noticeable, resulting in a bluish skin tone. Products of the oxidation of chlorpromazine may appear blue or purple⁵
• Donning garments that are excessively snug and restrict your range of motion, being in extremely frigid temperatures, medications for the treatment of hypertension, seizures, overdose on drugs, and exposure to toxins also cause cyanosis

Diagnosis

The evaluation of cyanosis may be impacted by the existence of jaundice, skin tone, ambient temperature, or exposure to light. A contributing factor to cyanosis is also anaemia or polycythaemia. 

For each level of haemoglobin, there are differences in the amount of hypoxia needed to cause clinically evident cyanosis. It is more challenging to diagnose cyanosis when haemoglobin levels are low. Put another way, a patient suffering from chronic anaemia may not exhibit cyanosis clinically.² 

Apart from medical history and physical examination, further evaluation is necessary to identify the root cause of cyanosis. 

Oxygenation status could be evaluated by measuring haemoglobin oxygen saturation, partial pressure of oxygen, and total haemoglobin. Different devices measure oxygen saturation, but the variables that are measured vary. Two spectrophotometry methods are used to measure arterial blood oxygenation, co-oximetry and pulse oximetry.

• Pulse oximetry is a non-invasive method, while co-oximetry requires a sample of arterial blood³ 
• Co-oximetry can be utilised for arterial blood gas analysis as well as oxygen saturation measurement

Normal arterial oxygenation, or 85–100%, is seen in peripheral cyanosis according to arterial blood gas measurement. In contrast, central cyanosis is characterised by low arterial oxygen saturation. Additionally, the value of haemoglobin derivatives such as deoxygenated, oxygenated, and dyshaemoglobins (methemoglobin, carboxyhaemoglobin, sulfhaemoglobin, etc.) is determined by this test.³ Peripheral blood film, haemoglobin concentration, blood glucose, and sepsis analysis should be taken into consideration to assess the causes of cyanosis, depending on the clinical context.

In addition, to assess the cardiopulmonary cause, a CT scan, ECG, and chest X-ray can be performed. In certain situations, an invasive cardiac examination and echocardiography could be required.⁶

Management and treatment

• Initial stabilisation and airway control are necessary for cyanotic cardiac disorders, and cardiology referrals for evaluation and intervention are made
• Surgery is required for the cure of congenital cardiac disease
• Diuretics, ACE inhibitors, and inotropic medications are investigated for heart failure, whereas medications such as prostaglandin E1 infusion are employed for ductal-dependent diseases
• To avoid bacterial endocarditis, antibiotic prophylaxis is required. For methemoglobinemia-induced cyanosis, methylene blue is utilized
• For blue discolouration brought on by exposure to gold and silver salts, the best course of treatment is to eliminate the offending chemicals⁶ 

Although peripheral cyanosis is typically curable, prompt treatment is necessary to enhance results and avoid problems. Blood vessel-relaxing drugs, lifestyle modifications, and mild heating and massage are all part of the treatment. It could be required to make long-term lifestyle adjustments, such as cutting back on caffeine and nicotine. Since most central cyanosis can result in extremity cyanosis, an interprofessional strategy comprising multiple subspecialties is required to identify and treat the true cause of cyanosis.³ 

It is important to inform patients and their families about the risk factors and preventative steps that can be taken to stop the disease from getting worse. Some suggestions are to steer clear of smoking and preserve control over blood pressure, cholesterol, temperature and immobility.⁴

Summary

Adult cyanosis is an important clinical signal that frequently indicates major underlying medical disorders, especially those involving the respiratory and cardiovascular systems. Because of the high concentration of deoxygenated haemoglobin, it appears as a bluish discolouration of the skin and mucous membranes. A comprehensive clinical examination, a history, and several diagnostic procedures are necessary for an effective diagnosis to pinpoint the precise cause.

Whether it is medicinal management, lifestyle modifications, or surgery, the goal of treatment is to address the underlying disease. Timely and suitable administration has the power to enhance results and avert difficulties. Managing and lowering the incidence of cyanosis requires educating patients about risk factors and preventive strategies. All things considered, the knowledge of cyanosis and its consequences is critical for early identification, efficient treatment, and better patient care.