Overview

What is Cyanosis

Cyanosis, which comes from the Greek word kuaneos, indicating deep blue colour, is used to describe the blue tint of the skin, nailbeds, or mucous membranes.¹ The presence of >5 g/dL of deoxygenated haemoglobin can be observed and measured using pulse oximetry. Detection becomes challenging unless arterial saturation is at or below 85% and is most noticeable in the tongue and oral mucosa.²

Types

1. Acrocyanosis: It is the bluish discolouration seen in the limbs, specifically in the palms and the soles. It is also visible on the skin surrounding the lips. Acrocyanosis is common in infants and is usually not a concern as long as there is no cyanosis in the central body³
2. Central cyanosis: It is related to bluish discoloration seen on central areas of the body, such as the mouth, head, and torso. Central cyanosis is always abnormal in newborns and is typically associated with decreased blood oxygen levels. The cause might be related to an issue with the heart, lungs, or blood⁴

Causes

Cyanosis typically results from a deficiency of oxygen in the bloodstream. This could be due to a lack of oxygen in a newborn’s blood or exposure of blood vessels to cold temperatures. The flow of blood throughout a newborn’s body helps maintain the warmth of their organs and body parts. However, when the weather is extremely cold, the blood vessels in a newborn’s hands, feet, and ears constrict to maintain their body's temperature. Several factors can lead to insufficient oxygen levels in a newborn’s bloodstream.⁵

Respiratory disorder

Respiratory issues (such as upper and lower airway problems) should be taken into account when assessing any baby with cyanosis. Upper airway disorders like choanal atresia, Pierre Robin Sequence, airway hemangioma, vascular rings/slings, cystic hygroma, and micrognathia can lead to breathing difficulties, noisy breathing, and bluish skin coloration. For instance, choanal atresia is typically detected at birth and can present with breathing difficulties that can get better with crying.

Infants, who are obligate nasal breathers, typically inhale through the nose while at rest but switch to breathing through the mouth when crying. Due to their blocked nasal passage, these babies will experience breathing difficulties when trying to breathe through their nose. It is frequently identified when the doctor cannot insert a catheter through the nostrils.

Pneumonia and atelectasis are the main lower airway disorders that lead to cyanosis due to a ventilation-perfusion mismatch. Neonatal pneumonia is usually detected on chest X-rays by the presence of widespread infiltrates. Escherichia coli and group B streptococci are the pathogens most frequently encountered. Take into account Chlamydia in infants who have experienced apnea and cough.

Less frequently seen lung conditions consist of persistent pulmonary hypertension in newborns (often linked to a diaphragmatic hernia), interstitial lung disease (abnormal diffusion), arteriovenous malformations (shunts outside the heart), congenital cystic adenomatoid malformation, pulmonary sequestration, and congenital lobar emphysema.

Hemoglobinopathies

Cyanosis will occur with any hemoglobin disorder that disrupts the transportation of oxygen. Both polycythemia and anemia may cause cyanosis to occur. Polycythemia can lead to pulmonary hypertension due to the elevated thickness of the blood. On the other hand, severe anemia can lead to cyanosis as a result of insufficient oxygen reaching crucial tissues. An anomalously structured hemoglobin molecule might have a hindered capacity for transporting oxygen.

Methemoglobinemia is a condition caused by an abnormal hemoglobin molecule, often due to exposure to oxidizing chemicals but it can also be genetic, dietary, or idiopathic in origin.

In this condition, the ferrous (Fe2+) ions in heme undergo oxidation and are converted to the ferric (Fe3+) state. Hemoglobin is only able to carry oxygen when the iron is in the ferrous state, therefore, this oxidation causes the oxygen dissociation curve to move to the left. Babies under 3 months old are at a higher risk of methemoglobinemia due to various factors: 

1. Reduced levels and activity of NADH-cytochrome b5 reductase
2. Lower gastric pH causes the growth of intestinal flora that turns nitrates into nitrites
3. Fetal haemoglobin can be oxidized to methemoglobin more readily compared to adult hemoglobin. Infants with methemoglobinemia typically display central cyanosis without any respiratory difficulties

Infections

Considering sepsis is always crucial when assessing a neonate with cyanosis. Sepsis causes cyanosis due to higher oxygen consumption. Individuals with the highest susceptibility to sepsis include babies born to mothers who test positive for group B streptococcus (GBS), babies born to mothers who have a history of infection during pregnancy, babies born after a prolonged rupture of membranes lasting over 18 hours, and premature babies. E. coli, GBS, and Listeria monocytogenes are the most frequent pathogens found in neonatal sepsis.

Cardiac causes

Cardiac conditions linked to reduced pulmonary blood flow leading to cyanosis are tricuspid atresia, pulmonary atresia, pulmonary stenosis, tetralogy of Fallot (TOF), and Ebstein’s anomaly. TOF is a prevalent cyanotic congenital heart condition seen in newborns, with the level of cyanosis varying based on the extent of pulmonary stenosis. These five cardiac defects are some of the most prevalent types of heart defects that rely on a patent ductus arteriosus to connect the pulmonary and systemic circulations.

Hypoplastic left heart syndrome, critical aortic stenosis, interrupted aortic arch, and transposition of the great arteries are cardiac conditions that result in severe heart failure and cyanosis in neonates. These lesions rely on the ductus for blood flow, so infants might appear cyanotic and in shock once the ductus arteriosus closes. Newborns with ductal-dependent abnormalities might show no symptoms when they are born but could experience shock and/or cyanosis within the first 2-3 weeks of life when they come to the emergency department.⁶

Diagnostic evaluation

Using the Pediatric Assessment Triangle, the severity of the illness can be quickly determined based on appearance, work of breathing, and circulation during the initial visual assessment. Babies with cyanotic congenital heart disease may seem to exhibit reduced muscle strength and awareness, heightened fussiness, and/or a feeble cry. Symptoms may include increased effort in breathing, abnormal noises from the airway, indrawing of the chest wall, and/or head movements.

Assessing the baby's breathing efforts can be very beneficial, as infants with breathing problems often show cyanosis when struggling to breathe (accompanied by retractions), while infants with heart issues and methemoglobinemia may have cyanosis without experiencing severe distress. During a skin examination, the baby might show signs of paleness, patchy skin discolouration, and/or bluish skin.⁶

The doctor should observe the heart rate, heart and breath sounds; feel for thrills on the precordium; check peripheral pulses; examine skin and capillary refill; inspect for surgical scars; listen for bruits, murmurs, and gallops in the head, chest, and abdomen; and look for hepatomegaly.

It is important to mention that not all clinically significant cardiac lesions exhibit murmurs. An example is when transposition of the great arteries frequently does not show a murmur. While it is important to customize the investigation according to the specific potential diagnoses, it is recommended to begin the evaluation for neonatal cyanosis with the following tests:

1. Pulse oximetry
2. Arterial blood gas analysis
3. Chest X-ray
4. Chest computed tomography (CT) scan
5. Complete blood count (CBC)
6. Electrocardiogram (EKG)
7. Echocardiogram
8. Pulmonary function tests
9. Cardiac catheterization: This procedure can also assist in diagnosing heart conditions⁷
10. Other tests include
    • blood culture
    • urinalysis
    • urine culture
    • and cerebrospinal fluid analysis
11. Hypoglycemia
    • hyperglycemia
    • metabolic acidosis
    • and jaundice⁸

Treatment

How the cyanotic newborn is treated is determined by the root cause of the cyanosis. Every patient should be promptly given oxygen using a non-rebreather mask until the airway is established. Put the patient on a cardiorespiratory monitor and observe for any alterations in vital signs.

It is highly recommended to provide prostaglandin E1 (PGE1) at a rate of 0.05-0.1 microg/kg per minute for any newborn showing cyanosis due to suspected congenital heart disease to maintain patency of the ductus arteriosus. Getting ready for endotracheal intubation is crucial because PGE1 can lead to apnea. It is important to consult with a pediatric cardiology expert early on, as echocardiography is crucial for diagnosing and managing the patient effectively.

If you suspect a respiratory disorder, provide oxygen as indicated and address the root cause of the disorder. Get ready for inserting a tube into the windpipe, as newborn babies can quickly deteriorate to the point of no longer being able to breathe.

Methylene blue is the preferred therapy for methemoglobinemia as it serves as an oxidizing agent that is transformed into leukomethylene blue, leading to the reduction of methemoglobin to haemoglobin. Methylene blue should be used if methemoglobin levels are over 25% or if the patient is showing symptoms of hypoxia, such as lethargy or respiratory distress. In newborns, the recommended dosage is 0.3-1 mg/kg of a 1% solution administered intravenously over 3-5 minutes, with effects typically seen within 30 minutes.

Ultimately, since sepsis is often characterized by cyanosis and shock in newborns, it is important to conduct a thorough sepsis evaluation with blood, urine, and cerebrospinal fluid cultures and promptly start intravenous antibiotics. It is important to administer powerful antibiotics, such as vancomycin and cefotaxime, promptly without waiting for a lumbar puncture.⁸

Summary

Cyanosis is a condition where the skin, nailbeds, or mucous membranes have a bluish tint because of decreased oxygen levels in the blood. Respiratory disorders, hemoglobinopathies, infections, and cardiac conditions are possible causes for it.

Diagnosis includes pulse oximetry, analyzing arterial blood gases, and conducting imaging examinations. Treatment involves giving oxygen, and prostaglandin E1 for congenital heart disease, treating the root cause, and giving methylene blue for methemoglobinemia. Quick assessment and care are crucial for handling cyanosis in newborns.