Approach to Neonatal Cyanosis

Click for pdf: Neonatal Central Cyanosis

General Presentation

Central cyanosis is a bluish discoloration of the skin, mucus membranes and tongue that is observed when deoxygenated hemoglobin is > 3g/dL in arterial blood or > 5g/dL (>3.1mmol/L) in capillary blood. It is associated with a low arterial partial pressure of oxygen (PaO2) and low hemoglobin oxygen saturation (SaO2) as measured by oxymetry. Cyanosis is dependent on the absolute concentration of deoxy Hb, not on the ratio of oxy Hb/deoxy Hb. For instance, in a normal neonate with a Hb concentration of 17 g/dL, when hemoglobin oxygen saturation (SaO2) is 82%, deoxy Hb is > 3g/dL. However, in polycythemia, cyanosis is detectable at a higher value of SaO2, whereas in anemia, the reverse is true. Thus, in severe anemia, cyanosis cannot be detected by observation.

Another type of cyanosis, called peripheral cyanosis, involves a bluish discoloration of the skin but sparing of the mucus membranes & tongue. In this type, a normal PaO2 value is detected. In this case, increased oxygen extraction due to sluggish movement through the capillaries leads to increased deoxygenated blood on the venous side. Vasomotor instability, and vasoconstriction caused by cold, low cardiac output and polycythemia can all cause this slow movement through the capillaries. Peripheral cyanosis is often a normal finding in newborns, especially when only the extremities are affected (acrocyanosis) due to vasoconstriction as a result of transient hypothermia; however, it is important to rule out serious causes of peripheral cyanosis, such as sepsis.

Questions to Ask

Explore pregnancy and labor history as suggested below. Also ask about family history of congenital heart disease and fetal ultrasound results, as the latter may reveal structural deformities such as congenital heart disease, diaphragmatic hernia and congenital cystic adenomatoid malformation (CCAM).

Pregnancy HX	Associated causes of cyanosis
Gestational diabetes mellitus (GDM)	TTN, RDS, hypoglycemia, TGA
Oligohydramnios	Pulmonary hypoplasia
Pregnancy induced hypertension	IUGR, polycythemia, hypoglycemia
Lithium intake (1st trimester)	Ebstein’s anomaly
Advanced maternal age	Trisomy 21 associated with many congenital heart defects (cyanotic and acyanotic)

Labour Hx	Associated causes of cyanosis
PROM, fever, GBS +ve	Sepsis
Sedatives/anesthetics	Respiratory depression, apnea
C-section	TTN, PPHN
Preterm infant	RDS
Meconium	MAS (pneumonia)

Abbreviations: TTN = transient tachypnea of the newborn, RDS = respiratory distress syndrome, TGA = transposition of the great arteries, IUGR = intrauterine growth retardation, PPHN = persistent pulmonary hypertension of the newborn, also known as persistent fetal circulation, MAS = meconium aspiration syndrome

Physical Examination

Determine whether the cyanosis is central or peripheral

Check the vitals: signs of respiratory distress such as tachypnea, retractions, nasal flaring & grunting usually indicate a respiratory problem

Congenital heart disease is often accompanied by absent or effortless tachypnea.
Sepsis often has the following findings: peripheral cyanosis, HR, Increase RR, Decrease BP, Increase/Decrease temp (DDX: left-sided obstructive lesions: hypoplastic left heart syndrome, critical aortic stenosis & severe coarctation of the aorta).
Rule out choanal atresia. If in doubt, attempt to insert a catheter through the nares

Listen for murmurs: a systolic murmur audible in most forms of cyanotic CHD (exception: d-TGA with intact ventricular septum & no pulmonary stenosis).

Assess the abdomen: scaphoid abdomen in diaphgragmatic hernia

Consider neurological disorders: observe for apnea and periodic breathing, which may be related to immaturity of the nervous system. Seizures can cause cyanosis if the infant fails to breathe during the episodes.

Differential Diagnosis

To determine the underlying cause of cyanosis in a newborn, it is important to think about the various mechanism of cyanosis. Then, organize your thoughts by anatomical systems.

Ventilation/perfusion mismatch

Airway disease: transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), pneumonia, aspiration (meconium, blood, amniotic fluid), atelectasis, diaphragmatic hernia, pulmonary hypoplasia, pulmonary hemorrhage, CCAM
Extrinsic compression of the lungs: pneumothorax, pleural effusion, hemothorax,

Right-to-left shunt

Intracardiac: The 5 T’s: Tetralogy of Fallot, Tricuspid atresia, Transposition of the great arteries, Total anomalous pulmonary venous return, Truncus arteriosus; and pulmonary atresia, Ebsteins anomaly (abnormal tricuspid valve), hypoplastic left heart
Great vessel level: persistent pulmonary, hypertension of the newborn
Intrapulmonary level: pulmonary arteriovenous malformation

Alveolar Hypoventilation

CNS depression: asphyxia, maternal sedation, intraventricular hemorrhage, seizure, meningitis, encephalitis
Airway obstruction: choanal atresia, laryngomalacia, Pierre Robin syndrome
Neuromuscular disease: phrenic nerve inury, neonatal myasthenia gravis

Diffusion Impairment

Pulmonary edema: left-sided obstructive cardiac disease (aortic stenosis), cardiomyopathy
Pulmonary fibrosis

Decrease Hemoglobin O2 affinity

Methemoglobinemia (congenital, drugs)

Decrease Peripheral circulation (peripheral cyanosis)

Sepsis, shock of any cause, polycythemia, hypothermia, hypoglycemia, low cardiac output (hypocalcemia, cardiomyopathies, etc)

Investigations:

CBC & diff :

Increase or decrease WBC : sepsis
Hematocrit > 65% : polycythemia

Serum glucose:

to detect hypoglycemia

Arterial Blood Gases (ABGs):

Arterial PO2: to confirm central cyanosis : SaO2 not as good an indicator due to Increase fetal Hb affinity for O2 (left-shift)
Increase PaCO2: may indicate pulmonary or CNS disorders, heart failure
Decrease pH: sepsis, circulatory shock, severe hypoxemia
Methemoglobinemia: Decrease SaO2, normal PaO2, chocolate-brown blood

Hyperoxia test:

Administer 100 % oxygen for > 10 min
PaO2 > 100 mmHg: pulmonary disease likely
PaO2 < 70 mmHg, rise by < 30 mmHg or SaO2 unchanged: cardiac cause (R-L shunt) likely
Total anomalous pulmonary venous return may respond
Pulmonary disease with a massive intrapulmonary shunt may not respond

Pre-ductal & Post-ductal PaO2 or SaO2 measurements (pre- and post- ductus arteriosus):

Preductal artery (right radial) PaO2 10 – 15 mmHg > post ductal artery (umbilical artery line) PaO2 : R – L ductal shunt (e.g., pulmonary diseases, commonly PPHN)
SaO2 can also be measured (right hand & right or left leg) : significant if > 10-15 % difference.

CXR:

To identify pulmonary causes of cyanosis: pneumothorax, pulmonary hypoplasia, diaphragmatic hernia, pulmonary edema, pleural effusion, etc.
Useful in evaluating congenital heart disease: e.g., cardiomegaly & vascular congestion: heart failure
- TGA : egg-on-a-string (anterior/posterior relationship of great vessels)
- TOF : boot-shaped heart (RVH)
- TAPVR : snowman, figure 8 (anomalous drainage chamber in superior mediastinum)

Echocardiography

Indicated if abnormal cardiac examination suggestive of congenital heart defect, failed hyperoxia test (cardiac disease suspected) or has unclear diagnosis

Initial Management

Monitor Airway, breathing, circulation (ABCs) with respiratory compromise, establish an airway & provide supportive therapy (e.g., oxygen, mechanical ventilation)
Monitor Vital signs
Establish vascular access for sampling blood & administering meds (if needed): umbilical vessels convenient for placement of intravenous & intraarterial catheters
If sepsis is suspected or another specific cause is not identified, start on broad spectrum antibiotics (e.g., ampicillin and gentamycin) after obtaining a CBC, urinalysis, blood & urine cultures (if possible). Left untreated, sepsis may lead to pulmonary disease & left ventricular dysfunction.

An infant who fails the hyperoxia test & does not have PPHN or a CXR showing pulmonary disease likely has a congenital heart defect that’s ductus-dependent. If cardiac disease is suspected, immediately start PGE1 infusion. Complications of PGE1 infusion include hypotension, tachycardia, apnea. Secure a separate intravenous catheter to provide fluids for resuscitation and ensure accessibility of intubation equipment should they be required.

Conclusion:

Central cyanosis in a newborn is an abnormal finding and one must consider all of the possible etiologies with a complete history, physical examination and relevant investigations. Remember to think about the various mechanisms causing cyanosis and go through each systematically until you have your diagnosis. Prompt management should be undertaken while you are trying to figure out your diagnosis. Putting all of this together, you will be sure not to miss an important diagnosis and keep your patient safe at the same time!

References

Sasidharan, P. An approach to diagnosis and management of cyanosis in term infants. Pediatr Clin N Am 2004;

51:999-1021.

Robbert LG, Armsby, L. Evaluation and initial management of cyanotic heart disease in the newborn. UpToDate 2006. www.uptodate.com.

Stack, AM. Etiology and evaluation of cyanosis in children. UpToDate 2009. www.uptodate.com.

Rudolph AM et al. Rudolph’s Fundamentals of Pediatrics. 2002; 142-144.

Neonatal Handbook: Cyanosed Infant Assessment.

http://www.rwh.org.au/nets/handbook/index.cfm?doc_id=903.

Tricia LG et al. Neonatology: Management, Procedures, On-Call Problems, Diseases and Drugs. 1999; 212-215.

Acknowledgments

Written by: Vitharani Kunanithy

Edited by: Anne Marie Jekyll, MD (Pediatric Resident)