Cyanosis resident survival guide (pediatrics)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Usman Ali Akbar, M.B.B.S.[2]

Synonyms and keywords: Cyanosis approach in children, Cyanosis workup pediatrics, Cyanosis management in newborn, Approach to blue discoloration of skin in infants, Hypoxemia approach in children, Hypoxia approach in children

Overview

Cyanosis can be defined as bluish discoloration of skin and mucosa and can also be a manifestation of oxygen desaturation of arterial or capillary blood. Cyanosis, hypoxemia, and hypoxia should be differentiated and can occur independently. The causes of cyanosis in a newborn range from congenital cardiac conditions to life-threatening conditions such as exposure to toxic gases or infections leading to sepsis. The management of cyanosis depends upon the etiology and emergent cases with respiratory distress need rapid evaluation and response with immediate establishment of airway access and oxygen support.

Causes

The causes of cyanosis are diverse and are listed below.^[1]^[2]


Life-Threatening Causes	Pulmonary Causes	Congenital Cardiac Conditions	Hematological Causes	Peripheral Cyanosis
Decreased inspired FiO2 Smoke inhalation Exposure to toxic gases	Asthma Bronchiolitis Bronchopulmonary dysplasia Cystic fibrosis Empyema Hyaline membrane disease Pneumonia	Atrioventricular canal defect Epstein anomaly Hypoplastic left heart syndrome Pulmonary atresia Pulmonic stenosis Tetralogy of Fallot Total anomalous pulmonary venous drainage Transposition of the great vessels Truncus arteriosus	Methemoglobinemia Polycythemia	Acrocyanosis Cold exposure Shock Vasomotor instability Hypothermia Arterial or venous obstruction
Upper airway obstruction Tracheitis Croup Epiglottitis Foreign body aspiration	Pulmonary vascular disorders Pulmonary edema Pulmonary embolism Pulmonary hemorrhage Pulmonary hypertension
	Other Causes Flail chest Hemothorax Open pneumothorax Pneumothorax

FIRE: Focused Initial Rapid Evaluation

Patients presenting to the emergency department with cyanosis and respiratory distress require emergency supplementation of oxygen, use of pulse oximetry and airway, breathing, and circulation support.

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify the patients in need of immediate intervention.^[3]

Patient presents with cyanosis

No Respiratory Distress

Respiratory Distress

Peripheral Cyanosis

Central cyanosis

Differential Cyanosis

No Obstruction

Obstruction

Reassurance and Warming

Hypoxia Test

Cardiac Evaulation

Hypoxia Test

Give oxygen and Positive Pressure Ventilation

PaO2<100

PaO2 100-150

PaO2 <100

PaO2 100-150

PaO2 >150

ENT Evaluation

Cardiac Evaluation

Persistent pulmonary hypertension of newborn, Cardiac Evaluation

Cardiac Cause

Persistent pulmonary hypertension of newborn

Respiratory management, Give oxygen and positive pressure Ventilation

Complete Diagnostic Approach

Shown below is an algorithm summarizing the diagnosis of cyanosis in newborns according to the American Academy of Neonatology guidelines:

Patient presents with cyanosis

History

Age: Certain conditions are more common in neonates as compared to older children such as cyanotic heart conditions and polycythemia.
Presence/Absence of Fever: A history of fever shows the presence of existing infection.
History of Trauma: Chest wall trauma can cause central cyanosis.
Exposure to toxic gases: Exposure to certain gases and smoke can cause cyanosis. Nitrates containing food can also cause methemoglobinemia.
Medication Induced Cyanosis: Certain medications such as amiodarone can be a cause of cyanosis.
Co-existing Pulmonary Pathology: Conditions such as asthma or bronchopulmonary dysplasia can result in cyanosis.
History of Congenital Heart Disease: Central cyanosis can be caused by a number of cyanotic congenital cardiac conditions and may result in shock.
History of Neurological Disease: Respiratory depression due to drug or toxin ingestion, CNS lesions, a history of seizures, breath-holding spells in infants, and neuromuscular disease should be asked and rule out while pursuing causes of cyanosis.

Physical Examination

Fever: An intrinsic pulmonary pathology such as pneumonia can cause fever and cyanosis in children.
Pulmonary Examination: Pulmonary examination may elicit flaring, grunting, retractions, and respiratory distress. Tachypnea is an important finding in patients with the respiratory causes of cyanosis. An upper airway obstruction can cause stridor. Pulmonary edema can cause rales or crackles. Clear lung sounds may be associated with cardiac conditions which cause cyanosis. Injury to lung may present with abnormal chest wall movement, sucking chest wound, ecchymosis on chest wall, tracheal deviation, subcutaneous crepitus and abnormal breathing sounds.
Cardiac Examination: Look for cardiac murmur. A loud or single second heart sound can be present in cyanotic cardiac conditions or pulmonary hypertension.
Skin Examination: Cold exposure can cause peripheral vasoconstriction causing cyanosis whereas central cyanosis due to methemoglobinemia may present with gray appearing skin.

Diagnostic Studies

CBC with differential: An elevated white blood cell may indicate infection.
Arterial Blood Gases:
PaO2>150 mmHg may indicate Pulmonary Parenchymal Disease.
PaO<150 and Normal PCO2 shows the presence of Intra or Extra-Pulmonary Right to Left Shunts.
PaO2>150 mmHg and elevated PCO2 may cause central hyperventilation.
PaO2 <150 mm Hg, usually <50 mmHg and normal PCO2 may include transposition physiology.
Normal PaO2 and PCO2 may be due to hemoglobin disorders.
Hematocrit: Polycythemia or elevated hematocrit may be present in plethoric children.
Chest X-ray: Chest X-ray may show findings in pulmonary pathology. Egg-on-end appearance and pulmonary venous congestion may be present in the transposition of great arteries.
ECG: It is helpful in congenital cardiac conditions. This can be sometimes augmented with echocardiography to specifically identify cardiac pathology.
Methemoglobinemia serum level: It is measured in a cyanotic patient having normal PaO2 with excluded cardiac pathology. Difference between calculated oxygen saturation on ABGs analysis and direct measurement by co-oximetry may indicate methemoglobinemia.
Differential Saturation (pre-ductal vs post-ductal): It is absent in pulmonary parenchymal disease and present if there is right to left shunt at ductus arteriosus. Post-ductal differential saturation is present in the transposition of great vessels.

Treatment

Shown below is an algorithm summarizing the treatment of cyanosis:^[3]^[4]

Treatment depends upon the etiology of cyanosis

Respiratory Compromise

No Respiratory Compromise

*An adequate airway should be established and supplemental oxygen is given.

Continuous positive airway pressure (CPAP) or intubation for positive pressure ventilation can be done for infants with respiratory distress and carbon dioxide retention.
If there is an airway obstruction, prone positioning or oral airway is established to relieve cyanosis.

Depending upon etiology

Sepsis: Broad-spectrum antibiotics should be initiated such as ampicillin and gentamicin.

Blood cultures should be obtained to identify the causative agent.

Neonatal Hypoglycemia: Adequate blood glucose should be maintained in range of >45 to 50 mg/dl.
Cyanotic Congenital Cardiac Conditions should be approached with proper pediatric consultation.
Prostaglandin E1 should be infused at 0.01-0.05mcg/kg/min.

TGA, TAPVR ,Truncus arteriosus

TOF

Ebstein anomaly

Hypoplastic left heart syndrome

Sepsis, shock, low cardiac output state, cold exposure, metabolic disorder, polycythemia

Eisenmenger syndrome with pulmonary hypertension

Methemoglobinemia

Infusion of prostaglandin, diuretic therapy, and surgery.^[5]

Infusion of prostaglandin for keeping patency of ductus arteriosus, infusion of vasodilator for reduced systemic resistance, mechanical ventilation in shock state and imposing hypercapnia and alveolar hypoxia for increased pulmonary resistance

Tricuspid valve repair^[6]

Hypoplastic left heart syndrome

Treatment of underlying disorder

Phosphodiesterase-5 inhibitor (sildenafil, tadalafil). Endothelin receptor antagonist (bosentan,macitentan, ambrisentan).^[7]

Infusion of methylene blue, dextrose, N-acetyl cysteine

Do’s

Hypoplastic left heart syndrome in infants should be considered with signs and symptoms such as:^[8]
- Sudden onset of shock
- Collapse
- Severe academia in the first week of life
- Neonatal sepsis
- Metabolic disorders
In Ebstein anomaly, repair of tricuspid valve is indicated if the following criteria is met:^[6]
In differential cyanosis, if oxygen saturation of right arm is more than that of legs and improves with oxygen supplemental therapy, then think about the following:
In the presence of central cyanosis + hemolytic anemia (jaundice, heinz body, fragment RBC) + renal failure, consider diagnosis of methemoglobinemia and treat accordingly.
Hydration is important in tetralogy of fallot to maintain pulmonary blood flow through atretic pulmonary artery and reducing right to left shunt through VSD.^[9]
If paradoxical embolism is suspected, proceed with a Brain CT scan in the presence of new neurological symptoms in a patient with cyanotic congenital heart disease. It occurs due to passing of emboli from right to left shunt and hyperviscosity ultimately leading to thrombosis.^[10]

Don’ts

There are certain cyanotic congenital heart diseases that are dependent on patent ductus arteriosus (PDA). Don’t give indomethacin to patients with the following ductal dependent congenital conditions:

References

↑ McMullen, SM; Patrick, W (2013). “Cyanosis”. The American journal of medicine. 126 (3): 210–2. doi:10.1016/j.amjmed.2012.11.004. ISSN 0002-9343. PMID 23410559.
↑ Sasidharan, Ponthenkandath (2004). “An approach to diagnosis and management of cyanosis and tachypnea in term infants”. Pediatric clinics of North America. Elsevier BV. 51 (4): 999–1021. doi:10.1016/j.pcl.2004.03.010. ISSN 0031-3955. PMID 15275985.
↑ ^3.0 ^3.1 Dasgupta, Soham; Bhargava, Vidit; Huff, Monica; Jiwani, Amyn K.; Aly, Ashraf M. (2016-09-30). “Evaluation of The Cyanotic Newborn: Part I—A Neonatologist’s Perspective”. NeoReviews. American Academy of Pediatrics (AAP). 17 (10): e598–e604. doi:10.1542/neo.17-10-e598. ISSN 1526-9906.
↑ “Congenital Heart Disease”. NCBI Bookshelf. 2010-07-22. Retrieved 2020-10-13.
↑ Rao, P. Syamasundar (2013). “Consensus on Timing of Intervention for Common Congenital Heart Diseases: Part II – Cyanotic Heart Defects”. The Indian Journal of Pediatrics. 80 (8): 663–674. doi:10.1007/s12098-013-1039-2. ISSN 0019-5456.
↑ ^6.0 ^6.1 Holst KA, Connolly HM, Dearani JA (2019). “Ebstein’s Anomaly”. Methodist Debakey Cardiovasc J. 15 (2): 138–144. doi:10.14797/mdcj-15-2-138. PMC 6668741 Check |pmc= value (help). PMID 31384377.
↑ de Campos F, Benvenuti LA (2017). “Eisenmenger syndrome”. Autops Case Rep. 7 (1): 5–7. doi:10.4322/acr.2017.006. PMC 5436914. PMID 28536680. Vancouver style error: initials (help)
↑ Gobergs R, Salputra E, Lubaua I (2016). “Hypoplastic left heart syndrome: a review”. Acta Med Litu. 23 (2): 86–98. doi:10.6001/actamedica.v23i2.3325. PMC 5088741. PMID 28356795.
↑ O’Brien, Patricia; Marshall, Audrey C. (2014). “Tetralogy of Fallot”. Circulation. 130 (4). doi:10.1161/CIRCULATIONAHA.113.005547. ISSN 0009-7322.
↑ . doi:10.1161/STROKEAHA.116.012882Stroke. Missing or empty |title= (help)

[McMullen_Patrick_2013_pp._210–2-1] McMullen, SM; Patrick, W (2013). “Cyanosis”. The American journal of medicine. 126 (3): 210–2. doi:10.1016/j.amjmed.2012.11.004. ISSN 0002-9343. PMID 23410559.

[Sasidharan_2004_pp._999–1021-2] Sasidharan, Ponthenkandath (2004). “An approach to diagnosis and management of cyanosis and tachypnea in term infants”. Pediatric clinics of North America. Elsevier BV. 51 (4): 999–1021. doi:10.1016/j.pcl.2004.03.010. ISSN 0031-3955. PMID 15275985.

[Dasgupta_Bhargava_Huff_Jiwani_pp._e598–e604-3] 3.0 ^3.1 Dasgupta, Soham; Bhargava, Vidit; Huff, Monica; Jiwani, Amyn K.; Aly, Ashraf M. (2016-09-30). “Evaluation of The Cyanotic Newborn: Part I—A Neonatologist’s Perspective”. NeoReviews. American Academy of Pediatrics (AAP). 17 (10): e598–e604. doi:10.1542/neo.17-10-e598. ISSN 1526-9906.

[NCBI_Bookshelf_2010-4] “Congenital Heart Disease”. NCBI Bookshelf. 2010-07-22. Retrieved 2020-10-13.

[Rao2013-5] Rao, P. Syamasundar (2013). “Consensus on Timing of Intervention for Common Congenital Heart Diseases: Part II – Cyanotic Heart Defects”. The Indian Journal of Pediatrics. 80 (8): 663–674. doi:10.1007/s12098-013-1039-2. ISSN 0019-5456.

[pmid31384377-6] 6.0 ^6.1 Holst KA, Connolly HM, Dearani JA (2019). “Ebstein’s Anomaly”. Methodist Debakey Cardiovasc J. 15 (2): 138–144. doi:10.14797/mdcj-15-2-138. PMC 6668741 Check |pmc= value (help). PMID 31384377.

[pmid28536680-7] Campos F, Benvenuti LA (2017). “Eisenmenger syndrome”. Autops Case Rep. 7 (1): 5–7. doi:10.4322/acr.2017.006. PMC 5436914. PMID 28536680. Vancouver style error: initials (help)

[pmid28356795-8] Gobergs R, Salputra E, Lubaua I (2016). “Hypoplastic left heart syndrome: a review”. Acta Med Litu. 23 (2): 86–98. doi:10.6001/actamedica.v23i2.3325. PMC 5088741. PMID 28356795.

[O’BrienMarshall2014-9] O’Brien, Patricia; Marshall, Audrey C. (2014). “Tetralogy of Fallot”. Circulation. 130 (4). doi:10.1161/CIRCULATIONAHA.113.005547. ISSN 0009-7322.

[10] . doi:10.1161/STROKEAHA.116.012882Stroke. Missing or empty |title= (help)

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