Congenital heart diseases (CHDs) are conventionally categorized based on whether or not they produce cyanosis.[1,2] Shunt lesions without cyanosis are characterized by the left-to-right shunt, while right-to-left shunt is the hemodynamic hallmark of cyanotic CHDs. In tetralogy physiology, with obstructed pulmonary outflow, the pulmonary blood flow is reduced. Cyanosis in admixture lesions and transposition physiology, on the other hand, results from the bidirectional shunt, often leading to increased pulmonary blood flow. The extent of right-to-left shunt determines the degree of hypoxemia, with some CHDs having only mild hypoxemia. Despite mild hypoxemia, nonetheless, most CHDs with a right-to-left shunt have unfavorable clinical outcomes if not treated in time. The lack of cardiac murmurs and other physical signs in some of these patients further highlights the importance of detecting hypoxemia even in the absence of visible cyanosis.
Despite rapidly improving health facilities, even today, it is not uncommon, to encounter missed diagnoses or delayed referral of patients with serious CHDs.[3-5] Although seen less frequently in high-income countries, the problem of delayed detection of CHDs is not unique to low- and middle-income countries.[6,7] Interestingly, delayed detection is frequent in cyanotic CHDs, with delayed detection by the doctor as the reason in more than half.[4,7] Needless to say, timely detection is the key to optimal clinical outcomes with acceptable morbidity, mortality, and cost to the health-care infrastructure. Early detection of CHDs by optimal utilization of sparse resources is possibly the easiest step in tackling the challenges of inequitable healthcare in low- and middle-income countries. Therefore, the question is - it is justified to rely on cyanosis to detect hypoxemia, more so with the easy availability of much more accurate pulse oximetry to detect hypoxemia?.
PATHOPHYSIOLOGY OF CYANOSIS
Cyanosis is bluish discoloration of the skin and mucous membranes due to increased deoxyhemoglobin in superficial capillaries, arterioles, and venules.[10,11] There has been a lot of confusion over the absolute concentration of deoxyhemoglobin required for cyanosis. It is primarily because some investigators have mistakenly equated arterial levels of deoxyhemoglobin with capillary levels.[11-14] Although some have suggested a much lower cut-off, the average amount of deoxyhemoglobin believed to produce cyanosis is 3.48 g/dL and 5.35 g/dL in the arterial and capillary blood, respectively.[15,16]
CYANOSIS IS NOT THE SAME AS HYPOXEMIA
Cyanosis is a clinical sign of hypoxemia, but both are not the same. Cyanosis and hypoxemia, although interrelated, can each exist independently of the other. On most occasions, cyanosis represents hypoxemia, although some cases with abnormal hemoglobin can also have cyanosis despite normoxemia.[1,2] The reverse, however, is not true, and hypoxemia does not always lead to cyanosis. The measurement of partial pressure of oxygen and oxygen saturation in arterial blood is the gold standard for assessing the level of oxygenation, but is invasive and not always feasible. Pulse oximetry is yet another accurate method of estimating oxygen saturation in the blood and is the standard of care, with some even claiming it to be the fifth vital sign. With a few exceptions of abnormal hemoglobin and poor peripheral perfusion, oxygen saturation (SpO2) <94% reflects hypoxemia.
Cyanosis, on the other hand, besides the level of deoxyhemoglobin in the arterial blood, relies heavily on the hemoglobin concentration of the patient, lighting conditions, the skin color of the patient, and the experience of the observer.[11,13,14] Consequently, it is not uncommon for parents and even treating pediatricians to miss mild cyanosis, while trained pediatric cardiologists may detect the same with ease.
CYANOSIS AS A DIAGNOSTIC TEST TO IDENTIFY CONGENITAL HEART DISEASES WITH RIGHT-TO-LEFT SHUNT
Despite challenges in detection, cyanosis has helped generations of clinicians in the clinical diagnosis of CHDs with a right-to-left shunt. Nevertheless, clinical detection of hypoxemia using cyanosis is notoriously unreliable.[11,13] The clinical detection of cyanosis varies widely among clinicians and has only mid-range agreement among observers. In a study with 105 medical students and 22 physicians observing 20 subjects inhaling varying levels of oxygen concentration, as many as 25% of observers could not detect cyanosis at arterial saturation of 71%–75%, while 17% of observers believed cyanosis to be present when arterial saturations were 91%–95%. Not just mild hypoxemia, health professionals have even missed serious CHDs such as transposition of great arteries and pulmonary atresia while basing their assessment solely on the detection of cyanosis. With a cut-off of 80% oxygen saturation at a hemoglobin concentration of 12 g/dL, cyanosis has a sensitivity of 79%–95% and a specificity of 72%–95% for detecting severe hypoxemia, with a positive and negative likelihood ratio of 7.4 and 0.2, respectively. Although the detection of cyanosis can be improved by training and experience, it is unlikely to reach the desired level of clinical accuracy as pulse oximetry.
PULSE OXIMETRY SCREENING FOR CONGENITAL HEART DISEASES WITH RIGHT-TO-LEFT SHUNT
Cyanosis-based identification of CHDs with right-to-left shunt was acceptable in an earlier era when the diagnostic tools and therapeutic options were limited. Nonetheless, it is no longer acceptable as the natural history of most of the CHDs can be favorably altered if treated in time. Screening tools and techniques with greater sensitivity and specificity, therefore, are the need of the hour. At present, perhaps, it is not acceptable to miss even a single patient with cyanotic CHD during infancy, if not in the neonatal period.
An echocardiography-based universal screening for CHDs is ideal, but considering additional costs, it is an impractical approach. Pulse oximetry-based screening for arterial desaturation, on the other hand, is cheap, easy to perform, and widely available. Besides being cost-effective, pulse oximetry screening is acceptable to both parents and health professionals.[18,19] In the last two decades, neonatal pulse oximetry screening for critical CHDs has become the standard of care. Pulse oximetry screening is moderately sensitive and highly specific in detecting cyanotic CHDs[20,21] and reduces the diagnostic gap. When combined with antenatal ultrasound screening and the newborn physical examination, pulse oximetry screening has permitted the detection of so-called cyanotic CHDs in 92%–96% of neonates. The benefits accrued from neonatal pulse oximetry screening, both in improved diagnostic yield and reduced mortality from cyanotic CHDs, have prompted many countries to recommend the test in all neonatal care units.[20,24,25]
LESSONS LEARNED FROM NEONATAL PULSE OXIMETRY SCREENING
A pulse oximetry-based detection of hypoxemia, irrespective of age, is likely to help in the timely detection of CHDs with a right-to-left shunt. Besides, pulse oximetry facing no challenges of transitional circulation beyond the neonatal period ought to be more reliable. The measurement of SpO2 following exercise may also help unmask exercise-related right-to-left shunt, making the test even more sensitive for detecting CHDs with mild hypoxemia. The ease of availability, performance, and interpretation makes pulse oximetry an attractive and effective and possibly a better alternative to cyanosis-based detection of CHDs with a right-to-left shunt.
WHAT NEEDS TO CHANGE?
Cyanosis is a valuable clinical sign providing information about the type of CHD. Nevertheless, the diagnostic accuracy of cyanosis for the detection of hypoxemia, especially when mild, is limited. Pulse oximetry-based detection of arterial desaturation, on the other hand, is much more accurate and reproducible. Rapidly accumulating experience with the use of pulse oximetry underscores the utility of arterial desaturation-based detection of CHDs with a right-to-left shunt. Therefore, for bedside detection of hypoxemia, it is possibly better to detect arterial desaturation by pulse oximetry instead of relying on clinical detection of cyanosis.
The suggested approach is to improve the timely detection of CHD with right-to-left shunt and not to propose discontinuation of the widely used term “cyanotic CHD.” The time only will decide if, in future, clinicians will prefer “CHD with arterial desaturation” over “cyanotic CHD.”
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