Cyanosis is a physical sign characterized by a bluish discoloration of the mucous membranes, skin, or nail beds. Cyanosis results from hypoxemia (decreased arterial oxygen saturation) or abnormal hemoglobin molecules. Cyanosis does not become clinically apparent until the absolute concentration of deoxygenated hemoglobin is at least 3.0 g/dL and sometimes not until 5 g/dL. The ability to detect cyanosis varies with skin color and total hemoglobin level. Studies have shown that detection of cyanosis by the clinically trained eye is unreliable with significant inter-observer variability. Due to the potential inaccuracy of clinical assessment, providers should exert caution when making judgments about patient’s oxygenation based on visual perceptions alone.

The differential diagnosis of cyanosis is broad, encompassing multiple organ systems. Included in this differential are the following abnormalities: intracardiac right-to-left shunting, intrapulmonary ventilation-perfusion mismatch, impairment of oxygen diffusion across the alveolus, alveolar hypoventilation, and diminished affinity of hemoglobin for oxygen. The degree of cyanosis is affected by the total hemoglobin concentration and by any factor that affects the O₂ dissociation curve (pH, Pco₂, temperature, and ratio of adult-to-fetal hemoglobin). Cyanosis will be evident sooner and be more pronounced under the following conditions: high hemoglobin concentration (polycythemic patient), lower pH (acidosis), elevated Pco₂, elevated temperature, and elevated ratio of adult-to-fetal hemoglobin.

Detection of cyanosis and concomitant hypoxemia is important for several reasons. Cyanosis is often one of the first signs of many neonatal diseases including congenital heart disease (CHD). And importantly, cyanosis may be an early sign of cardiorespiratory failure. Early identification of cyanosis and prompt intervention may be life saving.

Central cyanosis refers to discoloration of the trunk, lips, and mucus membranes. Central cyanosis should not be confused with acrocyanosis (blueness of the distal extremities only). Acrocyanosis is caused by peripheral vasoconstriction and is a normal finding especially during the first 24 to 48 hours of life. Differential cyanosis is present when the oxygen saturation in the right upper extremity is greater than the lower extremities. Fetuses have minimal blood flow through the fluid-filled lungs due to high pulmonary vascular resistance. As a result, blood crosses from the right side of the heart (pulmonary artery) to the left side of the heart (aorta) in
utero via the patent ductus arteriosus (PDA). The arteries that supply the right arm arise from the ascending aorta prior to the insertion of the PDA and are considered “pre-ductal;” therefore, the right upper extremity oxygen saturation represents the saturation of the blood leaving the left ventricle. The arterial saturations measured in either lower extremity are considered “post-ductal,” as the arterial supply to the lower extremities occurs after the point of ductal insertion in the aortic isthmus. If the ductus arteriosus is patent following delivery, deoxygenated blood may continue to shunt from the pulmonary artery to the descending aorta leading to desaturation in the lower extremities. In the neonatal period, differential cyanosis is observed commonly in patients with persistent pulmonary hypertension of the newborn (PPHN) or CHD lesions with left ventricular outflow tract obstruction (e.g., interrupted aortic arch, coarctation of the aorta, and critical aortic stenosis). Differential cyanosis is an important diagnostic finding in the evaluation of a cyanotic newborn.

In the unusual situation where the pre-ductal saturation is lower than the postductal saturation, reverse differential cyanosis is present. Reverse differential cyanosis results from transposition of the great arteries (TGA) with PPHN or TGA with concurrent left ventricular outflow obstruction (Table 24-1).