As an example, 3 g/dL of reduced hemoglobin is associated with an oxygen saturation of 67 percent when the total hemoglobin concentration is 9 g/dL, and 85 percent when the hemoglobin concentration is 20 g/dL.
This characteristic aids in fetal uptake of oxygen from the placenta but results in less oxygen delivery to the tissues
Those that increase the affinity of hemoglobin for oxygen (shifting the oxygen dissociation curve to the left), decrease the concentration of reduced hemoglobin at a given arterial P02, and lower the PO2 at which cyanosis first appears. These factors include alkalosis, hyperventilation (low PC02), cold temperature, and low levels of 2,3 diphosphoglycerate (show figure 2)  . In contrast, acidosis, fever, or increased adult hemoglobin shift the curve to the right. As a result, at a given arterial PO2, there is increased oxygen delivery to the tissues resulting in a greater concentration of reduced hemoglobin, and cyanosis appears more readily.
Methemoglobinemia- An oxidized form of hemoglobin, cannot carry oxygen and, when present in significant quantities, will cause cyanosis. Acquired or congenital disorder due to nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase deficiency and hemoglobin M disorder.
Lithium- Ebstein anomaly Fetal hydantoin synd- PS, AS Fetal alcohol- VSD,ASD Connective tissue disorder- congenital complete heart block associated with anti-Ro/SSA and anti-La/SSB antibodies. Congenital infections- cytomegalovirus, herpesvirus, rubella, or coxsackie virus can lead to cardiac structural abnormalities or functional impairment.
several of the most serious anatomic abnormalities, such as transposition of the great arteries, produce only a very soft murmur or no murmur at all.
Probe site — Postductal probe placement is the optimal site because defects with right-to-left shunting of desaturated blood through the ductus arteriosus will not be detected with preductal placement. Signal quality and infant behavior  — Measurements should not be performed when the infant is crying or moving as it reduces the quality of the signal and the accuracy of the test.
oxygen. With dyshemoglobinemia it is possible to have a substantial reduction in the blood’s oxygen carrying capacity and yet have normal functional saturation. Thus, normal functional saturation does not ensure adequate oxygen carrying capacity, so a functional saturation reading could mislead someone who did not know the difference between functional and fractional saturation- methemoglobinemia and carboxyhemoglobinemia
Approach to a neonate with cyanosis
Approach to a Neonate withCyanosisDr. Sunil Agrawal1styr MD pediatrics
Contents• Introduction• Central, Peripheral and Differential cyanosis• Mechanism• Etiology• Approach• Principles of Treatment• Conclusion• References
Introduction• Bluish discoloration of the tissues thatresults when the absolute level of reducedhemoglobin in the capillary bed exceeds 3g/dL• Depends upon the total amount ofreduced hemoglobin rather than the ratioof reduced to oxygenated hemoglobin.
Central cyanosis• Pathologic condition caused by reducedarterial oxygen saturation.• Involves highly vascularized tissues, suchas the lips and mucous membranes,through which blood flow is brisk and thearteriovenous difference is minimal.• Cardiac output typically is normal, andpatients have warm extremities.
Peripheral cyanosis• Normal systemic arterial oxygen saturationand increased oxygen extraction, resultingin a wide systemic arteriovenous oxygendifference• The increased extraction of oxygen resultsfrom sluggish movement of blood throughthe capillary circulation
Peripheral cyanosis• Causes-– vasomotor instability, vasoconstriction causedby exposure to cold, venous obstruction,elevated venous pressure, polycythemia, andlow cardiac output• Affects the distal extremities andcircumoral or periorbital areas .
Differential cyanosis• Upper half of the body is pink and thelower half cyanotic, or vice versa• Requires pulmonary vascular resistanceelevated to a systemic level and a patentductus arteriosus.
Mechanism of cyanosis• Alveolar hypoventilation• Diffusion impairment• Ventilation-perfusion mismatch• Right-to-left shunting at the intracardiac,great vessel, or intrapulmonary level• Hemoglobinopathy (includingmethemoglobinemia) that limits oxygentransport
Factors affecting the detection ofcyanosis in the newborn• Hemoglobin concentration -– Detected at higher levels of saturation inpolycythemic than in anemic patients.– Significant oxygen desaturation can bepresent in an anemic patient without clinicallydetectable cyanosis.
The arterial oxygen saturation level at which cyanosis isdetectable at different total hemoglobin concentrations isillustrated above. The solid red portion of each bar represents 3gm/dL reduced hemoglobin. Reproduced with permission from:Lees, MH. Cyanosis of the newborn infant. J Pediatr 1970;77:484.
Factors affecting the detection ofcyanosis in the newborn• Fetal hemoglobin —– Binds oxygen more avidly than adult hemoglobin.– The oxygen dissociation curve is shifted to the left, sothat for a given level of oxygen tension (PO2), theoxygen saturation (SO2) is higher in the newborn thanolder infants or adults– It also follows that for a given level of oxygensaturation, the PO2 is lower in newborns.– As a result, cyanosis is detected at a lower PO2 innewborns compared with older patients. Thus, inevaluating a cyanotic newborn, PO2 should bemeasured in addition to SO2 to provide morecomplete data.
Factors affecting the detection ofcyanosis in the newborn• Other physiologic factors common in sicknewborns affect the oxygen dissociationcurve.
Factors affecting the detection ofcyanosis in the newborn• Skin pigmentation -– Less apparent in the skin of patients withdarker pigmentation.– Examination should include the nail beds,tongue, and mucous membranes, which areless affected by pigmentation.
Non-cardiac causes• Hemoglobinopathy– Methemoglobinemia: congenital or secondary to toxicexposure– Other hemoglobinopathies• Diffusion impairment– Pulmonary edema: left-sided obstructive cardiacdisease, cardiomyopathy– Pulmonary fibrosis– Congenital lymphangiectasia
Cardiac causes• Decreased pulmonary blood flow-– Tetralogy of Fallot– Tricuspid valve anomaly– Pulmonary valve atresia– Critical valvular pulmonary steanosis• Increased pulmonary blood flow-– Transposition of great arteries– Truncus arteriosus– Total anomalous pulmonary venous connection
Cardiac causes• Severe heart failure-– Hypoplastic left heart syndrome– Coarctation of the aorta– Interrupted aortic arch– Critical valvular aortic steanosis
Mnemonic• Cardiac causes- "five Ts" of cyanotic CHD:– Transposition of the great arteries– Tetralogy of Fallot– Truncus arteriosus– Total anomalous pulmonary venous connection– Tricuspid valve abnormalities.• A sixth "T" is often added for "tons" of other diseases,such as double outlet right ventricle, pulmonary atresia,multiple variations of single ventricle, hypoplastic leftheart syndrome, or anomalous systemic venousconnection (left superior vena cava connected to the leftatrium).
Differential cyanosis• With normally related great arteries, oxygensaturation may be higher in the upper than lowerextremity in patients if there is right-to-leftshunting through the ductus arteriosus.• Seen with severe coarctation or interruptedaortic arch.• May also occur in patients persistent pulmonaryhypertension of the newborn• The differential effect is reduced if there is alsoright-to-left shunting at the level of the foramenovale, or if there is left-to-right shunting across acoexisting ventricular septal defect
Differential cyanosis• Reversed differential cyanosis is a rarefinding that may occur in patients withtransposition of the great arteriesassociated with either coarctation orpulmonary hypertension.• In these infants, oxygen saturation ishigher in the lower than upper extremity.
Aim• Differentiate physiologic from pathologiccyanosis• Differentiate cardiac from non- cardiaccause of cyanosis• Find cause which needs urgent treatmentor referral
Not so serious• Acrocyanosis– Bluish color in the hands and feet and around themouth (circumoral cyanosis). The mucus membranesgenerally remain pink.– Reflects benign vasomotor changes in the diffusevenous structures in the affected areas.– Does not indicate pathology unless cardiac output isextremely low, resulting in cutaneous vasoconstriction• Cyanosis soon after birth- transition fromintrauterine to extrauterine life• Hand or leg prolapse
History• Methemoglobinemia may be acquiredfollowing exposure to aniline dyes,nitrobenzene, nitrites, and nitrates.
Onset of cyanosis in cardiac lesions-• Depends on-– Nature and severity of the anatomic defect– In utero effects of the structural lesion– Alterations in cardiovascular physiologysecondary to the effects of transitionalcirculation like closure of ductus arteriosusand the fall in pulmonary vascular resistance
Onset of cyanosis in cardiac lesionsAge on admission In order of frequency0-6 days D- transposition of great arteriesHypoplastic left ventriclesTetralogy of fallot7-13 days Coarctation of aortaHypoplastic left ventricleD-transposition of great arteriesTetralogy of fallot14-28 days Coarctation of aortaTetralogy of fallotD- transposition of great arteriesNeonatology- Pathophysiology and management of newborn, 5thedition ed.1999. Philadelphia; Lippincott Williams and Wilkins
History- Risk factors• Pneumonia/ sepsis-– PROM– Foul smelling liquor– Maternal pyrexia– Maternal GBS• TTN –– Birth by cesarean sectionwith or without labor– Male sex– Family history of asthma(especially in mother)– Macrosomia– Maternal diabetes• Polycythemia-– small-for-gestational age• MAS-– Post maturity– Small for gestational age– Placental dysfunction– Fetal distress– Meconium stained liquor• Pneumothorax-– Aggressive resucitation– IPPV– Meconiun aspiration– HMD– Hypoplastic lung– Staph pneumonia• Hyaline membranedisease-– Premature infant– Infant of diabetic mother
History• Choanal atresia-– Cyanosis decreases during crying– Confirmed by failure to pass a soft No. 5F to8F catheter through each nostril
Physical Examination• Vital signs-–Hypothermia or hyperthermia- infection.–Tachycardia-hypovolemia.–Weak pulses- Hypoplastic left heartsyndrome or hypovolemia.–Pulses or blood pressures stronger inthe upper than in the lower extremities-coarctation of the aorta.
Physical Examination• Congenital heart disease-– Respirations often are unlabored unless thereis pulmonary congestion or complicated bythe development of heart failure or acidosis,which will affect the respiratory pattern.• CVS-– Presence or absence of a heart murmur is oflittle assistance. Loud S2 suggests pulmonaryor systemic hypertension or malposition of theaorta.
Physical Examination• Inspiratory stridor-–upper airway obstruction• Chest-– Asymmetric chest movement combined withsevere distress-• alarming sign for tension pneumothorax,diaphragmatic hernia– Transillumination of the chest-• Pneumothorax on an emergent basis
Physical Examination• Central nervous depression-– Causes shallow, irregular respirations andperiods of apnea.– Affected infants typically appear hypotonicand lethargic.
Pulse oximetry screening• Difficulty in visual detection of cyanosis• Potentially severe consequences of missing anearly sign of CHD• “5thvital sign”• Sensitivity and specificity varies-– Criteria used for abnormal test– Timing of screening– Probe site– Quality of the equipment– Signal quality and neonate behaviour– Health care workers expertise
Pulse Oximetry• Oxygen saturation should be performedinitially on room air to serve as a baseline.• Subsequently can be served todifferentiate between cardiogenic and non-cardiogenic causes
Limitations of pulse oximetry• effects of ambient light• skin pigmentation• dyshemoglobinemia• low peripheral perfusion states• motion artifact
Hyperoxia test• If a low-pulse oximeter reading persists, itmay be appropriate to proceed to ahyperoxia test. It is indicated if the pulseoximeter reading is less than 85% in bothroom air and 100% oxygen• It is not recommended in preterm infants.• Useful in distinguishing cardiac frompulmonary causes of cyanosis.
Hyperoxia test• Arterial oxygen tension is measured in the rightradial artery (preductal) and in a lower extremityartery while the patient breathes 100 percentoxygen (postductal).• Pulse oximetry cannot be used- in neonate given100% inspired O2 a value of 100% saturationmay be obtained with an arterial PO2 rangingfrom 80 torr( abnormal) to 680 torr (normal)
Hyperoxia testDisease Result- Increasein PaO2Lung disease is more likely thanCHD>150 mmHgTGA or severe pulmonary outflowobstruction<50 to 60 mmHgIn lesions with intracardiac mixingand increased pulmonary bloodflow such as truncus arteriosus->75 to 150mmHg
Differential cyanosis• To detect differential cyanosis, oxygensaturation should be measured in sitesthat receive blood flow from both preductal(right hand) and postductal (foot) vessels.It is preferable to use the right (rather thanleft) upper extremity, since the leftsubclavian artery arises close to theductus arteriosus, and some of its flowmay come from the ductus and thus notreflect preductal values
Chest X-Ray• Aberrancy of the cardiothymic silhouette-– Suggest the presence of structural heartdisease, and– Abnormalities of the lung fields may be helpfulin distinguishing a primary pulmonary problemsuch as meconium aspiration
Chest X- Ray• Pulmonary vascular markings-– Decreased in CHD with obstructed pulmonaryblood flow such as tetralogy of Fallot, severepulmonary stenosis or atresia, and tricuspidatresia.– Increased in admixture lesions liketransposition of the great arteries, totalanomalous pulmonary venous connection,and truncus arteriosus.
Total Anomalous PulmonaryVenous Return• Snowman
Transposition of GreatArteries• Egg on astring
Investigation• If central cause-– appropriate scan and drug levels• Methemoglobinemia-– Place few drops of pt blood on filter paper– Appear chocolate brown
Treatment• Goals-– Provide adequate tissue oxygen and CO2removal• Principles-– Establish airway– Ensure oxygenation– Ensure adequate ventilation– Correct metabolic abnormalities– Alleviate the cause of respiratory distress
Treatment- Buy time• Prostaglandin E1– For ductal dependant CHD/ reducedpulmonary blood flow- Fail hyperoxia test( Anarterial PO2 of less than 100 torr in theabsence of clear- cut lung disease)– Infusion of prostaglandin E1 at a dose of 0.05-0.1mcg/kg/min intravenously to maintainpatency
Treatment- buy time• Prostaglandin E1-– S/E- hypoventilation, apnea, edema and lowgrade fever– Benefits- Can be stabilized more easily,allowing for safe transport to a tertiary carecenter. More time is also available forthorough diagnostic evaluation and patientscan be brought to surgery in a more stablecondition.
Conclusion• Identify those that are life-threatening.• complete maternal and newborn history• perform a thorough physical examination• recognize the common respiratory andcardiac disorders• differentiate among various diagnosticentities• For ductal dependent lesion, startprostaglandin E1 and early referral