Dr.Afnan Shamraiz

Contents Introduction Central, Peripheral and Differential

cyanosis Mechanism Etiology Approach Principles of Treatment Conclusion

IntroductionCyanosis is derived from the colour ‘cyan’, which

comes from ‘kyanous’, the Greek word for blue It is defined as the bluish discoloration of the skin

and the mucous membranes, resulting from an increase in the reduced Haemoglobin or of haemoglobin derivatives in the small vessels of those areas.

Bluish discoloration of the tissues that results when the absolute level of reduced hemoglobin in the capillary bed exceeds 3- 4 g/dL

Depends upon the total amount of reduced hemoglobin rather than the ratio of reduced to oxygenated hemoglobin.

Sites to detect cyanosis Lips Nail beds Ears Malar Prominences Palms and Soles Tongue Mucous membranes of gum,soft palate,cheeks

Types of Cyanosis Central Cyanosis Peripheral Cyanosis Mixed Cyanosis

Other Types Enterogenous/Pigment Cyanosis Differential Cyanosis Acrocyanosis Orthocyanosis

Central cyanosis Pathologic condition

caused by reduced arterial oxygen saturation.

Involves highly vascularized tissues, such as the lips and mucous membranes, through which blood flow is brisk and the arteriovenous difference is minimal.

Cardiac output typically is normal, and patients have warm extremities.

Mechanism Decreased arterial oxygen saturation due to

marked decrease in oxygen tension in the arterial blood(arterial PaO2 is reduced)

Sites- Tongue (margins & undersurface) Inner aspect of lips Mucous membranes of gums,soft palate,cheeks

Peripheral cyanosis

Causes-

○ vasomotor instability, vasoconstriction caused by exposure to cold, venous obstruction, elevated venous pressure, polycythemia, and low cardiac output,

Affects the distal extremities and circumoral or periorbital areas .

Mechanism Normal systemic arterial oxygen saturation and

increased oxygen extraction, resulting in a wide systemic arteriovenous oxygen difference

The increased extraction of oxygen results from sluggish movement of blood through the capillary circulation

• Sites• Tip of nose• Ear lobules• Outer aspect of lips,chin,cheek• Tips and nailbeds of fingers,toes• Palms,soles

Mixed Cyanosis

Cardiogenic shock+ pulmonary oedema CCF due to lt.sided heart failure Polycthemia (rare)

Orthocyanosis Present in upright position due to hypoxia

occuring in erect posture in Pulmonary Arteriovenous Malformation

Enterogenous/pigment cyanosis Due to presence of excessive –

sulphaemoglobin(>0.5g/dl),methaemoglobin(>1.5g/dl

Causes Hereditary haemoglobin M disease Poisoning by aniline dyes Drugs-

nitratres,nitrites,phenacetin,sulphonamides Carboxyhaemoglobinaemia

Differential Cyanosis Hands red (less blue) and feet blue seen in PDA with reversal of

shunt (Differential Cyanosis) Requires pulmonary vascular resistance elevated to a systemic level and a patent ductus arteriosus

L R shunt

Pulmonary hypertension

R to L

Reversal of shunt

Desaturated blood from the ductus enters the aorta distal to the left subclavian artery, sparing the brachiocephalic circulation.

Reverse Differential Cyanosis Hands blue and feet red seen in

Coarctation of Aorta with TGA(Reverse Differential Cyanosis

Intermittent Cyanosis seen in Ebstein’s Anomaly

Central Vs Peripheral Cyanosis SITES TONGUE,ORAL CAVITY TONGUE UNAFFECTED

HANDSHAKE FEELS WARM FEELS COLD

APPLICATION OF WARMTH,COLD

NO CHANGE WARMTH-CYANOSIS INCR,COLD-DECREASES

APPLICATION PURE O2 MAY IMPROVE NO RESPONSE

CLUBBING,POLYCYTHAEMIA

USUALLY PRESENT ABSENT

PULSE VOLUME MAYBE HIGH LOW VOL

DYSPNOEA PT BREATHLESS NO RESPIRATORY PROBLEM

Acrocyanosis

Condition in which there is arterial vasoconstriction,and secondary dilation of capillaries and venules with resulting persistant cyanosis of the hands and less fequently the feet.part of normal transitionmay last 72hrbeware APGAR of 10

○ hypoperfused○ severe anemia

Psuedocyanosis

Bluish tinge to the skin and or mucous membranes that is not associated with either Hyoxemia or Peripheral Vasoconstriction

Metals Drugs

Factors altering cyanosis

Colour of the cutaneous pigment Thickness of the skin State of cutaneous capillaries

Cyanosis becomes apparent when the concenteration of the reduced haemoglobin in capillary blood vessels exceeds 40 g/l or 4g/dl

Factors affecting the detection of cyanosis in the newborn Hemoglobin concentration -

Detected at higher levels of saturation in polycythemic than in anemic patients.

Significant oxygen desaturation can be present in an anemic patient without clinically detectable cyanosis.

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.

The arterial oxygen saturation level at which cyanosis is detectable at different total hemoglobin concentrations is illustrated above. The solid red portion of each bar represents 3 gm/dL reduced hemoglobin.

Factors affecting the detection of cyanosis in the newborn Fetal hemoglobin — 

Binds oxygen more avidly than adult hemoglobin. The oxygen dissociation curve is shifted to the left, so

that for a given level of oxygen tension (PO2), the oxygen saturation (SO2) is higher in the newborn than older infants or adults

It also follows that for a given level of oxygen saturation, the PO2 is lower in newborns.

As a result, cyanosis is detected at a lower PO2 in newborns compared with older patients. Thus, in evaluating a cyanotic newborn, PO2 should be measured in addition to SO2 to provide more complete data.

Factors affecting the detection of cyanosis in the newborn Other physiologic factors common in

sick newborns affect the oxygen dissociation curve.

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

For fetal hemoglobin, the normal curve (a) is shifted to the left (b)

Cyanosis

0

10

20

30

40

50

60

70

80

90

100

0 20 40 60 80

HCT

% S

atu

rati

on

Cyanosis…

Cyanosis is dependent on HCT and % Sat

Florescent light makes cyanosis hard to see.

Except in the extreme, cyanosis is not obvious

Any question, check a pulse ox

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.

For fetal hemoglobin, the normal curve (a) is shifted to the left (b)

Factors affecting the detection of cyanosis in the newborn Skin pigmentation -

Less apparent in the skin of patients with darker pigmentation.

Examination should include the nail beds, tongue, and mucous membranes, which are less affected by pigmentation.

Etiology Can be divided in to,,

Site of cynosis Central causes Peripheral causes

Mecanism of cynosis

Alveolar hypoventilation Diffusion impairment Ventilation-perfusion

mismatch Right-to-left shunting at the

intracardiac, great vessel, or intrapulmonary level

Hemoglobinopathy (including methemoglobinemia) that limits oxygen transport

Central Cyanosis:- Decreased arterial oxygen saturation Decreased atmospheric pressure-High altitude Impaired pulmonary function Alveolar hypoventilation Pulmonary ventilation perfusion imbalance Impaired oxygen diffusion Anatomic Shunts –ASD,VSD,PDA Congenital Heart Diseases-Fallots Tetrology,TGA Pulmonary AV fistulas Mutiple small intrapulmonary shunts Haemoglobin Abnormalities

Peripheral Cyanosis Decreased Cardiac Output Cold Exposure Redistribution Of blood from extremities Arterial Obstruction-embolus,raynauds

phenomenon Venous Obstruction-thrombophlebitis,SVC

syndrome Frost bite CCF,shock,Peripheral Circulatory Failure Hyperviscosity -Multiple myeloma,Polycythemia Peripheral Vascular Diseases-

atherosclerosis,buerger’s Mitral Stenosis Cryoglobulinemia

Non- cardiac causes

Alveolar hypoventilation Central nervous system depression:

asphyxia, maternal sedation, intraventricular hemorrhage, seizure, meningitis, encephalitis

Neuromuscular disease: Werdnig-Hoffman disease, neonatal myasthenia gravis, phrenic nerve injury

Airway obstruction: choanal atresia, laryngotracheomalacia, macroglossia, Pierre Robin syndrome

Non- cardiac causes Ventilation/perfusion mismatch

Airway disease: pneumonia, aspiration, cystic adenomatoid malformation, diaphragmatic hernia, pulmonary hypoplasia, labor emphysema, atelectasis, pulmonary hemorrhage, hyaline membrane disease, transient tachypnea of the newborn

Extrinsic compression of lungs: pneumothorax, pleural effusion, chylothorax, hemothorax, thoracic dystrophy

Non-cardiac causes Hemoglobinopathy

Methemoglobinemia: congenital or secondary to toxic exposure

Other hemoglobinopathies

Diffusion impairment Pulmonary edema: left-sided obstructive cardiac

disease, cardiomyopathy Pulmonary fibrosis Congenital lymphangiectasia

Cardiac causes Decreased pulmonary blood flow-

Tetralogy of FallotTricuspid valve anomalyPulmonary valve atresiaCritical valvular pulmonary steanosis

Increased pulmonary blood flow-Transposition of great arteriesTruncus arteriosusTotal anomalous pulmonary venous connection

Cardiac causes

Severe heart failure-Hypoplastic left heart syndromeCoarctation of the aortaInterrupted aortic archCritical valvular aortic steanosis

The 6 T’s

Total Anomalous Pulmonary Veins Tetrology of Fallot Tricuspid Atresia Transposition Truncus Arteriosus

Total AcardiaTotal Acardia

Mnemonic

A 7T" is often added for "tons" of other diseases, such as double outlet right ventricle, pulmonary atresia, multiple variations of single ventricle, hypoplastic left heart syndrome, or anomalous systemic venous connection (left superior vena cava connected to the left atrium

Differential cyanosis With normally related great arteries, oxygen

saturation may be higher in the upper than lower extremity in patients if there is right-to-left shunting through the ductus arteriosus.

Seen with severe coarctation or interrupted aortic arch.

May also occur in patients persistent pulmonary hypertension of the newborn

The differential effect is reduced if there is also right-to-left shunting at the level of the foramen ovale, or if there is left-to-right shunting across a coexisting ventricular septal defect

Differential cyanosis

Reversed differential cyanosis is a rare finding that may occur in patients with transposition of the great arteries associated with either coarctation or pulmonary hypertension.

In these infants, oxygen saturation is higher in the lower than upper extremity.

Aim

Differentiate physiologic from pathologic cyanosis

Differentiate cardiac from non- cardiac cause of cyanosis

Find cause which needs urgent treatment or referral

Not so serious Acrocyanosis

Bluish color in the hands and feet and around the mouth (circumoral cyanosis). The mucus membranes generally remain pink.

Reflects benign vasomotor changes in the diffuse venous structures in the affected areas.

Does not indicate pathology unless cardiac output is extremely low, resulting in cutaneous vasoconstriction

Cyanosis soon after birth- transition from intrauterine to extrauterine life

Hand or leg prolapse

Perinatal history Drug intake

Causing neonatal depression Lithium- Ebstein anomaly Phenytoin- PS and AS Fetal hydantoin synd- Fetal alcohol- VSD,ASD

Maternal diabetes- TGA, ventricular septal defect (VSD), and hypertrophic

cardiomyopathy Connective tissue disorder- Heart blocks associated with

anti-Ro/SSA and anti-La/SSB antibodies. Congenital intrauterine infections cytomegalovirus,

herpesvirus, rubella, or coxsackie virus can lead to cardiac structural abnormalities or functional impairment

Antenatal fetal echocardiography

History

Methemoglobinemia may be acquired following exposure to aniline dyes, nitrobenzene, nitrites, and nitrates.

Advanced maternal age Trisomy 21 associated with many congenital heart defects (cyanotic and acyanotic)

Oligohydramnios …..Pulmonary hypoplasia

Onset of cyanosis in cardiac lesions-

Depends on-Nature and severity of the anatomic defectIn utero effects of the structural lesionAlterations in cardiovascular physiology secondary

to the effects of transitional circulation like closure of ductus arteriosus and the fall in pulmonary vascular resistance

A ductal dependent lesion is one that depends on the ductus to get adequate blood flow to the pulmonary and systemic circuits, or provide mixing

○ PS

○ CoA○ TGA

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)

Onset of cyanosis in cardiac lesionsAge on admission In order of frequency

0-6 days D- transposition of great arteries

Hypoplastic left ventricles

Tetralogy of fallot

7-13 days Coarctation of aorta

Hypoplastic left ventricle

D-transposition of great arteries

Tetralogy of fallot

14-28 days Coarctation of aorta

Tetralogy of fallot

D- transposition of great arteries

Neonatology- Pathophysiology and management of newborn, 5th edition ed. 1999. Philadelphia; Lippincott Williams and Wilkins

History- Risk factors Pneumonia/ sepsis-

PROM Foul smelling liquor Maternal pyrexia Maternal GBS

TTN – Birth by cesarean section

with 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 membrane disease- Premature infant Infant of diabetic mother

History Choanal atresia-

Cyanosis decreases during cryingConfirmed by failure to pass a soft No. 5F to

8F catheter through each nostril

Physical Examination

Vital signs-Hypothermia or hyperthermia- infection.Tachycardia-hypovolemia.Weak pulses- Hypoplastic left heart

syndrome or hypovolemia.Pulses or blood pressures stronger in

the upper than in the lower extremities- coarctation of the aorta.

Physical Examination Congenital heart disease-

Respirations often are unlabored unless there is pulmonary congestion or complicated by the development of heart failure or acidosis, which will affect the respiratory pattern.

CVS-Presence or absence of a heart murmur is of little

assistance. Loud S2 suggests pulmonary or systemic hypertension or malposition of the aorta.

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

Physical Examination Inspiratory stridor-

upper airway obstruction Chest-

Asymmetric chest movement combined with severe distress- ○ alarming sign for tension pneumothorax,

diaphragmatic hernia Transillumination of the chest-

○ Pneumothorax on an emergent basis

Physical Examination

P/A-Scaphoid abdomen

○ Congenital diaphragmatic hernia

Hepatosplenomegaly-○ congestive heart failure, maternal diabetes,

or congenital infection.

Physical Examination

Central nervous depression-Causes shallow, irregular respirations and

periods of apnea.Affected infants typically appear hypotonic

and lethargic.

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

If central cause- appropriate scan and drug levels

Hb electropheresis…..Hb M Decrease pH: sepsis, circulatory shock,

severe hypoxemia Decrease pH: sepsis, circulatory shock,

severe hypoxemia Sepsis screening

Pulse oximetry screening Difficulty in visual detection of cyanosis Potentially severe consequences of

missing an early sign of CHD “5th vital sign” Sensitivity and specificity varies-

Criteria used for abnormal testTiming of screeningProbe siteQuality of the equipmentSignal quality and neonate behaviourHealth care workers expertise

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 saturation should be performed initially on room air to serve as a baseline.

Subsequently can be served to differentiate between cardiogenic and non-cardiogenic causes

Terms

PaO2 Arterial Oxygen Pressure

Measured on an ABG machine Oxygen dissolved in plasma

○ 0.003 ml O2/mmHg/dl plasma

SaO2 Percent Oxygen Saturation

Measured by saturation monitor (pulse-Ox) ~1.34ml O2/g Hb

Hyperoxia test If a low-pulse oximeter reading persists, it

may be appropriate to proceed to a hyperoxia test. It is indicated if the pulse oximeter reading is less than 85% in both room air and 100% oxygen

Useful in distinguishing cardiac from

pulmonary causes of cyanosis.

Hyperoxia test Arterial oxygen tension is measured in the

right radial artery (preductal) and in a lower extremity artery while the patient breathes 100 percent oxygen (postductal).

Hyperoxia Test

Infant on Room Air, get ABG Infant on 100% oxygen, get ABG PaO2 unchanged = fixed shunt = CCHD

Max PaO2 <100 = CCHD

Max PaO2 >200 = No CCHD

Hyperoxia testDisease Result- Increase

in PaO2

Lung disease is more likely than CHD

>150 mmHg

TGA or severe pulmonary outflow obstruction

<50 to 60 mmHg

In lesions with intracardiac mixing and increased pulmonary blood flow such as truncus arteriosus-

>75 to 150 mmHg

Differential cyanosis To detect differential cyanosis, oxygen

saturation should be measured in sites that receive blood flow from both preductal (right hand) and postductal (foot) vessels. It is preferable to use the right (rather than left) upper extremity, since the left subclavian artery arises close to the ductus arteriosus, and some of its flow may come from the ductus and thus not reflect preductal values

Chest X-Ray 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

Aberrancy of the cardiothymic silhouette- Suggest the presence of structural heart disease,

and Abnormalities of the lung fields may be helpful in

distinguishing a primary pulmonary problem such as meconium aspiration

Chest X- Ray

Pulmonary vascular markings-Decreased in CHD with obstructed

pulmonary blood flow such as tetralogy of Fallot, severe pulmonary stenosis or atresia, and tricuspid atresia.

Increased in admixture lesions like transposition of the great arteries, total anomalous pulmonary venous connection, and truncus arteriosus.

Total Anomalous Pulmonary Venous Return

Snowman

Tetralogy of Fallot

Boot shape

Transposition of Great Arteries

Egg on a string

Echocardiography

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

Treatment Goals-

Provide adequate tissue oxygen and CO2 removal

Principles-Establish airwayEnsure oxygenationEnsure adequate ventilationCorrect metabolic abnormalitiesAlleviate the cause of respiratory distress

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

Treatment-

Prostaglandin E1For ductal dependant CHD/ reduced

pulmonary blood flow- Fail hyperoxia test( An arterial PO2 of less than 100 torr in the absence of clear- cut lung disease)

Infusion of prostaglandin E1 at a dose of 0.05- 0.1mcg/kg/min intravenously to maintain patency

Treatment-

Prostaglandin E1-S/E- hypoventilation, apnea, edema and low

grade feverBenefits- Can be stabilized more easily,

allowing for safe transport to a tertiary care center. More time is also available for thorough diagnostic evaluation and patients can be brought to surgery in a more stable condition.

Conclusion Identify those that are life-threatening. complete maternal and newborn history perform a thorough physical examination recognize the common respiratory and

cardiac disorders differentiate among various diagnostic

entities For ductal dependent lesion, start

prostaglandin E1 and early referral

References Nelson textbook of pediatrics Cloherty manual of neonatal care Approach To Cyanotic Heart Disease In The First

Month Of Life , Harry J. D'Agostino, Jr., M.D. and Eric L. Ceithaml, M.D.

Pediatrics in Review. 1999;20:350-352.)© 1999, Consultation with the Specialist, Nonrespiratory Cyanosis, Jon Tingelstad, MD

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