Cyanosis resident survival guide

Cyanosis Resident Survival Guide Microchapters
Overview
Causes
Diagnosis
Differential Diagnosis
Treatment
Do's
Don'ts

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Chandrakala Yannam, MD [3]

Synonyms and keywords: Cyanosis approach, Cyanosis workup, Cyanosis management, Approach to blue discoloration of skin, Hypoxemia approach, Hypoxia approach

Overview

Cyanosis is defined as bluish discoloration of skin and mucous membrane due to decreased oxygenation of tissue. Approximately 2% of oxygen dissolved in plasma and 98% is carried by hemoglobin. In central cyanosis, there is decreased oxygen saturation (less than 85%) or abnormal or nonfunctional hemoglobin, depending on whether reduced hemoglobin or desaturated hemoglobin exceeds 5 g/dl. Common signs of central cyanosis include the tongue and conjunctiva appearing blue in color and the extremities becoming warm with rapid capillary filling. In peripheral cyanosis, the oxygen saturation is normal but there is inadequate delivery of oxygen to tissue or increased oxygen extraction by tissue due to peripheral vasoconstriction. In peripheral cyanosis extremities are cyanotic, pale, cool but tongue and conjunctiva are pinkish. All causes of central cyanosis may lead to peripheral cyanosis. In the presence of anemia and severe hypoxemia, cyanosis may not be apparent due to fewer levels of reduced hemoglobin. Conversely, in polycythemia and mild hypoxemia, cyanosis may be easily apparent due to an increased level of reduced hemoglobin.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

• Carbon monoxide poisoning
• Cyanide poisoning
• Malathion
• Parathion
• Ethylene glycol
• Epiglottitis
• Foreign body aspiration
• Pulmonary embolism
• Tension pneumothorax
• Hemothorax
• Pulmonary hemorrhage
• Pulmonary hypertension
• Myocardial infarction
• Congestive heart failure
• Disseminated intravascular coagulation
• Tetralogy of fallout
• Cardiac tamponade
• Eisenmenger syndrome
• Anaphylaxis
• Birth asphyxia
• Amniotic fluid embolism

Common Causes

Cyanosis

Central cyanosis

Peripheral cyanosis

Hematologic abnormalities: ❑ Methemoglobinemia (congenital or acquired) ❑ Sulfhemoglobinemia (acquired) ❑ Hemoglobin mutations with low oxygen affinity: ❑ Hb Kansas ❑ Hb Beth israel ❑ Hb Saint Mande ❑ Hb Bruxells ❑ Polycythemia vera ❑ Disseminated intravascular coagulation Metabolic disorders: ❑ Severe hypoglycemia ❑ Inborn errors of metabolism Miscellaneous: ❑ Drugs and chemicals: ❑ Beta blockers ❑ Nitrite or nitrate-containing compounds (eg, nitroglycerin) ❑ Dapsone ❑ Sulfonamides ❑ Benzocaine ❑ Chloroquine ❑ Heroin ❑ Venomous snakebites ❑ Brief resolved unexplained events (BRUE) ❑ High altitude ❑ Congenital diaphragmatic hernia ❑ Cirrhosis of liver ❑ Drowning ❑ Chocking ❑ Hanging ❑ Hypothermia

Hypoventilation:: Upper airway obstruction: ❑ Foreign body aspiration ❑ Pertussis / Croup ❑ Epiglottitis ❑ Bacterial tracheitis ❑ Traumatic disruption (thermal injury, fractures) ❑ Acute chest syndrome ❑ Congenital airway abnormalities: ❑ Choanal atresia ❑ Laryngotracheomalacia ❑ Macroglossia ❑ Micrognathia or retrognathia (eg, Pierre-Robin syndrome) Neurologic abnormalities: ❑ CNS depression ❑ Birth asphyxia ❑ Severe head trauma ❑ Apnea of prematurity ❑ Obstructive sleep apnea ❑ Infections (eg, meningitis, encephalitis) ❑ Intraventricular hemorrhage ❑ Seizures ❑ Cyanotic breath holding spells ❑ Coma Neuromuscular disorders: ❑ Myasthenia gravis ❑ Injury to the phrenic nerve ❑ Type 1 spinal muscular dystrophy (Wernig-Hoffman disease) Intrinsic lung diseases: ❑ Asthma ❑ COPD ❑ Pneumonia ❑ Bronchiolitis ❑ Respiratory distress syndrome (Hyaline membrane disease) ❑ Empyema ❑ Pleural effusion ❑ Cystic fibrosis ❑ Atelectasis ❑ Bronchopulmonary dysplasia ❑ Alveolar capillary dysplasia

Vascular causes: ❑ Cardiac tamponade ❑ Cyanotic congenital heart diseases (Right to left shunts): ❑ Decreased pulmonary flow: ❑ Tetralogy of fallout ❑ Tricuspid valve anomalies: ❑ Tricuspid atresia ❑ Tricuspid stenosis ❑ Ebstein's anomaly ❑ Pulmonary stenosis (critical valvular) ❑ Pulmonary atresia with intact ventricular septum ❑ Increased pulmonary flow: ❑ TGA (Transposition of great arteries, most common dextro type) ❑ Truncus arteriosus ❑ TAPVC (Total anamalous pulmonary venous connection) ❑ Heart failure: Condition that present with cyanosis and severe heart failure include: ❑ Left sided obstructive lesion (HLHS) ❑ Coarctation of aorta ❑ Critical valvular aortic stenosis ❑ Eisenmenger syndrome ❑ Congestive heart failure ❑ Atrial septal defect ❑ Pulmonary hypertension ❑ Pulmonary edema ❑ Pulmonary hemorrhage ❑ Pulmonary embolism ❑ Pulmonary arteriovenous malformations ❑ Multiple small intrapulmonary shunts ❑ Shock ❑ Sepsis ❑ Amniotic fluid embolism

Conditions associated with decreased concentration of inspired oxygen (FiO2): ❑ Smoke inhalation most commonly from house fires ❑ Carbon monoxide poisoning ❑ Hydrogen cyanide poisoning ❑ Intentional or unintensional exposure to asphyxiating gases (eg, Propane, methane, butane, hydrogen sulphide) Impairment of chest wall or lung expansion: ❑ External compression ❑ Pneumothorax ❑ Hemothorax ❑ Flail chest

Causes: ❑ Cold exposure ❑ Acrocyanosis ❑ Erythrocyanosis ❑ Raynaud's phenomenon ❑ Raynaud's disease ❑ Arterial obstruction: ❑ Peripheral vascular disease ❑ Buergers disease ❑ Venous obstruction: ❑ Thromboembolism ❑ Deep vein thrombosis ❑ Superior vena cava syndrome ❑ Decreased cardiac output: ❑ Left sided heart failure ❑ Shock ❑ Hypovolemia ❑ Redistribution of blood flow from extremities

Pseudocyanosis

Metals

Extensive tattoos

Drugs

Pigmentary lesions

Consumption of dyed food

Diagnosis

Abbreviations: TGA: Transposition of great arteries; COPD: Chronic obstructive pulmonary disease; PDA: Patent ductus arteriosus  ; ASD: Atrial septal defect; VSD: Ventricular septal defect; TAPVR: Total anomalous pulmonary venous return; TOF: Tetralogy of fallot; ILD: Interstitial lung disease; ARDS: Acute respiratory distress syndrome;

Mechanism of hypoxemia

V/Q mismatch: ❑ Common cause of hypoxemia ❑ High proportion in apex of the lung due to higher ventilation compared with perfusion ❑ Easily corrected by supplemental oxygen therapy ❑ widened (A-a )oxygen gradient ❑ High V/Q mismatch such as pulmonary embolism that ventilation is higher than perfusion ❑ Asthma ❑ COPD ❑ Bronchectasia ❑ Cystic fibrosis ❑ Interstitial lung disease (ILD) ❑ Pulmonary hypertension due to lung disease Diffusion limitation: ❑ Normal PCO2 level ❑ Good response to oxygen therapy ❑ widened P(A-a)O2 level ❑ Alveolocapillary impairment ❑ ILD ❑ Emphysemia

Right to left shunt: ❑ Poor response to oxygen therapy ❑ Normal PCO2 level ❑ Widened P(A-a) O2 gradient ❑ Presence of Small physiologic pulmonary shunt about 2-3% of cardiac output due to deraining of bronchial veins into pulmonary veins and deraining coronary veins into left ventricle ❑ If the shunt fraction reaches 50%, hypercapnia may be present ❑ Shunt fraction<20% if PaO2/FIO2>200 ❑ Shunt fraction>20% if PaO2/FIO2<200 ❑ Cyanotic congenital heart disease with right to left shunt ❑ Pneumonia ❑ Pulmonary edema ❑ Acute respiratory distress syndrome(ARDS) ❑ Alveolar collapse ❑ Pulmonar arterionenous connection

Hypoventilation: ❑ High PCO2 level ❑ Low ventilation leading to Low PAO2, PaO2 level ❑ Normal P(A-a)O2 gradient due to normal alveolar capillary memberane ❑ longstanding hypoventilation leading to atelectasia and widened P(A-a)O2 gradient ❑ Corrected by supplemental oxygen therapy ❑ One Cause of respiratory failure in COPD, Asthma,ILD ❑ Disorders leading to hypoventilation include: ❑ Impaired central drive: ❑ Opiom overdose, benzodiazepine, alcohol ❑ Brain stem infarct, hemorrhage ❑ Primary alveolar hyperventilation ❑ Spinal cord level: ❑Amiotrophic lateral sclerosis ❑Cervical spinal cord injury ❑nerve supplying respiratory muscle: ❑Guillain-Barre syndrome ❑ Neuromascular junction: ❑Myasteni-Graves ❑Lambert-eaton syndrome ❑Respiratory muscle: ❑Myotony ❑ Defect in chest wall: ❑Kyphoscoliosis ❑Thoracoplasty ❑Fibrothorax

PAO2 is the mean alveolar oxygen pressure. PH2O is the water vapor pressure (47 mmHg at 37°C). PaCO2 is the alveolar carbon dioxide tension and is equal to arterial PCO2. R is the respiratory quotient and is 0.8 on the standard diet. FiO2 is the fractional concentration of inspired oxygen. It is 0.21 at room air. PAO2 = FiO2× (Pb − PH2O) − (PACO2/R)=0.21× (760 − 47) − (40/0.8)=100 mmHg.

Differential Diagnosis of Peripheral and Central Cyanosis

Eisenmenger disease

Increased pulmonary vascular resistant leading to right to left shunt, systemic arterial desaturation, central cyanosis

Tamponad

low cardiac output, low stroke volume, elevated cardiac filling pressures, increased sympathetic tone( tachycardia, peripheral vasoconstriction, peripheral cyanosis)

Pulmonary thromboembolism

Pulmonary artery vasoconstriction, hypoxia, right ventricle pressure overload, right to left shunt via patent foramen ovale,central cyanosis

Cardiogenic shock

Decreased myocardial perfusion, muscle hypoxia,necrosis, impaired myocardial contraction., decreased cardiac out put, Increased vasoconstrictor,peripheral cyanosis

Tetralogy of fallot

Episods of Tet spell between 2-4 months of age, aggravated with crying ,feeding stooling,dehydration,in patients with severe pulmonary stenosis and large VSD, central cyanosis

Differential diagnosis of peripheral and central cyanosis

Methemoglubinemia

Increased level of reduced hemoglobin, congenital or due to medication, central cyanosis

Chronic obstructive pulmonary disease

Central cyanosis, respiratory failure, PO2<60 mmHg, PCO2>45mmHg while breathing at sea level, peripheral edema due to right heart failure

Pulmonary edema

Decreased arterial oxygen saturation, central cyanosis

High altitude

Hypoxia, peripheral cyanosis due to ischemia and occlusion small peripheral vessels, central cyanosis due to pulmonary edema in acute mountain sickness, pulmonary hypertension in chronic mountain sickness

Pneumonia

Central cyanosis due to impaired gas exchange and intrapulmonary shunt

ARDS

Acute pulmonary parenchimal disease other than cardiac origin or volume overload, alveolar filling with exudates or alveolar collapse, central cyanosis due to decreased oxygen saturation and intrapulmonary shunting

Approach to Cyanosis at Birth

Differentiating cardiac and pulmonary causes of cyanosis at birth: ❑ History and physical exam ❑ Blood pressure measurement in four limbs ❑ Oxygen saturation measurement ❑ ECG ❑ Chest-X-ray

Cardiac cause: ❑ Cardiomegaly in CXR ❑ Relatively comfortable at rest ❑ Cyanosis may worsen with crying ❑ Cardiac murmur ❑ Abnormal rhythm or axis in ECG ❑ Normal PCO2 level ❑ NO response to O2 therapy

Pulmonary cause: ❑ Respiratory distress,tachypnea at rest ❑ Rale, crackle, wheezing in chest auscultation ❑ Normal cardiac margine in CXR ❑ Ground glass appearance, pneumonia, atelectasia,pneumothorax in CXR ❑ Normal ECG finding ❑ Elevated PCO2 level ❑ Corrected with oxygen therapy

Cyanosis in Congenital heart disease

Cyanosis + pulmonary edema at the time of birth:

❑ TGA (Transposition of great vessel) without associated PDA,VSD,ASD: two great arteries are misplaced, oxygenated pulmonary blood re-enter the pulmonary circulation via morphologic left ventricle and deoxygenated aorta blood re-enter the systemic circulation via morphologic right ventricle ❑ Total anomalous pulmonary venous connection(TAPVR):connection between pulmonary veins and right system and mixing the oxygenated and deoxygenated blood ❑ Truncus arteriosus: one great vessel arise from both ventricle then the gives rise to the aorta and pulmonary artery

Cyanosis +shock and collapse within hours or days after birth:

❑ Tetralogy of fallot: pulmonary stenosis (valvular, subvalvular) with ventricular septum defect and overridding aorta ❑ Severe pulmonary stenosis with intact ventricular septum ❑ Ebstein anomaly: small functional right ventricle, huge right atrium, severe tricuspid regurgitation, right to left shunt via ASD or PFO

Cyanosis +shock and collapse in the first week of birth:

❑ Hypoplastic left heart syndrome ❑ Severe coarctation of aorta ❑ Severe aortic stenosis ❑ Tachycardia induced cardiomyopathy due to atrial flutter or PSVT ❑ Dilated cardiomyopathy Other differential diagnosis: neonate sepsis, menangitis or hypoglycemia

Differencial cyanosis ( upper limbs O2 saturation > lower limbs O2 saturation):

❑ Severe pulmonary hypertension with PDA ❑ Severe aortic coactation or interruption

Differencial cyanosis ( lower limbs O2 saturation> upper limbs O2 saturation):

❑ TGA + severe pulmonary hypertension + PDA ❑ TGA + severe aortic arch interruption + PDA ❑ Connection right subclavian artery to right pulmonary artery Right upper limb oxygen saturation is lower than left upper and left lower limbs oxygen saturation

Treatment

Shown below is an algorithm summarizing the treatment of cyanosis.

TGA, TAPVR ,Truncus arteriosus

Infusion of Prostaglandin, Diuretic therapy,surgery

TOF

Hydration, modified blalock taussing shunt, insertion stent in PDA and right ventricular outflow tract, total repair

Ebstein anomaly

Tricuspid valve repair

Treatment of Cyanosis

Hypoplastic left heart syndrome

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

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

Treatment of underlying disorder

Eisenmenger syndrome with pulmonary hypertension,

Phosphodiesterase-5 inhibitor (sildenafil, tadalafil), Endothelin receptor antagonist (bosentan,macitentan, ambrisentan)

Methemoglobinemia

Infusion of Methylenblue,dextrose,N-acetyl cystein,cimethidin,ketoconazole

Do's

• Quickly think about hypoplastic left heart syndrome in infants with sudden onset of shock, collapse and severe anemia in the first week of life, as well as neonate sepsis and metabolic disorders.
• In ebstein anomaly, repair of tricuspid valve indicates if there is :Cyanosis, Right-side heart failure, Poor functional capacity, Paradoxical emboli.
• In differential cyanosis if oxygen saturation of right arm is more than legs and improves with O2 supplemental therapy, consider severe coarctation of aorta, aortic arch interruption, primary pulmonary hypertension.
• In the presence of central cyanosis + hemolytic anemia (jundic,heinze body,fragment RBC)+ renal failure consider methemoglobinemia.
• Quickly correct dehydration and any distress in infants with cyanotic tet spell in Tetralogy of Fallot to maintain pulmonary blood flow through atretic pulmonary artery and reduce right to left shunt through VSD.

• Consider paradoxical embolism and perform a Brain CT scan in the presence of new neurologic symptoms in cyanotic congenital heart disease because of passing the emboli from right to left shunt and hyperviscosity leading to thrombosis.

Don'ts

• Cyanotic congenital heart diseases that pulmonary congestion is independent on patent ductus arteriosus(PDA) and which do not worsen with dehydration include :
• Transposition of great arteries(TGA)
• Truncus arteriosus(TA)
• Total anomalous pulmonary venous connection(TAPVR)