Cyanosis resident survival guide

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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 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 or increased oxygen extraction due to peripheral vasoconstriction. Typically, 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.

Common Causes

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cyanosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Central cyanosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Peripheral cyanosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematologic abnormalities: [13]

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: [14][15]

Beta blockers
Nitrite or nitrate-containing compounds (eg, nitroglycerin)
Dapsone
Sulfonamides
Benzocaine
Chloroquine
Heroin

❑ Venomous snakebites [16] ❑ Brief resolved unexplained events (BRUE) [17]
High altitude [18]
Congenital diaphragmatic hernia
Cirrhosis of liver
Drowning
❑ Chocking
❑ Hanging

Hypothermia
 
 
 
 
 
Hypoventilation::
Upper airway obstruction: [19][3]

Foreign body aspiration
Pertussis / Croup
Epiglottitis
Bacterial tracheitis
❑ Traumatic disruption (thermal injury, fractures)
Acute chest syndrome [20] ❑ Congenital airway abnormalities:

Choanal atresia
Laryngotracheomalacia
Macroglossia
Micrognathia or retrognathia (eg, Pierre-Robin syndrome)

Neurologic abnormalities: [21][22][23]
CNS depression
Birth asphyxia
❑ Severe head trauma
Apnea of prematurity
Obstructive sleep apnea
❑ Infections (eg, meningitis, encephalitis)
Intraventricular hemorrhage
Seizures
❑ Cyanotic breath holding spells [24]
Coma
Neuromuscular disorders:
Myasthenia gravis
❑ Injury to the phrenic nerve
❑ Type 1 spinal muscular dystrophy (Wernig-Hoffman disease)
Intrinsic lung diseases:[25][26][27][28][29]
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): [30][31][8]

Decreased pulmonary flow:
Tetralogy of fallout [8]
❑ 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 [12]
 
 
 
 
 
Conditions associated with decreased concentration of inspired oxygen (FiO2): [32]

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 [33]
Hemothorax

Flail chest
 
 
 
Causes: [34][35]

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[36]
❑ 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[37]
Asthma
COPD
Bronchectasia
Cystic fibrosis
Interstitial lung disease (ILD)
Pulmonary hypertension due to lung disease

Diffusion limitation:
❑ Normal PCO2 level[38]
❑ 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[39]
❑ 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[37]
❑ 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)[40]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary thromboembolism
 
Pulmonary artery vasoconstriction, hypoxia, right ventricle pressure overload, right to left shunt via patent foramen ovale,central cyanosis[41]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiogenic shock
 
Decreased myocardial perfusion, muscle hypoxia,necrosis, impaired myocardial contraction., decreased cardiac out put, Increased vasoconstrictor,peripheral cyanosis[42]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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[43]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Differential diagnosis of peripheral and central cyanosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Methemoglubinemia
 
Increased level of reduced hemoglobin, congenital or due to medication, central cyanosis[44]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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[45]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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[46]
 
 
 
 
 
 




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[43]
❑ 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[47]
❑ Severe aortic coactation or interruption

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

TGA + severe pulmonary hypertension + PDA[48]
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 [49]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TOF
 
Hydration, modified blalock taussing shunt, insertion stent in PDA and right ventricular outflow tract, total repair [43]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ebstein anomaly
 
Tricuspid valve repair[50]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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)[51]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Methemoglobinemia
 
Infusion of Methylenblue,dextrose,N-acetyl cystein,cimethidin,ketoconazole
 
 
 
 
 
 

Do's

Don'ts

References

  1. Olson K, Smollin C (July 2008). "Carbon monoxide poisoning (acute)". BMJ Clin Evid. 2008. PMC 2907971. PMID 19445736.
  2. Parker-Cote JL, Rizer J, Vakkalanka JP, Rege SV, Holstege CP (February 2018). "Challenges in the diagnosis of acute cyanide poisoning". Clin Toxicol (Phila): 1–9. doi:10.1080/15563650.2018.1435886. PMID 29417853.
  3. 3.0 3.1 Zoorob RJ, Campbell JS (November 2003). "Acute dyspnea in the office". Am Fam Physician. 68 (9): 1803–10. PMID 14620600.
  4. Just-Viera JO, Norwood T, Yeager GH (April 1967). "Importance of shock and cyanosis in pulmonary embolism". Ann. Surg. 165 (4): 528–35. PMC 1617449. PMID 6021453.
  5. Barton ED (July 1999). "Tension pneumothorax". Curr Opin Pulm Med. 5 (4): 269–74. PMID 10407699.
  6. Wang RF, Hung TY, Chong CF, Wang TL, Chen CC (February 2008). "Central cyanosis due to severe pulmonary hypertension combined with pericarditis as the initial manifestation of systemic lupus erythematosus". Am J Emerg Med. 26 (2): 248.e1–2. doi:10.1016/j.ajem.2007.04.007. PMID 18272123.
  7. Costello RA, Nehring SM. PMID 28722864. Missing or empty |title= (help)
  8. 8.0 8.1 8.2 Bailliard F, Anderson RH (January 2009). "Tetralogy of Fallot". Orphanet J Rare Dis. 4: 2. doi:10.1186/1750-1172-4-2. PMC 2651859. PMID 19144126.
  9. Bodson L, Bouferrache K, Vieillard-Baron A (October 2011). "Cardiac tamponade". Curr Opin Crit Care. 17 (5): 416–24. doi:10.1097/MCC.0b013e3283491f27. PMID 21716107.
  10. Komine S (February 1964). "In vitro studies on the degradation and synthesis of serum proteins in placentae. I. Synthesis of serum proteins". Nippon Juigaku Zasshi. 26 (1): 15–23. PMID 4173631.
  11. Steinhorn RH (September 2008). "Evaluation and management of the cyanotic neonate". Clin Pediatr Emerg Med. 9 (3): 169–175. doi:10.1016/j.cpem.2008.06.006. PMC 2598396. PMID 19727322.
  12. 12.0 12.1 Kaur K, Bhardwaj M, Kumar P, Singhal S, Singh T, Hooda S (2016). "Amniotic fluid embolism". J Anaesthesiol Clin Pharmacol. 32 (2): 153–9. doi:10.4103/0970-9185.173356. PMC 4874066. PMID 27275041.
  13. Martínez de Zabarte Fernández JM, García Íñiguez JP, Domínguez Cajal M (February 2018). "Metahemoglobinemia in infants over one year". Med Clin (Barc). doi:10.1016/j.medcli.2017.12.009. PMID 29439874.
  14. Günal E, Akkuş Y, Çığşar G, Çiftçi H, Kahramanca Ş, Özdemir M (October 2017). "Methemoglobinemia incidence after the application of lidocaine for small surgical procedures". Agri. 29 (4): 173–176. PMID 29171648.
  15. Hilbert P, Zur Nieden K (September 2004). "[Suicidal fatal beta-blocker intoxication]". Anaesthesist (in German). 53 (9): 826–9. doi:10.1007/s00101-004-0721-1. PMID 15249969.
  16. Hifumi T, Sakai A, Kondo Y, Yamamoto A, Morine N, Ato M, Shibayama K, Umezawa K, Kiriu N, Kato H, Koido Y, Inoue J, Kawakita K, Kuroda Y (2015). "Venomous snake bites: clinical diagnosis and treatment". J Intensive Care. 3 (1): 16. doi:10.1186/s40560-015-0081-8. PMC 4393627. PMID 25866646.
  17. Kondamudi NP, Virji M. PMID 28722926. Missing or empty |title= (help)
  18. Jensen JD, Vincent AL. PMID 28613569. Missing or empty |title= (help)
  19. Gossman WG, Burns B. PMID 29261942. Missing or empty |title= (help)
  20. Jain S, Bakshi N, Krishnamurti L (December 2017). "Acute Chest Syndrome in Children with Sickle Cell Disease". Pediatr Allergy Immunol Pulmonol. 30 (4): 191–201. doi:10.1089/ped.2017.0814. PMC 5733742. PMID 29279787.
  21. Kondamudi NP, Dulebohn SC. PMID 28722923. Missing or empty |title= (help)
  22. Kondamudi NP, Wilt AS. PMID 28722998. Missing or empty |title= (help)
  23. Memon J, Manganaro SN. PMID 28722938. Missing or empty |title= (help)
  24. Bergeron M, Cohen AP, Cotton RT (2017). "The Management of Cyanotic Spells in Children with Oesophageal Atresia". Front Pediatr. 5: 106. doi:10.3389/fped.2017.00106. PMC 5430373. PMID 28555179.
  25. Maitre B, Similowski T, Derenne JP (September 1995). "Physical examination of the adult patient with respiratory diseases: inspection and palpation". Eur. Respir. J. 8 (9): 1584–93. PMID 8575588.
  26. Hermansen CL, Mahajan A (December 2015). "Newborn Respiratory Distress". Am Fam Physician. 92 (11): 994–1002. PMID 26760414.
  27. Bishop NB, Stankiewicz P, Steinhorn RH (July 2011). "Alveolar capillary dysplasia". Am. J. Respir. Crit. Care Med. 184 (2): 172–9. doi:10.1164/rccm.201010-1697CI. PMC 3172887. PMID 21471096.
  28. Justice NA, Le JK. PMID 28722988. Missing or empty |title= (help)
  29. Reuter S, Moser C, Baack M (October 2014). "Respiratory distress in the newborn". Pediatr Rev. 35 (10): 417–28, quiz 429. doi:10.1542/pir.35-10-417. PMC 4533247. PMID 25274969.
  30. Woods WA, McCulloch MA (November 2005). "Cardiovascular emergencies in the pediatric patient". Emerg. Med. Clin. North Am. 23 (4): 1233–49. doi:10.1016/j.emc.2005.07.003. PMID 16199347.
  31. Driscoll DJ (February 1990). "Evaluation of the cyanotic newborn". Pediatr. Clin. North Am. 37 (1): 1–23. PMID 2407997.
  32. Dueñas-Laita A, Burillo Putze G, Alonso JR, Bajo A, Climent B, Corral E, Felices F, Ferrer A, Hernández Frutos MP, Nogué S, Puiguriguer J (December 2010). "[Basis for the clinical management of fire smoke poisoning "Docohumo Madrid 2010"]". Med Intensiva (in Spanish; Castilian). 34 (9): 609–19. doi:10.1016/j.medin.2010.07.007. PMID 21051109.
  33. Costumbrado J, Ghassemzadeh S. PMID 29083723. Missing or empty |title= (help)
  34. Fardoun MM, Nassif J, Issa K, Baydoun E, Eid AH (2016). "Raynaud's Phenomenon: A Brief Review of the Underlying Mechanisms". Front Pharmacol. 7: 438. doi:10.3389/fphar.2016.00438. PMC 5110514. PMID 27899893.
  35. Das S, Maiti A (November 2013). "Acrocyanosis: an overview". Indian J Dermatol. 58 (6): 417–20. doi:10.4103/0019-5154.119946. PMC 3827510. PMID 24249890.
  36. Belda, F.J.; Soro, M.; Ferrando, C. (2013). "Pathophysiology of respiratory failure". Trends in Anaesthesia and Critical Care. 3 (5): 265–269. doi:10.1016/j.tacc.2013.05.003. ISSN 2210-8440.
  37. 37.0 37.1 Petersson J, Glenny RW (October 2014). "Gas exchange and ventilation-perfusion relationships in the lung". Eur. Respir. J. 44 (4): 1023–41. doi:10.1183/09031936.00037014. PMID 25063240.
  38. Gunning, Kevin EJ (2003). "Pathophysiology of Respiratory Failure and Indications for Respiratory Support". Surgery (Oxford). 21 (3): 72–76. doi:10.1383/surg.21.3.72.14672. ISSN 0263-9319.
  39. AVIADO DM, DALY MD, LEE CY, SCHMIDT CF (March 1961). "The contribution of the bronchial circulation to the venous admixture in pulmonary venous blood". J. Physiol. (Lond.). 155: 602–22. doi:10.1113/jphysiol.1961.sp006650. PMC 1359878. PMID 13685279.
  40. Kearns, Mark J.; Walley, Keith R. (2018). "Tamponade". Chest. 153 (5): 1266–1275. doi:10.1016/j.chest.2017.11.003. ISSN 0012-3692.
  41. Morrone, Doralisa; Morrone, Vincenzo (2018). "Acute Pulmonary Embolism: Focus on the Clinical Picture". Korean Circulation Journal. 48 (5): 365. doi:10.4070/kcj.2017.0314. ISSN 1738-5520.
  42. Khalid L, Dhakam SH (February 2008). "A review of cardiogenic shock in acute myocardial infarction". Curr Cardiol Rev. 4 (1): 34–40. doi:10.2174/157340308783565456. PMC 2774583. PMID 19924275.
  43. 43.0 43.1 43.2 43.3 O’Brien, Patricia; Marshall, Audrey C. (2014). "Tetralogy of Fallot". Circulation. 130 (4). doi:10.1161/CIRCULATIONAHA.113.005547. ISSN 0009-7322.
  44. Dekker, Jan; Eppink, Michel H. M.; van Zwieten, Rob; de Rijk, Thea; Remacha, Angel F.; Law, Lap Kay; Li, Albert M.; Cheung, Kam Lau; van Berkel, Willem J. H.; Roos, Dirk (2001). "Seven new mutations in the nicotinamide adenine dinucleotide reduced–cytochrome b5 reductase gene leading to methemoglobinemia type I". Blood. 97 (4): 1106–1114. doi:10.1182/blood.V97.4.1106. ISSN 1528-0020.
  45. Gupta, Amol; Gupta, Ravi; Kumar, Vinod; Samarany, Samir (2020). "Blue Toes at High Altitude: Peripheral Cyanosis". The American Journal of Medicine. 133 (5): 573–575. doi:10.1016/j.amjmed.2019.08.057. ISSN 0002-9343.
  46. Bourenne J, Carvelli J, Papazian L (March 2019). "Evolving definition of acute respiratory distress syndrome". J Thorac Dis. 11 (Suppl 3): S390–S393. doi:10.21037/jtd.2018.12.24. PMC 6424760. PMID 30997228.
  47. Singh, Jaspreet; Singh, Akashdeep (2013). "Differential Cyanosis". The American Journal of Medicine. 126 (10): e9. doi:10.1016/j.amjmed.2013.03.014. ISSN 0002-9343.
  48. Marino BS, Bird GL, Wernovsky G (March 2001). "Diagnosis and management of the newborn with suspected congenital heart disease". Clin Perinatol. 28 (1): 91–136. doi:10.1016/s0095-5108(05)70071-3. PMID 11265513.
  49. Rao, P. Syamasundar (2013). "Consensus on Timing of Intervention for Common Congenital Heart Diseases: Part II - Cyanotic Heart Defects". The Indian Journal of Pediatrics. 80 (8): 663–674. doi:10.1007/s12098-013-1039-2. ISSN 0019-5456.
  50. 50.0 50.1 Holst KA, Connolly HM, Dearani JA (2019). "Ebstein's Anomaly". Methodist Debakey Cardiovasc J. 15 (2): 138–144. doi:10.14797/mdcj-15-2-138. PMC 6668741 Check |pmc= value (help). PMID 31384377.
  51. de Campos F, Benvenuti LA (2017). "Eisenmenger syndrome". Autops Case Rep. 7 (1): 5–7. doi:10.4322/acr.2017.006. PMC 5436914. PMID 28536680. Vancouver style error: initials (help)
  52. Gobergs R, Salputra E, Lubaua I (2016). "Hypoplastic left heart syndrome: a review". Acta Med Litu. 23 (2): 86–98. doi:10.6001/actamedica.v23i2.3325. PMC 5088741. PMID 28356795.
  53. . doi:10.1161/STROKEAHA.116.012882Stroke. Missing or empty |title= (help)
  54. Kim HS, Jeong K, Cho HJ, Choi WY, Choi YE, Ma JS, Cho YK (December 2014). "Total anomalous pulmonary venous return in siblings". J Cardiovasc Ultrasound. 22 (4): 213–9. doi:10.4250/jcu.2014.22.4.213. PMC 4286644. PMID 25580197.