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Basics ⬇

Basics

Definition

A bluish discoloration of the skin and mucous membranes owing to an increase in the amount of reduced, or deoxygenated, hemoglobin within the blood.

Pathophysiology

  • Concentration of deoxygenated hemoglobin-must be >5 g/dL to detect condition; thus anemia (PCV <15%) may obscure recognition of cyanosis.
  • Central-associated with systemic arterial hypoxemia or hemoglobin abnormalities.
  • Peripheral-limited to one or more extremities of the body; associated with diminished peripheral blood flow; arterial oxygen tension and saturation typically normal.

Arterial Hypoxemia

  • Decreased fraction of inspired oxygen-high altitude.
  • Hypoventilation-upper airway obstructive disorders; restrictive or obstructive lung diseases; pleural space disorders; neuromuscular failure.
  • Ventilation-perfusion mismatching-pulmonary parenchymal or thromboembolic diseases.
  • Diffusion impairment-thickening of the alveolar barrier through which oxygen must pass to reach the RBCs.
  • Addition of venous blood to the arterial circulation-congenital right-to-left shunting cardiac defects (e.g., tetralogy of Fallot, transposition of the great vessels); reversed shunting cardiac defects caused by high pulmonary vascular resistance (e.g., right-to-left shunting PDA, ASD, VSD).
  • Anatomic shunts-distinguished from other causes of hypoxemia by the failure to respond to supplemental oxygen.

Abnormal Hemoglobin

  • Methemoglobin-most common abnormal heme pigment; unable to bind oxygen; normally formed at a low rate in erythrocytes.
  • NADH-MR-intracellular reductive enzyme; maintains the methemoglobin: hemoglobin ratio at <2%; deficiency and/or exposure to oxidizing agents causes methemoglobinemia.
  • Hypoxia-when >20–40% of hemoglobin has been oxidized to methemoglobin.

Other

  • Peripheral cyanosis-results from increased oxygen extraction from the arterial supply to an area (e.g., a limb); caused by severe vasoconstriction, poor peripheral blood flow, obstruction to flow associated with arterial thromboembolism, or stagnation or obstruction of venous blood flow.
  • Differential cyanosis-with reverse shunting PDA, the head and neck receive oxygenated blood via the brachiocephalic trunk and left subclavian artery, which arise from the aortic arch; the rest of the body receives desaturated blood through the ductus located in the descending aorta.

Systems Affected

  • Central-all systems affected.
  • Peripheral-may diminish or abolish neuromuscular function of the affected limb(s).

Signalment

  • Right-to-left cardiac shunts in association with high pulmonary vascular resistance and pulmonary hypertension (Eisenmenger physiology)-dogs: Keeshonden, English bulldogs, and beagles; some cats; generally young animals.
  • Tracheal collapse-usually young or middle-aged small-breed dogs (e.g., Pomeranians, Yorkshire terriers, poodles).
  • Congenital laryngeal paralysis-young animals; reported in Dalmatians, Bouvier des Flandres, and Siberian huskies.
  • Acquired laryngeal paralysis-most common in old large-breed dogs (e.g., retrievers).
  • Hypoplastic trachea-identified in young English bulldogs; occasionally other breeds.
  • Brachycephalic airway syndrome-dogs: English and French bulldogs, Pekinese, Pugs; cats: Himalayan, Persian.
  • Asthma (cats)-higher incidence reported in Siamese.

Signs

Historical Findings

  • Central-stridor; respiratory distress; cough; voice change; episodic weakness; syncope; exposure to oxidizing substances or drugs causing methemoglobinemia.
  • Peripheral-limb paresis or paralysis.

Physical Examination Findings

  • Heart murmur or splitting of the second heart sound-with cardiac disease or pulmonary hypertension.
  • Pulmonary crackles or wheezes-with pulmonary edema or respiratory disease.
  • Muffled heart sounds-owing to pleural space or pericardial disease.
  • Upper airway stridor with laryngeal paralysis.
  • Honking cough-typical of tracheal collapse; often induced by tracheal palpation.
  • Dyspnea-may be inspiratory, expiratory, or a combination (see “Differential Diagnosis”).
  • Limbs-may be cyanotic, cool, pale, painful, and edematous; can lack a pulse in conditions causing peripheral cyanosis.
  • Weakness-can be generalized and persistent with severe cardiac diseases; can be episodic and especially noticeable with exercise or excitement.
  • Posterior paresis or paralysis-can be seen with distal aorta arterial thromboembolism; differentiated from primary neuromuscular disease by absence (or near absence) of pulses.

Causes

Respiratory System

  • Larynx-paralysis (acquired or congenital); collapse; spasm; edema; trauma; neoplasia; granulomatous disease.
  • Trachea-collapse; neoplasia; foreign body; trauma; hypoplasia.
  • Lower airway and parenchyma-pneumonia (viral, bacterial, fungal, eosinophilic, mycobacteria, aspiration); chronic bronchitis; hypersensitivity bronchial disease or asthma; bronchiectasis; neoplasia; foreign body; parasites (Filaroides, Paragonimus, Pneumocystis jiroveci, toxoplasmosis, Aelurostrongylus spp.); pulmonary contusion or hemorrhage; non-cardiogenic edema (inhalation, snake bite, electric shock); near drowning.
  • Pleural space-pneumothorax; infectious (bacterial, fungal, FIP); chylothorax; hemothorax; neoplasia; trauma.
  • Thoracic wall or diaphragm-congenital (pericardial, diaphragmatic hernia); trauma (diaphragmatic hernia, fractured ribs, flail chest); neuromuscular disease (tick bite paralysis, coonhound paralysis).

Cardiovascular System

  • Congenital defects-Eisenmenger physiology (right-to-left shunting PDA, VSD, ASD); tetralogy of Fallot; truncus arteriosus; double outlet right ventricle; anomalous pulmonary venous return; atresia of aortic or tricuspid or pulmonary valves.
  • Acquired disease-mitral valve disease; cardiomyopathy.
  • Pericardial effusion-idiopathic disease; neoplasia.
  • Pulmonary thromboembolic disease-hyperadrenocorticism; immune-mediated hemolytic anemia; protein-losing nephropathy; dirofilariasis.
  • Pulmonary hypertension-idiopathic; right-to-left cardiac shunts.
  • Peripheral vascular disease-arterial thromboembolism (feline cardiomyopathies); venous obstruction; reduced cardiac output; shock, arteriolar constriction.

Neuromusculoskeletal System

  • Brainstem dysfunction-encephalitis; trauma; hemorrhage; neoplasia; drug-induced depression of respiratory center (morphine, barbiturates).
  • Spinal cord dysfunction-edema; trauma; vertebral fractures; disk prolapse.
  • Neuromuscular dysfunction-overdose of paralytic agents (succinylcholine, pancuronium); tick bite paralysis; botulism; acute polyradiculoneuritis (coonhound paralysis); dysautonomia; myasthenia gravis.

Methemoglobinemia

  • Congenital-NADH-MR deficiency (dogs).
  • Ingestion of oxidant chemicals-acetaminophen; nitrates; nitrites; phenacetin; sulfonamides; benzocaine; aniline dyes; dapsone.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Generalized-systemic hypoxemia or heme abnormality.
  • Peripheral only-reduced blood flow to extremities.
  • Caudal body-right-to-left shunting PDA.
  • Cardiac versus respiratory causes-differentiation can be difficult; cardiac murmur may suggest cardiac disease but murmurs are often heard in older patients with primary respiratory disease; thoracic radiography and echocardiography useful for differentiation.
  • Central or peripheral neurologic signs-should prompt concern of arterial hypoxemia owing to primary neuromuscular disease.

Breathing Pattern

  • May help define cause.
  • Inspiratory effort-often associated with obstructive upper airway or pleural space disease; stridor frequently localizes problem to the larynx or cervical trachea.
  • Expiratory effort-generally seen with obstructive lower airway disease.
  • Rapid shallow (restrictive)-may be associated with pleural space disease or neuromuscular abnormalities of the thoracic wall.

CBC/Biochemistry/Urinalysis

  • Color of blood-may be darkened; chocolate brown with methemoglobinemia.
  • Polycythemia-often accompanies congenital heart disease; may occur with chronic hypoxemia owing to severe respiratory disease.
  • Proteinuria-accompanies protein-losing nephropathies, which may result in secondary pulmonary thromboembolism.
  • Panhypoproteinemia-accompanies protein-losing enteropathies, which may lead to pulmonary thromboembolism.

Other Laboratory Tests

  • Methemoglobin concentrations-measure through a laboratory; alternatively, shake a blood sample in air 15 minutes: red, reduced hemoglobin with cardiac or respiratory disease; chocolate brown, methemoglobin.
  • Arterial blood gas analysis.
  • Urine protein:creatinine ratio-with suspected pulmonary thromboembolism secondary to a protein-losing nephropathy.

Imaging

  • Radiography-essential for determining cause.
  • Echocardiography with Doppler-aids in diagnosis of congenital or acquired cardiac disease, pulmonary hypertension, and pulmonary thromboembolism.
  • Computed tomography-can further define obstructive nasal, pulmonary or pleural space disease.

Diagnostic Procedures

  • Pulse oximetry-determine oxygen saturation.
  • Laryngoscopic examination-evaluate laryngeal structure and arytenoid function.
  • Bronchoscopy-often useful in the diagnosis of airway and pulmonary diseases.
  • Transtracheal wash, bronchoalveolar lavage, or fine-needle lung aspirate-often required to characterize bronchopulmonary diseases.
  • Thoracocentesis-required for diagnosis and treatment of pleural space disorders.
  • Electrocardiography-may reveal heart enlargement changes; unreliable; echocardiography better.
  • Lung biopsy-can be necessary for diagnosis of interstitial lung disease.

Treatment ⬆ ⬇

Treatment

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

  • Oxygen therapy-provide as soon as possible.
  • Additional drug therapy depends on final diagnosis.
  • Furosemide-aggressive use indicated with suspected cardiogenic pulmonary edema.
  • Methemoglobinemia as a result of ingestion of oxidizing substances (acetaminophen)-give acetylcysteine as soon as possible (140 mg/kg PO or IV; then 70 mg/kg q4h for five treatments); cimetidine (10 mg/kg PO; then 5 mg/kg PO q6h for 48 hours) is a useful adjunct to acetylcysteine; ascorbic acid (30 mg/kg PO q6h for seven treatments) may be of some value but do not use as the sole agent.
  • Sildenafil citrate-phosphodiesterase type 5 inhibitor used to treat pulmonary arterial hypertension at 1–3 mg/kg PO q8–12h.

Contraindications

Avoid using paralytic agents (succinylcholine, pancuronium) and agents that cause profound depression of the respiratory center (morphine, barbiturates).

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Patients in an oxygen cage should be disturbed as infrequently as possible for monitoring.
  • Assess efficacy of therapy-changes in depth and rate of respiration; color of mucous membranes (should return to a normal pink color if the cause is not an anatomic shunt and patient has adequate reserves); pulse oximetry or arterial blood analysis.
  • Instruct client to monitor mucous membrane color and respiratory effort and advise immediate veterinary care if cyanotic condition returns.

Possible Complications

Advanced pulmonary or airway disease and severe cardiac disease-poor long-term prognosis.

Miscellaneous ⬆

Miscellaneous

Associated Conditions

  • Obesity-can complicate or exacerbate underlying respiratory or cardiac diseases.
  • Ascites-can complicate or exacerbate respiratory effort and reduce lung capacity due to cranial displacement of diaphragm.

Age-Related Factors

Congenital cardiac abnormalities-usually the cause in young patients.

Pregnancy/Fertility/Breeding

  • Advanced pregnancy may exacerbate signs because of pressure on the diaphragm and reduced lung expansion.
  • Fetuses are likely to be harmed or aborted by hypoxemia associated with cyanosis.

Abbreviations

  • ASD = atrial septal defect
  • FIP = feline infectious peritonitis
  • MR = methemoglobin reductase
  • NADH-MR = nicotinamide adenine dinucleotide dependent-methemoglobin reductase
  • PCV = packed cell volume
  • PDA = patent ductus arteriosus
  • RBC = red blood cell
  • VSD = ventricular septal defect

Author Ned F. Kuehn

Consulting Editor Lynelle R. Johnson

Client Education Handout Available Online

Suggested Reading

Krotje LJ. Cyanosis: Physiology and pathogenesis. Compend Contin Educ Pract Vet 1987, 9:271–278.

Lee JA, Drobatz KJ. Respiratory distress and cyanosis in dogs. In: King LG, ed., Textbook of Respiratory Disease in Dogs and Cats. Philadelphia: Saunders, 2004, pp. 1–12.

Petrie JP. Cyanosis. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 6th ed. St. Louis, MO: Elsevier, 2005, pp. 219–222.