II. Definitions

  1. Edema
    1. Abnormal interstitial fluid accumulation in the intracellular space
  2. Anasarca
    1. Severe, diffuse Generalized Edema with causes including CHF, Renal Failure, liver failure, Nephrotic Syndrome or severe Malnutrition

III. Epidemiology

  1. Lower Extremity Edema is common in older adults, approaching 20% in those over age 50 years

IV. Pathophysiology

  1. Mechanisms
    1. Loss of vascular integrity
      1. Changes in capillary hemodynamics
    2. Oncotic pressure gradient changes across the capillary membrane (between capillary and interstitial space)
      1. Increased tissue oncotic pressure (increased interstitial Protein concentration) or
      2. Decreased plasma oncotic pressure (decreased Serum Albumin)
    3. Increase in capillary hydrostatic pressure
      1. Norepinephrine results in renal Vasoconstriction
      2. Renin results in Sodium absorption
      3. Aldosterone results in water retention
  2. Generalized Edema
    1. See Sodium and Water Homeostasis
    2. See Generalized Edema Below the Diaphragm
    3. See Generalized Edema Above the Diaphragm
    4. Implies >3 Liters interstitial fluid accumulation
    5. Sodium and water retention mediated by renal Vasoconstriction and renin and Aldosterone (as above)
      1. Kidney senses decreased perfusion
      2. Kidney senses decreased circulating volume
  3. Localized Edema
    1. See Localized Edema
    2. Mechanism related to underlying cause (e.g. venous or lymph obstruction, local inflammatory response)

V. Causes

  1. Unilateral Edema
    1. Acute Unilateral or Localized Edema (<3 months, especially last 72 hours)
      1. Deep Vein Thrombosis (DVT)
      2. Superficial Venous Thrombosis
      3. Cellulitis or other soft tissue infection (e.g. Necrotizing Fasciitis)
      4. Local Trauma
        1. Bite (e.g. Insect Bite, Animal Bite)
        2. Soft Tissue Injury (e.g. Ruptured tendon, Fracture, Compartment Syndrome)
    2. Chronic Localized Edema (>3 months)
      1. Venous Insufficiency
      2. Popliteal Cyst (Baker's Cyst)
      3. Localized lymphatic obstruction (Lymphedema)
      4. Postthrombotic Syndrome
      5. Complex Regional Pain Syndrome
      6. Proximal vein compression
      7. May-Thurner Syndrome (chronic left Leg Edema due to left common iliac vein compression, risk for DVT)
  2. Generalized Edema
    1. See Generalized Edema Above the Diaphragm
    2. See Generalized Edema Below the Diaphragm
    3. Acute Bilateral or Generalized Edema or Anasarca (<3 months)
      1. Acute Congestive Heart Failure
      2. Acute Renal Failure
      3. Acute Liver Failure (e.g. fulminant liver failure)
      4. Nephrotic Syndrome
      5. Proximal Deep Vein Thrombosis or Obstruction (e.g. Inferior Vena Cava thrombosis, Superior Vena Cava Syndrome)
    4. Chronic Bilateral or Generalized Edema (>3 months)
      1. Chronic Congestive Heart Failure
      2. Chronic Renal Failure
      3. Chronic Liver Failure (Cirrhosis)
      4. Chronic Venous Insufficiency
      5. Lymphedema
      6. Pregnancy (e.g. Preeclampsia, Dependent Edema)
      7. Pulmonary Hypertension
      8. Obstructive Sleep Apnea
      9. Hypothryoidism or Hyperthyroidism
      10. Lipedema (fat accumulation in the buttocks and lower legs)
    5. Miscellaneous Generalized Edema Types (acute or chronic)
      1. Medication Causes of Edema
      2. Exercise edema
      3. Idiopathic Edema
      4. High Altitude Edema (Facial and lower limb edema)
      5. Tropical Edema
      6. Periodic edema

VI. History

  1. Onset Timing?
    1. Chronic (>3 months)
    2. Acute (<3 months)
      1. Hyperacute presentations (<72 hours) warrant urgent evaluation (e.g. DVT, Cellulitis, Trauma)
  2. Unilateral or bilateral?
    1. See Localized Edema Causes
    2. See Generalized Edema Above the Diaphragm
    3. See Generalized Edema Below the Diaphragm
    4. See Medication Causes of Edema
  3. Dependent Edema worse with prolonged standing?
    1. Venous Insufficiency or obstruction improves with limb elevation
    2. Other causes of Dependent Edema will not improve with elevation
      1. Decreased plasma oncotic pressure (e.g. Cirrhosis, Nephrotic Syndrome, malabsorption)
  4. Painful edema?
    1. Deep Vein Thrombosis
    2. Chronic Venous Insufficiency (extremity ache or heaviness)
    3. Complex Regional Pain Syndrome
    4. Trauma
  5. Associated Symptoms or risk factors?
    1. Dyspnea or Orthopnea (e.g. CHF)
    2. Hot or Cold intolerance (e.g. Thyroid Disease)
    3. Venous Thromboembolism Risk Factors (e.g. prolonged travel or immobility, cancer, Trauma, Estrogens)
    4. Prior Radiation Therapy or Lymph Node resection (e.g. Lymphedema)
    5. Travel History (e.g. DVT, Tropical Edema)
    6. New medications or increased dosing
      1. See Medication Causes of Edema

VII. Symptoms

  1. Unexplained weight gain (Generalized Edema)
  2. Ring tightness
  3. Shoe tightness
  4. Facial swelling or puffiness
  5. Swollen arms or legs
  6. Abdominal Distention

VIII. Signs

  1. See Edema Exam
  2. General exam for underlying etiologies
    1. Thyromegaly
    2. Cardiopulmonary findings (e.g. rales, loud murmur)
    3. Abdominal Distention and fluid wave (Ascites)
  3. Palpable swelling of skin or subcutaneous tissue
    1. Evaluate for symmetry (bilateral or unilateral)
    2. Pitting Edema (graded 1 to 4)
      1. Deep Vein Thrombosis
      2. Congestive Heart Failure
      3. Liver Failure
      4. Renal Failure
      5. Venous Insufficiency
      6. Early Lymphedema
    3. Non-Pitting Edema (Brawny Edema)
      1. Pretibial Myxedema (Hypothyroidism)
      2. Chronic, longstanding Lymphedema
      3. Chronic, longstanding Venous Stasis
  4. Associated Findings
    1. Tender, erythematous extremity
      1. Deep Vein Thrombosis
      2. Superficial Thrombophlebitis
      3. Cellulitis
      4. Venous Stasis Dermatitis
      5. Lipedema (fat accumulation in thighs and buttocks)
        1. Contrast with Lymphedema which is not typically tender
    2. Swelling is prominent in the first web space, but spares the dorsal feet
      1. Lymphedema
    3. Stasis Dermatitis Changes (e.g. Hyperpigmentation, medial ankle ulcers, vericose veins)
      1. Venous Insufficiency

IX. Diagnostics

X. Imaging

  1. Chest XRay Indications
    1. Dyspnea or
    2. BNP not available
  2. Echocardiogram Indications
    1. Suspected Pulmonary Hypertension (e.g. Obstructive Sleep Apnea)
    2. Suspected Congestive Heart Failure
      1. Increased BNP or
      2. Generalized Leg Edema in age over 45 years old (or other risks for Cardiomyopathy or CHF)
      3. Blankfield (1998) Am J Med 105:192-7 [PubMed]
  3. Extremity Doppler Ultrasound Indications
    1. Unilateral or asymmetric extremity edema
    2. Deep Vein Thrombosis suspected
    3. Confirm Venous Insufficiency
  4. Indirect radionuclide lymphoscintigraphy
    1. Confirmation of Lymphedema
  5. Magnetic Resonance Angiography with venography of lower extremity and Pelvis
    1. Pelvic or thigh Deep Vein Thrombosis suspected despite negative venous Doppler Ultrasound

XI. Labs

  1. Thyroid Stimulating Hormone (TSH)
  2. B-Type Natriuretic Peptide
    1. CHF unlikely if BNP normal
      1. Test Sensitivity 90%: BNP <100 pg/ml
      2. Test Sensitivity 96%: BNP <50 pg/ml)
    2. Maisel (2001) N Engl J Med 347(3): 161-7 [PubMed]
  3. Urinalysis
    1. Evaluate for large Proteinuria (Nephrotic Syndrome)
    2. Consider quantifying Proteinuria with Urine Protein to Creatinine Ratio
  4. Comprehensive metabolic panel
    1. Renal Function test (Serum Creatinine, Blood Urea Nitrogen or BUN)
    2. Liver Function Test
      1. Optional if examiner can reliably exclude significant Ascites based on examination or Bedside Ultrasound
    3. Serum Albumin
      1. Hypoalbuminemia may be present in severe Malnutrition, Chronic Liver Disease or Nephrotic Syndrome
  5. Other testing (not typically indicated, but consider in specific cases)
    1. Urine test for Thiazides or Phenolphthalein
      1. Indicated in suspected Eating Disorder
      2. Confirms Diuretic abuse or Laxative abuse

XII. Approach: Unilateral Leg Edema

  1. Exclude Deep Vein Thrombosis (most important, single diagnosis to identify)
    1. Consider VTE Risk factors and DVT Probability
      1. Low risk patients with a negative D-Dimer may safely have DVT excluded without further testing
      2. Moderate to high risk patients should undergo DVT Ultrasound
    2. DVT Ultrasound
      1. Formal DVT Ultrasound OR
      2. Focused Lower Extremity Venous Ultrasound (Two Point DVT Ultrasound, DVT POCUS)
        1. Consider repeat formal Ultrasound in 1 week if initially negative
  2. Consider other causes
    1. Skin and Soft Tissue Infection (e.g. Cellulitis)
    2. Trauma
    3. Asymmetric Venous Insufficiency or Lymphedema

XIII. Approach: Bilateral Leg Edema in Emergency Department

  1. Most critical causes to exclude
    1. Congestive Heart Failure
    2. Nephrotic Syndrome
    3. Cirrhosis
  2. Diagnostics
    1. B-Type Natriuretic Peptide (BNP)
      1. Obtain Echocardiogram if BNP >100 pg/ml (especially if age >45)
    2. Comprehensive metabolic panel
      1. Adding Liver Function Tests and Serum Albumin is optional (if Ascites excluded on exam or Bedside Ultrasound)
    3. Urinalysis
      1. Evaluate for large Proteinuria
    4. Thyroid Stimulating Hormone (TSH) with reflex to Free T4
      1. Evaluate for Hypothyroidism (pretibial Myxedema)
    5. Bedside Abdominal Ultrasound
      1. Evaluate for Ascites (if body habitus or other confounding factors limit exam)
      2. Consider Inferior Vena Cava Ultrasound for Volume Status
  3. Consider important other diagnoses (if diagnostics and examination otherwise negative above)
    1. See Generalized Edema Below the Diaphragm
    2. See Generalized Edema Above the Diaphragm
    3. See Medication Causes of Edema
    4. Pelvic Mass
    5. Pregnancy Induced Hypertension (after 20 weeks gestation)
    6. Deep Vein Thrombosis evaluation indications
      1. Unilateral or asymmetric edema or
      2. Bilateral extremity edema and significant VTE Risk factors
        1. Cancer in last year
        2. Joint replacement
        3. Trauma
        4. Immobilization
        5. Hypercoagulability or prior Venous Thromboembolism
  4. Consider common alternative diagnoses (if diagnostics and examination otherwise negative above)
    1. Cyclic edema
    2. Venous Insufficiency (most common)
    3. Lymphedema
      1. See Stemmer's Sign (pathognomonic)

XIV. Management: General

  1. Treat specific underlying cause (e.g. DVT, CHF)
  2. Elevate legs
  3. Limit Dietary Sodium to 1500-2000 mg/daily
  4. Consider Medication Causes of Edema
    1. Amlodipine (Norvasc) is a common cause of edema (avoid doses >5 mg, consider adding an ACE Inhibitor)
  5. Compression Stockings (Venous Insufficiency)
    1. Contraindicated in Peripheral Arterial Disease (consider Ankle-Brachial Index before compression stocking use)
    2. Mild edema: 20-30 mmHg
    3. Severe edema: 30-40 mmHg
  6. Consider Lymphedema clinic referral
  7. Diuretics if indicated (see below)
    1. AVOID in venous or lymphatic insufficiency

XV. Management: Diuretics

  1. Precautions
    1. Avoid Diuretics in conditions where they are unlikely to offer benefit
      1. Venous Insufficiency
      2. Lymphatic insufficiency (Lymphedema)
      3. Cyclic edema
    2. Close interval follow-up (within 7-10 days) to monitor progression
    3. Monitor Serum Potassium
    4. Monitor weight loss to keep above dry weight (base weight)
  2. Diuretic indications
    1. Pulmonary Edema
    2. Congestive Heart Failure
    3. Nephrotic Syndrome
    4. Cirrhosis
  3. Diuretic dosing (initiation)
    1. Furosemide 10-20 mg orally twice daily
    2. Add Spironolactone in Cirrhotic Ascites

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