II. Definitions
- Edema
- Abnormal interstitial fluid accumulation in the intracellular space
- Anasarca
- Severe, diffuse Generalized Edema with causes including CHF, Renal Failure, liver failure, Nephrotic Syndrome or severe Malnutrition
III. Epidemiology
- Lower Extremity Edema is common in older adults, approaching 20% in those over age 50 years
IV. Pathophysiology
- Mechanisms
- Loss of vascular integrity
- Changes in capillary hemodynamics
- Oncotic pressure gradient changes across the capillary membrane (between capillary and interstitial space)
- Increased tissue oncotic pressure (increased interstitial Protein concentration) or
- Decreased plasma oncotic pressure (decreased Serum Albumin)
- Increase in capillary hydrostatic pressure
- Norepinephrine results in renal Vasoconstriction
- Renin results in Sodium absorption
- Aldosterone results in water retention
- Loss of vascular integrity
- Generalized Edema
- See Sodium and Water Homeostasis
- See Generalized Edema Below the Diaphragm
- See Generalized Edema Above the Diaphragm
- Implies >3 Liters interstitial fluid accumulation
- Sodium and water retention mediated by renal Vasoconstriction and renin and Aldosterone (as above)
-
Localized Edema
- See Localized Edema
- Mechanism related to underlying cause (e.g. venous or lymph obstruction, local inflammatory response)
V. Causes
-
Unilateral Edema
- Acute Unilateral or Localized Edema (<3 months, especially last 72 hours)
- Deep Vein Thrombosis (DVT)
- Superficial Venous Thrombosis
- Cellulitis or other soft tissue infection (e.g. Necrotizing Fasciitis)
- Local Trauma
- Bite (e.g. Insect Bite, Animal Bite)
- Soft Tissue Injury (e.g. Ruptured tendon, Fracture, Compartment Syndrome)
- Chronic Localized Edema (>3 months)
- Venous Insufficiency
- Popliteal Cyst (Baker's Cyst)
- Localized lymphatic obstruction (Lymphedema)
- Postthrombotic Syndrome
- Complex Regional Pain Syndrome
- Proximal vein compression
- May-Thurner Syndrome (chronic left Leg Edema due to left common iliac vein compression, risk for DVT)
- Acute Unilateral or Localized Edema (<3 months, especially last 72 hours)
- Generalized Edema
- See Generalized Edema Above the Diaphragm
- See Generalized Edema Below the Diaphragm
- Acute Bilateral or Generalized Edema or Anasarca (<3 months)
- Acute Congestive Heart Failure
- Acute Renal Failure
- Acute Liver Failure (e.g. fulminant liver failure)
- Nephrotic Syndrome
- Proximal Deep Vein Thrombosis or Obstruction (e.g. Inferior Vena Cava thrombosis, Superior Vena Cava Syndrome)
- Chronic Bilateral or Generalized Edema (>3 months)
- Chronic Congestive Heart Failure
- Chronic Renal Failure
- Chronic Liver Failure (Cirrhosis)
- Chronic Venous Insufficiency
- Lymphedema
- Pregnancy (e.g. Preeclampsia, Dependent Edema)
- Pulmonary Hypertension
- Obstructive Sleep Apnea
- Hypothryoidism or Hyperthyroidism
- Lipedema (fat accumulation in the buttocks and lower legs)
- Miscellaneous Generalized Edema Types (acute or chronic)
- Medication Causes of Edema
- Exercise edema
- Idiopathic Edema
- High Altitude Edema (Facial and lower limb edema)
- Tropical Edema
- Periodic edema
VI. History
- Onset Timing?
- Chronic (>3 months)
- Acute (<3 months)
- Hyperacute presentations (<72 hours) warrant urgent evaluation (e.g. DVT, Cellulitis, Trauma)
- Unilateral or bilateral?
-
Dependent Edema worse with prolonged standing?
- Venous Insufficiency or obstruction improves with limb elevation
- Other causes of Dependent Edema will not improve with elevation
- Decreased plasma oncotic pressure (e.g. Cirrhosis, Nephrotic Syndrome, malabsorption)
- Painful edema?
- Deep Vein Thrombosis
- Chronic Venous Insufficiency (extremity ache or heaviness)
- Complex Regional Pain Syndrome
- Trauma
- Associated Symptoms or risk factors?
- Dyspnea or Orthopnea (e.g. CHF)
- Hot or Cold intolerance (e.g. Thyroid Disease)
- Venous Thromboembolism Risk Factors (e.g. prolonged travel or immobility, cancer, Trauma, Estrogens)
- Prior Radiation Therapy or Lymph Node resection (e.g. Lymphedema)
- Travel History (e.g. DVT, Tropical Edema)
- New medications or increased dosing
VII. Symptoms
- Unexplained weight gain (Generalized Edema)
- Ring tightness
- Shoe tightness
- Facial swelling or puffiness
- Swollen arms or legs
- Abdominal Distention
VIII. Signs
- See Edema Exam
-
General exam for underlying etiologies
- Thyromegaly
- Cardiopulmonary findings (e.g. rales, loud murmur)
- Abdominal Distention and fluid wave (Ascites)
- Palpable swelling of skin or subcutaneous tissue
- Evaluate for symmetry (bilateral or unilateral)
- Pitting Edema (graded 1 to 4)
- Non-Pitting Edema (Brawny Edema)
- Pretibial Myxedema (Hypothyroidism)
- Chronic, longstanding Lymphedema
- Chronic, longstanding Venous Stasis
- Associated Findings
- Tender, erythematous extremity
- Deep Vein Thrombosis
- Superficial Thrombophlebitis
- Cellulitis
- Venous Stasis Dermatitis
- Lipedema (fat accumulation in thighs and buttocks)
- Contrast with Lymphedema which is not typically tender
- Swelling is prominent in the first web space, but spares the dorsal feet
- Stasis Dermatitis Changes (e.g. Hyperpigmentation, medial ankle ulcers, vericose veins)
- Tender, erythematous extremity
IX. Diagnostics
-
Electrocardiogram
- Indicated for Chest Pain
X. Imaging
-
Chest XRay Indications
- Dyspnea or
- BNP not available
-
Echocardiogram Indications
- Suspected Pulmonary Hypertension (e.g. Obstructive Sleep Apnea)
- Suspected Congestive Heart Failure
- Increased BNP or
- Generalized Leg Edema in age over 45 years old (or other risks for Cardiomyopathy or CHF)
- Blankfield (1998) Am J Med 105:192-7 [PubMed]
- Extremity Doppler Ultrasound Indications
- Unilateral or asymmetric extremity edema
- Deep Vein Thrombosis suspected
- Confirm Venous Insufficiency
- Indirect radionuclide lymphoscintigraphy
- Confirmation of Lymphedema
- Magnetic Resonance Angiography with venography of lower extremity and Pelvis
- Pelvic or thigh Deep Vein Thrombosis suspected despite negative venous Doppler Ultrasound
XI. Labs
- Thyroid Stimulating Hormone (TSH)
-
B-Type Natriuretic Peptide
- CHF unlikely if BNP normal
- Test Sensitivity 90%: BNP <100 pg/ml
- Test Sensitivity 96%: BNP <50 pg/ml)
- Maisel (2001) N Engl J Med 347(3): 161-7 [PubMed]
- CHF unlikely if BNP normal
-
Urinalysis
- Evaluate for large Proteinuria (Nephrotic Syndrome)
- Consider quantifying Proteinuria with Urine Protein to Creatinine Ratio
- Comprehensive metabolic panel
- Renal Function test (Serum Creatinine, Blood Urea Nitrogen or BUN)
- Liver Function Test
- Optional if examiner can reliably exclude significant Ascites based on examination or Bedside Ultrasound
- Serum Albumin
- Hypoalbuminemia may be present in severe Malnutrition, Chronic Liver Disease or Nephrotic Syndrome
- Other testing (not typically indicated, but consider in specific cases)
- Urine test for Thiazides or Phenolphthalein
- Indicated in suspected Eating Disorder
- Confirms Diuretic abuse or Laxative abuse
- Urine test for Thiazides or Phenolphthalein
XII. Approach: Unilateral Leg Edema
- Exclude Deep Vein Thrombosis (most important, single diagnosis to identify)
- Consider VTE Risk factors and DVT Probability
- Low risk patients with a negative D-Dimer may safely have DVT excluded without further testing
- Moderate to high risk patients should undergo DVT Ultrasound
- DVT Ultrasound
- Formal DVT Ultrasound OR
- Focused Lower Extremity Venous Ultrasound (Two Point DVT Ultrasound, DVT POCUS)
- Consider repeat formal Ultrasound in 1 week if initially negative
- Consider VTE Risk factors and DVT Probability
- Consider other causes
- Skin and Soft Tissue Infection (e.g. Cellulitis)
- Trauma
- Asymmetric Venous Insufficiency or Lymphedema
XIII. Approach: Bilateral Leg Edema in Emergency Department
- Most critical causes to exclude
- Diagnostics
- B-Type Natriuretic Peptide (BNP)
- Obtain Echocardiogram if BNP >100 pg/ml (especially if age >45)
- Comprehensive metabolic panel
- Adding Liver Function Tests and Serum Albumin is optional (if Ascites excluded on exam or Bedside Ultrasound)
- Urinalysis
- Evaluate for large Proteinuria
- Thyroid Stimulating Hormone (TSH) with reflex to Free T4
- Evaluate for Hypothyroidism (pretibial Myxedema)
- Bedside Abdominal Ultrasound
- Evaluate for Ascites (if body habitus or other confounding factors limit exam)
- Consider Inferior Vena Cava Ultrasound for Volume Status
- B-Type Natriuretic Peptide (BNP)
- Consider important other diagnoses (if diagnostics and examination otherwise negative above)
- See Generalized Edema Below the Diaphragm
- See Generalized Edema Above the Diaphragm
- See Medication Causes of Edema
- Pelvic Mass
- Pregnancy Induced Hypertension (after 20 weeks gestation)
- Deep Vein Thrombosis evaluation indications
- Unilateral or asymmetric edema or
- Bilateral extremity edema and significant VTE Risk factors
- Cancer in last year
- Joint replacement
- Trauma
- Immobilization
- Hypercoagulability or prior Venous Thromboembolism
- Consider common alternative diagnoses (if diagnostics and examination otherwise negative above)
- Cyclic edema
- Venous Insufficiency (most common)
- Lymphedema
- See Stemmer's Sign (pathognomonic)
XIV. Management: General
- Treat specific underlying cause (e.g. DVT, CHF)
- Elevate legs
- Limit Dietary Sodium to 1500-2000 mg/daily
- Consider Medication Causes of Edema
- Amlodipine (Norvasc) is a common cause of edema (avoid doses >5 mg, consider adding an ACE Inhibitor)
-
Compression Stockings (Venous Insufficiency)
- Contraindicated in Peripheral Arterial Disease (consider Ankle-Brachial Index before compression stocking use)
- Mild edema: 20-30 mmHg
- Severe edema: 30-40 mmHg
- Consider Lymphedema clinic referral
-
Diuretics if indicated (see below)
- AVOID in venous or lymphatic insufficiency
XV. Management: Diuretics
- Precautions
- Avoid Diuretics in conditions where they are unlikely to offer benefit
- Venous Insufficiency
- Lymphatic insufficiency (Lymphedema)
- Cyclic edema
- Close interval follow-up (within 7-10 days) to monitor progression
- Monitor Serum Potassium
- Monitor weight loss to keep above dry weight (base weight)
- Avoid Diuretics in conditions where they are unlikely to offer benefit
- Diuretic indications
-
Diuretic dosing (initiation)
- Furosemide 10-20 mg orally twice daily
- Add Spironolactone in Cirrhotic Ascites
XVI. References
- Borhart et al in Herbert (2013) EM:Rap 13(7):5-6
- Traves (2013) Am Fam Physician 88(2): 102-110 [PubMed]
- Patel (2022) Am Fam Physician 106(5): 557-64 [PubMed]