The patient with bilateral leg edema: what tests are warranted?

Authors: Wells Weymouth, MD (EM Resident Physician, SAUSHEC, USA) and David Ong, MD (EM Attending Physician, SAUSHEC, USA) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Case: A 56-year-old female presents to the emergency department with a 5 day history of lower extremity edema. Her legs aren’t especially painful, and she denies chest pain or shortness of breath. She is slightly hypertensive at 143/74, and on exam her lungs are clear but she has notable bilateral pitting edema up to her knees.

Clinical Question: What organ systems could be involved, and what evaluation is warranted for testing?

Background on Lower Extremity Edema

The basic principle underlying peripheral edema is based on a change of capillary hemodynamics that favors fluid movement from the vascular space into the interstitium. This is a result of hydrostatic or oncotic forces, or both. The loss of intravascular fluid causes the kidneys to begin retaining sodium and water.

In the ED, what organ systems could contribute to edema that we must diagnose?

-Heart Failure

-Nephrotic syndrome

-Cirrhosis

ED Evaluation:

The ED evaluation focuses on these three organ systems and potential conditions.

1. Heart Failure –

Heart failure (HF) is the most common cause of hospitalization in patients over the age of  Unfortunately, as a clinical diagnosis it is not always apparent. Early HF or right sided heart failure can cause lower extremity swelling, so it is prudent to consider HF even in cases of isolated lower extremity edema. What can help you differentiate edema from other causes and heart failure in the patient with no history or other exam findings of heart failure?

BNP: BNP is highly sensitive for ruling out acute HF in patients with dyspnea, according to the authors of the multinational Breathing Not Properly study, who found that the BNP was the single most accurate predictor of the presence or absence of congestive HF.   There is little guidance for the utility of BNP levels in identifying HF in patients that present primarily with leg edema and without dyspnea.  However, studies have demonstrated that congestion may precede symptoms of HF by 7 to 10 days  and that rising BNP levels in patients with CHF are at higher risks for decompensation .[viii]^,[ix]  The European Society of Cardiology recommends using BNP as a screening tool for HF or subclinical cardiovascular disease in the non-acute setting or patients without acute HF .[x]^,[xi],[xii]    The Heart Failure Society of America and the American College of Cardiology both recommend checking a BNP when HF diagnosis is unclear. If the BNP is greater than 100, refer the patient for an outpatient cardiac echo. This doesn’t necessarily require admission, however,

What’s the rationale behind obtaining a BNP? Unless a patient is complaining of chest pain or shortness of breath, a Chest X-ray is of low yield  since a B-type natriuretic peptide cutoff value of 100 pg per milliliter has a sensitivity of 90 percent, a specificity of 76 percent, and an accuracy of 83 percent for differentiating congestive heart failure from other causes of dyspnea.  BNP <50 pg/mL has 96% sensitivity for ruling out HF .^[xiv] Compare this to clinical judgment (including a chest film) which had a sensitivity of 49% and specificity of 96%, at an 80% cutoff level of certainty of CHF.^[xv]

While BNP is a valuable test to rule out CHF, it is no substitute for clinical judgement, which may in turn direct you to bedside ultrasound and CXR, if warranted. According to a meta-analysis by Martindale et. al., ultrasound with demonstration of B lines demonstrates the greatest ability for heart failure with pulmonary involvement with a likelihood ratio (LR) of 7.4 (compare this to auscultation of S3 on physical exam which had an LR of 4.0).One might incorporate the modified lung and cardiac US (LuCUS) protocol recently discussed by Russel et. al., which demonstrated a specificity of 100% in diagnosing acute decompensated CHF. ^[xvi],[xvii]

Reassuringly, lower extremity edema is not an independent predictor of cardiogenic edema, and therefore the other causes of edema are less serious in the well-appearing patient. Those without a cardiac cause for edema have decreased mortality (25% vs. 8% at 2 years, p < 0.01) when compared with those with a cardiogenic etiology.^[xviii]

2. Renal Failure –

Due to renal involvement in fluid status, any alteration in renal function can result in edema. Several laboratory assessments can assist in evaluating renal function.

Urinalysis (UA): The UA is obtained to primarily search for proteinuria, which may reveal nephrotic syndrome. This finding may require further testing with an in-depth history and physical exam searching for symptoms of diabetes mellitus, systemic lupus erythematosus, HIV infection, or medication complications.^[xix] Patients with nephrotic syndrome should be referred to nephrology for further workup given the potential for accelerated atherosclerosis, a tendency to venous or arterial thrombosis, and increased susceptibility to infection.^[xx]

BMP: The basic metabolic panel evaluates for renal injury/failure as defined by absolute increase in the serum creatinine concentration of ≥0.3 mg/dL (26.4 micromol/L) from baseline, a percentage increase in the serum creatinine concentration of ≥50%, or oliguria of <0.5 mL/kg per hour for more than six hours (per Acute Kidney Injury Network guidelines).^[xxi]

3. Liver disease – 

Edema from liver disease is predominantly due to protein loss from decreased albumin production. Severe liver disease should present with other signs of failure, such as ascites. Ascites which presents with budging and or shifting fluid, or an ultrasound demonstrating ascites, warrants Liver Function Tests (LFT).

LFTs: These comprise AST/ALT, bilirubin, alk phosphatase, GGT, and bilirubin. LFT’s are unnecessary without ascites, given peripheral edema in cirrhosis is a late finding in the disease.^[xxii] New onset ascites warrants paracentesis to assist in determining the etiology.

Are there other tests that are needed?

In the setting of the bilateral lower extremity edema AND concern for one of the following, certain tests should accompany the above testing.

 The decision to perform a biltateral US is a combination of risk stratification, decision rules, and clinical judgement.

Woman of childbearing age: Pregnancy test is needed. Increased venous pressure caused by enlarging uterus may commonly lead to lower extremity edema and varicosities. Combined with hypertension, this edema may point one to evaluate further for preeclampsia. Although once considered a factor in diagnosing preeclampsia, it no longer included in the criteria.^[xxvi]

Symptoms of heart failure left sided heart failure with pulmonary congestion: Chest X-ray and an EKG. In the chest film look for pulmonary congestion, effusions, and cardiomegaly, in addition to assessing for other causes of dyspnea like focal consolidation or pneumothorax. Up to 20% of patients have no signs of congestion on CXR, so one must use a combination of findings.^[xxvii]  As discussed above, CHF is one of the major pathologies one should evaluate for in the emergency department if symptomatic, either for further outpatient workup or inpatient treatment if severe.

History or symptoms of thyroid dysfunction (i.e. fatigue, cold intolerance, weight gain, constipation, dry skin): TSH, T3, T4. Nonpitting edema (myxedema) occurs in severe hypothyroidism and may be generalized. It results from infiltration of the skin with glycosaminoglycans with associated water retention.^[xxviii]

History of malignancy: consider abdominal computed tomography (CT) to evaluate for mass effect.

History of trauma: consider plain films to rule out fracture.

Once these disorders have been ruled out, several other diagnoses remain. Consider the following:

Medications: Calcium channel blockers and nonsteroidal anti-inflammatory drugs (NSAIDS) are commonly implicated in peripheral edema. Patients should discontinue any NSAID medications and follow up with their primary doctor.^[xxix]

Lymphedema: Insidious onset of swelling, usually following lymph node dissection and/or radiation is characteristic for lymphedema. Stemmer’s sign (the inability to pinch skin at the base of the skin at the second toe on the dorsum) is indicative.^[xxx]

Venous insufficiency: In the emergency department this is truly the diagnosis of exclusion given the typical symptoms of leg pain, fatigue, heaviness, and pigment changes and their differential. This disease is defined as abnormally functioning veins caused by valvular incompetence with or without associated venous outflow obstruction, which may affect either the superficial or deep venous system.[xxxi] Unfortunately, it is also the most common cause of bilateral edema in older patients. It affects up to 60% of the population over 80 years old.^[xxxii] Skin changes such as hyperpigmentation, lipodermatosclerosis, atrophie blanche and ulceration should prompt referral to their primary physician for follow up ultrasound, given this is the diagnostic modality of choice to demonstrate reflux.^{[xxxiii],[xxxiv]} This is a different study than the one commonly ordered in the emergency department to assess for DVT.

Principles of treatment:

Patients requiring acute treatment are those with pulmonary edema, but patients may benefit from diuretics.^[xxxv] For CHF, diuretics are the mainstay of therapy. Because of the avidity of the kidney for sodium in patients with the nephrotic syndrome, potent loop diuretics, such as furosemide, are also a significant part of the treatment regimen.^[xxxvi] Some providers will start 20-40mg of Furosemide, but treatment is warranted only if you are certain it is CHF or nephrotic syndrome.^[xxxvii] Since these diagnoses require close follow up, the practice is controversial, and there are no guidelines or recommendations supporting the initiation of treatment without consultation.  All of these groups would benefit from decreasing sodium intake. One could also recommend compression stockings, lymphedema massage, and leg elevation as conservative measures.

Take home points:

-Major organ systems involved with peripheral edema include the heart, kidneys, and liver.

–History and exam are the most important aspects of the evaluation of lower extremity edema.

-Look for signs of cirrhosis and ascites. If ascites is present, obtain LFTs and perform paracentesis.

-Consider a BNP or bedside ultrasound (if clinically indicated), BMP, and a UA to evaluate for heart failure and nephrotic syndrome.

-Consider other tests as indicated (i.e. history of malignancy-DVT ultrasound, woman of childbearing age-pregnancy test, etc.).

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References/Further Reading: 

1. [Levick, J. R., & Michel, C. C. (2010). Microvascular fluid exchange and the revised Starling principle. Cardiovascular research, cvq062.]
2. [Cho, S., & Atwood, J. E. (2002). Peripheral edema. The American journal of medicine, 113(7), 580-586.]
3. [Colucci, W. S., & Braunwald, E. (1997). Pathophysiology of heart failure. Heart disease, 5, 401.]
4. [Fang, J., Mensah, G. A., Croft, J. B., & Keenan, N. L. (2008). Heart failure-related hospitalization in the US, 1979 to 2004. Journal of the American College of Cardiology, 52(6), 428-434.]
5. [Ekman, I., Cleland, J. G., Swedberg, K., Charlesworth, A., Metra, M., & Poole-Wilson, P. A. (2005). Symptoms in patients with heart failure are prognostic predictors: insights from COMET. Journal of cardiac failure, 11(4), 288-292.]
6. [Yamamoto, A., Mankumo, M., Kawaguchi, A., Nishizawa, H., Toyoshima, H., & Kangawa, K. (2001). Leg edema, ST-T abnormalities, and high BNP values are important signs of heart failure in the elderly. Archives of gerontology and geriatrics, 33(1), 37-52.]
7. [Fang, J., Mensah, G. A., Croft, J. B., & Keenan, N. L. (2008). Heart failure-related hospitalization in the US, 1979 to 2004. Journal of the American College of Cardiology, 52(6), 428-434.]
8. [Ekman, I., Cleland, J. G., Swedberg, K., Charlesworth, A., Metra, M., & Poole-Wilson, P. A. (2005). Symptoms in patients with heart failure are prognostic predictors: insights from COMET. Journal of cardiac failure, 11(4), 288-292.]
9. [Yamamoto, A., Mankumo, M., Kawaguchi, A., Nishizawa, H., Toyoshima, H., & Kangawa, K. (2001). Leg edema, ST-T abnormalities, and high BNP values are important signs of heart failure in the elderly. Archives of gerontology and geriatrics, 33(1), 37-52.]
10. [McCullough, P. A., Duc, P., Omland, T., McCord, J., Nowak, R. M., Hollander, J. E., … & Storrow, A. B. (2003). B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study. American Journal of Kidney Diseases, 41(3), 571-579.]
11. [Maisel, A. S., & Daniels, L. B. (2012). Breathing not properly 10 years later: what we have learned and what we still need to learn. Journal of the American College of Cardiology, 60(4), 277-282.]
12. [Whellan, D. J., Droogan, C. J., Fitzpatrick, J., Adams, S., Mccarey, M. M., Andrel, J., … & Keith, S. (2012). Change in intrathoracic impedance measures during acute decompensated heart failure admission: results from the Diagnostic Data for Discharge in Heart Failure Patients (3D-HF) Pilot Study. Journal of cardiac failure, 18(2), 107-112.]
13. [Maisel, A. S., Krishnaswamy, P., Nowak, R. M., McCord, J., Hollander, J. E., Duc, P., … & Clopton, P. (2002). Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. New England Journal of Medicine, 347(3), 161-167.]
14. [Di Somma, S., Magrini, L., Pittoni, V., Marino, R., Mastrantuono, A., Ferri, E., … & Mulè, P. (2010). In-hospital percentage BNP reduction is highly predictive for adverse events in patients admitted for acute heart failure: the Italian RED Study. Critical care, 14(3), R116.]
15. [McMurray, J. J., Adamopoulos, S., Anker, S. D., Auricchio, A., Böhm, M., Dickstein, K., … & Jaarsma, T. (2012). ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. European journal of heart failure, 14(8), 803-869.]
16. [McCullough, P. A., Duc, P., Omland, T., McCord, J., Nowak, R. M., Hollander, J. E., … & Storrow, A. B. (2003). B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study. American Journal of Kidney Diseases, 41(3), 571-579.]
17. [Todd, J., Austwick, T., Berridge, D., Tan, L. B., & Barth, J. H. (2011). B-type natriuretic peptide in lymphedema. Lymphology, 44(1), 29.]
18. [McCullough, P. A., Nowak, R. M., McCord, J., Hollander, J. E., Herrmann, H. C., Steg, P. G., … & Storrow, A. B. (2002). B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure. Circulation, 106(4), 416-422.]
19. [Russell, F. M., & Ehrman, R. R. (2017). A Modified Lung and Cardiac Ultrasound Protocol Saves Time and Rules in the Diagnosis of Acute Heart Failure. The Journal of Emergency Medicine.]
20. [Martindale, J. L., Wakai, A., Collins, S. P., Levy, P. D., Diercks, D., Hiestand, B. C., … & Sinert, R. (2016). Diagnosing Acute Heart Failure in the Emergency Department: A Systematic Review and Meta‐ Academic Emergency Medicine, 23(3), 223-242.]
21. [Shah, M. G., Cho, S., Atwood, J. E., & Heidenreich, P. A. (2006). Peripheral edema due to heart disease: diagnosis and outcome. Clinical cardiology, 29(1), 31-35.]
22. [Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis 1997; 30:621.
23. [Crew, R. J., Radhakrishnan, J., & Appel, G. (2004). Complications of the nephrotic syndrome and their treatment. Clinical nephrology, 62(4), 245-259.]
24. [Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11:R31.]
25. [Cárdenas, A., & Arroyo, V. (2003). Mechanisms of water and sodium retention in cirrhosis and the pathogenesis of ascites. Best Practice & Research Clinical Endocrinology & Metabolism, 17(4), 607-622.]
26. [Naidich, J. B., Torre, J. R., Pellerito, J. S., Smalberg, I. S., Kase, D. J., & Crystal, K. S. (1996). Suspected deep venous thrombosis: is US of both legs necessary?[comment]. Radiology, 200(2), 429-431.]
27. [Naidich, J. B., Torre, J. R., Pellerito, J. S., Smalberg, I. S., Kase, D. J., & Crystal, K. S. (1996). Suspected deep venous thrombosis: is US of both legs necessary?[comment]. Radiology, 200(2), 429-431.]
28. [Sheiman, R. G., & McArdle, C. R. (1995). Bilateral lower extremity US in the patient with unilateral symptoms of deep venous thrombosis: assessment of need. Radiology, 194(1), 171-173.]
29. [Rosen, N. (1997). Suspected deep venous thrombosis: Is Us of both legs necessary?. Annals of Emergency Medicine, 29(1), 199.]
30. [Zlatnik, F. J. (2004). Hypertension in pregnancy. The Iowa Perinatal Letter, 25, 5-9.]
31. [Cárdenas, A., & Arroyo, V. (2003). Mechanisms of water and sodium retention in cirrhosis and the pathogenesis of ascites. Best Practice & Research Clinical Endocrinology & Metabolism, 17(4), 607-622.]
32. [Fonseca, C., Mota, T., Morais, H., Matias, F., Costa, C., Oliveira, A. G., & Ceia, F. (2004). The value of the electrocardiogram and chest X‐ray for confirming or refuting a suspected diagnosis of heart failure in the community. European journal of heart failure, 6(6), 807-812.].
33. [SMITH, T. J., BAHN, R. S., & GORMAN, C. A. (1989). Connective Tissue, Glycosaminoglycans, and Diseases the Thyroid. Endocrine Reviews, 10(3), 366-391.]
34. [Frishman, W. H. (2002). Effects of nonsteroidal anti-inflammatory drug therapy on blood pressure and peripheral edema. The American journal of cardiology, 89(6), 18-25.]
35. [Szuba, A., & Rockson, S. G. (1998). Lymphedema: classification, diagnosis and therapy. Vascular medicine, 3(2), 145-156.]
36. [Porter, J. M., Moneta, G. L., on Chronic, A. I. C. C., & Disease, V. (1995). Reporting standards in venous disease: an update. Journal of Vascular Surgery, 21(4), 635-645.]
37. [Robertson, L., Evans, C., & Fowkes, F. G. R. (2008). Epidemiology of chronic venous disease. Phlebology, 23(3), 103-111.]
38. [Coleridge-Smith, P., Labropoulos, N., Partsch, H., Myers, K., Nicolaides, A., & Cavezzi, A. (2006). Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs—UIP consensus document. Part I. Basic principles. European journal of vascular and endovascular surgery, 31(1), 83-92.]
39. [Lees, T. A., & Lambert, D. (1993). Patterns of venous reflux in limbs with skin changes associated with chronic venous insufficiency. British Journal of surgery, 80(6), 725-728.]
40. [Gupta, S., & Neyses, L. (2005). Diuretic usage in heart failure: a continuing conundrum in 2005. European heart journal, 26(7), 644-649.]
41. [Orth, S. R., & Ritz, E. (1998). The nephrotic syndrome. New England Journal of Medicine, 338(17), 1202-1211.]
42. [Brater, D. C. (1998). Diuretic therapy. New England Journal of Medicine, 339(6), 387-395.]