Assessment of peripheral oedema

ECG is a useful test when cardiac dysfunction is suspected. It provides additional evidence to modify the post-test probability of ischaemic systolic heart failure as a cause of peripheral oedema. It is not a definitive test, as it cannot define the cardiac function. Normal ECG or only minor abnormalities makes left ventricular cardiac dysfunction unlikely as cause of the peripheral oedema.[57] Davie AP, Francis CM, Love MP, et al. Value of the electrocardiogram in identifying heart failure due to left ventricular systolic dysfunction. BMJ. 1996 Jan 27;312(7025):222.Full text| Abstract

CXR is a reasonable screening test to provide supplemental clues as to cardiopulmonary aetiology of venous congestion, but it does not define cardiac function.

A low normal BNP level (<100 nanograms/L [<100 picograms/mL]) or a low NT-proBNP level (<300 nanograms/L [<300 picograms/mL]) is helpful in excluding congestive heart failure.[51] National Institute for Health and Care Excellence. Acute heart failure: diagnosis and management. Nov 2021 [internet publication].Full text An NT-proBNP level <400 nanograms/L (<400 picograms/mL) in an untreated person with chronic symptoms makes a diagnosis of heart failure less likely.[52] National Institute for Health and Care Excellence. Chronic heart failure in adults: diagnosis and management. Sep 2018 [internet publication].Full text Several other cardiac and non-cardiac conditions may also be associated with elevated levels.[23] Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-1032.Full text| Abstract

Performed if acute cardiac ischemia is suspected as the cause of heart failure.

Echocardiography is best employed for patients who have a suggestion of cardiopulmonary disease on history, physical examination, and screening ECG and CXR. A cardiac cause of oedema is difficult to predict based solely on physical examination and history.[58] Shah MG, Cho S, Atwood JE, et al. Peripheral edema due to heart disease: diagnosis and outcome. Clin Cardiol. 2006 Jan;29(1):31-5.| Abstract

ECG is a useful test when cardiac dysfunction is suspected as a cause of peripheral oedema. It is not a definitive test, as it cannot define the cardiac function. A normal ECG or only minor abnormalities makes left ventricular cardiac dysfunction unlikely as cause of the peripheral oedema.[57] Davie AP, Francis CM, Love MP, et al. Value of the electrocardiogram in identifying heart failure due to left ventricular systolic dysfunction. BMJ. 1996 Jan 27;312(7025):222.Full text| Abstract

CXR is a reasonable screening test to provide supplemental clues as to a cardiopulmonary aetiology of venous congestion, but it does not define cardiac function.

Echocardiography is best employed for patients who have a suggestion of cardiopulmonary disease on history, physical examination, or screening ECG and CXR. One study found that 23% of patients referred for echocardiography to evaluate peripheral oedema had evidence of cardiac aetiology.[58] Shah MG, Cho S, Atwood JE, et al. Peripheral edema due to heart disease: diagnosis and outcome. Clin Cardiol. 2006 Jan;29(1):31-5.| Abstract Demonstrates impaired ventricular relaxation. Approximately half of patients with clinical signs of heart failure have preserved ejection fraction on echocardiography.[59] Gheorghiade M, Filippatos G, De Luca L, et al. Congestion in acute heart failure syndromes: an essential target of evaluation and treatment. Am J Med. 2006 Dec;119(12 suppl 1):S3-10.| Abstract

A low normal BNP level (<100 nanograms/L [<100 picograms/mL]) or a low NT-proBNP level (<300 nanograms/L [<300 picograms/mL]) is helpful in excluding congestive heart failure.[51] National Institute for Health and Care Excellence. Acute heart failure: diagnosis and management. Nov 2021 [internet publication].Full text An NT-proBNP level <400 nanograms/L (<400 picograms/mL) in an untreated person with chronic symptoms makes a diagnosis of heart failure less likely.[52] National Institute for Health and Care Excellence. Chronic heart failure in adults: diagnosis and management. Sep 2018 [internet publication].Full text Several other cardiac and non-cardiac conditions may also be associated with elevated levels.[23] Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-1032.Full text| Abstract

A finding of elevated pulmonary arterial pressure in the absence of left heart failure should prompt an evaluation for pulmonary or pulmonary vascular disease underlying the pulmonary hypertension.

Right heart catheterisation is the most accurate method of measurement of right ventricular and pulmonary pressures but is rarely required.

In the evaluation of peripheral oedema, if the echocardiography demonstrates pulmonary hypertension, then subsequent testing will be needed to establish the cause. Polysomnography would be part of this evaluation especially for patients with history and examination features of obstructive sleep apnoea.

This test should be ordered only if results will change management. Unilateral oedema with acute or subacute onset in a patient with low clinical pre-test probability (Wells score <2) is where it has greatest utility. Patients with high pre-test probability (Wells score ≥2) should proceed directly to duplex ultrasound. Ultrasound can safely be omitted in patients with a low pre-test probability of deep vein thrombosis and a negative D-dimer.[17] Di Nisio M, van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet. 2016 Dec 17;388(10063):3060-73.| Abstract

Ultrasound is indicated when there is asymmetrical oedema of acute or subacute onset. Sensitivity is 77% to 100% with a weighted mean sensitivity of 89% for symptomatic patients.[60] Kearon C, Julian JA, Newman TE, et al. Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines. Ann Intern Med. 1998 Apr 15;128(8):663-77.| Abstract Patients at very high risk for thrombosis may merit evaluation for deep vein thrombosis even when the oedema is bilateral. Ultrasound may also detect iliac venous stenosis of May-Thurner syndrome.[61] Oğuzkurt L, Özkan U, Tercan F, et al. Ultrasonographic diagnosis of iliac vein compression (May-Thurner) syndrome. Diagn Interv Radiol. 2007 Sep;13(3):152-5.Full text| Abstract

Definitive test for evaluation of venous thrombus. May also be used to provide alternative visualisation of venous compression or stenosis even in the absence of thrombus.

Clinical features alone can make the diagnosis of venous insufficiency in up to 75% of patients.[63] Valencia IC, Falabella A, Kirsner RS, et al. Chronic venous insufficiency and venous leg ulceration. J Am Acad Dermatol. 2001 Mar;44(3):401-21.| Abstract Testing is usually used when surgery is being considered. A number of imaging modalities are available to diagnose venous insufficiency, but triplex ultrasound is the definitive standard.[64] Mantoni M, Larsen L, Lund JO, et al. Evaluation of chronic venous disease in the lower limbs: comparison of five diagnostic methods. Br J Radiol. 2002 Jul;75(895):578-83.| Abstract

A finding of low serum albumin prompts investigation to determine whether the aetiology is due to loss in the urine, hepatic synthetic dysfunction, or gastrointestinal losses.

New-onset renal dysfunction may contribute to volume overload in conjunction with protein wasting.[69] Hilton R. Acute renal failure. BMJ. 2006 Oct 14;333(7572):786-90.Full text| Abstract

A finding of high-grade proteinuria on screening urinalysis requires further evaluation with urine microscopy and quantitative urinary protein measurement.

Transaminases may be elevated, but this can be misleading, as elevation may be absent in chronic cirrhosis. Transaminases may also be elevated from passive hepatic congestion in cardiopulmonary dysfunction. Prothrombin time is a useful indicator of liver synthetic function.

Hepatic ultrasound may demonstrate findings suggestive of the underlying aetiology of the cirrhosis.

Oedema in the context of normal pregnancy is common. In pre-eclampsia the oedema is associated with hypertension and proteinuria.

ECG may be done as part of initial evaluation but is not diagnostic for pericardial effusion.

CXR may be done as part of initial evaluation but is not diagnostic for pericardial effusion.

Echocardiography is best employed for patients who have a suggestion of cardiopulmonary disease on history, physical examination, or screening ECG and CXR. In tamponade, echocardiography will demonstrate effusion, inspiratory increase in right ventricle size, and decreased left ventricle size. Plethora of the inferior vena cava (i.e., <50% decrease in inferior vena cava diameter with deep inspiration) and diastolic collapse of the right heart chambers are seen.

Pericardial calcification is often best seen on lateral CXR, but the finding is non-specific.

ECG may be done as part of initial evaluation but is not specific for constrictive pericarditis.

Other findings suggestive of constrictive pericarditis include flattening of the left ventricular posterior wall during diastole, rapid left atrial emptying, and a dilated inferior vena cava.

ECG may be done as part of initial evaluation but is not diagnostic for restrictive cardiomyopathy.

Important to distinguish restrictive cardiomyopathy from constrictive pericarditis.

Typically, severe regurgitation would be seen if peripheral oedema is clinically evident.

In May-Thurner syndrome, the compression affects the left common iliac vein between the right common iliac artery and the overlying vertebrae.[61] Oğuzkurt L, Özkan U, Tercan F, et al. Ultrasonographic diagnosis of iliac vein compression (May-Thurner) syndrome. Diagn Interv Radiol. 2007 Sep;13(3):152-5.Full text| Abstract

CTV or MRV can help to demonstrate the extent of compression if the duplex ultrasound is insufficient.[65] Taha MAH, Busuttil A, Bootun R, et al. A clinical guide to deep venous stenting for chronic iliofemoral venous obstruction. J Vasc Surg Venous Lymphat Disord. 2022 Jan;10(1):258-66.e1.| Abstract[66] Mahnken AH, Thomson K, de Haan M, et al. CIRSE standards of practice guidelines on iliocaval stenting. Cardiovasc Intervent Radiol. 2014 Aug;37(4):889-97.Full text| Abstract​ CTV or MRV may also be used to exclude extravascular pathologies causing obstruction.

May be used to provide alternative visualisation of venous compression or stenosis even in the absence of thrombus.[67] Garrie A, Jones LE, Chen JF, et al. New vein compression entities in patients with unexplained leg swelling. Ann Vasc Surg. 2017 Nov;45:173-8.| Abstract

The level of abnormalities in the liver function panel depends on how acutely the venous obstruction has developed. Fulminant Budd-Chiari syndrome can cause marked transaminase and alkaline phosphatase elevation and may lead to acute hepatic failure.

In Budd-Chiari syndrome, the obstruction will be found at the level of the hepatic veins, usually from thrombus secondary to intravascular webs or compression from a mass. A more chronic form of hepatic venous obstruction is hepatic veno-occlusive disease (HVOD) (sinusoidal obstruction syndrome), which may occur after stem cell transplantation, chemotherapy, or abdominal radiation. In HVOD, reversal of portal blood flow may be observed on imaging.

MRI is more accurate than CT and allows optimal delineation of venous obstruction for therapeutic decisions.[68] Kamath PS. Budd-Chiari syndrome: radiologic findings. Liver Transpl. 2006 Nov;12(11 suppl 2):S21-2.Full text| Abstract

Serial testing of serum creatinine, in parallel with close monitoring of urine output, is key to the diagnosis of renal failure. Oliguric or anuric renal failure results in net body fluid overload and represents a need for urgent evaluation and treatment.[70] Babuin L, Alegria JR, Oh JK, et al. Brain natriuretic peptide levels in constrictive pericarditis and restrictive cardiomyopathy. J Am Coll Cardiol. 2006 Apr 4;47(7):1489-91.| Abstract Lesser degrees of renal insufficiency may be a contributing factor to peripheral oedema in combination with other aetiologies. Further evaluation for aetiology of renal failure indicated if increased creatinine is detected.

Serial testing of serum urea, in parallel with close monitoring of urine output, is key to the diagnosis of renal failure. The urea-creatinine ratio can be used to help distinguish pre-renal from intrinsic renal failure.

Close monitoring of urine output is needed; and oliguric or anuric renal failure with fluid overload causing peripheral oedema merits nephrology consultation.[70] Babuin L, Alegria JR, Oh JK, et al. Brain natriuretic peptide levels in constrictive pericarditis and restrictive cardiomyopathy. J Am Coll Cardiol. 2006 Apr 4;47(7):1489-91.| Abstract

Typical findings vary with type of renal failure: pre-renal failure shows few hyaline casts; post-renal failure shows few hyaline casts and possible RBCs; acute tubular necrosis shows epithelial cells, muddy-brown coarsely granular casts, and white blood cells (WBCs); allergic interstitial nephritis shows WBCs, RBCs, epithelial cells, eosinophils, possible WBC casts, and low to moderate proteinuria; glomerulonephritis shows RBC casts, dysmorphic RBCs, and moderate to severe proteinuria.

Finding of low serum albumin prompts investigation to determine whether the aetiology is due to loss in the urine, hepatic synthetic dysfunction, or gastrointestinal losses. History of significant diarrhoea in conjunction with ruling out alternative causes makes the diagnosis.

Ordered in cases of angio-oedema without urticaria. A low level is suggestive of either hereditary or acquired angio-oedema.

Ordered in cases with a high suspicion of hereditary angio-oedema. A low level is highly suggestive of the diagnosis.

Rarely, patients can have normal levels of C1-esterase inhibitor yet low function.

Given that rare patients can have normal levels of C1-esterase inhibitor yet low function, this test is ordered in cases with a high suspicion of hereditary angio-oedema, with a low level confirming the diagnosis.

Ordered to help differentiate between hereditary and acquired angio-oedema.

Blood cultures should be taken immediately, and preferably before antibiotics are started, provided their sampling will not delay administration of antibiotics. Other cultures (for example, sputum, stool, and urine) should be taken as clinically indicated.

Elevated serum lactate indicates tissue hypoperfusion, and is most reliably assessed using an arterial sample.

WBC count is sensitive but not specific for the diagnosis of sepsis.

Elevated creatinine may occur in sepsis associated with renal dysfunction.

Sepsis can originate from hepatic or peri-hepatic infections.

Comorbid hepatic disease can affect drug metabolism.

Septic shock can compromise hepatic blood flow and metabolism.

An ECG should be arranged to help exclude other differential diagnoses, including myocardial infarction, pericarditis, and myocarditis. Sepsis also predisposes to myocardial dysfunction and arrhythmias.

Performed if meningitis suspected.

The perfusion pressure of a compartment (the compartment delta pressure) is defined as the difference between the diastolic BP and the intra-compartmental pressure (i.e., diastolic BP minus compartment pressure). A delta pressure of ≤30 mmHg is considered a strong indicator for fasciotomy.[31] Olson SA, Glasgow RR. Acute compartment syndrome in lower extremity musculoskeletal trauma. J Am Acad Orthop Surg. 2005 Nov;13(7):436-44.Full text| Abstract[32] Shadgan B, Menon M, O'Brien PJ, et al. Diagnostic techniques in acute compartment syndrome of the leg. J Orthop Trauma. 2008 Sep;22(8):581-7.| Abstract[33] McMillan TE, Gardner WT, Schmidt AH, et al. Diagnosing acute compartment syndrome-where have we got to? Int Orthop. 2019 Nov;43(11):2429-35.Full text| Abstract​ However, care should be taken when using this criterion in patients who are receiving vasodilatory drugs and whose diastolic BP is low.

Patients with a high suspicion for compartment syndrome may require immediate surgery.

Imaging may be a helpful adjunct in the evaluation of trauma of the extremity but cannot make the diagnosis of compartment syndrome. If compartment syndrome is suspected then compartment pressure should be measured.

Isotope lymphoscintigraphy has a sensitivity of 73% to 97% and a specificity of 100%.[71] Tiwari A, Cheng KS, Button M, et al. Differential diagnosis, investigation, and current treatment of lower limb lymphedema. Arch Surg. 2003 Feb;138(2):152-61.Full text| Abstract This diagnostic test would not generally be ordered if diagnosis of lymphoedema was evident based on clinical history (e.g., history of radical lymph node dissection).[72] Executive Committee of the International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2020 Consensus Document of the International Society of Lymphology. Lymphology. 2020;53(1):3-19.Full text| Abstract

Isotope lymphoscintigraphy has a sensitivity of 73% to 97% and a specificity of 100%.[71] Tiwari A, Cheng KS, Button M, et al. Differential diagnosis, investigation, and current treatment of lower limb lymphedema. Arch Surg. 2003 Feb;138(2):152-61.Full text| Abstract This diagnostic test would not generally be ordered if diagnosis of lymphoedema was evident based on clinical history (e.g., history of radical lymph node dissection).

Microfilariae of Wuchereria bancrofti and Brugia spp. exhibit a nocturnal periodicity, and an accurate diagnosis is best achieved on blood collected at night.[73] Centers for Disease Control and Prevention. Laboratory identification of parasites of public health concern: lymphatic filariasis. Aug 2019 [internet publication].Full text

A finding of low serum albumin prompts an investigation to determine whether the aetiology is due to loss in the urine, hepatic synthetic dysfunction, gastrointestinal losses, or reduced intake. The history and examination would usually suggest malnutrition as a cause of severe hypoproteinaemia and oedema.

Severe hypothyroidism is associated with myxoedema. At its most extreme, myxoedema coma is an endocrinological emergency.

All of these increase the likelihood of a malignant mass.