Discuss the causes, clinical approach, investigations and management of a patient presenting with generalised oedema (anasarca).

Definition

Oedema is clinically detectable accumulation of fluid in the interstitial space; anasarca is severe generalised oedema involving subcutaneous tissue, serous cavities (ascites, pleural effusion, pericardial effusion) and often the face. Approximately 2.5–3 litres of excess interstitial fluid must accumulate before pitting oedema becomes clinically apparent, which is why weight gain precedes visible swelling.

Pathophysiology — Starling Forces

Fluid movement across the capillary is governed by the balance of hydrostatic and oncotic pressures. Oedema results from one or more of:

• Increased capillary hydrostatic pressure — heart failure, venous obstruction, salt and water retention.
• Reduced plasma oncotic pressure (hypoalbuminaemia) — nephrotic syndrome, cirrhosis, malnutrition, protein-losing enteropathy.
• Increased capillary permeability — sepsis, burns, anaphylaxis, inflammation.
• Impaired lymphatic drainage — filariasis, malignancy, post-surgical.
• Renal sodium and water retention — the final common pathway in most cases, driven by reduced effective arterial blood volume activating the renin–angiotensin–aldosterone system and ADH.

Causes

Clinical Approach

History:

• onset and progression
• distribution — whether swelling began in the legs (cardiac, hepatic) or the face and eyes (renal)
• diurnal variation (renal oedema worse in the morning, cardiac worse in the evening)
• breathlessness, orthopnoea and PND
• frothy urine and reduced output
• jaundice, alcohol intake, previous hepatitis
• dietary history
• drug history
• residence in a filaria-endemic area.

Examination:

• Confirm pitting by sustained pressure for 15 seconds over the tibia or sacrum. Non-pitting oedema suggests myxoedema or lymphoedema.
• Jugular venous pressure — the single most useful discriminating sign. Raised in cardiac causes and constrictive pericarditis, normal or low in nephrotic syndrome, cirrhosis and malnutrition.
• Assess for ascites (shifting dullness, fluid thrill), pleural effusion, and sacral oedema in the bedbound.
• Cardiovascular: apex beat, S3, murmurs, Kussmaul's sign and pericardial knock in constriction.
• Abdomen: hepatomegaly (tender and pulsatile in right heart failure), splenomegaly, stigmata of chronic liver disease.
• General: pallor, jaundice, thyroid status, nutritional status, muscle wasting, skin and hair changes.

Investigations

• Urinalysis — the first and most informative test: proteinuria (3+ or 4+ suggests nephrotic syndrome), haematuria and casts in glomerulonephritis. Quantify with spot urine protein:creatinine ratio or 24-hour protein (> 3.5 g/day = nephrotic range).
• Serum albumin and total protein; renal function and electrolytes; liver function tests with prothrombin time.
• Complete blood count — anaemia; thyroid function tests.
• Lipid profile — hyperlipidaemia supports nephrotic syndrome.
• Chest X-ray — cardiomegaly, pulmonary venous congestion, pleural effusion.
• ECG and echocardiography — ventricular function, valvular disease, pericardial disease; constrictive pericarditis must be actively excluded as it is surgically curable.
• Ultrasound abdomen — liver echotexture, portal vein, ascites, kidney size and echogenicity.
• Ascitic fluid analysis with serum-ascites albumin gradient (SAAG): ≥ 1.1 g/dL indicates portal hypertension; < 1.1 suggests peritoneal disease such as tuberculosis or malignancy.
• Selected: renal biopsy, night blood smear for microfilaria, NT-proBNP, 24-hour urinary protein, and screening for HIV, hepatitis B and C in nephrotic syndrome.

Management

General principles

• Treat the underlying cause — this is definitive; diuretics alone address only the symptom.
• Dietary sodium restriction to about 2 g of sodium (5 g salt) daily — the foundation of oedema management, and frequently neglected.
• Fluid restriction where there is hyponatraemia or severe fluid overload.
• Daily weight and strict input-output charting — weight is a more reliable guide to fluid balance than examination. Aim for a loss of about 0.5–1 kg/day, and no more than 0.5 kg/day where ascites is present without peripheral oedema, to avoid intravascular depletion and renal failure.
• Leg elevation, graduated compression and skin care to prevent cellulitis in chronic oedema.

Diuretics

• Loop diuretics (furosemide, torsemide) — first-line for significant oedema; may require higher doses in renal impairment and hypoalbuminaemia.
• Spironolactone — the diuretic of choice in cirrhotic ascites because of secondary hyperaldosteronism; combined with furosemide in a defined ratio.
• Thiazide added for diuretic resistance (sequential nephron blockade).
• Monitor electrolytes, renal function and blood pressure; watch for hypokalaemia, hyponatraemia, hypotension and acute kidney injury.

Cause-specific

• Cardiac: diuretics, ACE inhibitor or ARB, beta-blocker, mineralocorticoid antagonist, SGLT2 inhibitor; treat arrhythmia and ischaemia; pericardiectomy for constriction.
• Nephrotic syndrome: corticosteroids and immunosuppression as dictated by histology, ACE inhibitor or ARB for proteinuria, statin, and attention to thromboembolic risk.
• Cirrhosis: salt restriction, spironolactone with furosemide, therapeutic paracentesis with albumin cover for tense ascites, and treatment of complications such as spontaneous bacterial peritonitis.
• Nutritional: graded protein and calorie repletion with micronutrients, monitoring for refeeding syndrome.
• Hypothyroidism: thyroxine replacement.
• Drug-induced: withdraw or substitute the offending drug.

Complications

Skin breakdown, ulceration and cellulitis; pleural effusion and respiratory compromise; pulmonary oedema; electrolyte disturbance and acute kidney injury from over-diuresis; malnutrition; and venous thromboembolism, particularly in nephrotic syndrome due to urinary loss of antithrombin III.