Undifferentiated Oedema — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mr James Whitfield, 70 years old, retired builder. [1]

Presenting complaint: Three weeks of progressive bilateral leg oedema, abdominal distension, and exertional dyspnoea. He is now breathless on walking 20 metres and has noticed his trousers no longer fit at the waist. [1]

Past history: Heart failure with reduced ejection fraction (EF 34 per cent on the last echocardiogram, six months ago; prior NSTEMI eight years ago with a drug-eluting stent). Cirrhosis from non-alcoholic fatty liver disease (diagnosed three years ago; no varices on the last endoscopy; no prior ascites). Type 2 diabetes (15 years; metformin; last HbA1c 62 mmol per mol). Hypertension (15 years). He smoked 30 pack-years and stopped after the NSTEMI. He drinks 20 g of alcohol per day. He lives with his wife and is normally independent, walking 500 metres before stopping with breathlessness. [1]

Examination findings (trainee elicits):

• Blood pressure 132/78, heart rate 82 in sinus rhythm, respiratory rate 20, SpO2 94 per cent on room air, temperature 36.8.
• JVP raised to the angle of the jaw at 45 degrees.
• Bilateral basal fine crackles to mid-zones.
• A gallop rhythm (third heart sound).
• Apex beat displaced 2 cm lateral to the mid-clavicular line.
• Abdomen: shifting dullness with a positive fluid thrill; liver span 10 cm; no splenomegaly.
• 4+ pitting oedema to the sacrum and the thighs.
• Stigmata of chronic liver disease: palmar erythema, three spider naevi on the chest.
• Peripheral pulses palpable, ankle-brachial index 1.0. [1]

Investigations (available results):

• Haemoglobin 122 g per litre, white cell count 7.2, platelets 110 (baseline low from the cirrhosis).
• Sodium 130 mmol per litre, potassium 4.6, creatinine 145 micromoles per litre (baseline 110), eGFR 42.
• Albumin 28 g per litre, bilirubin 28, ALT 42, ALP 140, INR 1.3.
• TSH 2.8 mU per litre.
• NT-proBNP 2100 pg per mL.
• Urinalysis: 1+ proteinuria, no blood, no leucocytes, no nitrites.
• Chest X-ray: cardiomegaly (cardiothoracic ratio 0.58), bilateral pleural effusions, pulmonary oedema.
• ECG: sinus rhythm, Q waves in leads V1 to V3 (the old infarct), left ventricular hypertrophy by voltage criteria.
• Diagnostic ascitic tap: ascitic albumin 14 g per litre, neutrophil count 30 per microlitre, no organisms on the Gram stain. [1]

Drug chart (current): aspirin 100 mg daily, atorvastatin 80 mg nocte, bisoprolol 5 mg daily, ramipril 5 mg daily, spironolactone 25 mg daily, dapagliflozin 10 mg daily, furosemide 80 mg daily, amlodipine 10 mg daily, metformin 1 g twice daily. [1]

Candidate's structured presentation (model)

Opening statement (SASPOP): [1]

"Mr James Whitfield is a 70-year-old retired builder presenting with three weeks of progressive bilateral leg oedema, abdominal distension and exertional dyspnoea, on a background of heart failure with reduced ejection fraction (EF 34 per cent), cirrhosis from non-alcoholic fatty liver disease, type 2 diabetes and hypertension. He is a 30-pack-year ex-smoker. His main problems are a decompensated heart failure with the raised JVP to the jaw, the bilateral basal crackles, the gallop and the NT-proBNP of 2100; a cirrhotic ascites with the portal hypertension confirmed by the SAAG of 14 g per litre; a rising creatinine (145 from the baseline 110) that may be the pre-renal AKI, the early hepatorenal syndrome, or the progression of the diabetic nephropathy; and a drug-induced component from the amlodipine 10 mg daily. My immediate priorities are the ABCDE assessment, the cautious intravenous diuresis with the monitoring of the renal function, the reduction or the discontinuation of the amlodipine, the consideration of the large-volume paracentesis with the albumin replacement for the symptomatic ascites, and the continuation of the four pillars of the heart failure therapy." [1]

Management plan: [1]

1. ABCDE with the cautious diuresis. Increase the furosemide to 120 mg daily (orally, or intravenously if the gut oedema is suspected), with the daily weight, the daily renal function, and the daily electrolytes. The target weight loss is up to 1 kg per day (he has both the peripheral oedema and the ascites). Check the sodium (already 130, the dilutional hyponatraemia — restrict the free water if the sodium falls below 125).
2. Reduce and discontinue the amlodipine. The amlodipine is contributing to the peripheral oedema through the arteriolar vasodilatation and is not an evidence-based therapy for the heart failure. Switch to the uptitration of the ramipril and the consideration of the ARNI if the heart failure therapy is being optimised.
3. Continue the four pillars of the heart failure therapy. The bisoprolol, the ramipril (hold temporarily if the creatinine rises by more than 30 per cent or the potassium exceeds 5.5), the spironolactone (monitor the potassium), and the dapagliflozin (continue unless the eGFR falls below the threshold or the volume depletion develops).
4. Consider the large-volume paracentesis with the albumin replacement (6 to 8 g per litre removed) for the symptomatic ascites, to relieve the discomfort and the respiratory compromise.
5. Monitor for the hepatorenal syndrome. The rising creatinine that does not respond to the diuresis and the albumin is the early warning; the management is the terlipressin and the albumin if the diagnosis is confirmed.
6. Send the further investigations. The spot urine protein-to-creatinine ratio to quantify the proteinuria; the echocardiogram to reassess the ejection fraction and the right heart; the liver ultrasound with the elastography and the consideration of the liver transplant evaluation; the screening for the hepatocellular carcinoma (the alpha-fetoprotein and the ultrasound every six months). [1]

Communication and shared decision-making: Explain to Mr Whitfield and his wife that his body is holding excess fluid from a combination of his heart, his liver and the blood pressure tablet (the amlodipine), and that the immediate priorities are to remove the excess fluid safely while protecting the kidneys. Explain that the amlodipine will be stopped because it is contributing to the swelling. Explain that the next 48 to 72 hours will tell whether the treatment is working and whether the kidneys are tolerating the diuresis. Surface the advance care planning — a patient with the heart failure and the cirrhosis should have an early conversation about the goals of care and the ceiling of the treatment. [1]

Examiner discussion questions

Q1: "His SAAG is 14. Walk me through your calculation and interpretation." [1]

"The SAAG is the serum albumin minus the ascitic fluid albumin: 28 minus 14 equals 14 g per litre. A SAAG of 11 g per litre or above indicates portal hypertension with an accuracy of approximately 97 per cent, as established by the Runyon study of 901 paired samples [3]. This confirms the portal hypertension as the mechanism of his ascites, consistent with his cirrhosis. The ascitic neutrophil count of 30 per microlitre is below 250, which excludes the spontaneous bacterial peritonitis. The teaching point is that the SAAG has replaced the transudate-exudate classification, which was correct only 55.6 per cent of the time in the Runyon study — the registrar who applies the transudate-exudate concept has revealed a knowledge gap."

Q2: "How do you balance the heart failure and the cirrhosis in his diuretic strategy?" [1]

"I use the furosemide uptitration for the cardiac component and the spironolactone for the cirrhotic component, and I monitor the renal function and the electrolytes daily. The target weight loss in a patient with both the peripheral oedema and the ascites is up to 1 kg per day — the cirrhotic target is 0.5 kg per day without the peripheral oedema and 1 kg per day with it, but the cardiac component allows the slightly more aggressive diuresis because the raised JVP to the jaw and the crackles indicate the significant volume overload. If the creatinine rises by more than 30 per cent from the baseline (above approximately 143), I slow the diuresis and reassess — the differential is the pre-renal AKI from the over-diuresis, the hepatorenal syndrome from the cirrhotic decompensation, or the cardiorenal syndrome. The integrated approach — the furosemide and the spironolactone, with the monitoring — addresses both the cardiac and the cirrhotic components in parallel." [1]

Q3: "He is on amlodipine. Why does it cause oedema, and what do you do about it?" [1]

"The amlodipine causes the oedema by the preferential arteriolar vasodilatation that goes unmatched in the venous circulation, raising the capillary hydrostatic pressure and driving the fluid into the interstitium [2]. The oedema is a local vasodilatory phenomenon, not a systemic fluid retention, which is why the diuretics are ineffective and potentially harmful — they reduce the plasma volume and may worsen the capillary pressure mismatch. My management is to reduce and discontinue the amlodipine and to switch his antihypertensive to the uptitration of the ramipril (or the ARNI if the heart failure therapy is being optimised). The teaching point is that the diuretic is not the answer to the amlodipine oedema — the dose reduction, the switch, or the addition of the venodilator (the ACE inhibitor or the ARB) is the answer."

Q4: "His NT-proBNP is 2100. How do you interpret this in the context of his cirrhosis and his renal impairment?" [1]

"The NT-proBNP of 2100 is above the PRIDE rule-in cutpoint of 900 pg per mL for a patient over 50, which supports the cardiac contribution to his oedema and his dyspnoea [4]. But I interpret it in the clinical context — he has the cirrhosis, the rising creatinine, and the acute decompensation, all of which elevate the peptide, and the value does not by itself quantify the cardiac contribution. The false-positive causes of the elevated NT-proBNP include the renal failure (the reduced clearance), the cirrhosis (the reduced clearance and the cardiac stress), and the acute illness. The synthesis is that the peptide confirms the cardiac component but does not exclude the cirrhotic or the renal contribution, and I weigh the value with the JVP, the crackles, the gallop, and the echocardiogram. The trap is treating the number rather than the patient — the diuresis is titrated to the clinical response, not to a target NT-proBNP."

Q5: "His creatinine has risen from 110 to 145. How do you approach this?" [1]

"The rising creatinine is the early warning. My first step is to assess the volume status — if he is over-diuresed (the dry mucous membranes, the postural drop, the low JVP), I slow the diuresis and give a fluid challenge. If he is volume-overloaded (the raised JVP, the crackles, the ascites), the rising creatinine is the hepatorenal syndrome or the cardiorenal syndrome, and I am more cautious with the diuresis but I do not stop it — the treatment of the decompensated heart failure requires the diuresis, and the cardiorenal syndrome often improves as the congestion is relieved. I would hold the ramipril temporarily if the creatinine rises by more than 30 per cent from the baseline and the potassium exceeds 5.5, and I would monitor the trend. If the creatinine continues to rise despite the correction of the volume status, I would consider the hepatorenal syndrome and the terlipressin with the albumin. The teaching point is the daily monitoring — the weight, the renal function, and the readiness to adjust the diuretic and the ACE inhibitor." [1]

Q6: "What is your plan for his long-term management after this admission?" [1]

"The admission is an opportunity to optimise all the contributing diseases. For the heart failure, I confirm the four pillars at the target doses (the bisoprolol, the ramipril or the ARNI, the spironolactone, the dapagliflozin) guided by the 2021 ESC Heart Failure Guidelines [4], and I reassess the ejection fraction on the echocardiogram. For the cirrhosis, I evaluate for the liver transplant (the MELD score, the hepatology referral), I screen for the hepatocellular carcinoma (the alpha-fetoprotein and the ultrasound every six months), and I optimise the portal hypertension management (the spironolactone, the consideration of the TIPS for the refractory ascites). For the diabetes, I optimise the glycaemic control (the metformin and the SGLT2 inhibitor, with the consideration of the GLP-1 receptor agonist for the weight and the cardiovascular benefit). For the hypertension, I replace the amlodipine with the uptitration of the ramipril and the consideration of the thiazide-like diuretic if the blood pressure requires it. And I address the advance care planning — a patient with the heart failure and the cirrhosis should have an early conversation about the goals of care, the ceiling of the treatment, and the next steps if the treatment does not work."

Q7: "What is the single most important lesson from this case for a registrar managing undifferentiated oedema?" [1]

"The single most important lesson is to resist the anchoring error. Mr Whitfield has the heart failure, and the easy diagnosis is the decompensated heart failure — but the actual picture is the heart failure plus the cirrhotic ascites plus the rising creatinine (the early hepatorenal syndrome) plus the amlodipine contribution plus the mild proteinuria from the diabetic nephropathy. The registrar who stops at 'heart failure' and uptitrates only the furosemide has missed the SAAG (which confirms the portal hypertension and the separate management pathway), the amlodipine (which requires the discontinuation, not the diuresis), and the hepatorenal risk (which limits the diuresis). The integrated approach — the Starling forces framework, the focused examination, the first-tier investigations interpreted together, and the parallel management of the competing mechanisms — is what keeps the complex oedematous patient safe. The corollary is the reassessment: the patient whose creatinine is rising despite the treatment is telling the registrar that the working diagnosis is incomplete or that the treatment is causing harm." [1]

DCE Short Case — The Examination for Oedema

Instruction

"You are the medical registrar assessing a 65-year-old woman on the ward with bilateral leg oedema of two months duration. Examine her for oedema, present your findings, and offer a differential diagnosis. You have 5 minutes to outline your examination approach and 5 minutes for discussion." [1]

Provided data: The patient is a 65-year-old woman with a history of rheumatoid arthritis (on methotrexate and prednisolone 5 mg daily) and hypertension (on amlodipine 10 mg daily). On examination: blood pressure 142/86, JVP not elevated, no cardiac murmurs, no hepatomegaly, no ascites. Bilateral 3+ pitting oedema to the knees, with haemosiderin staining and lipodermatosclerosis at the medial gaiter. The Stemmer sign is negative. The peripheral pulses are palpable, ABI 1.0. [1]

Presentation template

"I have examined this woman for oedema. The oedema is bilateral, from the feet to the knees, grade 3 pitting (a 6 mm pit that recovers in more than 30 seconds). There is no periorbital oedema and no sacral oedema. The JVP is not elevated, the cardiovascular examination is normal, there is no hepatomegaly and no ascites. The skin over the medial gaiter shows the haemosiderin staining and the lipodermatosclerosis of the chronic venous insufficiency. The Stemmer sign is negative, excluding the lymphoedema. The peripheral pulses are palpable and the ABI is 1.0, excluding the significant arterial disease. My findings are most consistent with the chronic venous insufficiency, exacerbated by the amlodipine and the rheumatoid arthritis, and I would manage this with the graduated compression stockings (after the arterial assessment), the dose reduction or the discontinuation of the amlodipine, and the skin care." [1]

Discussion

Examiner: "What is your differential diagnosis, and how do you discriminate?" [1]

"My leading diagnosis is the chronic venous insufficiency — the haemosiderin, the lipodermatosclerosis and the pitting oedema at the medial gaiter are the classic triad, and the rheumatoid arthritis is a recognised association (the venous stasis from the reduced mobility and the joint deformity). The amlodipine is a significant contributor — the arteriolar vasodilatation raises the capillary hydrostatic pressure and the oedema is the local vasodilatory phenomenon. The differential includes the cardiac oedema (excluded by the normal JVP and the normal cardiovascular examination), the hepatic oedema (excluded by the absence of the stigmata of the chronic liver disease and the normal albumin), the renal oedema (excluded by the absence of the proteinuria and the normal renal function), and the lymphoedema (excluded by the negative Stemmer sign and the pitting quality). The urinalysis, the albumin, the NT-proBNP and the TFTs are the first-tier investigations that I would send to confirm the exclusion of the systemic causes." [1]

Examiner: "She is on amlodipine. How do you manage the contribution?" [1]

"I would reduce and discontinue the amlodipine — the mechanism is the arteriolar vasodilatation and the diuretics are ineffective and potentially harmful. I would switch to an alternative antihypertensive — the ACE inhibitor (the venodilatation balances the arteriolar vasodilatation) or the ARB, or the thiazide-like diuretic (the chlorthalidone or the indapamide) if the blood pressure requires it. The dose reduction or the switch to the lercanidipine (which has less oedema because of its greater vascular selectivity) is the alternative. The teaching point is that the drug history is the single most cost-effective investigation in the oedematous patient, and the discontinuation of the offending drug is often the entire treatment." [1]

Examiner: "What is the lesson about the compression stockings?" [1]

"The lesson is that the compression stockings are the first-line therapy for the chronic venous insufficiency (they reduce the venous hypertension, they improve the venous return, and they prevent the skin changes and the ulceration), but they are contraindicated in the significant arterial disease. The registrar must check the ankle-brachial index before prescribing the compression — an ABI below 0.8 contraindicates the compression stockings, and the patient requires the vascular assessment and the revascularisation first. The grade of the compression (20 to 30 mmHg for the mild to the moderate venous insufficiency, 30 to 40 mmHg for the severe), the application before the standing, and the replacement every 3 to 6 months are the practical points. The corollary is that the compression is the maintenance therapy, not the curative therapy — the definitive treatment of the varicose veins (the endovenous laser ablation, the radiofrequency ablation) is the vascular surgeon's domain." [1]