Oncologic Emergencies — Written Clinical Reasoning

SAQ 1 — Concurrent Febrile Neutropenia and Tumour Lysis Syndrome (20 marks, 30 minutes)

Prompt: Outline your integrated management plan for this patient, who has two simultaneous oncologic emergencies. Address: (a) the immediate life-threats and your triage decisions; (b) the management of the hyperkalaemia and the cardiac risk; (c) the empiric antibiotic regimen, the cultures, and the timing; (d) the management of the tumour lysis syndrome, including the choice between allopurinol and rasburicase and the reasons; (e) the supportive care in the first 48 hours, including fluid management and renal replacement therapy thresholds; and (f) the common exam trap in this scenario. [1]

Model Answer

(a) Immediate life-threats and triage (3 marks): [1]

This patient has two concurrent, immediately life-threatening oncologic emergencies: severe symptomatic hyperkalaemia with ECG changes (the peaked T waves are pre-arrest), and established clinical tumour lysis syndrome with acute kidney injury (the Cairo-Bishop criteria are met: laboratory TLS with hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia, plus the clinical complication of AKI with a creatinine more than 1.5 times baseline) [3]. He is also profoundly neutropenic and febrile, at high risk of septic shock. The triage order is: treat the hyperkalaemia first (it can kill in minutes), then begin the tumour lysis syndrome protocol and the empiric antibiotics in parallel, and admit to a high-dependency or intensive care bed for cardiac monitoring, frequent electrolyte checks and the likely need for renal replacement therapy.

(b) Management of the hyperkalaemia and the cardiac risk (4 marks): [1]

The peaked T waves mandate immediate membrane stabilisation with intravenous calcium gluconate 10 mL of 10 per cent (10 mmol) over 2 to 5 minutes, repeated if the ECG changes persist. This does not lower the potassium but stabilises the myocardium to prevent ventricular fibrillation. Immediately afterwards, give intravenous insulin (10 units of Actrapid) with 25 g of 50 per cent dextrose to shift potassium intracellularly; the effect begins within 15 to 30 minutes and lasts 4 to 6 hours, with close blood glucose monitoring. Salbutamol nebulisers or intravenous salbutamol are an adjunct. These are temporising measures — the potassium will continue to rise from the ongoing tumour lysis — so the definitive treatment is renal replacement therapy, which I would arrange immediately with the intensive care and nephrology teams. Do not give calcium for the hypocalcaemia unless the patient is symptomatic from it (tetany, seizure, arrhythmia from the hypocalcaemia rather than the hyperkalaemia); correcting calcium in the presence of severe hyperphosphataemia worsens calcium phosphate deposition and renal injury [3].

(c) Empiric antibiotic regimen, cultures, and timing (3 marks): [1]

Take two sets of blood cultures — one from each lumen of his central line and one peripheral — plus urine culture and swabs of any obvious source, then give the first dose of antibiotic within one hour. The IDSA standard is an antipseudomonal beta-lactam as monotherapy; I would give intravenous piperacillin-tazobactam 4.5 g [1]. I would add vancomycin because he is unstable and at risk of line infection; the IDSA guideline recommends adding vancomycin for haemodynamic instability, a suspected catheter-related infection, severe mucositis, or known MRSA colonisation [1]. The antibiotic must not be delayed for the cultures, the count, or any review. I would not use G-CSF routinely — it is reserved for severe or prolonged neutropenia unresponsive to standard therapy, or as secondary prophylaxis in a subsequent cycle.

(d) Management of the tumour lysis syndrome — rasburicase, not allopurinol (4 marks): [1]

This patient already has established clinical TLS with hyperuricaemia (620 micromol per litre), so the agent is rasburicase 0.2 mg per kg intravenously daily, not allopurinol. Rasburicase is a recombinant urate oxidase that converts existing uric acid to the soluble allantoin, lowering the serum uric acid within hours; allopurinol only prevents the formation of new uric acid by inhibiting xanthine oxidase and does not lower uric acid that has already formed [4]. The GRAAL1 trial established rasburicase as rapidly and reliably urate-lowering in adult high-grade lymphoma [4]. I would send a G6PD screen before the dose if there is any possibility of G6PD deficiency (African, Mediterranean, South-East Asian ancestry), because rasburicase is contraindicated in G6PD deficiency — the hydrogen peroxide generated causes haemolysis and methaemoglobinaemia. If the screen is positive or pending, continue hydration and arrange renal replacement therapy while the uric acid is managed supportively. Alkalinisation of the urine is not recommended, because an alkaline urine increases calcium phosphate deposition and worsens the renal injury [3].

(e) Supportive care in the first 48 hours, including fluid management and dialysis thresholds (4 marks): [1]

• Aggressive intravenous hydration — isotonic saline at 100 mL per hour (or 3 litres per square metre per day), aiming for a urine output above 100 mL per hour; hydration is the cornerstone of both TLS prevention and the support of the failing kidney. With an established AKI and oliguria, the fluid must be guided by the volume status and the cardiac and renal function, and I would involve nephrology early.
• Electrolyte monitoring every 6 hours — potassium, phosphate, calcium, urate, urea and creatinine; more frequently if the patient is unstable.
• Cardiac monitoring — continuous ECG for the hyperkalaemia and the arrhythmia risk.
• Renal replacement therapy thresholds — I would dialyse for refractory hyperkalaemia (potassium above 6.5 despite medical therapy, or persistent ECG changes), severe metabolic acidosis (pH below 7.1), volume overload unresponsive to diuretics, and symptomatic uraemia. Continuous renal replacement therapy is preferred in the haemodynamically unstable patient; intermittent haemodialysis is effective if the patient is stable.
• Avoid nephrotoxins — no NSAIDs, no aminoglycosides unless essential, no contrast unless essential. [1]

(f) The common exam trap (2 marks): [1]

The cardinal trap in this scenario is treating the tumour lysis syndrome with allopurinol instead of rasburicase. Allopurinol is prophylaxis for low-risk patients and does not lower uric acid that has already formed; in a patient with established TLS and hyperuricaemia it is the wrong agent and the uric acid will continue to crystallise in the renal tubules. The second trap is correcting the hypocalcaemia with intravenous calcium in an asymptomatic patient — this worsens the calcium phosphate deposition and the renal injury. The third trap is delaying the antibiotic while attending to the metabolic emergency; the febrile neutropenia and the TLS are managed in parallel, and the door-to-antibiotic time of one hour is non-negotiable. [1]

SAQ 2 — Malignant Spinal Cord Compression with Hypercalcaemia (10 marks)

Prompt: A 54-year-old woman with metastatic breast cancer (bone-only disease) presents with a one-month history of progressive thoracic back pain and a one-week history of difficulty walking. On examination she has bilateral leg weakness (MRC grade 3 of 5), a sensory level at T7, hyperreflexia and extensor plantars. Her corrected calcium is 3.1 mmol per litre and she is confused but rousable. Outline: (a) the immediate management priorities and the order in which you act; (b) the steroid regimen; (c) the imaging and the surgical decision; (d) the hypercalcaemia management in this specific context; and (e) the communication with the patient and family. [1]

Model Answer

(a) Immediate management priorities and the order (2 marks): [1]

Two concurrent emergencies: malignant spinal cord compression (the time-critical neurological emergency) and symptomatic hypercalcaemia (the metabolic emergency causing the confusion). The order is: intravenous dexamethasone 16 mg immediately for the cord compression (it works within hours to reduce oedema and may improve the deficit), urgent MRI of the whole spine, and intravenous normal saline for the hypercalcaemia in parallel, with the calcium-lowering agent (zoledronic acid) given after rehydration. The cord compression takes priority because the window for neurological recovery is short, but the hypercalcaemia is addressed simultaneously. [1]

(b) The steroid regimen (2 marks): [1]

Intravenous dexamethasone 16 mg as an immediate loading dose, then 16 mg daily in divided doses (for example 8 mg twice daily), continued through the period of decompression and radiotherapy, then tapered [5]. The 16 mg dose is the standard evidence-based regimen; higher loading doses (up to 96 mg) have been used but increase complications (hyperglycaemia, immunosuppression, psychosis, gastritis) without clear additional benefit. I would monitor the blood glucose (steroid hyperglycaemia), give gastrointestinal protection (a proton pump inhibitor), and review the dose daily.

(c) Imaging and the surgical decision (3 marks): [1]

Urgent MRI of the whole spine — not the symptomatic thoracic level alone, because breast cancer frequently causes multiple levels of vertebral involvement and the cord may be compressed at an adjacent or distant level [5]. Plain films and bone scans do not visualise the cord. After the MRI, urgent neurosurgical and clinical oncology review. If there is a single compressive level, spinal instability, or retropulsion of bone into the canal, the Patchell trial supports direct decompressive surgery plus radiotherapy over radiotherapy alone — surgery improved ambulation (84 per cent versus 57 per cent), retained ambulation longer (median 122 versus 13 days), and gave non-ambulatory patients a better chance of regaining the ability to walk [6]. If there are multiple compressive levels, a very poor performance status, or complete paraplegia for more than 24 to 48 hours, the management is dexamethasone and palliative radiotherapy. This patient is ambulatory (grade 3 of 5) and has bone-only disease (a relatively good prognosis), so I would favour surgical assessment if the MRI shows a single compressive level.

(d) Hypercalcaemia management in this context (2 marks): [1]

Intravenous normal saline at a rate guided by her volume status and her cardiac and renal function (typically 3 to 6 litres over 24 hours in the haemodynamically stable patient), then intravenous zoledronic acid 4 mg over 15 minutes, dose-reduced if her renal function is impaired [7]. The zoledronic acid takes 48 to 72 hours to work, so for the first 48 hours I would add subcutaneous calcitonin 4 to 8 IU per kg every 12 hours for a rapid calcium-lowering bridge while her confusion (a hypercalcaemic symptom) is addressed. Her breast cancer bone metastases make this a lytic bone disease hypercalcaemia, in which the phosphate is typically normal or high and the bisphosphonate (and ongoing denosumab) are highly effective. I would continue zoledronic acid or denosumab monthly as part of her bone-targeted therapy.

(e) Communication with the patient and family (1 mark): [1]

I would speak with her and her family in a quiet room, in plain language. I would explain that the cancer has pressed on the spinal cord and that we are giving a steroid and arranging an urgent scan and a surgical opinion to give her the best chance of walking again; that the confusion is from a high calcium that we are treating with fluids and a bone medicine; and that the aim is to preserve her function and her comfort. I would be honest that the next 48 hours are critical for the walking, document the agreed plan, and involve the palliative care team for symptom control and family support throughout. [1]