26.1 Neutropenic Sepsis, Spinal Cord Compression & SVC Obstruction

Oncological emergencies represent acute, potentially life-threatening clinical conditions that develop directly from malignant disease or secondary to antineoplastic therapy. Rapid recognition, immediate physiological stabilization, and guideline-directed emergency pharmacotherapy are core competencies frequently tested in the MRCP(UK) Part 1 examination.

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1. Neutropenic Sepsis

Clinical Definition & Risk Stratification

According to UK National Institute for Health and Care Excellence (NICE CG151) guidelines, neutropenic sepsis is defined as:

• An absolute neutrophil count (ANC) < 0.5 × 10⁹/L, OR an ANC expected to fall below 0.5 × 10⁹/L within 48 hours;
• AND either a temperature > 38.0 °C OR symptoms/signs consistent with clinically significant sepsis (hypotension, tachycardia, tachypnoea, rigors, altered mental status, or localized tissue infection), regardless of body temperature (elderly or immunocompromised patients may be hypothermic).

The nadir for neutrophil suppression characteristically occurs 7 to 14 days following cytotoxic chemotherapy (particularly with intensive anthracycline-, taxane-, and platinum-based regimens).

Emergency Protocol: The "Door-to-Needle" One-Hour Rule

Neutropenic sepsis is a medical emergency with a mortality rate exceeding 20% if antimicrobial therapy is delayed. The door-to-needle time must not exceed 1 hour from initial clinical presentation:

1. Do NOT wait for laboratory confirmation: Broad-spectrum intravenous antipseudomonal antibiotics must be administered immediately upon clinical suspicion. Do NOT delay administration to obtain a full blood count, wait for blood culture bottles to arrive, or await central line swab results.
2. Diagnostic Sampling (Simultaneous with or immediately preceding antibiotics):
   • Blood cultures: Mandatory paired cultures—one set drawn from a peripheral vein and separate sets drawn from each lumen of every indwelling central venous catheter (e.g. Hickman, PICC, Port-a-Cath).
   • Serum lactate, full blood count, urea and electrolytes, liver function tests, C-reactive protein, and coagulation screen.
   • Urinalysis and culture, sputum culture, chest radiograph, and stool testing for Clostridioides difficile toxin if diarrhoea is present.
   • Important Exam Negative: Digital rectal examination (DRE) is strictly contraindicated in neutropenic patients due to the risk of mucosal trauma and introducing enteric flora into the systemic circulation, precipitating fatal polymicrobial sepsis.

Empirical Antimicrobial Regimens

• First-Line Monotherapy: Intravenous piperacillin-tazobactam (Tazocin) 4.5 g every 6 hours (or 4.5 g every 8 hours depending on renal function).
• Severe Penicillin Allergy (Anaphylaxis, Angioedema, Bronchospasm): Intravenous meropenem 1 g every 8 hours (carbapenems provide robust Pseudomonas aeruginosa coverage and broad-spectrum anaerobic/Gram-negative efficacy). Alternatively, intravenous aztreonam plus vancomycin or ciprofloxacin plus vancomycin.
• Specific Add-On Indications:
  • Suspected Central Venous Catheter Infection or MRSA Colonisation: Add intravenous vancomycin (or teicoplanin).
  • Septic Shock / Severe Haemodynamic Instability: Add an intravenous aminoglycoside (e.g. gentamicin or amikacin) for synergistic Gram-negative coverage.
  • Suspected Invasive Fungal Infection: If fever persists beyond 72–96 hours despite broad-spectrum antibacterials, initiate empirical antifungal therapy (e.g. liposomal amphotericin B or voriconazole/caspofungin).

Granulocyte Colony-Stimulating Factor (G-CSF)

• Recombinant G-CSF (Filgrastim, Pegfilgrastim): Stimulates neutrophil proliferation, differentiation, and survival in the bone marrow.
• Primary Prophylaxis: Indicated when the anticipated risk of febrile neutropenia for a given chemotherapy regimen exceeds 20%, administered 24–72 hours post-chemotherapy completion.
• Secondary Prophylaxis: Given in subsequent cycles if the patient experienced febrile neutropenia in a prior cycle without dose reduction.
• Therapeutic G-CSF in Established Neutropenic Sepsis: NOT routinely recommended for all patients. Reserved strictly for patients with established sepsis who have high-risk adverse prognostic features: profound shock, multi-organ dysfunction, pneumonia, invasive fungal sepsis, or absolute neutrophil count < 0.1 × 10⁹/L with anticipated prolonged myelosuppression.

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2. Metastatic Spinal Cord Compression (MSCC)

Epidemiology & Anatomical Distribution

Metastatic spinal cord compression affects 5–10% of all cancer patients and represents an oncological and neurosurgical emergency. Irreversible paraplegia ensues within hours to days if compressive ischemia is untreated.

• Commonest Primary Malignancies:
  1. Prostate carcinoma (most common in males);
  2. Breast carcinoma (most common in females);
  3. Lung carcinoma (small cell and non-small cell);
  4. Renal cell carcinoma;
  5. Multiple myeloma and lymphoma.
• Anatomical Levels:
  • Thoracic spine (60–70%): Most frequent due to the large number of vertebral bodies and narrow spinal canal.
  • Lumbosacral spine (20–30%): Compresses the conus medullaris or cauda equina.
  • Cervical spine (10%): High risk of quadriplegia and respiratory compromise.

Clinical Presentation & Red Flag Symptoms

• Spinal Pain (Earliest Sign, >90% of cases):
  • Severe, unremitting, progressive localized back pain, typically preceding neurological deficits by weeks.
  • Worse on lying flat (due to distension of the epidural venous plexus) and waking the patient at night.
  • Exacerbated by straining, coughing, sneezing, or movement.
  • Radicular "Band-Like" Pain: Sensation of a tight band wrapping circumferentially around the chest or abdomen (thoracic root compression).
• Motor Dysfunction: Progressive symmetrical or asymmetrical lower-extremity weakness; difficulty climbing stairs or standing from a chair; upper motor neuron signs (spasticity, brisk patellar/Achilles reflexes, clonus, extensor/upgoing plantar responses).
• Sensory Deficits: Sensation of walking on cotton wool, ascending paraesthesias, and a well-demarcated sensory level corresponding to the anatomical cord lesion (e.g. T4 at nipples, T10 at umbilicus).
• Autonomic / Sphincter Disturbance (Late & Ominous Sign): Urinary hesitancy progressing to painless urinary retention with overflow incontinence; constipation and loss of anal sphincter tone. Sphincter loss indicates severe, often irreversible neurological injury.

Emergency Investigation Algorithm

• Gold Standard: Urgent contrast-enhanced whole-spine MRI (sagittal and axial T1, T2, and STIR sequences).
• Timeline Mandate: Must be performed within 24 hours of presentation if MSCC is clinically suspected, and immediately within 6 hours if progressive motor weakness or neurological signs are already established.
• Whole-Spine Requirement: Imaging the entire spine is mandatory because 20–30% of patients have multiple non-contiguous spinal metastases that dictate surgical and radiation portals.

Emergency Management Protocol

1. High-Dose Corticosteroids (Immediate): Administer oral dexamethasone 16 mg daily (either 16 mg as a single morning dose or 8 mg twice daily with meals) co-prescribed with a proton pump inhibitor (PPI, e.g. omeprazole 20 mg daily) for gastroprotection. Dexamethasone rapidly reduces vasogenic spinal cord oedema and improves microvascular perfusion.
2. Immobilisation & Nursing Care: Strict bed rest with flat spine precautions and log-rolling until spinal mechanical stability is confirmed by the neurosurgical/spinal team.
3. Definitive Treatment Consultation: Immediate contact with the regional MSCC Coordinator / Spinal Surgery / Clinical Oncology:
   • Surgical Decompression & Posterior Fixation (Patchell Criteria): First-line for patients with single-level cord compression, mechanical spinal instability, bony fragment retropulsion, unknown primary histology, radioresistant tumours (renal cell, melanoma), and neurological deficit duration < 48 hours in patients with an expected survival > 3 months.
   • External Beam Radiotherapy (EBRT): Primary treatment for radiosensitive tumours (myeloma, lymphoma, small cell lung cancer), multilevel disease, non-ambulatory patients with prolonged paraplegia (>48 hours), or patients unfit for surgical intervention.

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3. Superior Vena Cava (SVC) Obstruction

Pathophysiology & Etiology

The superior vena cava is a thin-walled, low-pressure vascular vessel situated in the middle/anterior mediastinum, encircled by rigid nodal stations and the trachea. Extrinsic compression, direct transmural invasion, or secondary intraluminal thrombosis causes obstruction to venous drainage from the head, neck, and upper extremities.

• Malignant Causes (>85% of cases):
  • Small cell lung cancer (SCLC): ~40% (rapidly growing, central mediastinal mass).
  • Non-small cell lung cancer (NSCLC): ~40% (squamous cell, adenocarcinoma).
  • Non-Hodgkin lymphoma: ~10–15% (particularly diffuse large B-cell and lymphoblastic lymphoma in young adults).
  • Metastatic disease (germ cell tumours, breast adenocarcinoma, thymoma).
• Non-Malignant Causes (<15%): Thrombosis secondary to indwelling central venous lines, pacemakers, or mediastinal fibrosis.

Clinical Presentation

• Facial Oedema & Plethoric Suffusion: Facial fullness, puffy eyelids, conjunctival chemosis/suffusion, and periorbital oedema, classically pronounced in the morning upon waking.
• Venous Distension: Markedly engorged, non-pulsatile neck veins and extensive subcutaneous collateral venous networks over the anterior chest and abdominal wall.
• Pemberton's Sign: Elevation of both arms above the head for 1 minute induces marked facial congestion, cyanosis, and inspiratory stridor due to increased intrathoracic pressure and thoracic inlet crowding.
• Respiratory & Neurological Symptoms: Dyspnoea (most common symptom), orthopnoea, cough, hoarseness (recurrent laryngeal nerve compression), stridor (indicates life-threatening laryngeal oedema requiring emergent intubation), headache, dizziness, and visual blurring (cerebral venous hypertension).

Investigation & Emergency Management

• Investigation: Contrast-enhanced CT thorax with intravenous contrast is the diagnostic investigation of choice, defining the level of venous occlusion, collateral pathways, presence of intraluminal thrombus, and underlying parenchymal/nodal mass.
• Medical Management:
  • Elevate the head of the bed to 45° to enhance gravitational venous drainage.
  • Administer high-dose oral dexamethasone 16 mg daily with PPI cover (rapidly reduces peritumoral inflammation and laryngeal oedema).
• Definitive Treatment:
  • Endovascular SVC Stenting: The definitive treatment of choice for rapid symptom relief, providing dramatic clinical improvement in 80–90% of patients within 24–48 hours, irrespective of underlying histology.
  • Urgent Systemic Chemotherapy: Indicated for highly chemosensitive malignancies (SCLC, lymphoma, germ cell tumours).
  • Urgent Radiotherapy: Indicated for radioresponsive malignancies (NSCLC) where stenting is unavailable or contraindicated.
  • Anticoagulation: Full therapeutic anticoagulation (low molecular weight heparin or DOAC) if intraluminal thrombus is demonstrated.

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