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Oncological Emergencies in the ICU

CICM Fellowship LO CICMF_SPECIAL_5 2,014 words
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Overview

Oncological emergencies encompass a spectrum of life-threatening complications arising from malignancy itself or its treatment. They demand rapid recognition, organ-system-focused assessment, and coordinated multidisciplinary management. In the ICU setting, these patients frequently present with concurrent organ dysfunction, immunosuppression, and complex analgesic or haemodynamic needs. The four core emergencies - malignant spinal cord compression (MSCC), superior vena cava (SVC) syndrome, hypercalcaemia of malignancy, and tumour lysis syndrome (TLS) - each carry distinct pathophysiology, diagnostic imperatives, and treatment targets.


Malignant Spinal Cord Compression (MSCC)

Pathophysiology and Epidemiology

MSCC occurs in 5-10% of all cancer patients and is the first manifestation of malignancy in approximately 10% of those affected. The majority of lesions are epidural, arising from haematogenous spread to vertebral bodies with subsequent anterior compression of the cord. Direct extension from paraspinal lymph nodes also occurs. The thoracic spine is most frequently involved (~70%), followed by lumbosacral and cervical regions. Vascular compromise, oedema, and demyelination follow cord compression, with ischaemia driving irreversible neurological injury if untreated.

Clinical Recognition

Feature Detail
Presenting symptom Back or neck pain (>95%) - often precedes neurology by days to weeks
Motor deficit Proximal leg weakness, paraparesis, or paraplegia
Sensory level Pain/temperature level on trunk localises lesion
Bladder/bowel Retention, incontinence - late features indicating severe compression
Spinal shock Areflexia acutely; hyperreflexia supervenes within days

The only evidence-based predictor of spinal malignancy in acute back pain is a previous history of cancer. In the ICU, any cancer patient with new back pain, leg weakness, or urinary retention must be treated as MSCC until proven otherwise.

Diagnostic Approach

MRI with gadolinium is the investigation of choice - it visualises the cord throughout its length, defines the extent and level of compression, and identifies additional clinically silent lesions. Whole-spine imaging is preferred given the frequency of multilevel disease. CT myelography is an alternative if MRI is contraindicated.

Urgency: MRI must be completed and neurosurgical/radiation oncology assessment initiated within 24 hours of clinical suspicion, and immediately if there is rapidly progressive or dense neurological deficit.

Treatment

Corticosteroids

Dexamethasone should be commenced immediately upon clinical suspicion, before imaging where there is high clinical certainty.

Clinical Scenario Dexamethasone Dose
Neurological deficit (standard) 8-10 mg IV bolus, then 16 mg/day in divided doses
Dense paraparesis / paraplegia Higher doses considered (up to 96 mg/day in some protocols)
Maintenance during radiotherapy Continue 16 mg/day, then taper

Mechanism: reduce vasogenic oedema around the compressed cord, decrease tumour-related inflammation, and potentially inhibit prostaglandin-mediated vascular damage.

Radiotherapy

First-line definitive treatment for the majority. Effective in arresting and reversing deficits in approximately 75% of ambulatory patients at diagnosis. Only ~10% of patients who are already paraplegic regain meaningful ambulation. Time is critical: fixed motor deficits present for >12 hours are unlikely to reverse; beyond 48 hours, prognosis for motor recovery is poor.

Surgery

Decompressive surgery (laminectomy or vertebral body resection) is indicated when: - Neurological deficits worsen despite radiotherapy - Maximum tolerated radiotherapy dose has been previously delivered to the site - Vertebral instability or pathological fracture contributes to compression - Tissue diagnosis is required - Disease is radioresistant (e.g., renal cell, melanoma)

The NOMS framework (Neurologic, Oncologic, Mechanical, Systemic) guides decision-making, integrating neurological grade, radiosensitivity, mechanical instability score, and patient fitness.

Analgesia

Acute pain is severe, with mixed nociceptive, inflammatory, and neuropathic components. Escalate directly to strong opioids (bypassing the WHO Step II) when simple analgesics are inadequate. Pain may worsen transiently during early radiotherapy. Anticipate incident pain during patient positioning for treatment.


Superior Vena Cava (SVC) Syndrome

Pathophysiology

SVC obstruction produces raised venous pressure in the upper body, impeding cerebral and upper limb venous drainage. The SVC is vulnerable due to its thin wall, low intraluminal pressure, and mediastinal location. Approximately 85% of cases are due to malignancy - predominantly lung cancer (non-small cell > small cell), followed by lymphoma. The remainder are largely due to thrombosis of central venous catheters or intravascular devices.

Clinical Features

Feature Mechanism
Facial and periorbital oedema Venous hypertension in facial veins
Arm swelling Upper limb venous obstruction
Dyspnoea, cough Tracheal compression, laryngeal oedema
Dilated neck veins Elevated SVC pressure
Collateral chest wall veins Compensatory venous drainage
Headache, confusion, visual change Raised intracranial venous pressure
Stridor, tracheal deviation Life-threatening large mediastinal mass

CXR shows widening of the superior mediastinum; approximately 25% of patients have a right-sided pleural effusion. CT chest with contrast delineates the site and extent of obstruction, identifies thrombosis, and characterises the primary lesion.

ICU-Specific Concerns

Treatment

Endovascular Stenting

Stenting is the preferred intervention for rapid symptom relief, regardless of underlying aetiology. It provides symptom relief in >90% of patients within 24-72 hours and is the treatment of choice when: - Diagnosis is already established - Immediate symptom relief is needed - Prior radiotherapy has failed - Haemodynamic compromise is present

Symptoms recur in 10-30% and can be re-palliated with repeat stenting or balloon dilatation.

Radiation Therapy

Treatment of choice for non-small cell lung cancer once stenting has stabilised the patient. Chemotherapy is added to radiotherapy for small cell lung cancer and lymphoma, where response rates are high.

Catheter-Related Thrombosis

Central venous catheter clots should be removed and anticoagulation initiated. Low-dose warfarin (1 mg/day) may prevent catheter-related thrombosis in high-risk patients.

Supportive Measures

Elevate the head of bed, supplemental oxygen, and diuretics (cautiously - reducing preload may worsen haemodynamics). Dexamethasone (8-16 mg/day) may reduce peritumoral oedema but evidence of effect on SVC syndrome per se is weak.


Hypercalcaemia of Malignancy

Pathophysiology

Hypercalcaemia of malignancy occurs in approximately 10% of cancer patients and is the most common paraneoplastic emergency. Primary mechanisms include:

Mechanism Key Cancers Notes
Humoral hypercalcaemia (PTHrP) Lung (squamous), breast, renal, head/neck Most common; osteoclast activation via PTH-receptor
Osteolytic metastases Breast, myeloma Local cytokines (IL-1, IL-6, TNF-α)
Calcitriol excess Lymphoma Extrarenal 1-hydroxylation
Ectopic PTH Rare True ectopic secretion

Hypoalbuminaemia (common in malignancy) means ionised calcium may be significantly elevated even when total calcium appears borderline - always measure ionised calcium or apply correction: $Ca_{corrected} = Ca_{measured} + 0.02 \times (40 - albumin\,[g/L])$.

Clinical Features by Severity

Corrected Calcium Features
2.6-3.0 mmol/L Fatigue, anorexia, constipation, polyuria, mild confusion
3.0-3.5 mmol/L Nausea, vomiting, dehydration, confusion, arrhythmias
>3.5 mmol/L Stupor, coma, renal failure, short QT, Osborn waves, life-threatening arrhythmias

ECG findings: shortened QTc, PR prolongation, widened QRS, arrhythmias.

Treatment Algorithm

1. IV Fluid Resuscitation Normal saline 200-500 mL/hr titrated to urine output 100-150 mL/hr. Corrects dehydration, promotes calciuresis. Frusemide only after adequate volume repletion (it worsens dehydration if given early).

2. Bisphosphonates (antiresorptive therapy)

Agent Dose Onset of effect Duration
Zoledronate 4 mg IV over 15-30 min 24-72 hours 3-4 weeks
Pamidronate 60-90 mg IV over 4 hours 48-72 hours 2-3 weeks
Ibandronate 6 mg IV over 1-2 hours 48-72 hours 2-3 weeks

Zoledronate is more potent than pamidronate. Renal function monitoring is essential - dose adjust for creatinine clearance; avoid if eGFR <30 mL/min (relative contraindication, use ibandronate or pamidronate with extended infusion time).

3. Denosumab A human monoclonal antibody against RANKL (receptor activator of nuclear factor kappa-B ligand), denosumab blocks osteoclast development and bone resorption independently of renal function. Dose: 120 mg SC. Onset within 24-72 hours. Preferred in renal impairment and bisphosphonate-refractory hypercalcaemia. Delays onset of moderate-to-severe bone pain and skeletal-related events.

4. Calcitonin 4-8 IU/kg SC/IM q6-12h. Rapid onset (hours), modest effect (~0.5 mmol/L reduction), tachyphylaxis within 48 hours. Used as bridge to bisphosphonate effect in severe/symptomatic hypercalcaemia.

5. Glucocorticoids Prednisolone 40-60 mg/day (or equivalent IV). Effective for lymphoma and myeloma (mediated via calcitriol suppression). Limited role in solid tumour hypercalcaemia.

6. Dialysis Haemodialysis with low-calcium dialysate for refractory or severe hypercalcaemia with renal failure or cardiac compromise - rarely needed but immediately effective.


Tumour Lysis Syndrome (TLS)

Pathophysiology

TLS results from massive, rapid release of intracellular contents - potassium, phosphate, nucleic acids (metabolised to uric acid), and lactate dehydrogenase - following tumour cell death. This may be spontaneous or treatment-induced (chemotherapy, radiotherapy, immunotherapy, corticosteroids). High-risk tumours include Burkitt's lymphoma, acute lymphoblastic leukaemia (ALL), and other high-grade haematological malignancies.

Diagnostic Criteria (Cairo-Bishop Definition)

Laboratory TLS (≥2 of the following within 3 days before or 7 days after therapy onset):

Parameter Threshold
Uric acid ≥476 μmol/L (8 mg/dL) or ≥25% rise
Potassium ≥6.0 mmol/L or ≥25% rise
Phosphate ≥1.45 mmol/L (adults) or ≥25% rise
Calcium ≤1.75 mmol/L or ≥25% fall

Clinical TLS = Laboratory TLS + one or more of: creatinine ≥1.5× ULN, arrhythmia, seizure, death.

Consequences of Metabolic Derangements

Derangement Consequence
Hyperkalaemia Ventricular arrhythmia, cardiac arrest
Hyperphosphataemia Calcium-phosphate precipitation, tissue calcification
Hypocalcaemia (secondary) Tetany, seizures, QTc prolongation, arrhythmia
Hyperuricaemia Urate crystal nephropathy, acute kidney injury
AKI Fluid overload, worsening electrolyte clearance

Prevention and Treatment

Risk Stratification and Prophylaxis:

Risk Definition Intervention
Low Solid tumours; indolent lymphoma Hydration, allopurinol
Intermediate DLBCL, CLL with high burden Hydration, allopurinol ± rasburicase
High Burkitt, ALL, AML, LDH >2× ULN Aggressive hydration + rasburicase

Hyperhydration: IV normal saline at 200-300 mL/hr to achieve urine output >100 mL/hr (or >3 mL/kg/hr in children). Avoid urinary alkalinisation - urate solubility benefits are outweighed by calcium-phosphate precipitation risk in hyperphosphataemia.

Rasburicase: Recombinant urate oxidase that converts uric acid to allantoin (5-10× more soluble). Dose: 0.2 mg/kg/day IV for 5-7 days. - Contraindicated in G6PD deficiency (causes severe haemolysis) - Blood samples must be transported on ice immediately - in vitro enzymatic activity degrades uric acid in the sample tube, causing falsely low results

Allopurinol: Xanthine oxidase inhibitor; prevents new uric acid production but does not clear existing urate. Dose: 300-600 mg/day. Inferior to rasburicase in established hyperuricaemia.

Electrolyte Management:

Electrolyte Management
Hyperkalaemia Calcium gluconate (membrane stabilisation), insulin-dextrose, salbutamol, resonium, RRT
Hyperphosphataemia Phosphate binders (sevelamer, calcium carbonate with caution), dietary restriction, RRT
Hypocalcaemia Only replace if symptomatic - calcium may precipitate calcium-phosphate in setting of hyperphosphataemia

Renal Replacement Therapy (RRT): Indicated for refractory hyperkalaemia, severe AKI with oliguria, fluid overload, or persistent hyperphosphataemia/hyperuricaemia despite medical management. Continuous RRT (CRRT) preferred for haemodynamically unstable patients - provides superior electrolyte clearance over time and avoids disequilibrium.


CICM Final Implications

Hot Case / Viva Framework

When presenting an oncological emergency in the ICU hot case, structure your response around: diagnosis → organ dysfunction assessment → immediate stabilisation → definitive intervention → goals of care.

Emergency "Don't miss" action Time-critical threshold
MSCC MRI whole spine + dexamethasone immediately Fixed deficit >12-48 h = poor recovery
SVC syndrome Secure lower limb IV access; consider airway risk Stenting within 24-48 h for haemodynamic compromise
Hypercalcaemia Ionised calcium; aggressive saline resuscitation first iCa >3.5 mmol/L = ICU-level emergency
TLS Check G6PD before rasburicase; uric acid sample on ice AKI + hyperkalaemia = early RRT discussion

Goals of Care Integration

In oncological emergencies, early goals-of-care discussion is mandatory and should not await clinical stabilisation. Key considerations: - Reversibility of the presenting complication vs. trajectory of the underlying malignancy - Performance status trajectory and patient wishes regarding life-sustaining therapy - Whether the intervention (e.g., surgical decompression for MSCC) is consistent with realistic functional recovery goals - Palliative care integration for symptom management regardless of escalation decisions

Monitoring Targets

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