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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Cancer and its treatment may lead to a range of potentially life-threatening conditions that require urgent action to correct them. This article discusses the following:
- Tumour lysis syndrome.
- Raised intracranial pressure.
- Spinal cord compression.
- Cauda equina syndrome.
- Superior vena cava obstruction.
- Syndrome of inappropriate ADH secretion.
Other oncological emergencies include hypoglycaemia, pericardial effusion and cardiac tamponade, seizures, hyperviscosity syndrome (this is usually associated with Waldenström's macroglobulinemia) and airway obstruction.
Adverse effects of chemotherapy may also require urgent intervention - eg, extravasation and anaphylactic reactions.
See also separate Hypercalcaemia article.
This is the most common, serious metabolic disorder associated with malignancy, affecting up to one third of cancer patients at some point in their disease course. Malignancies most commonly associated include lung cancer, breast cancer, renal cancer, multiple myeloma and adult T-cell lymphoma. Its symptoms may mimic the features of terminal malignancy. Hypercalcaemia is a poor prognostic indicator in malignant disease and may indicate uncontrolled tumour progression and metastasis. The 30-day mortality rate of cancer patients admitted to hospital with hypercalcaemia is almost 50%.
The symptoms of hypercalcaemia are nonspecific; delayed recognition can worsen morbidity and mortality. Presenting features include nausea and vomiting, anorexia, thirst and polydipsia, polyuria, lethargy, bone pain, abdominal pain, constipation, confusion and weakness. Renal tract stones may occur. There is no absolute level of calcium at which patients become symptomatic; the rate of increase is usually more significant than the magnitude of elevation.
Ionised calcium is the most reliable laboratory test. If total calcium is used, it is important to calculate the corrected calcium level to allow for hypoalbuminaemia. Other investigations should include alkaline phosphatase, renal function and electrolytes, X-rays (may show lytic or sclerotic lesions of the bone) and a bone scan (to identify any metastases).
There may be a palliative benefit from improving the symptoms of hypercalcaemia, even in patients with advanced malignancies. Urgent intervention is required to treat symptomatic hypercalcaemia. Management includes intensive rehydration and intravenous bisphosphonates.
See also separate Neutropenic Patients and Neutropenic Regimes article.
Febrile neutropenia is most often seen as an effect of cytotoxic therapy. The neutrophil count usually reaches its lowest level 5 to 10 days after the last dose of chemotherapy. Febrile neutropenia is defined as an oral temperature ≥38.5°C or two consecutive readings of ≥38.0°C for two hours and an absolute neutrophil count ≤0.5 x 109/L. There is a significant mortality from febrile neutropenia, of between 5% in people with solid tumours to 11% in those with haematological malignancies. Signs and symptoms can be minimal, especially in those also on corticosteroids. Infection is responsible for at least half of the cases of neutropenic fever.
- Gram-positive cocci are now responsible for the majority of culture-positive cases of neutropenic fever, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Enterococcus faecalis and Enterococcus faecium. Corynebacterium is the most likely Gram-positive bacillus.
- Gram-negative bacilli include Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa.
- Candida is the most common fungal infection but aspergillosis and other systemic mycoses can cause more serious infections.
- Often no causative organism is found (in which case the prognosis is better than in those with proven bacteraemia) and the patient improves as the neutrophil count increases.
The vulnerability to infection substantially rises at a neutrophil count less than 1 x 109/L but the risk continues to increase as the neutrophil count falls.
- The patient should have an infection screen, including blood cultures, urine cultures, swabs of any indwelling catheters, intravenous cannulae and central lines, CXR, sputum cultures, cultures from any open wounds and stool cultures.
- Empirical antibiotic therapy should be started immediately based on local guidelines, with modification based on the results of microbiological investigations.
- The addition of antifungal coverage should be considered in high-risk patients who remain febrile after 3-7 days of broad-spectrum antibiotics with no identified causative organism.
- The National Institute for Health and Care Excellence (NICE) does not recommend the use of granulocyte-colony stimulating factor (G-CSF) for the routine prevention of neutropenic sepsis.
Tumour lysis syndrome
Tumour lysis syndrome is a severe metabolic disturbance caused by the abrupt release of large quantities of cellular components into the blood following the rapid lysis of malignant cells. It is characterised by hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia. It occurs most often in patients with haematological malignancies - eg, acute lymphoblastic leukaemia (ALL) or Burkitt's lymphoma. Treatment-provoked tumour lysis syndrome can occur following chemotherapy, radiotherapy, surgery or ablation procedures.
Typically, onset is within 1-5 days of starting chemotherapy (but can be delayed by days or weeks in patients with a solid tumour). The metabolic disturbances can cause seizures, acute kidney injury and cardiac arrhythmias. Although such clinical tumour lysis syndrome is rare (affecting 3-6% of patients with high-grade tumours), the mortality is as high as 15% and a third of patients require dialysis. Patients particularly at risk have treatment-sensitive tumours, renal impairment or volume depletion. High pre-treatment urate, lactate and lactate dehydrogenase (LDH) are also risk factors.
Full metabolic and biochemical profile to detect the above abnormalities. Monitoring of serum lactate, urate and LDH may predict the imminent onset of the syndrome.
The key to the management of tumour lysis syndrome is prevention, with a risk assessment for all patients with any haematological malignancy prior to receiving chemotherapy:
- Low-risk patients: vigilant monitoring of electrolyte levels and fluid status.
- Intermediate-risk patients: seven days of allopurinol along with increased hydration. Urinary alkalinisation is no longer recommended.
- High-risk patients: prophylaxis, usually with a fixed single dose of 3 mg rasburicase (recombinant urate oxidase), along with increased hydration. Allopurinol is unnecessary and may reduce the effectiveness of rasburicase.
Clinical signs of tumour lysis syndrome require a multidisciplinary approach with involvement of haematologists, nephrologists and intensive care physicians, with transfer to an intensive care/high dependency facility. Treatment includes:
- Intravenous hydration (without potassium).
- Daily rasburicase infusion.
- Intravenous calcium gluconate for symptomatic hypocalcaemia .
- Cardiac monitoring
- Dialysis (not peritoneal) may be needed in severe cases.
- Alkalinisation of the urine is not recommended.
Leukostasis is associated with a very high white cell count, respiratory failure, intracranial haemorrhage (but it can affect any organ system) and early death. Without prompt treatment the mortality rate can be up to 40%. Leukostasis occurs in 5-13% of patients with acute myeloid leukaemia (AML) and 10-30% of adult patients with ALL. The risk is greater for younger patients, and infants are most often affected. A white cell count greater than 50,000/m3 indicates a particularly poor prognosis.
There is usually a high fever and examination may show papilloedema, retinal vein bulging, retinal haemorrhage and focal neurological deficits. Myocardial infarction, limb ischaemia, renal vein thrombosis and disseminated intravascular coagulation may occur. Thrombocytopenia is usually present.
- Rapid cytoreduction is the initial treatment, ideally with induction chemotherapy, which can dramatically reduce the white cell count within 24 hours.
- There is a very high risk of tumour lysis syndrome and so close monitoring of electrolytes and prophylaxis with allopurinol or rasburicase are required.
- Leukophoresis is usually started when the blast count is greater than 100,000/m3 or in the presence of symptoms.
- Cytoreduction can also be achieved by hydroxyurea but is usually reserved for patients with asymptomatic hyperleukocytosis who are unable to receive immediate induction chemotherapy.
Raised intracranial pressure
See also separate Raised Intracranial Pressure article.
Cranial metastases affect around a quarter of patients who die from cancer. Lung, breast and melanoma are the tumours that most commonly metastasise to the brain. The clinical picture varies with site of metastases and the rate of rise of intracranial pressure. Small metastases may bleed and cause acute symptoms. Common symptoms and signs include:
- Nausea and vomiting.
- Behavioural changes.
- Focal neurological deficit.
- Falling level of consciousness.
- Unilateral ptosis or third and sixth cranial nerve palsies.
- Bradycardia (late sign).
CT or MRI scanning should be conducted urgently to delineate the lesion, if the result is likely to affect the patient's management.
- If the patient has lost consciousness and requires ventilation, then higher than average respiratory rate should be used to aim for low normal pCO2 (30-35 mm Hg), which helps reduce intracranial pressure.
- Mannitol may be given as a diuretic along with dexamethasone to reduce symptoms and the likelihood of cerebral herniation.
- Further management may involve cranial irradiation, surgery ± radiation or 'gamma knife' radiosurgery, depending on the site, type and number of metastases.
- High-dose dexamethasone alone may be appropriate in the palliative situation. The usual starting dose is 8 mg morning and mid-day, reducing after three days as the symptoms improve or stopping completely after seven days if there has been no improvement.
Spinal cord compression
This condition must be diagnosed and treated quickly to prevent permanent neurological disability. It may occur because of extradural spread from a vertebral body metastasis, direct metastases or from a vertebral crush fracture. Cancers that most often metastasise to bone and cause spinal cord compression are cancers of the breast, kidney, thyroid, prostate and lung. See separate Spinal Cord Injury and Compression article.
Cauda equina syndrome
See separate Cauda Equina Syndrome article.
Superior vena cava obstruction
This may be due to compression of the superior vena cava, caused by primary or secondary tumours. Lung cancer (~85% of cases), lymphoma and metastatic tumours are the most common causes.
Therapy is directed at the underlying cause. This is normally chemotherapy for lymphoma/small cell lung cancer, with early response and resolution of superior vena cava obstruction within weeks being the usual outcome. Radiotherapy is usually used for non-chemosensitive tumours or patients who do not respond to chemotherapy. See separate Superior Vena Cava Obstruction article.
Syndrome of inappropriate ADH secretion
See also separate Hyponatraemia article.
Tumour cells may secrete ADH, particularly in the case of small cell lung cancer. The syndrome of inappropriate ADH secretion affects 1-2% of cancer patients. The condition should be considered whenever a patient with malignancy presents with hyponatraemia. It is often asymptomatic but may cause:
- Depression and lethargy.
- Irritability and other behavioural changes.
- Muscle cramps.
- Depressed consciousness leading to coma.
- Neurological signs (such as impaired deep tendon reflexes and pseudobulbar palsy).
Successful treatment of the underlying malignancy will improve the condition. Fluid restriction is recommended.
Further reading and references
Palliative and Supportive Care; Bandolier
Higdon ML, Higdon JA; Treatment of oncologic emergencies. Am Fam Physician. 2006 Dec 174(11):1873-80.
Lewis MA, Hendrickson AW, Moynihan TJ; Oncologic emergencies: Pathophysiology, presentation, diagnosis, and treatment. CA Cancer J Clin. 2011 Aug 19. doi: 10.3322/caac.20124.
Scottish Palliative Care Guidelines: Hypercalcaemia; Scottish Partnership for Palliative Care. NHS Scotland, June 2015
Management of febrile neutropenia: ESMO Clinical Practice Guidelines; European Society for Medical Oncology (2010)
Neutropenic sepsis: prevention and management in people with cancer; NICE Clinical Guideline (September 2012)
Guidelines for the Management of Tumour Lysis Syndrome in Adults and Children with Haematological Malignancies; on behalf of the British Committee for Standards in Haematology (2015)
Cervantes A and Chirivella I; Oncological Emergencies. Annals of Oncology 200415 Suppl 4: iv 299-306. [Full Text]
Hyponatraemia; NICE CKS, March 2015 (UK access only)