Approximately 1 in 500 children is diagnosed with cancer by age 15. The physical and emotional burden on children and their families can be overwhelming. As clinicians, we should be aware that initial presentation, disease progression and/or complications of treatment can all present as an emergency. Early recognition and treatment of oncological emergencies can prevent deterioration and associated morbidity and mortality.
This article will work through several paediatric oncological emergencies, which we should be familiar with.
1. Febrile neutropenia
A 3-year-old girl recently diagnosed with acute lymphoblastic leukaemia (ALL) is on the third week of chemotherapy and presents to ED with a fever of 38.5 oC.
NICE defines febrile neutropenia as a temperature >38oC or any symptoms and signs of sepsis in a person with an absolute neutrophil count <0.5×10^9/L. Febrile neutropenia is the most common complication of cancer therapy, and mortality can be as high as 25% if not treated early.
Due to the severity of immunosuppression in children with cytotoxic-induced neutropenia, infections may present with non-specific symptoms and can be challenging to identify. Moreover, children treated with steroids may not mount the same febrile response. The source of infection may not be found in 10-40% of cases. It is therefore important to start broad-spectrum antibiotics with pseudomonas cover as early as possible. Common bacterial pathogens include gram-positive bacterial infections such as Staphylococcus, Streptococcus, and Enterococcus species. Unfortunately, drug-resistant organisms are increasingly seen. These include Pseudomonas aeruginosa, Acinetobacter, Escherichia coli, and Klebsiella species. A thorough investigation search for a source is important. This includes cultures from all central lines. Children with cancer are more vulnerable to vasodilation from sepsis and early fluid resuscitation should be guided by hydration status.
A 12-year-old boy with a recent history of lethargy presents to ED with a fever, headache, nose bleeds and blurred vision.
Hyperleukocytosis is an emergency in which a markedly raised white cell count leads to increased blood viscosity. This increases the risks of clot formation and microvascular haemorrhage. This is defined as a white blood cell count >100×10^9 L though white cell counts may be higher than 300×10^9 L. It most commonly occurs in T-cell ALL (Acute Lymphoblastic Leukaemia), infant ALL and AML (Acute Myeloid Leukaemia). Mortality is highest in the latter (AML) because the myeloblasts are much larger. Symptoms can be related to any organ system, though children commonly present with neurological signs, breathing difficulties or haemoptysis, or other sequalae of haemorrhage. Treatment of hyperleukocytosis consists of hyperhydration with intravenous fluids. Speak to a haematologist if there is a need for red blood cell or platelet transfusion. Red blood cell transfusion can further increase the viscosity of blood, although platelets do not have quite the same effect of increasing viscosity. Threshold values vary in different regions and on an individual basis. Coagulation abnormalities will occur if children develop disseminated intravascular coagulation with widespread clotting and consumption of clotting factors. This can lead to bleeding. These coagulation abnormalities should be promptly corrected. Chemotherapy, targeted at the underlying cause, should be initiated as soon as possible. These children need to be monitored for signs of tumour lysis syndrome.
3. Tumour lysis syndrome
A 6-year-old boy with presents with a seizure. He is found to have to a high potassium and low calcium on his bloods.
In tumour lysis syndrome, there is rapid break down of tumour cells. Intracellular contents are then released into the blood. These include uric acid, potassium and phosphate. This phosphate forms complexes with calcium (causing hypocalcaemia). These complexes, and the uric acid itself, may deposit in the kidneys and lead to a rapidly progressive renal failure. Children with any bulky and/or rapidly progressing disease are most at risk on initiation of cytotoxic chemotherapy. However, Tumour lysis syndrome can occasionally occur spontaneously unrelated to chemotherapy.
Symptoms are related to the consequences of these biochemical abnormalities. They can include gastrointestinal symptoms, tetany, arrhythmias, lethargy, and seizures. Due to the renal deposits and associated acute kidney injury, children can also present with haematuria, sediment in urine, flank pain and a metabolic acidosis on their blood gas. LDH, as an intracellular enzyme, also rises in the presence of cell lysis. Although hypocalcaemia is often seen, a normal or high calcium does not exclude the diagnosis of tumour lysis syndrome.
Early treatment involves aggressive fluid resuscitation and emergent treatment of electrolyte abnormalities. Start allopurinol or rasburicase (not to be used in G6PD patients) for the high urate (on the advice of the haematology or oncology team). These medications will decrease the levels of uric acid. Children with tumour lysis syndrome may also require renal replacement therapy in PICU.
A 5-year-old boy with known Rhabdomyosarcoma is brought into ED by his parents with a 4-day history of nausea, abdominal pain and increased tiredness.
Fortunately, hypercalcaemia is rare in children. However, it is seen in many children with leukaemia, lymphoma, rhabdomyosarcoma, bone tumours, brain tumours and neuroblastoma. Causes of hypercalcaemia include bony tumour invasion, releasing calcium from the bones, or the direct release of parathyroid hormone or calcitriol from the tumour itself.
Symptoms include gastrointestinal upset, bony pain, renal stones, fatigue, malaise, increased urination, lethargy and confusion. Initial treatment is with aggressive intravenous fluids. Further treatment with furosemide may be suggested by haematology or oncology.
5. Raised intracranial pressure
An 8-year-old girl who was previously fit and well presents to ED with a month-long history of worsening early morning headaches associated with vomiting. Her parents noticed that she was missing the ball at football and on further questioning realised she was suffering with double vision.
Raised intracranial pressure may be secondary to mass lesions within the brain, impaired drainage of cerebrospinal fluid, or more widespread intracranial inflammation. Symptoms include headaches that are worse in morning, vomiting especially early in the morning, visual disturbances as well as other neurological signs and symptoms. Although these are the classic symptoms, presentations may be subtle and resources such as HeadSmart can help identify symptoms. In infants whose skulls haven’t fused, raised intracranial pressure may present with an increasing head circumference and tense fontanelles. Infants may also present with more subtle symptoms such as lethargy and reduced feeding.
Children presenting with signs of raised intracranial pressure need urgent imaging (often CT) and discussion with neurosurgery. Their head should be tilted at 30 degrees to reduce ICP; if they seize, they will require anticonvulsants. Intravenous mannitol or hypertonic saline can draw fluid out of the brain by osmosis. These children may require early intubation and ventilation.
6. Posterior Reversible Encephalopathy Syndrome
A 15-year-old boy develops a headache and becomes confused whilst receiving a course of chemotherapy for ALL.
Posterior reversible encephalopathy syndrome (PRES) occurs when the posterior part of the brain is swollen by oedema. Vasogenic oedema occurs because of a leaky blood brain barrier. Fluid shifts outside the capillaries and into the interstitium of the brain. The exact cause of PRES is not fully understood but it may be made more likely by hypertension, steroids, cytotoxic agents (which can destruct the lining of blood vessels and make them leakier), and renal failure. PRES is not exclusive to oncology patients but is more common in this cohort.
Children with PRES may present with headaches, visual changes, seizures, confusion, and weakness. An MRI scan visualises vasogenic oedema to make the diagnosis. Management consists of anticonvulsants if seizing, removing causative drugs such as steroids or chemotherapy, giving intravenous fluids, maintaining oxygen and blood glucose levels, correcting electrolyte and clotting abnormalities and controlling high blood pressure with IV nicardipine or labetalol.
7. Spinal cord compression
A 6-year-old girl is brought to the children’s assessment unit. She was previously walking well without support but over the last few months has been falling frequently and now barely walks at all.
Spinal cord compression (SCC) may be caused by direct compression of the cord by a tumour or vasogenic oedema. In younger children, this may be due to a yolk sac tumour or neuroblastoma; they may present with symptoms such as stopping walking or clumsiness. In older children, non-Hodgkin’s lymphoma and Ewing’s sarcoma are the most common causes of SCC. They make up 50% of all causes of SCC in paediatric oncology patients.
Children with SCC may present with back pain, limb weakness, incontinence, or gait abnormalities. A discoloured swelling at the base of the spine may also be seen in yolk sac tumours.
Children presenting with these symptoms require an urgent MRI of their spine and discussion with neurosurgery. Early IV dexamethasone reduces inflammation and the pressure effects of the tumour. Children will often also require a catheter due to urinary retention and laxatives to help with constipation. Never attempt a lumbar puncture in these children.
8. Superior vena cava obstruction
A 6-year-old boy presents to the Emergency Department with swelling of his neck and face, distended neck veins and difficulty breathing.
Superior vena cava obstruction (SVCO) may be due to internal compression, external compression, or a large blood clot. Mediastinal masses causing compression are usually due to lymphoma, germ cell tumours, neuroblastoma, thymoma, or leukaemia. If a child presents without a mass, the obstruction is most likely because of a thrombus, particularly in patients with a long-term central venous catheter or hyperleukocytosis.
Symptoms of SVCO include cyanosis and oedema of the upper body and face with distended neck veins. These may get worse when the child lifts their arms above their head, such as when cuddling a parent (Pemberton’s sign). Additional symptoms include difficulty breathing, wheeze, and stridor – all of which are worse when lying flat.
Children with SVCO can deteriorate very quickly and rapidly lose their airway when lying on their back. Proning or lateral proning may help to alleviate some symptoms. Care must be taken when they are sent for imaging because of the risk of deterioration when they lie flat. Intubation is a last resort since muscle relaxation may reduce the child’s own airway splinting and allow the mass to further compress the airways. It may even act as a one-way valve making ventilation challenging and potentially dangerous. Urgent cardiothoracic, anaesthetics, haematology, oncology, and PICU support are needed due to the risk of rapid deterioration. Ultimately, the underlying pathology needs to be addressed as soon as possible with chemotherapy, steroids, radiotherapy or thrombectomy.
9. Malignant GI obstruction
A 5-year-old with Burkitt’s Lymphoma is brought to hospital by his parents because he has not opened his bowels all week and they have noticed a lump in his abdomen.
Malignant obstruction is a mechanical obstruction of the bowel in children and young people with cancer. It may be due to intussusception (when the bowel folds in on itself internally) in children with lymphoma but can also occur due to adhesions or strictures from previous surgeries or radiotherapy. The tumours themselves may also compress the bowel. Alternatively, a paralytic ileus (when the bowel isn’t physically blocked but is stunned and the muscle contractions that push stool through stop working) secondary to opiate analgesia or due to certain cancer treatments.
Symptoms of malignant obstruction include passing blood in stool, an inability to pass stool or wind, vomiting, abdominal pain and a palpable mass on examination. Malignant bowel obstruction is rare in paediatrics and may represent a sign of advanced disease. Treatment options and prognosis depend on the underlying cause.
A 3-year-old girl with ALL has recently started chemotherapy. Her dad noticed that she had a fever today at home. Over the last few days, she has had diarrhoea and abdominal pain.
Typhlitis is a necrotising enterocolitis of the gastrointestinal tract due to immunosuppression and chemotherapy. Organisms invade the bowel wall leading to inflammation and ischaemia, and subsequent bowel perforation. Typhlitis normally effects the caecum and presents with right lower quadrant pain, fever, and diarrhoea. This may be misidentified as appendicitis. They may also have inflamed oral mucosa. It is a diagnosis that should always be considered in children with neutropenia. It occurs most often 10-14 days after chemotherapy.
Children with possible typhlitis should undergo imaging (usually CT) to confirm the diagnosis and be started on IV antibiotics. They may develop clotting abnormalities that require correction with an infusion of coagulation products such as cryoprecipitate or fresh frozen plasma. They may require surgery if there is perforation, ongoing bleeding, or sepsis.
This article has outlined ten critical paediatric oncological emergencies. We are in a privileged position to be able to see these vulnerable children and young people. A caring, cautious approach, with an awareness of the potential emergencies, should allow us to start early treatment and seek appropriate specialist support. Be mindful of your impact on parents and caregivers and adopt a supportive approach.
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