Oncologic EmergenciesOncologic Emergencies

I. Metabolic EmergenciesI. Metabolic Emergencies

II. Haematologic EmergenciesII. Haematologic Emergencies

III. InfectionsIII. Infections

IV. Neurological EmergenciesIV. Neurological Emergencies

V. Miscellaneous EmergenciesV. Miscellaneous Emergencies

I. Metabolic EmergenciesI. Metabolic EmergenciesA. Tumour Lysis SyndromeMassive tumour cell death with rapid

release of intracellular metabolites, which exceeds theexcretory capacity of the kidneys leading to acute renal failure. Can occur before chemotherapy is started.

More common in:Iymphoproliferative tumours with

abdominal involvement (e.g. B cell/ T cell Iymphoma, leukaemias and Burkitt's Iymphoma)

Characterized by :↑ Uric acid↑ K+↑ PO4 with associated ↓ Ca++

Risk factors for tumour Iysis syndrome:

• Bulky disease• Rapid cellular turnover.• Tumour which is exquisitely sensitive to chemotherapy.• ↑↑ LDH / se uric acid• Depleted volume• Concentrated urine or acidic urine.• Poor urine output

a. Hyperuricaemia: Release of intracellular purines increase uric acid

b. Hyperkalaemia Occurs secondary to tumour cell Iysis itself or

secondary to renal failure from uric acid nephropathy or ↑↑ PO4.

c. Hyperphosphotaemia (↑PO4) with associated ↓Ca++)

Most commonly occurs in Iymphoproliferative disorders because Iymphoblast PO4 contents is 4 times higher than normal lymphocytes.

Causes: Tissue damage secondary to CaPO4 precipitation.

Occurs when Ca X PO4 > 60 mg/dl. Results in renal failure, pruritis with gangrene and inflammation of the eyes and joints.

Hypocalcaemia leading to altered sensorium, photophobia, neuromuscular irritability, seizures, carpopedal spasm and GIT symptoms

d. Renal failure

Multifactorial: Uric acid, phosphorus and potassium are excreted

by kidneys

The environment of the collecting ducts of the kidney is acidic coupled with lactic acidosis due to high leukocyte associated poor perfusion – uric acid crystallizes causing uric acid obstructive nephropathy. Usually occur when levels > 20 mg/dl.

Increased phosphorus excretion causing calcium phosphate precipitation in microvasculature and tubules.

Risk increases if renal parenchymal is infiltrated by tumour eg: lymphoma or ureteral/venous obstruction from tumour compression (lymph nodes)

Management (Prevention):

To be instituted in every case of acute leukaemia or Iymphoma prior to induction chemotherapy.

1. Hydration: 3000 ml/m2/day (i.e. double hydration) No potassium should be added.

2. Alkalization of urine: Adding NaHCO3 at 150-200 mmol/m2/day (3 mls/kg/day NaHCO3 8.4%) into IV fluids to keep urine pH 7.0 - 7.5. Avoid over alkalinization. (Aggravate hypocalcemia and cause hypoxanthine and xanthine precipitation, also precipitation of calcium phosphate in pH >8)

3. Allopurinol 10mg/kg/day, max 300mg/day.

4. KIV delay chemotherapy until metabolic status stabilizes

5. Close electrolyte monitoring- BUSE, Ca2+, PO4 2-, uric acid, creatinine, bicarbonate.

6. Strict I/O charting. Make sure urine is flow is adequate once hydrated. Usediuretics with caution

Management (Treatment):

1. Treat hyperkalemia – resonium, dextrose-insulin-bicarb, dialyze if indicated

2. Diuretics

3. Hypocalcaemia management depends on the PO4 level:

• If PO4 is ↑, then management is directed to correct the ↑PO4

• If PO4 is normal OR if child is symptomatic, then IV Ca++ replacement is given.• And if hypocalcaemia is refractory to treatment, associated

hypomagnesaemia (Mg2++) is to be excluded

4. Dialysis if indicated. Haemodialysis most efficient at correcting electrolyte abnormalities, peritoneal dialysis ineffective in removing phosphates

B. Other Metabolic Emergencies

a. Hyponatraemia (↓ Na+) Usually occurs in AML. Treat as for hyponatraemia.

b. Hypokalaemia (↓ K+) Common in AML. Rapid cellular generation leads to

uptake of K+ into cells. (Intracellular K+ is 30 - 40 X higher than extracellular K+). Therefore may develop ↑ K+ after chemotherapy.

c. Hypercalcaemia (Ca++) Associated with Non Hodgkin and Hodgkin

Lymphoma, alveolar rhabdo, rhabdoid tumours, etc. Management: 1. Hydration. 2. Oral PO4 3. IV Lasix (which increases Ca2- excretion) 4. Mithramycin

II II Haematologic Haematologic EmergenciesEmergencies

1. Hyperleucocytosis2. Coagulopathy3. Bone Marrow Depression

1.Hyperleukocytosis Occurs in acute leukaemia TWBC ≥ 100 000 Associated in

• ALL with high risk of tumour Iysis• AML with leucostasis (esp monocytic)

• Affecting the lungs causing SOB, hypoxaemia and RV failure

• Affecting the CNS causing headaches, papilloedema, seizures,haemorrhage or infarct.

• Others: renal failure, priapism, dactylitis

Mechanism: Excessive leukocytes form aggregates and thrombi in

small veins⇒ obstruction; worsens when blood is viscous.

Excessive leukocytes compete for oxygen and damage vessel wall⇒ bleeding

Management of Hyperleukocytosis

Hydration• to facilitate excretion of toxic metabolites• to reduce blood viscosity

Avoid ↑ blood viscosity.• Cautious use of blood transfusion and

diuretics.During induction in hyperleukocytosis, keep

platelet >20 000 and coagulation profile near normal

Exchange transfusions and leukopheresis should not be used alone as rapid rebound usually occur. Concurrent drug treatment should therefore be initiated soonest possible

2. CoagulopathyAML especially M3 associated with an initial

bleeding diathesis secondary to consumptive coagulopathy

Due to release of a tissue factor with procoagulant activity from cells

ManagementPlatelet transfusions – 6units/m2

- should increase platelets by 50,000/ml3.FFP or cryoprecipitateVitamin K+/- heparin therapy (10u/kg/hr)

- controversial

3. Depression of bone marrow activity

Depression of normal bone marrow activity results in anaemia, thrombocytopenia, and neutropenia.

Best treated with supportive care, regardless of their etiology

Supportive care often includes transfusion of individual blood components

III. InfectionsIII. Infections

A. Febrile neutropaeniaFebrile episodes in oncology patients MUST be

treated with urgency especially if associated with neutropenia.

Nearly all episodes of bacteraemia or disseminated fungal infections occur when the absolute neutorphil count (ANC) <500.

Risk increases maximally if ANC < 100 and greatly reduced if the ANC > 1000.

Other ManagementOther Management

1. If central line present, culture from central line from both lumens, add anti Staph cover e.g.cloxacillin.

2. Repeated P/E to look for new clues and signs and symptoms of possible sources.

3. Close monitoring of patient’s well-being – vital signs, perfusion, BP, I/O.

4. Repeat cultures if indicated5. Investigative parameters, FBC, CRP, BUSE as per

necessary .6. In presence of oral thrush or other evidence of

candidal infection, start antifungals. 7. Try to omit aminoglycoside and vancomycin if on

Cisplatinum - nephrotoxic and ototoxic. If required, monitor renal function closely.

B. TyphilitisNecrotizing colitis localised to the caecum occuring in

neutropenic patients.Pathophysiology:Bacterial invasion of mucosa causing inflammation. Can lead

on to full thickness infarction and perforation.Organisms: Clostridium, PseudomonasX-ray shows non specific thickening. At the other end of the

spectrum, there can be presence of pneumatosis intestinalis +/- evidence of free gas

ManagementUsually conservative (unless surgically indicated) with broad

spectrum antibiotics coveringGram negative organisms and anaerobes (metronidazole),

mortality 20-100%Criteria for surgical intervention:• Persistent GI bleed despite resolution of neutropenia and

thrombocytopenia and correction of coagulation abnormalities.

• Evidence of perforation• Clinical deterioration suggesting uncontrolled sepsis

(controversial)

C. ShockCommon causes of shock in child with cancer

Management:

Ascertain cause and treat accordingly.

IV Neurological IV Neurological EmergenciesEmergencies

Spinal Cord CompressionSpinal Cord CompressionPathophysiology.The most common scenario for cord

compression is the direct extension of a metastatic lesion from the vertebrae into the epidural space.

Although metastatic lesions are more common, cord compression may be the initial presentation of the tumor.

Half of the metastatic lesions are due to lung, breast, or prostate cancer.

The most common site of compression is the thoracic spine (70%). The lumbar spine 20%, cervical spine 10%.

Intradural: Spinal cord tumour

Prolonged compression leads to permanent neurologic sequelae.

Epidural extension: Iymphoma, neuroblastoma and soft tissue sarcoma

Presentation:Back pain-localized or radicular,

aggravated by movement, straight leg raising, neck flexion.

Later – weakness, sensory loss, incontinence.

Diagnosed by CT myelogram/MRI

Management:The goal of therapy is to decompress the

spinal cord 1. Laminectomy urgently (If deterioration

within 72 hours).2. Once paralysis have been there longer

than 72hours, chemotherapy might be the better option if tumour is chemosensitive

especially for lymphoma. This avoids vertebral damage. Other chemosensitve tumour include neuroblastoma and Ewing’s with an onset of action similar to radiotherapy.

3. Prior IV Dexamethasone 0.5mg/kg 6 hourly to reduce oedema

4. +/- Radiotherapy

Increased ICP and brain herniationIncreased ICP and brain herniation

Cause : brain tumours e.g. astrocytoma, PNET, usually infratentorial and block the 3rd or 4th ventricle.

Signs and symptoms vary according to age/site.

Infant; vomiting, lethargy, regression of milestones, seizures, symptoms of obstructive hydrocephalus.

Older: early morning recurrent headaches with or without vomiting.

Cerebellar: ipsilateral hypotonia and ataxia

Herniation of cerebellar tonsil – head tilt and neck stiffness

Tumours near 3rd ventricle – cranio, germinoma, optic glioma, hypothal and pit tumours- visual loss, increased ICP and hydrocephalus - obstruction of aqueduct of Sylvius due to pineal tumour – raised ICP and Parinaud’s synd (impaired upward gaze, convergence nystagmus and altered pupillary response)

Management:1. Assessment of vital signs, look for focal

neurological deficit.2. Look for evidence of raised ICP

(bradycardia, hypertension and apnea) and3. Look for evidence of herniation (changes

in respiratory pattern, pupil size and reactivity.

4. Dexamethasone 0.5 mg/kg (tp decrease edema)

5. Urgent CT to determine cause6. Prophylactic antiseizures7. LP is contraindicated8. Decompression- ie shunting +/- surgery. -Because of their multiple nature, surgical

resection of intracerebral metastases is usually not a therapeutic option.

Cerebrovascular accidentCerebrovascular accident

Direct or metastatic spread of tumour, antineoplastic agent, haematologic abnormality.

L-Asparaginase associated with venous or lateral and sagittal sinus thrombosis caused by rebound hypercoagulable state

AML especially APML associated with DIVC and CVA. Due to release of procoagulant.

ManagementSuportiveUse of anticoagulant potentially

detrimentalIn L-Aspa induced, recommended

BD FFP

VV Miscellaneous Miscellaneous EmergenciesEmergencies

A. Superior Vena Cava ObstructionCommon in NHL/Hodgkin Lymphoma/ALL .Rarely: malignant teratoma, thymoma,

neuroblastoma, rhabdo or Ewing’s may present with anterior or middle mediastinal mass and obstruction.

50% associated with thrombosis.Presentation: shortness of breath, facial &

upper body edema , headache, nausea, dizziness, vision changes, hoarseness, cough, dysphagia or syncope.

Stridor and dyspnea, especially when the patient is supine, are associated with airway obstruction.

Physical examination is often remarkable for neck vein distention, facial edema, and trunk and upper extremity swelling.

Enlarged, dilated, cutaneous vessels in the anterior chest and upper abdomen provide evidence for collateral blood flow.

Plethora and tachypnea may also be noted. In later stages, papilledema, lethargy,

mental status changes, seizures, and coma may develop (dt. Cerebral edema & increase ICP)

Management:1) Tissue diagnosis is important but should

be established by the least invasive measure available. Circulatory collapse or respiratory failure may occur with sedation.a) BMAb) Biopsy of superficial LN under local anaesthesia.c) Measurement of serum markers eg α-FP

If tissue diagnosis is unobtainable, empiric treatment may be necessary based on the most likely diagnosis. Both chemo and radiotherapy may render histology uninterpretable within 48 hours, therefore biopsy as soon as possible.

2) Interim therapeutic measures such as elevation of the head, diuretics, and supplemental oxygen may be instituted for symptomatic relief.

3) Dexamethasone may be used in patients with evidence of intracerebral edema.

4) In patients with highly chemosensitive tumors, lymphoma, germ cell carcinoma, and small cell carcinoma of lung, chemotherapy plays a significant role in treatment.

5) However, in most patients, radiotherapy is the cornerstone of therapy.

6) Balloon angioplasty and stent placement can be used to relieve the obstruction.

B. ATRA (all-trans retinoic acid) syndrome

Characterised by: fever, respiratory distress, respiratory failure, oedema, pleural/pericardial, effusion, hypotension

Pathophysiology:Respiratory distress due to leukocytosis

associated with ATRA induced multiplication and differentiation of leukaemic promyelocytes.

Treatment:Dexamethasone 0.5 – 1mg/kg/dose BD.