14 - Oncological Emergencies Flashcards
What are some oncological emergencies?
- Neutropenic sepsis
- Metastatic spinal cord compression
- Hypercalcaemia
- VTE
- SVC
- Tumour lysis syndrome
What is the definition of neutropenic sepsis?
Fever > 38° or features of sepsis in a patient with an absolute neutrophil count of < 0.5 x 109/L
It is a medical emergency!!!!!!!! Should contact 24h number if any chemo patient unwell
What are some causes of neutropenia?
- Genetic
- Cytotoxic related (as targets bone marrow)
- Intrinsic disease of bone marrow
- Infections (e.g malaria, HHV 4/5)
- Immune mediated (e.g RA, Crohn’s)
- Folate and Vit B12 deficiency
What patients are at high risk of neutropenic sepsis?
- Have sustained, significant neutropenia that is expected to last more than 7 days.
- Are clinically unstable
- Have an underlying malignancy and are being treated with high-intensity chemo
- Have significant co-morbidities (e.g DM, COPD)
What are the most common causative organisms of neutropenic sepsis?
BACTERIA but cultures often negative
-
Gram-negative
- Escherichia coli
- Klebsiella spp
- Pseudomonas aeruginosa
-
Gram-positive bacteria
- Coagulase-negative staphylococci (e.g. S. epidermidis)
- Staphylococcus aureus
- Streptococcus pneumoniae
-
Other
- Clostridium difficile
Viruses and Fungi in high risk patients
How may neutropenic sepsis present?
Impaired immune system may have a blunted response with subtle signs so high index of suspicion
Patients may present with the signs and symptoms of a specific infection. For example a purulent cough indicating pneumonia or dysuria indicating a UTI
Often however patients simply present with a fever or (often non-specific) signs of systemic infection such as malaise and fatigue
What time frame after chemotherapy does neutropenic sepsis tend to occur?
7-14 days after
If you are about to start chemo for somebody and predict their neutrophil count could fall below 0.5 what should you do?
Start prophylactic fluoroquinolone
If you suspect neutropenic sepsis (e.g temp of >38 in someone receiving chemo), what should you immediately do?
- Take FBC and two sets of blood cultures and other bloods
- Take blood gas for serum lactate
- Antibiotics must be started immediately, do not wait for the WBC (Piperacillin with tazobactam/Tazocin)
- High flow oxygen
- IV fluids should be started, often 500ml of crystalloid over 15 minutes
- Measure urine output with catheter
What investigations should you do in neutropenic sepsis to try to locate the source of infection?
Do systems based exam to guide investigations e.g dysuria do urine sample
- 2 sets of blood cultures including one from CVAD if there is one
- Swabs from any indwelling lines
- FBC, WCC, CRP, U+Es , LFTs, Albumin
- CXR if clinically indicated
- Serology and PCR for viruses e.g. CMV
- Sputum, urine, stool samples, CT scans etc. where clinically indicated
How can the level of risk of a patient with suspected neutropenic sepsis be stratified once the initial sepsis 6 has been completed?
MASCC Risk Index
(Multinational Association for Supportive Care in Cancer Risk Index)
Looks at patients disease burden, co-morbidities, status at onset of fever and age
A high score is a patient at lower risk of severe infection that may be suitable for outpatient care
When can a patient with suspected neutropenic sepsis be treated as an outpatient?
What are some signs of severe neutropenic sepsis/signs that sepsis has progressed to late stage sepsis?
May consider G-CSF treatment
After sepsis 6 and MASCC score has been calculated what other management needs to be done for suspected neutropenic sepsis?
Daily measures of fever and baseline bloods until the patient is apyrexial and neutrophil count above 0.5x109
- NEWS every 15 minutes initially
- Discontinue chemotherapy on admission
- Consider Vancomycin for MRSA if CVAD
- Ask oncology if need to remove CVAD
- Aggressive fluid replacement in dehydration.
- Hourly urine output measurement
- Early critical care if deterioration, severe sepsis (any evidence of organ failure) or suspected invasive fungal infection
When can antibiotics in neutropenic sepsis be stopped?
When neutrophil count is normal, has been afebrile for 48 hours and blood tests have normalised
Always do daily FBC and U+Es
What should be done if neutropenic sepsis fever is unresponsive to antibiotics after 48 hours?
- Consider fungal cause and do investigations e.g HRCT
- Discuss with microbiology what to switch to
- Should discuss with micro every 48 hours regardless
What does a low MASCC score mean?
Higher morbidity and mortality
Mortality of 2 to 21%
How can we prevent neutropenic sepsis?
- Patient advice
- Lower dose of chemotherapy
- Prophylactic antibiotics
What is Malignant Spinal Cord Compression (MSCC)?
Dural sac and it’s contents of the cord/cauda equina are compressed by cancer
Which cancers have a high chance of spinal metastases and MSCC?
(important card)
BLP and Myeloma!
20% of cancer presentations are MSCC
Pancreatic has lowest
What are the causes of MSCC?
- 80% due to collapse of vertebral body due to metastatic arterial seeding
- 10% by direct tumour invasion
What part of the spine do metastases tend to occur?
Usually thoracic
How may MSCC present if the cord is compressed?
- Severe back pain is first sign before any neurology
- Symmetrical lower limb weakness
- UMN signs e.g Babinski reflex, hypereflexia
- Paraesthesia with sensory level
How may MSCC present if the cauda equina (below L2) is being compressed?
- LMN signs
- Usually unilateral
- Saddle anaesthesia
- Reduced anal tone
- Painless urinary retention (and overflow incontinence)
- Back pain
- Impotence
- Absent ankle jerk
What is the back pain in MSCC like?
- First symptom
- Unresponsive to analgesia
- Band-like
- Radicular
- Exacerbated by coughing, sneezing, straining, neck flexion
How is suspected MSCC investigated?
Urgent whole spine MRI if symptoms within 24 hours of presentation
How is MSCC managed?
Surgical Emergency
General
- Adequate analgesia
- VTE prophylaxis: LMWH and TED stockings
- Catheter
Definitive
- High dose dexamethasone with PPI
- Surgical decompression and reconstruction within 24h of diagnosis
- OR External Beam or Stereotactic radiotherapy
What patients would be eligible for surgery in a case of MSCC? (only have 48h from neurological signs to paraplegia)
- Fit and prognosis >3/12
- Good motor function at presentation
- Good performance status
- Limited co-morbidity
- Single level spinal disease
When would you use radiotherapy for MSCC and what are the two different options for this?
- External beam radiotherapy
- Stereotactic body radiotherapy: higher doses of radiotherapy to be targeted more directly at the tumour while minimising exposure to adjacent tissue 10-15% risk of vertebral collapse with this type of radiotherapy
What is some supportive care that needs to be done in the management of MSCC?
What is the prognosis with MSCC?
No recover of mobility: 1-3/12
Walking: 5-8/12
Loss of sphincter function is poor prognostic sign
How is high dose dexamethasone given?
- PO if possible
- High dose is 16mg (which is 8 2mg tablets); often have 8mg at breakfast (8:00am) then 8mg at lunchtime (12:00pm)
- Want to give in morning as can cause sleep disturbance
What is malignant hypercalcaemia and what cancers does this tend to occur in?
Calcium >2.6
Causes: breast, multiple myeloma, lymphoma and lung (e.g. squamous cell carcinoma)
Most common cause of hypercalcaemia
Usually poor prognostic sign
How is calcium distributed in the body?
What is the pathophysiology of malignant hypercalcaemia?
Osteolytic metastasis
Most common in breast cancer, 20% of cases of malignant hypercalcaemia. Deposition of tumour cells within bone leads to local production of inflammatory cytokines and other mediators stimulating osteoclasts
PTH-related protein (PTHrP) secretion (most common cause)
Cause PTH receptors to be activated so absorption of calcium from gut and bone
Increased 1,25-dihydroxyvitamin D production
Increased expression of activated vitamin D so more gut absorption of calcium. Common in Hodgkin’s lymphoma
How may hypercalcaemia present?
‘Stones, bones, thrones, abdominal groans and psychiatric moans’. (Renal stones, bone pain, polyuria, abdominal pain/constipation and psychiatric features)
Mild
- Often asymptomatic
- Polyuria and polydipsia
- Mild cognitive impairment
- Dyspepsia
Moderate
- All mild features
- Constipation
- Weakness
- Fatigue
- Dehydration
- Nausea
Severe
- All mild and moderate features
- Abdominal pain
- Vomiting
- Cardiac dysrhythmias
- Pancreatitis
- Coma
What are the four most common symptoms of malignant hypercalcaemia?
- Nausea and vomiting
- Constipation
- Thirst and polyuria
- Confusion
What are some other causes of hypercalcaemia apart from malignancy?
Primary Hyperparathyroidism
If somebody has hypercalcaemia and no cancer diagnosis what investigations need to be done to rule out/in a cancer diagnosis?
- PTH levels (will be suppressed if malignancy)
- Breast examination
- Myeloma screen (immunoglobulins, protein electrophoresis, urinary light chains)
- CT screen for cancer
What patients with malignant hypercalcaemia need admission?
>3mmol/L or symptomatic
Anything else can be managed as outpatient with 3-4L fluid a day
How is malignant hypercalcaemia managed?
1st Step
IV hydration: 3-4L 0.9% saline for 24 hours to correct any dehydration
2nd Step
Bisphosphonates: IV Pamidronate or Zoledronic Acid, inhibit osteoclast activity. Can cause renal failure so need adequate hydration first. Can take up to 4 days for effect but lasts weeks
Others
Calcitonin: promoting urinary calcium excretion and inhibits bone resorption. Its action begins after a few hours
Denosumab: monoclonal antibody used in osteoporosis
What monitoring should you do for patients after an episode of malignant hypercalcaemia?
- 2 to 3 weekly blood tests as high chance of recurrence
- May need regular bisphosphonate infusions
What is the prognosis once a cancer patient has had an episode of hypercalcaemia?
Poor prognostic indicator, less than 3 months
What are some complications of hypercalcaemia of malignancy?
- Bisphosphonate induced flu-like syndrome
- AKI
- Coma
- Acute pancreatitis
Other side effects of bisphosphonates: acute osteonecrosis of jaw, hypocalcaemia if given to pts with critical vit D deficiency
Patients with cancer are at an increased risk of VTE, are they given prophylaxis for this?
No as risk of bleeding still seen to outweigh risk of clot
Give if they have a clot for at least 6 months
What is the Well’s score for a DVT?
What is the Well’s score for a PE?
How is a VTE managed in cancer patients?
*Signs & symptoms would be same. Investigations also same (although don’t do d-dimer in cancer pt as it would be raised anyway)
VTE (excluding massive PE)
If the patient has active cancer
- DOAC (e.g. apixaban or rivaroxaban), unless this is contraindicated
- Continue for 3-6 months
Massive PE
- Thrombolysis using alteplase (give UFH prior to thrombolysis and stop within 24hrs of thrombolysis)
What blood work should be done for a suspected VTE?
- Baseline FBC
- U+Es
- LFTs
- PT and APTT
Do not do d-dimer as will be raised anyway
What is the first and second biggest mortality for oncological emergencies?
- Neutropenic sepsis
- VTE
What is SVCO and the aetiology of this?
Obstruction to the flow of blood through the superior vena cava secondary to a cancer
Usually lung cancer (NSCLC or SCLC) or NHL
Extrinsic compression, metastasis or thrombus
What are signs and symptoms of SVCO?
Usually dyspnoea, facial swelling, head fullness and cough
Symptoms
- Dyspnoea
- Facial swelling
- Head ‘fullness’
- Symptoms exacerbated by bending forwards / lying down
- Cough
- Dysphagia
- Blurred vision
Signs
- Facial swelling
- Distended neck and chest wall veins
- Upper limb oedema
- Pemberton’s sign
- Facial plethora
- Cyanosis
- Cognitive dysfunction
- Coma
How does SVCO lead to death?
Airway compromise or Cerebral Oedema
Stridor from laryngeal oedema
What is Pemberton’s sign?
Ask patient to elevate both arms above the head for 1-2 minutes
Positive if it causes congestion, cyanosis or respiratory distress
This occurs due to increased venous return from the upper extremities exacerbating any obstruction
What investigations are done to diagnose SVCO?
Initial: CXR as can exclude other causes of breathlessness e.g pneumonia. Findings include mediastinal widening and (malignant) pleural effusion.
Diagnostic: CT with contrast. Will show collateral vessels
Others: Duplex US, histology via bronchoscopy
If SVCO is presenting as an emergency with stridor or cerebral oedema, how is it managed?
- Sit upright/elevate head
- Oxygen
- Dexamethasone 16mg with PPI
- Stenting
How is SVCO managed generally if it is not an emergency?
Conservative
- Elevation of head and neck
- Oxygen
Medical
- Radiotherapy is first line therapy in patients with NSCLC and lymphomas
- Chemotherapy in chemosensitive tumours such as SCLC and NHL
- Anticoagulation or thrombolysis if due to intravascular thrombosis
Surgical therapy
- Endovenous stent placed percutaneously with access via the internal jugular, basilic or femoral veins under local anaesthetic
What are some complications of an endovascular stent used to manage SVCO?
- Infection
- PE
- Stent migration
- Perforation of SVC
What is the prognosis following SVCO?
Average life expectancy of 6 months
Negative prognostic indicator in terms of cancer survival. This reflects the extent of tumour or lymphadenopathy necessary to develop obstruction of the superior vena cava
What is tumour lysis syndrome and the electrolyte abnormalities that occur in this?
Metabolic disturbances arising from the breakdown of malignant cells following the initiation of treatment for malignancy
More common in haematological malignancies (lymphoma and leukaemia)
What are some of the complications of tumour lysis syndrome?
- AKI from uric acid and/or calcium phosphate crystals
- Seizures
- Arrhythmia
- Sudden death
What factors increase the risk of TLS?
- Haematological malignancy
- High proliferation rate
- Chemosensitivity
- Large tumour burden
- Pre-existing metabolic abnormalities e.g hyperuricaemia and hyperphosphataemi
- Renal impairment
Why do we need to risk stratify all cancer patients receiving cytotoxic therapy?
Assess the need for prophylactic treatment and the monitoring after initiating therapy.
What prophylaxis is given against TLS depending on the risk stratification?
Low-risk
Oral hydration
Intermediate risk
IV hydration and Allopurinol 300 mg daily for up to 7 days following the initiation of cytotoxic therapy is typical
High risk
IV hydration and one off dose of Rasburicase
DRUGS GIVEN TO PREVENT AKI BY LOWERING URIC ACID
When and how may TLS present?
First 3 to 7 days
Symptoms
- Lethargy
- N & V
- Diarrhoea
- Anorexia
- Muscle cramps
- Seizures
Signs
- Fluid overload
- Haematuria
- Tetany & paraesthesia (hypocalcaemia)
- Bronchospasm
What blood tests should you do to monitor for TLS if a patient is high risk?
Renal function, electrolytes, and serum urate every 4-6 hours
Serum urate levels taken in patients treated with rasburicase should be sent to the lab on ice to prevent falsely low levels
What additional blood tests can you do for TLS?
What is the diagnostic criteria for tumour lysis syndrome?
Cairo-Bishop scoring system
Laboratory diagnosis
Pesence of two or more abnormal serum values that occur three days prior to or seven days after beginning treatment
Clinical diagnosis
Patient who meets the laboratory diagnosis with the presence of one or more of the following features that cannot be attributed to a therapeutic agent:
- Serum creatinine (> 1.5 upper limit normal)
- Cardiac arrhythmia / sudden death
- Seizure
How can the severity of TLS be graded?
Also uses Cairo-Bishop system
Rating from 0-5 based on the laboratory rise in serum creatinine, the presence of cardiac arrhythmias and the development of seizures
Why are Allopurinol and Rasburicase used in TLS and how do they work on a cellular level?
Prevent hyperuricaemia and the subsequent precipitation of uric acid within the nephrons
Allopurinol: Xanthine oxidase inhibitor, can only be used for prophylaxis
Rasburicase: metabolises uric acid to allantoin, can be used for prophylaxis and treatment as works on uric acid in renal tubules
How is tumour lysis syndrome managed?
Correct electrolytes and renal impairment
Hyperphosphataemia:
- Adequate hydration and dietary restriction
- Phosphate binders may be used
- In severe cases, patients may require haemofiltration
Hyperkalaemia:
- IV calcium gluconate, insulin/dextrose infusion and nebulised salbutamol
- Cardiac monitoring for patients with potassium levels > 6 mmol/L or with a 25% increase compared to their baseline
Hypocalcaemia:
- May result in increased calcium phosphate deposits in the kidney so if asymptomatic do not treat
- IV replacement if arrhythmias or symptomatic
Renal impairment:
- Fluids rehydration
- Adjustment of drug doses
- Escalation to haemofiltration if needed
What are some indications for dialysis in TLS?
- Intractable fluid overload
- Refractory hyperkalemia
- Hyperphosphatemia-induced symptomatic hypocalcemia
- High calcium-phosphate product
What are some potential oncological emergencies that have not been discussed in this deck?
What are some risk factors for VTE in cancer patients?
- Patient related
- Cancer related
- Treatment related
- Biochemical markers
It is rare to give prophylaxis for VTE in cancer. What situations would you give prophylaxis in?
What score is used to determine whether a patient with neutropenic sepsis can be treated as an outpatient?
MASCC score
What is a venting gastronomy?
Palliative intervention in malignant bowel obstruction that prevents the need for an NG tube
What types of cancer tend to get malignant bowel obstruction?
- Bowel
- Gynaeocological
What medications are used in malignant bowel obstruction being treated palliatively?
- Analgesia
- Antiemetic: Haloperidol or Cyclizine
- Antimuscarinic: Hyoscine butyl bromide
- Corticosteroid
- Somatostatin analogue: Octreotide to lower gastric secretions and increase absorption of water from GI lumen
