Oncological Emergencies Flashcards
What is neutropenic sepsis?
Fever > 38
Or features of sepsis
In a patient with a neutrophil count of < 0.5 x 10^9/L
What are the causes of neutropenic sepsis?
Genetic - congenital neutropenia, syndromes such as Chediak-Higashi
Cytotoxic related - therapies
Intrinsic disease of bone marrow; haematological malignancies, tumour infiltration, aplastic anaemia, ionising radiation
Immune mediated - uncommon, IBD inflammatory conditions, arthritides
Drugs stimulating formation of antibodies damaging granulocytes e.g. anti-thyroid drugs, carbimazole
Nutritional deficiencies e.g. folate and Vitamin B12
Increased neutrophil turnover - bone marrow cannot adequately replace them
Bacterial infections and hypersplenism
What are the causative organisms of neutropenic sepsis?
Most commonly bacteria
Gram neg - E Coli, Klebsiella, pseudomonas aeruginosa
Gram pos - S. epidermis, Staph aureus, strep pneumoniae
Other - c. diff
Viruses in high risk patients, usually prevented by prophylactic antiviral therapy
Otherwise herpes, varicella zoster, EBV - secondary to reactivation of latent infections
Fungi - Candida, aspergillus
Patients with haematological malignancies often require anti-fungal prophylaxis e.g. fluconazole
What are the clinical features of neutropenic sepsis?
Patients may have blunted response and subtle signs
High index of suspicion
Patients may present with signs for specific infection, or fever and non-specific symptoms
Temp >38 or hypothermia <36
Resp rate >20 breaths/min
Blood pressure systolic < 90
HR >90 BPM
Cognition - acute confusion
Urine output <0.5-1ml/kg/hr
What are the investigations for neutropenic sepsis?
Bedside
Obs, sugar, preg test
Bloods VBG/ABG FBC CRP U&Es LFTs Bone profile Clotting Fungal assays BBV Screen
Cultures Blood, line Sputum, urine, stool C diff Viral PCR Wound swabs
Imaging
CXR, LP, ECHO
What is the sepsis six bundle?
Three In
High flow oxygen target of 94-98 unless COPD 88-92
IV fluids, 500ml crystalloid over 15 mins
Abx empirical e.g. tazocin
Three Out
Two sets of blood cultures
Serum lactate via blood gas - arterial or venous
Urine output
What is the Multinational Association for Supportive Care in Cancer (MASCC) Risk Index?
Patients with neutropenic sepsis can be risk stratified with this
Disease Burden
5 none/mild
3 moderate
0 severe
Co-morbidities 5 No hypotension 4 No COPD 4 Solid tumour/haematological but no previous fungal infection 3 no dehydration needing IVF
If yes to any = 0
Status of onset
3 outpatient
0 inpatient
Age
2 less than 60
0 60 or older
LOW RISK > 21
HIGH RISK < 21
What is the treatment of neutropenic sepsis?
LOW RISK
Oral abx, consider outpatient care
HIGH RISK
IV abx, inpatient management
Identify source of infection
Sepsis 6
What do you examine on a patient with ?neutropenic sepsis?
Cardio Resp Lymph nodes Lines focus on causes - GI exam
A patient in hospital with neutropenic sepsis has been treated for 5 days but there is still no change, what do you do?
Consider fungi/parasite causes
When should antibiotics be started for neutropenic sepsis?
As soon as suspected
Don’t wait for bloods
What is malignant cord compression?
Radiological evidence of indentation of the thecal sac secondary to cancer
or also cauda equina - collection of lumbar, sacral, coccygeal nerve roots descending from end of spinal cord at L1.
What can cause malignant compression of the spinal cord
Primary
Primary bone tumours
CNS malignancies
Secondary
Mets
Non-metastatic - mechanical structural weakness due to cancer
Paraneoplastic
What are other causes of cord compression important to recognise?
Trauma Intervertebral disc prolapse Haematoma Epidural abscess - secondary to osteomyelitis or discitis Cervical spondylitic myelopathy
What cancers are most commonly associated with cord compression secondary to metastatic disease?
Lung Breast Kidney Prostate Thyroid
Where do most cord compressions occur?
Thoracic - 60%
Lumbar 30%, cervical 10%
What are some of the causes of vertebral mets?
Arterial seeding
Shunting of blood through epidural venous plexus
Extension through intervertebral foramina
How many patients tend to get MSCC?
10% of patients with spinal mets
What are the consequences of early MSCC?
Cord compression –> oedema –> venous congestion
What are the consequences of late MSCC?
Irreversible vascular injury –> cord necrosis
What signs are indicative of metastatic spinal cord compression?
Back pain - worse on waking and aggravated by straining Spinal tenderness Limb weakness Sensory loss Incontinence Generally unwell Spasticity Babinski +ve Palpable bladder
How is MSCC investigated?
MRI within 24 hours
How is MSCC managed?
Bed rest with neutral spine alignment need to be (log rolled)
Dexamethasone (unless lymphoma suspected)
Analgesia
Bisphosphonates (myeloma, breast and prostate mets only)
Definitive treatment: Decompression or radiotherapy within 24hrs
Supportive care - VTE prophylaxis, catheter, bed sore management, temperature checks
Surgery
Decompression
Reconstruction
Vertebroplasty
Kyphoplasty
If unable to undergo full decompression and reconstruction
What is the role of radiotherapy in MSCC management?
Relieve compression of spine and nerves - cause cell death
Pain relief and stabilise neurological deficit
External beam radiotherapy as an adjuvant or definitive for those unable to undergo surgical intervention
What are the signs of cauda equina?
Back pain Radiculopathy Reduced anal tone Saddle anaesthesia Painless retention of urine, change to urine/bowels Paralysis Hyporeflexia Hypotonia
What is malignant hypercalcaemia?
Serum calcium >2.6 mmol/L
Secondary to malignant process
What is normal serum calcium?
Between 2.2-2.6 mmol/L
Mild is 2.6-3.0
Severe is >3.5
What are the most common malignancies associated with hypercalcaemia?
Breast cancer
Multiple myeloma
Lymphoma
Lung cancer e.g. squamous cell carcinoma
What are the three main mechanisms causing malignant hypercalcaemia?
Osteolytic metastasis
PTH related protein secretion
Increased 1.25-Vit D production
Why does PTHrP secretion cause hypercalcaemia?
Release of PTHrP from tumour cells e.g. breast carcinomas and non-Hodgkin’s lymphoma
Is structurally similar to PTH and leads to increased bone resorption
Distal renal tubular calcium absorption
Inhibition of proximal phosphate transport
How does osteolytic mets cause hypercalcaemia?
Commonly associated with breast cancer
Deposition of tumour cells in bone leads to local production of inflammatory cytokines and other mediators
Causes osteoclasts to be stimulated leading to bone resorption
In what malignancies can there be an increased production of 1.25-Vit D?
Increased Vit D leads to increased absorption of calcium
Hodgkin’s lymphoma
May also be seen in chronic granulomatous disease e.g. sarcoidosis
What are the clinical features of malignant hypercalcaemia?
Stones, bones, groans, psychiatric moans
Mild - often asymptomatic
Polyuria, polydipsia, mild cog impairment, dyspepsia
Mod - all mild features
Constipation, weakness
Fatigue, dehydr, nausea
Severe
Abdo pain, vomiting
Cardiac dysrhythmias
Pancreatitis, coma
What are the investigations needed for diagnosis of malignant hypercalcaemia?
Serum calcium level
Identification of underlying cancer
Biochemical markers can differentiate between primary hyperparathyroidism and malignant hypercalcaemia
In malignant hypercalcaemia, PTH should be suppressed
Full examination, breast exam
Investigations targeted to any potential cause
Myeloma screen - immunoglobulins, protein electrophoresis, urinary light chains
Imaging e.g. CT
What is the management of malignant hypercalcaemia?
Intravenous rehydration
Calcitonin and bisphosphonates
Admission for any patient with serum calcium >3mmol/L or if symptomatic and lower
and underlying malignancy
If underlying malignancy cannot be addressed - likely to recur within 2 weeks
Additional therapies e.g. glucocorticoids, denosumab, dialysis
What is the function of calcitonin?
Mod or severe hypercalcaemia
Promotes urinary calcium excretion and inhibits bone resorption
How do bisphosphonates work?
Analogues of inorganic pyrophosphate
Absorbed onto the surface of the bony network
Inhibit the action of osteoclasts
Pamidronate or zoledronic acid
What is the anatomy of the SVC?
Provides venous drainage for the upper limbs, head and neck
Originates posterior to lower aspect of right first costal cartilage
at union of right and left brachiocephalic veins
Descends to join the right atrium, valveless
What are the most common causes of SVCO?
Lung carcinoma most commonly NSCLC
Non-Hodgkin’s
What is the pathophysiology of SVCO?
Obstruction results in formation of collateral vessels
- azygous system
- internal mammary
- long thoracic
therefore if slow progressing obstruction, adequate time for collaterals and so mild symptoms
What are the clinical features of SVCO?
Symptoms Dyspnoea, facial swelling Head 'fullness', headache Symptoms exacerbated bending forwards/lying down Cough, blurred vision Dysphagia
Signs Facial swelling Distended neck and chest wall veins Upper limb oedema Facial plethora Cyanosis Cognitive dysfunction Coma
What is Pemberton’s sign?
Elevate both arms above head for 1-2 mins
Positive sign - causes congestion, cyanosis or resp distress
Occurs due to increased venous return from upper extremities exacerbating obstruction
How can SVCO be diagnosed?
80% have abnormal CXR
Need to see underlying cause
Findings include mediastinal widening, malignant pleural effusion
CT shows extent and level of obstruction and collateral vessels
Duplex USS in those with indwelling catheters
May need biopsy for malignant cause
What is the emergency management of SVCO?
Rare, to treat respiratory distress or cerebral oedema
Stridor may be present
Senior review, peri-arrest
Diuretics
Steroids
Related to thrombus - stent, not related - thrombolysis
What is the general management of SVCO?
Relieve obstruction
Imaging and histology
Elevation of head and neck
Oxygen titrated to sats
Stenting
Radiotherapy - NSCLC, lymphomas
Chemo
Anticoag or thrombolysis may be used if SVCO occurs secondary to intravascular thrombosis
Glucocorticoids may help reduce swelling; dex
Stent placed percutaneously, access via internal jugular, basilic or femoral veins
When is SVCO seen?
External compression from Lung cancer but can be from lymphoma
What is extravasation?
Leakage of IV drugs into extravascular space leading to nearby tissue damage
Why are chemo agents susceptible to causing extravasation?
Poorly soluble in aqueous media and are vesicant
How can extravasation be prevented?
Ensure IV fluid runs without resistance
Stop infusion if pain at injection site
Don’t leave infusion unattended if highly vesicant
Immediately stop infusion if suspicion
How does dehydration affect hypercalcaemia?
Exacerbate any underlying hypercalcaemia
What is tumour lysis syndrome?
Results from metabolic disturbances
arising from the breakdown of malignant cells
following initiation of treatment for malignancy
What electrolyte abnormalities are seen in TLS?
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
Hyperuricaemia
Phosphate produced by tumour cells binds to calcium
What factors are associated with increased risk of TLS?
High proliferation rate
Chemosensitivity
Large tumour burden
Pre-exisitng metabolic abnormalities e.g. hyperuricaemia and hyperphosphataemia
Renal impairment
Who is at low risk of TLS?
<1% chance of developing TLS
AML with certain WBC, LDH criteria CLL with WBC and tx criteria Multiple myeloma CML NHL normal LDH Other solid tumours
Who is at an intermediate risk of TLS?
Certain NHLs with high LDH and absence of bulky disease
Certain early stage NHLs
ALL, AML, CLL with certain WBC, LDH, Tx criteria
Bulky tumours highly sensitive to chemo e.g. germ cell, small cell
Who is at high risk of developing TLS?
Burkitt’s leukaemia
Certain Burkitt’s lymphoma
ALL with certain WBC, LDH
AML with high WBC
Certain NHLs with high LDH and bulky disease
Intermediate risk with evidence of high risk clinical factors e.g, renal dysfunction
What is the pathophysiology of tumour lysis syndrome?
Cytotoxic mediated lysis of tumour cells
Release of intracellular components
Hypocalcaemia develops secondary to hyperphosphataemia with precipitation of calcium in soft tissues
Can lead to AKI
What are the clinical features of TLS?
Tend to develop within the first 72 hours following tx initiation
Can occur up to 7 days post treatment
Symptoms
Lethargy, N&V, diarrhoea
Anorexia, muscle cramps, syncope, pruritus, arthritis
Signs
Fluid overload, haematuria, tetany, paraesthesia, bronchospasm
What are the investigations for TLS?
Renal function, electrolytes, serum urate to diagnose and assess severity
High risk patients may need serial bloods every 4-6 hrs
Urine dip, microscopy - uric acid crystals
Serum lactate, LDH
ECG, cardiac monitoring
Serum urate levels in patients on rasburicase sent on ice to prevent falsely low levels
What is required for a laboratory diagnosis of TLS?
Cairo Bishop definition - lab definition and clinical def
Presence of two or more abnormal serum values that occur three days prior to or seven days after beginning treatment
What clinical diagnosis is needed for TLS?
Meets lab diagnosis
Presence of one or more features not due to therapeutic agent
Serum creatinine >1.5 upper limit normal
Cardiac arrhythmias/sudden death
Seizure
What hypouricaemic agents are given to prevent TLS?
Prevent hyperuricaemia and the subsequent precipitation of uric acid in nephrons
Allopurinol - xanthine oxidase inhibitor
Does not act on pre-existing uric acid so is prophylactic
Rasburicase Recombinant urate oxidase Metabolises uric acid Works on established renal deposits Contraindicated with G6PD deficiency
What is involved in prophylaxis of TLS?
Low risk - oral hydration and monitor
Intermediate - saline, allopurinol up to 600mg OD
TLS screen
High risk - saline; aim for UO >100ml/hour, rasburicase, TLS screen
What is involved in the management of TLS?
Calcium glutinate, insulin, dextrose for hyperkalaemia
Hypouricaemic agents
Phosphate binders
IV hydration
What are some indications for haemofiltration in TLS?
Intractable fluid overload
Refractory hyperkalaemia
Hyperphosphataemia induced symptomatic hypocalcaemia
High calcium phosphate product
What do calcium phosphate precipitates lead to?
Calcium phosphate deposition in:
Renal tubules - AKI
Skin - Gangrene
Heart - Arrhythmia
What are the main risk factors for TLS?
Large volume disease
Chemosensitive
Haematological malignancy
Poor renal function
How could you manage a suspected line infection?
Line locks - if not systemically very poorly can give high concentration abx (commonly gentamicin) through the line to sterilise it and save it from needing removal
When would a bone scan for bony metastasis not be useful?
Multiple myeloma - bone scan works by picking up areas where there is increased uptake of radioactive traced indicating osteoblastic activity. Multiple myeloma produced purely lytic lesions so it is not useful.
What should you do in a suspected line infection?
Give Teicoplanin (provides gram +ve cover) Can do line lock with high dose Gentamicin
What are the most common causes of central line associated blood stream infections?
Coagulase negative staphylococci e.g. S epidermidis
Enteroccoci
Who does the risk of neutropenic sepsis increase with?
Prolonged neutropenia >7 days Severity of neutropenia Significant comorbidities Aggressive cancer Central lines Mucosal disruption Hospital inpatient
What are the most common responsible pathogens for neutropenic sepsis?
From endogenous flora
Gram positive cocci from indwelling catheters promoting colonisation
Staph aureus, epidermidis, enterococcus, streptococcus
MRSA and vancomycin resistant enterococcus increasingly prevalent
When do you need to give empirical IV antibiotics in neutropenic sepsis?
Within the hour
Where is the most common site of MSCC?
Thoracic
Below L2 vertebra = caudal equina
Who is likely to be fit for surgery for MSCC?
Fit and good prognosis Multiple myeloma, lymphoma, breast, prostate, renal cancers Good motor function at presentation Good performance status Limited comorbidity Single level spinal disease Absence of visceral mets Long interval from primary diagnosis
What is the management of SVCO?
Sit upright/elevate head Oxygen Dexamethasone 16mg plus PPI Opioids Benzodiazepines
Treatment
Steroids
Stent if not radio or chemo sensitive
Anticoag if thrombus
What are other potential oncological emergencies?
Toxicity with newer oncological treatments e.g. immune checkpoint inhibitors - pneumonitis, colitis Seizures SIADH PE Non-neutropenic sepsis Massive haemorrhage Uncontrolled pain
