Oncological Emergencies Flashcards
What is neutropenic sepsis?
Neutrophil count of 0.5 x 109 per litre or lower (check guidelines), plus:
Temp > 38oC
Other signs consisent with significant sepsis
What are some other terms for neutropenic sepsis?
Febrile neutropenia
Neutropenic fever
How does neutropenia predispose to infection?
Neutrophils are key component of the innate immune system
Lack of signs / symptoms causing isolated pyrexia
What are some causes of neutropenia?
Recent chemo (within 7-10 days) due to BM suppression
Malignant bone marrow infiltration
Extensive radiotherapy
Bone marror failure secondary to non-malignant disease (e.g. aplastic anaemia)
Hypersplenism
Megaloblastic anaemia
What increases the risk of developing neutropenic sepsis?
> 60
Advanced malignancy
Previous neutropenic sepsis
Mucositis (entry for bacteria)
Poor performance status
Co-morbidities
Indwelling central venous catheters
Corticosteroids (causing immunosuppression)
Prolonged hospital admission
Severe neutropenia
What are some non-specific symptoms of neutropenic sepsis?
Fatigue
Feeling warm / cold
Rigors / shaking
Sweaty / clammy
Palpitations
Dizziness
Confusion / disorientation
What symptoms may reflect a specific infective source in neutropenic sepsis?
Chest: SoB, cough, chest pain, sore throat
Urine source: dysuria, increased frequency, urgency, LUTS
Skin: rashes, blisters, pain
GI: diarrhoea, nausea, vomiting, rectal bleeding, abdo oain, sore mouth (mucositis)
Indwelling line source: pain around the line
What may the clinical findings in neutropenic sepsis be?
Haemodynamic instability (hypotension, tachycardia, tachypnoea, hypoxia)
Fever
Reduced urine output
Mottled / ashen appearance
What may be the examination findings of an identifiable source in neutropenic sepsis?
Chest: increased work of breathing, crepitations, dullness to percuss, reduced air entry
Urine: suprapubic / flank pain, cloudy urine in catheter bag
Skin: rashes, blistering, tenderness
GI: abdo tenderness, dehydration, evidence of oral mucositis, jaundice
Indwelling line source: surrounding erythema, tenderness on palpation
What else may cause a fever in cancer?
Underlying malignancy (both solid and haematological)
Immunotherapy toxicities
Inflammatory disorders (e.g. SLE, vasculitis, RA)
Drug induced
Hypothalamic dysfunction
Thyroiditis
What are the common gram-negative bacilli that cause neutropenic sepsis?
E. Coli
Klebsiella spp.
Pseudomonas aeruginosa
Enterobacter spp.
Proteus spp.
What are the most common gram-positive bacilli in neutropenic sepsis?
Staphylococcus aureus
Corynebacterium
Staphylococcus epidermidis
Streptococcus pneumoniae
Viridans streptococci
Enterococci
What are some common fungal causes of neutropenic sepsis?
Candida spp.
Aspergillus spp.
Mucorales
How may an infective cause be investigated in neutropenic sepsis?
Bedside = Urinalysis (UTI), ECG (all acutely unwell patients), Capillary blood glucose (exclude hypoglycaemia)
Lab investigations = Blood tests (FBC, U&E, coagulation, CRP, LFTs = WCC low / raised, CRP raised), Serum lactate, G&S (for transfusion), Blood cultures (two sets from peripheral vein, plus from indwelling line), ABG (extent and severity), cultures (wounds, urine, stool, sputum line tip), Viral resp swab
Imaging = CXR (pneumonia), chest CT (fungal pneumonia suspected), abdo ultrasound (biliary / abdo infection suspected)
Other = Bronchoalverlar lavage (atypical chest source = penumocystis jirovecii)
What is the management of neutropenic sepsis?
Empirical abx within one hour of arrival at hospital
Sepsis 6
Give example of empirical antibiotic therapy for neutropenic sepsis?
First-line = IV piperacillin with tazaobactam (tazocin)
Second-line (penicillin allergy) = IV meropenem
Additional anti-microbial cover = teicoplanin for gram positive organisms (e.g. for indwelling central venous catheters)
Antifungal = if fever persists beyond 4-6 days
What may be used for both prophylaxis and treatment of neutropenia to reduce the risk of sepsis?
Granulocyte-colony stimulating factor
How does G-CSF work?
Stimulates bone marrow to produce neutrophils (may form part of specific chemo regimens) e.g. filgrastim
What are some complications of neutropenic sepsis?
Single / multi-organ failure (renal failure, heart failure, ARDS)
VTE (PE)
DIC
Delerium
Psycholigical complications (anxiety around future infections and chemo treatment)
Delays in chemo leading to worse cancer outcomes
What is the spinal cord?
Part of CNS - main communication between brain and peripheral nerves
What is the spinal cord surrounded by?
Meninges
Dura
Arachnoid
Pia mater
What is the thecal sac?
Component of the dura mater (outermost meningeal layer)
What is malignant cord compression defined as?
Radiological evidence of indentation of the thecal sac
What is the cauda equina? (syndrome included in cord compression)
Lumbar, sacral and coccygeal nerve roots that descend from the end of the spinal cord at L1
Where does the spinal cord originate and end?
Base of medulla oblongata (exiting through the skull through foramen magnum) - ending at level of L1 / L2 spinal vertebrae
How many segments are there of the spinal cord?
31 segments
What is the terminal end of the spinal cord called? (Beyond which is cauda equina / horses tail)
Conus medullaris
When does malignant spinal cord compression occur?
Secondary to metastatic deposits within the spinal column
Which cancers are associated with cord compression?
Lung
Breast
Kidney
Prostate
Thyroid
What are the other causes of cord compression?
Trauma
Intebertebral disc prolapse
Haematoma
Episural asscess (secondary to osteomyelitis or discitis)
Cervical spondylitic myelopathy
Where does malignant cord compression most commonly occur?
Thoracic spine
What can cause vertebral metastasis?
Arterial seeding
Shunting of blood through epidural venous plexus (in prostate cancer)
What are the features of cord compression?
Pain - severe, progressive, radicular character
Weakness - symmetrical, pyramidal (affects the extensors in upper extermities and flexors in lower)
UMN lesions = increased tone
Hypereflexia - below level of lesions e.g. extensor plantar reflex (positive babinski)
Sensory symptoms - less common than motor symptoms
What are the features of cauda equina syndrome?
Lower motor neurone pattern
Unilateral features
Saddle anarsthesia
Reduced anal tone
Painless urinary retention (overflow incontinence)
Impotence
Absent ankle jerk
What is the investigation in malignant cord compression?
MRI scan
Other imagine (myelography, CT, bone scan, plain radiographs)
What is the management of acute cord compression?
Surgical emergency - prompt recognition and treatment
General measures (analgesia from WHO ladder, VTE prophylaxis - TED stockings, LMWH, catheter)
Glucocorticoids (high-dose dexamethasone, reducing oedema, relieving compression)
Definitive treament (External beam RT - adjuvant or stand alone)
Stereotactic body radiotherapy - enables higher doses of radiotherapy to be targeted more directly at the tumour - useful if radioresistant e.g. sarcoma, renal cell carcinoma
What are the surgical management options for cord compression?
Surgical decompression and reconstruction
Vertebroplasty
Kyphoplasty
What is malignant hyperclacaemia defined as?
Serum calcium > 2.6 mmol/L secondary to a malignant process
What are the most common causes of hypercalcalcaemia?
Primary hyperparathyroidism
Malignant hypercalcaemia
Where is calcium stored?
Bone (99%)
Intracellular
Extracellular (ionised - free pool, bound to albumin and globulin, complexed with phosphate and citrate)
How is the balance between stored calcium and extracellular calcium managed?
PTH (parathyroid hormone)
Vitamin D
Calcitonin
How does the body respond to decreased extracellular calcium?
Detected by calcium-sensing receptor (CaSR) on parathyroid glands
Parathyroid glands release PTH (stimulating resorption of calcium from bone, activation of vitamin D and increased renal tubular reabsorption of calcium)
How does activated vitamin D cause increases in calcium?
Calcium absorption from enterocytes
What effect does a rise in extracellular calcium have?
Reduction in release of PTH
Stimulates the release of calcitonin
What is the normal calcium range?
2.2-2.6 mmol/L
What are the grades of hypercalcaemia?
Mild = 2.6-3.0
Moderate = 3.0-3.5
Severe > 3.5
What is calcium corrected for?
The amount binded to albumin
What does acidosis do to the levels of calcium?
Decreases level of calcium
Which are the most common malignancies associated with hyperclaemia?
Breast cancer
Muliple myeloma
Lymphoma
Lung cancer
What are the three mechanisms which cause malignant hypercalcaemia?
Osteolytic metastasis
PTH-related protein (PTHrP) secretion
Increased 1,25-dihydroxyvitamin D production
What does PTHrP cause?
Increased bone resorption
Distal tubular calcium absorption
Inhibition of proximal phosphate transport
What is osteolytic metastasis most linked with?
Breast cancer
Why does calcium rise in osteolytic metastasis?
Deposition of tumour cells in bone causes local inflammatory cytokines and other mediators, stimulating osteoclasts causing bone resorption
Which cancer causes increased expression of activated vitamin D (causing increased absorption from GI tract)?
Hodgkin’s lymphoma
What are the clinical features of malignant hypercalcaemia?
Stones, bones, abdo groans, psychiatric moans
Stones = renal calculi
Bones = pains, fractures
Groans = abdo pain, pancreatitis
moans = mood disturbances, fatigue
thrones = polyuria, constipation
How does milde hypercalcaemia present?
Often asymptomatic
Polyuria
Polydipsia
Mild cognitive impairment
Dyspepsia
Nausea
How does severe hypercalcaemia present?
Abdo pain
Vomiting
Cardiac dysrhythmias
Pancreatitis
Coma
How is malignant hypercalcaemia diagnosed?
Measurement of serum calcium level
Identification of underlying cancer
How to investigations differentiate between hyperparathyroidism and malignant hypercalcaemia?
PTH should be suppressed
Which investigations are usually indicated in suspected malignant hypercalcaemia?
Full examination (including breast)
Myeloma screen (immunoglobulins, protein electrophoresis, urinary light chains)
CT
What form the management of malignant hypercalcaemia?
IV rehydration (prompts calcium diuresis - if HF loop diuretics may be required)
Calcitonin (promotes urinary calcium excretion, inhibits bone resorption)
Bisphosphonate therapy (inhibit osteoclasts e.g. pamidronate or zoledronic acid)
Admit if serum calcium > 3 mmol/L (if less then managed as outpatient with oral hydration (3-4 L / day)
What is malignant superior vena cava obstruction (SVCO)?
Obstruction to the flow of blood through the superior vena cava secondary to a cancer
What does the SVC provide drainage for?
Upper limbs
Head
Neck
What unites to form SVC?
Brachiocephalic veins
Which cancers commonly cause SVC obstruction?
Lung carcinoma (small cell)
non-Hodgkin’s lymphoma
Which collateral systems may develop in SVC?
Azygous system
Internal mammary
Long thoracic
Which lung cancer mostly causes SVCO?
Non-small cell lung cancer
How does SVCO present?
Dyspnoea
Facial swelling
Head fullness
Cough
Which signs may warrant urgent management in SVCO?
Airway obstruction (stridor)
Neurological symptoms (cerebral oedema)
What are the signs and symptoms of SVCO?
Symptoms
Dyspnoea
Facial swelling
Head ‘fullness’
Symptoms exacerbated by bending forwards / lying down
Cough
Dysphagia
Signs
Facial swelling
Distended neck veins
Upper limp oedema
Facial plethora
Cyanosis
Cognitive dysfunction
Coma
What is pemberton’s sign in SVCO?
Pt elevates both arms above head for 1-2 minutes
Positive if causes congestion, cyanosis and respiratory distress (increased venous return exacerbates obstruction)
What are the investigations in SVCO?
Initially
Abnormal chest radiograph (FINDINGS = mediastinel widening and malignant pleural effusion & helps exclude other causes of breathlessness)
Diagnostic
Extent and level of obstruction, presence of collateral vessel formation and underlying cause (PET CT, CT abdo / pelvis / MRI to identify mets)
Duplex ultrasound may be used to diagnose SVCO (indwelling catheters, MRI and contrast venography are rarely used)
How may a histological diagnosis be obtained?
Minimally invasive procedures = sputum / pleural fluid cytology, lymph node biopsy, bone marrow biopsy
Invasive = bronchoscopy, mediastinoscopy, video assisted thoracoscopy
What is the emergency management of SVCO?
(treats respiratory distress / cerebral oedema)
Thrombus related = stent / thrombolysis
Not thrombus related = stent
What is the general and definitive management of SVCO?
General = elevation of head and neck, titrated oxygen, glucocorticoids to reduce swelling (dex)
Definitive = stenting, RT, CT
How to choose between RT and CT in SVCO?
RT = NSCLC and lymphomas
Chemo = SCLC and NHL
What is the life expectancy of patients presenting with SVCO?
6 months
What causes tumour lysis syndrome?
Metabolic disturbances arising from breakdown of malignant cells following initiation of treatment for malignancy
What are the electrolyte imbalances in tumour lysis syndrome?
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
Hyperuricaemia (from metabolism of nucleic acids)
What may result from tumour lysis syndrome?
AKI
Arrythmias
Sudden death
Which tumour factors are associated with increased risk of TLS?
High proliferation rate
Chemosensitivity
Large tumour burden
Follwogin initation of cytotoxic therapy
Which clinical factors also increased likelihood of developing TLS?
Pre-existing metabolic abnormalities e.g. hyperuricaemia, hyperphosphataemia
Renal impairment
Why does hypocalcaemia occur in TLS?
Secondary to hyperphosphataemia (calcium precipitates in soft tissues)
When do features of TLS occur after initiation of chemo?
First 72 hours (up to 7 days post-treatment)
What are the symptoms and signs of TLS?
Symptoms = lethargy, N&V diarrhoea, anorexia, muscle cramps, syncope, pruritus, arthritis
Signs = fluid overload, haematuria, tetany & paraesthesia (hypocalcaemia), bronchospasm (wheezing)
Which investigations are essential to assess and diagnose severity of TLS?
Renal function
Electrolytes
Serum urate
Which other investigations may be required for TLS?
Urine dip
Urine microscopy (for uric acid crystals)
Serum lactate
Lactate dehydrogenase (LDH)
ECG
Cardiac monitoring
How is TLS diagnosed?
Cairo-Bishop definition
Lab diagnosis = 2 / more abnormal serum values in three days prior or seven days after treatment (uric acid, potassium, phosphate or calcium)
Clinical diagnosis = if lab diagnosis with presence of raised serum creatinine, cardiac arrhythmias, sudden death or seizure (can’t be attributed to therapeutic agent)
What hypouricaemic agent may be used to prevent hyperuricaemia?
Allopurinol
Rasburicase
What is the MOA for allopurinol?
Xanthine oxidase inhibitor (doesn’t act on pre-existing uric-acid)
How does rasburicase work?
Metabolises uric acid to allantoin
What are the options for prophylaxis against TLS?
Oral hydration
IV hydration
Allopurinol
Rasburicase
What is the management of TLS?
Hyperphosphataemia = hydration, dietary restriction, haemofiltration
Hyperkalaemia = IV calcium gluconate, insulin / dextrose infusion, nebulised salbutamol
Hypocalcaemia = shouldn’t be treated, causes increased calcium phosphate deposits in kidney if treated (if arrythmias then treat)
Hyperuricaemia = hypouricaemic agents
When is haemofiltration indicated in TLS?
Intractable fluid overload
Refractory hyperkalaemia
Hyperphosphataemia-induced symptomatic hypocalcaemia
High calcium-phosphate product
