What is neutropenic sepsis?
Neutropenic sepsis is a life threatening complication of anticancer treatment, the term is used to describe a significant inflammatory response to a presumed bacterial infection in a person with or without fever.
What are the diagnostic features of neutropenic spesis?
Within 6 weeks of recieving chemotherapy
- Temp >38.0oC
- Neutrophil count is <1.0 x 109/L
- Features of sepsis
What are diagnostic features of neutropenic fever/febrile neutropenia?
- Temp >38.0oC
- Neutrophil count is <1.0 x 109/L
- No haemodynamic compromise
What percentage of neutropenic sepsis cases are due to endogenous flora?
What proportion of neutropenic sepsis cases are due to gram negative bacilli?
What symptoms might a paitent with neutropenic sepsis report?
- Fever, chills rigors
- Symptoms related to a focus of infection
What might you find on examination of someone with neutropenic sepsis?
Signs of shock/Sympathetic drive
- Decreased cap refill
What investigations might you do in someone who you suspected had neutropenic sepsis?
Move to isolation room
- Bloods - FBC, U+E, LFT, Bone profile, CRP, coagulation screen
- Blood cultures
- Get a sample - MSSU, Stool culture, Throat swabs, Sputum culture, Skin swabs
How would you manage someone with suspected neutropenic sepsis?
- Oxygen therapy
STAGE 1 Broad spectrum antibiotics:
- Piperacillin/Tazobactam (tazocin) plus Gentamicin
- If mild penicillin allergy – Ceftazidime plus Gentamicin
- If severe penicillin allergy – consider Vancomycin and Gentamicin +/- Metronidazole
Consider G-CSF to boost neutrophil count
What dose of Tazocin would you give in someone with suspected neutropenic sepsis, who didn't have a penicillin allergy?
4.5g IV every 6 hours
If you were giving Gentamicin to someone with neutropenic sepsis, what dose would you use?
If you were using Ceftazidine to treat someone with neutropenic sepsis who had mild penicillin allergy, what dose would you give them?
2g IV every 8 hours
What antibiotics would you give someone who had neutropenic sepsis and was severely penicillin allergic?
Consider Vancomycin and Gentamicin +/- Metronidazole
How would you monitor someones initial response to therapy after treating them for neutropenic sepsis?
- Observations - temp, pulse, blood pressure, O2 sats, RR, urine output (catheterise if hypotensive)
- Check blood cultures - Optimise antibiotic therapy based on sensitivities
- Monitor Bloods - FBC, U+Es and CRP daily
When would you consider switching to stage 2 antibiotic therapy in someone with neutropenic sepsis?
If patient remains febrile on stage 1 antibiotics after 48 hrs, or if clinically deteriorating
What antibiotics would you give as Stage 2 treatment for neutropenic sepsis?
What dose of meropenem would you consider giving someone with neutropenic sepsis who had not improved clinically on stage 1 antibiotic treatment?
1g IV every 8 hours unless cultures suggest another more rational antibiotic regime
What cancers is malignant spinal cord compression most commonly seen in?
Cancers which typically spread to bone:
- Breast cancer
- Carcinoma of the bronchus
- Prostate cancer
- Renal cancer
5 B's go to Bone - Breast, bronchus, byroid, bidney, brostate
What are the main ways in which malignant spinal cord compression occurs?
- Compression fracture/collapse of vertebrae from metastatic disease
- Direct invasion into the verebral column by tumour
What are symptoms of spinal cord compression?
- Back pain
- Progressive Limb Weakness
- Urinary/faecal incontinence
- Sensory loss
If you suspected malignant spinal cord compression, how would you manage it??
- Investigate - urgent MRI/CT, Serum calcium
- Supportive treatment
- Surgery +/- Radiotherapy
What might you see on examination of someone with spinal cord compression?
- Spinal tenderness
- UMN findings below level of lesion - hypertonia, hyper-reflexia, clonus, upgoing plantars
- Can be LMN findings at level of lesion - radicular pain, flaccid paralysis, hyporeflexia, muscle wasting
- Sensory level - loss of sensation below the dermatomal level of compression
- Bladder - urine retention - overflow incontinence
- Increased anal tone - contipation - overflow incontinence
What supportive measures would you take for someone with malignant spinal cord compression?
- Keep patient lying flat until stability of spine determined
- Urinary catheter - if urinary retention
- Monitor bowel function - commence bowel regimen if required
- Consider prophylactic dalteparin - if bed-bound
What type and dose of steroids would you give someone with malignant spinal cord compression?
Dexamethasone - 16mg/24h - Oral preferred
When giving steroids for spinal cord compression, what else do you want to give/do?
- PPI - gastroprotection
- Blood glucose monitoring
What are steroids given for in malignant spinal cord compression?
Reduce swelling around the lesion
When is surgery indicated in malignant spinal cord compression?
- Patient is otherwise fit with low volume metastatic disease + life expectancy >3 months
Isolated posterior cord compression - decompression laminectomy may suffice
- Patient had good sensory and motor function prior to this episode
- No prior history of cancer
- Remainder of the spine is sufficiently strong to allow stabilisation
When is surgery avoided in someone with malignant spinal cord compression?
- Frailer patients with large volume metastatic disease, with prior poor mobility
- Anterior compression - due to tumour within the vertebral body compressing the spinal cord
What is the prognosis for recovery of function in those who have had motor or sensory loss from spinal cord compression for >48hrs?
Unlikely to recover function
When is radiotherapy used in malginant spinal cord compression?
Most commonly used treatment - often within 24 hours of MRI
When would chemotherapy be considered in malignant spinal cord compression?
- If tumour was chemosensitive
- If there is no rugery/radiotherapy option
What are common causes of superior vena cava obstruction?
Malignant causes (90%)
- Bronchogenic carcinoma - Typically SCLC
- Metastatic tumours - renal cancer, germ cell tumours
Benign causes (10%)
- SVC thrombosis
- Mediastinal fibrosis
What is superior vena cava syndrome?
Clinical syndrome created by reduced venous return from head, neck and upper limbs
What are the most common cancers to cause SVC syndrome?
- Lung cancer
- Metastatic - breast
- Germ cell
What are symptoms of SVC syndrome?
- Facial/arm swelling
- Dyspnoea - may coexist due to mediastinal compression
- Other features of malignancy
What signs might you see in someone with SVC syndrome?
- Distention of neck and chest wall veins
- Fixed (i.e. non-pulsatile) elevated JVP
- Facial oedema/Oedema of the arms
- Plethora of face
- Peripheral cyanosis
- Other signs of malignancy
- Pemberton's sign
What is pemberton's sign?
The development of facial flushing, neck distension, engorged neck veins, stridor and raised JVP when a patient raises and holds the arms above the head.
What is the mechanism behind pemberton's sign?
When the arms are raised, the ring of the thoracic inlet is brought upwards and gets stuck on obstructing tumour. The tumour is said to ‘cork’ the thoracic inlet and, in doing so, compress the adjacent internal jugular veins. Blood backs up, causing distension of the neck veins and facial plethora. Stridor occurs with pressure on the upper airway from any mass, be it tumour or goitre.
What investigations would you consider doing in someone with suspected SVC syndrome?
- Superior venocavogram
- Bronchoscopy - if lung primary suspected
How would you manage someone with SVC syndrome?
- Encourage patient to sit up
- Supportive measures
- Stenting of SVC
- Thrombolysis and anticoagulation - if SVCO due to thrombosis of SVC
What dose of steroids would you give someone with SVC syndrome?
If you were giving someone dexamethasone to treat SVC syndrome, what else would you want to give/do?
- PPI's - for gastroprotection
- Daily BMs
What will provide the most rapid relief in someone with SVC syndrome?
What proportion of those with myeloma develop hypercalcaemia?
What are causes of malignancy-associated hypercalcaemia?
- Bone metastases
- Para-neoplastic syndrome - production of PTH-rp (parathyroid hormone-related peptide)
What are features of hypercalcaemia?
Bones, stones, abdominal groans, thrones (osmotic features) and psychiatric undertones
- Osmotic features (thrones) - polydipsia, polyuria, deyhydration
- Neuro (psych undertones) - Cognitive impairment, fatigue, lethargy, psychosis, seizure, coma
- GI (Abdominal groans) - Constipation, nausea and vomiting
- Renal failure
- Kidney stones
- Cardiac arrhythmias
- Weight loss/anorexia
- Bone pain
What are Osmotic features of hypercalcaemia?
What are neurological features of hypercalaemia?
- Cognitive impairment
What are GI features of hypercalcaemia?
- Weight loss/anorexia
How would you investigate suspected hypercalcaemia?
Bloods - FBC, U+E's, Serum Ca2+, Corrected Ca2+, LFTs, Serum albumin, PTH
How would you manage someone with malignancy associated hypercalcaemia?
- Rehydration - 4-6 litres 0.9% saline /24hrs if no contraindications
- Bisphosphonates - zoledronate 4mg iv if renal function normal
- Calcitonin – rarely required, but more rapid effect than bisphosphonates
- Steroids - may be of benefit
What bisphosphonate is used to treat malignancy associated hypercalcaemia?