Management complications (Secondary To Treatment) Flashcards
What is Neutropenic sepsis?
- Relatively common complication of cancer therapy
- < 0.5 * 10^9 neutrophil count in a pt who is having anti-cancer treatment and one of the following:
- temp > 38 C
- Other signs of symptoms consistent with clinically significant sepsis
- MEDICAL EMERGENCY
When does neutropenic sepsis occur?
- most commonly 7-14 days after chemo
What to ask in history of a pt with neutropenic sepsis?
- Date of last chemo and which agent
- Symptoms of infection
- Ask about lines
- Drugs and allergies
What examination do you need to do in a pt with neutropenic sepsis?
- Temp, BP, HR, Oxygen sats, RR, peripheral perfusion, altered MS
- Search for source of infection e.g. chest exam, check central line devices, any wounds or skin lesions, mouth and throat
Pt presents with ?neutropenic sepsis, you have performed exam, what investigations do you do?
- START IV ABX STAT: IV tazocin OR IV meropenem if penicillin allergic - do no wait for WCC to come back
- URGENT FBC, U&Es- for any AKI, LFTs, CRP, glucose and lactate
- Cultures: peripheral and central line, MRSA screen, MSSU/CSU if symptomatic, sputum if available, stool culture if diarrhoea, wound swabs
- CXR if indicated e.g. hypoxia or chest signs
- Discuss with SpR or consultant
Pt with neutropenic sepsis is still febrile after 48 hours. Next steps?
- Consider taking futher cultures if pyrexia continues or condition detriorates.
- If fever persists > 48 hours despite IV abx discuss w microbiology. Consider presecribing alternative abx e.g. meropenem +/- vancomycin
- if patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections (e.g. HRCT), rather than just starting therapy antifungal therapy blindly
- there may be a role for G-CSF in selected patients
What is tumour lysis syndrome?
- potentially deadly condition related to treatment of high grade lymphomas and leukaemias
- Can occur in absence of chemo but usually triggered by introduction of combonation chem
- Can occur with steroid treatment alone
- Prophylatic medication can be given
How does tumour lysis syndrome occur?
- Occurs from the breakdown of the tumour cells and the subsequent release of the chemicals from the cell
Biochemical results in TLS?
tumour lysis syndrome
- High potassium
- High phosphate
- Low calcium
The hallmark features- but will also have high urate
Prophylaxis for TLS?
- IV allopurinol
- IV fluids
- Oral allopurinol- in lower risk groups
Passmed also says IV Rasburicase but in our teaching he said this is a treatement and not a prophylaxis. DO NOT GIVE allopurinol and rasburicase together
What is laboratory TLS?
Cairo-Bishop scoring system- abnormality in 2 or more of the following within 3 days before or seven days after chemo:
* uric acid > 475umol/l or 25% increase
* potassium > 6 mmol/l or 25% increase
* phosphate > 1.125mmol/l or 25% increase
* calcium < 1.75mmol/l or 25% decrease
What is clinical TLS?
Lab TLS plus one or more of the following:
* increased serum creatinine (1.5 x upper limit of normal)
* Cardiac arrythmia or sudden death
* Seizure
if progressed to clinical- more worrying
What is clinical TLS?
Lab TLS plus one or more of the following:
* increased serum creatinine (1.5 x upper limit of normal)
* Cardiac arrythmia or sudden death
* Seizure
if progressed to clinical- more worrying
Treatment of TLS?
According to lec:
* Rasburicase
* Dialysis if REALLY BAD
Clinical features of TLS?
- Biochemical changes
- Nausea
- Vomitting
- Diarrhoea
- Lethargy
- Anorexia
- Haematuria–> oliguria–> anuric
- Muscle pain/ tetany,/seizures
- Fluid overload
- Cardiac arrhythmia/arrest (peaked T waves, QTc derangeement)
What is acute N&V
Relating to chemo
- During the first 24 hour period immediately after chemo administration
What is delayed N&V?
Relating to chemo
- More than 24 hours after chemo
- And which may continue for up to 6 or 7 days
What is anticipatory N&V
Relating to chemo
- In days or hours bfore the beginning of a new cycle of chemo- either learned response or anxiety response
What is breakthrough N&V?
Relating to chemo
- Despite standard anti-emetic therapy
and which requires treatment with an additonal pharmcological agent
Patient specific RF for TLS?
- High volume/bulky disease
- Pre-treatment LDH high
- High circulating WCC
- Pre-existing renal dysfunction/ nephropathy
- Pre-treatment hyperuricaemia
- Hypovolemia
- Pretreatment diuretic use
- Urinary tract obstruction from tumour
What are the four inputs to the Vomiting Centre?
Vestibular Input
High Centres
CTZ
Vagal Afferents
Where in vomiting centre are dopamine receptors located?
CTZ
Vagal afferents
Dopamine antagonists?
- Domperidone (dopamine in gut)
- Metacloperamide
- Haloperidol (D2)
Where in vomiting centre are 5HT3 Receptors located?
CTZ
Vagal afferents
Antiemetic in chemo?
- Ondansetron
- Give pt metacloprimide to take home incase ondansetron doesn’t work
Antiemetic in bowel obstruction?
- Cyclzine- slows down gastric emptying
Ondansetron MOA?
- 5HT antagonist
What is Aprepritant?
- antiemetic
- NK1 antagonist
Role of dexamethsome in N&V ?
- useful in preventing delayed emesis
Role of Lorazepam in N&V?
- anticipatory nausea
Side effects of 5HT3 receptor antagonists
e.g. Ondansetron
- uncommon
- constipation
- Headache
- Elevated liver enzymes
- Long QT syndrome
- Extra-pyramidal effects- dystonia, parkinsonism
Side effects of D2 receptor antagonists?
- Galactorrhoea via prolactin release
- Extra-pyramidal effects- dystonia, psrkisonism
- Sudden cardiac death- long QT and VT
How to corticosteroids work to reduce N&V?
- Assumed to act on CTZ
- May also have properties of D2 receptor anatagonists
Side effects of steroids for N&V?
- Insomnia
- Increased appetite
- Increase blood sugar
Side effects of NK1 receptor antagonists?
- Headache
- Diarrhoea/constipation
- Stevens-Johnson Sydrome
RF for anticipatory N&V?
- Having nausea and vomiting, or feeling warm or hot after the last chemotherapy session.
- Being younger than 50 years.
- Being female.
- A history of motion sickness.
- Having a high level of anxiety in certain situations.
What are the RF for acute/delayed N&V?
- Had chemotherapy in the past.
- Had nausea and vomiting after previous chemotherapy sessions.
- Is dehydrated.
- Is malnourished.
- Had recent surgery.
- Received radiation therapy.
- Is female.
- Is younger than 50 years.
- Has a history of motion sickness.
- Has a history of morning sickness during pregnancy.
Non-drug treatments for N&V in chemo?
- Diet changes
- Acupuncture and acupressure (for more information, see Acupuncture).
- Relaxation methods such as guided imagery and hypnosis.
- Behavior therapy.
Signs and symptoms of Neutropenic Sepsis?
- Fever
- Tachycardia > 90
- HYPOTENSION < 90 systolic=urgent
- RR> 20
- Symptoms related to specific symptom e.g. cough, SOB, line, mucositis
- Drowsy
- Confused
What increases risk of Neutropenic Sepsis?
- Prolong neutropenia (> 7 days)
- Severity of neutropenia
- Significant comorbities (COPD, DM, renal/hepatic impairment)
- Aggressice cancer
- Central lines
- Mucosal distruption
- Hospital Inpatient
What pathogens are responsible for neutropenic sepsis?
- 80% of identified infections are from endogenous flora
- Source identified only in 20-30% of pts
- Increasing frequency of gram-positive cocci (indwelling plastic catheter
- Most frequent isolates: staph aureus, staph epidermis, enterococcus and streptococcus
- MRSA and VRE are increasingly prevalent
- Blood cultures are often negative
Causes of N&V in cancer pts?
- Infection: UTI, pneumonia, GE, thrush
- Metabolic: renal impairment, hepatic impairment, low Na, high Ca, tumour toxins, sepsis
- Drug Related: opiods, Abx, FeSO4, NSAIDS, diuretics, digoxin, SSRIs, chemo
- GI disturbance: constipation, gastriris, ulceration, obstruction
- Organ damage: distension, obstruction, RT
- Neurological: raised ICP, motion sickness (e.g. involvement of inner ear pathway), meningeal disease
- Psychological: Anxiety/ fear
Chemical cause of vomiting features?
- persistent
- Ofter severe nausea
- Unrelieved by vomiting
- Aggravated by the sight and smell of food
- Drowsiness and confusion
Treatment of chemical cause of vomiting?
- Haloperidol
- Metoclopramide
Features of gastric stasis?
- Fullness/regurgitation
- Reduced appetite
- Vomiting (often large amount) relieves nausea
- Epigastric discomfort
- Hiccups
How to treat N&V caused by gastric stasis?
- Metroclopramide
- Domperidone
N&V features of bowel obstruction?
- High: regurgitation, forceful vomiting of undigested food
- Low: colicky pain, large faeculant vomits, visible peristalsis
Which antiemetic is given in bowel obstruction?
- Cyclizine
- Dexamethasone
N&V features in raised ICP?
- Nausea worse in the morning
- Projectile vomiting
- Worse on head movement
- Headache
How to treat N&V caused by raised ICP?
- Cyclizine
- Dexamethasone- to reduce swelling
How to treat psychologically caused N&V?
- Non-drug
- Benzos
How to treat N&V caused by constipation?
- Metoclopramide
- Laxatives
What is immune mediated colitis?
- Adverse effect of Immune checkpoint inhibitors
- In patients who are being treated with CTLA-4 monotherapy (as well as others)
When does immune mediated colitis occur?
- Median onset of 6-7 weeks
- Can be rapid
Symptoms of immune mediated colitis?
- Bloody diarrhoea
- fatigue
- lethargy
*
What are the grades of immune mediated colitis?
- Grade 1:Asymptomatic
- Grade 2: abdo pain, blood or mucus in the stool
- Grade 3: presence of peritoneal signs with ileus and fever consistent with bowel perforation
- Grade 4:Life-threatening consequences such as perforation, ischemia, necrosis, bleeding, toxic megacolon
A patient has melanoma and being treated with Ipilimumab, a CTLA-4, he develops fatigue and bloody diarrhoea. What would your next steps be?
?Immune colitis due to medication he is on and his symptoms
* Need to rule out infections
* Colonscopy may be considered for persistent or severe symptoms
Appearance of Immune colitis on colonoscopy?
- Non-specific
- Non concordant with IBD
- Lack of chronic features
How to treat immune mediated colitis?
- Mild to moderate diarrhoea should be treated early with steroids over a prolonged period of time with slow taper (30-45 days)
- Severe diarrhoea should be treated immediately with high dose of IV steroids, adding infliximab if not improvement after 5-7 days.
What is mucositis?
- Acute injury to mucosal lining of GI or Resp tract induced by radiotherapy and/or chemo
- RT/Chemo affect the mucosa directly through the toxic effects on rapidly dividing epithelial stem cells and lead to interruption of the integrity of the mucosal barrier
When does radiation induced acute mucositis begin?
- 3rd or 4th week of radiotherapy
- Aggravates towards the end of treatment and gradually subsided once radiation finishes
- Severity is dose dependent
What are the symptoms of GI mucositis?
- Diarrhoea
- Ulcers around your rectum or anus
- Blood in stool
- Odynophagia
- Nausea
- Constipation
- Stomach cramps
- Bloating
Cancer pt presents w N&V, what causes do you need to rule out?
- Infection
- Renal impairement
- Raised ICP
- Gastric stasis
- New medication
What feeds into vomiting centre?
- Higher centres
- Autonomic afferents
What receptors are in CTZ?
- D2
- 5HT3
What receptors are on vomiting centre?
- Ach
- H1- histamine
Where does cyclizine work?
- Vomiting centres
- Slows down the gut
Haloperidol MOA?
- D2 receptor antagonist
When do you use Domperidone?
- In Parkinsons
- Long term- as using metoclopramide long term can lead to Parkinsonian symptoms
Route and regime for chem induced vomiting?
- Oral absorption likely to be poor
- SUbcut for at least 24 hours
- Regular anti-emetic
- COnsider alternative if not improving
- Consider more than 1 anti-emetic- with different mechanisms
- If cuase resolves- can stop
Non-pharmacological approach to vomiting for advanced disease?
- Advise and realistic
- Smell
- taste- small appropriate moods
- Hypnosis
- Acupuncture
Most common sites for mucositis?
- Labial
- Buccal
- Soft palate mucosa
GI/ oral and OP most common we need to know
Course of symptoms in mucositis?
- Symptomatic redness, erythema
- Progresses through solitary white elevated desquamative patched that are slightly painful to contact pressure
- Following this, large, painful contiguous pseudo membraneous lesions develop
- Associated dysphagia and decreased oral intake (in GI/ oral)
How can mucositis become life threatening?
complications
- severe physical obstruction of food and water intake
- Subsequent weight loss
- septic complications due to lost protective epithelial and basement membrane barriers
Risk factors for mucositis?
- concomitant chemotherapy
- bad oral hygiene
- below average nutritional status
- lack of antibiotic use at early stage mucositis
- smoking
Investigations for oropharyngeal mucositis and oesophagitis?
- Clinical and symptomatic assessment incl assessment of oral intake and nutritional status
- Body weight assessment with BMI calculation
- FBC and Biochem Profile
- CRp and viral swabs for HSV and candida for all severe persisiting mucositis
- Body weight/ fluid balance
Management of oesphogatitis/ OP mucositis?
- Good oral hygeine,
* pre-dental assessment, frequent rinsing with bland solutions such as normal saline with sodium bicarb
* use of soft toothbrush
* Rinse oral cavity after meals - Nutrition/ Fluids
* foods limited to food that do not require significant chewing; acidic, salty or dry food should be avoided
* NG/ NJ tube should be considered or TPN w severe OP mucositis/ oesophagitis - Adequate analgesia
- Treat candida, HSV oesophagitis, periodontitis, abcess formation, CMV oesophagitis accordingly
What is thrombocytopenia?
- low platelets in the blood
A cancer patient presents with thrombocytopenia- what should be considered?
- Is the underlying disease the causes of thrombocytopenia?
- Is there associated immune thrombocytopenia (assoc w Hodgkins and CLL)
- Has there been recent infection
- Has this pt received new medication e.g. Heparin- induced thrombocytopenia
- Has there been recent transfusion
- Does this pt have coagulopathy- some tumours can produce chronic DIC
- Is there chemotherapy- or transplant related thrombotic microangiopathy
- When was the last chemo or radiotherapy administered?
- What chemo was given?
What causes thrombocytopenia in cancer pts?
- Chemotherapy
- Radiotherapy
- The malignancy itself
Does chemotherapy always induce thrombocytopenia?
- No
- Most chemo regimens do not produce very high rates of thrombocytopenia and when it is occurs, it is often short-lived
How to treat chemotherapy induced thrombocytopenia?
- If possible, treat any other underlying cause of thrombocytopenia: stop antibiotics, treat infection and control coagulopathy
- Reduced chemo dose and/ or frequency or alter the chemo regimen
- Platelet transfusion support should be used if maintenance of chemo dose is vital for response or survival
- Antifibrinolytic agents e.g. tranexamic acid have been used in some thrombocytopenic cancer pts to decrease bleeding risk when platelet transfusions don’t work
*
Describe why patients have breathlessness (cancer/end of life pts)
Neurophysilogy of breathlessness:
* mismatch between patient’s percieved need to breathe (resp drive) and ability to do so (physiological capacity)
what are examples of treatable causes of breathlessness?
What are non pharmacological ways to manage intractable breathlessness?
- remain calm
- position patient - use gravity to aid and not hinder weak diaphragm/chest wall muscles
- use a fan or open window to allow air onto face (evidence this helps)
- trial oxygen (if hypoxic)
What are pharmacological ways to manage intractable breathlessness?
- oromorph 1-2mg PO PRN
- morphine 1-2mg SC PRN
- morphine 5-10mg/24hr in SCSD
- lorazepam 0.5-1mg SL PRN
- midazolam 2.5mg SC PRN
- midazolam 5-10mg/24hr SCSD
If giving opiod, give antiemetic if have N+V with these
How is malignant bowel obstruction managed?
(malig bowel ob = could be tumour inside gut wall or gut pressing on gut muscles/myenteric plexus = affect bowel movements)
- If only one obstruction = surgical intervention, but this leads to high post op morbidity and could reoccur
- endoscopic stenting
- venting gastrostomy to decompress
- In an inoperable bowel obstruction, how can you manage patient symptoms?
- When these (answers to number 1) do not work, and the bowel obstruction has not resolved, what can you do next to manage patient?
- rest bowel initially to see if it will resolve
- limit oral fluids to sips and give IVI
- NG tube for large volume of vomiting
- correct any electrolyte disturbances - e.g. low K, low Mg
- Analgesia (opiods, anti-spasmodics), antiemetics, antisecretory drugs
- trial dexamethasone
2.when these have not worked = syringe driver is key
* aim to reduce symtoms
* control pain and nausea
* minimise vomiting
* permit oral fluids to maintain hydration
* prognosis may be weeks-months
