supportive and palliative care Flashcards
what are the emesis pathways for CINV
peripheral emesis pathway: predominantly acute phase of CINV
central emesis pathway: predominantly delayed phase of CINV
what are the types of CINV
acute
- occurs 1-2hrs after administration, peak 5-6hrs, resolution in 12-24hrs
delayed
- peak at 48-72hrs after chemotherapy, diminishing in 1-3days
breakthrough
- N/V despite preventive treatment
anticipatory
- N/V prior to chemotherapy
- conditioned response
refractory
- N/V in subsequent cycles when antiemetic prophylaxis or rescue therapy has failed in previous cycle
what are the chemotherapy agents associated with high emetic risk and what is the frequency of emesis (IV)
frequency >90%
- anthracycline and cyclophosphamide
- carboplatin AUC ≥4
- cisplatin
- carmustine >250mg/m2
- cyclophosphamide >1500mg/m2
- doxorubicin ≥60mg/m2
- dacarbazine
- epirubicin ≥90mg/m2
- ifosfamide ≥2g/m2
- mechlorethamine
- streptozocin
what are the chemotherapy agents associated with moderate emetic risk and what is the frequency of emesis (IV)
frequency 30-90%
- aldesleukin ≥10-12 million IU/m2
- amifostine >300mg/m2
- arsenic trioxide
- azacitidine
- bendamustine
- busulfan
- carboplatin AUC <4
- cyclophosphamide ≤1500mg/m2
- carmustine ≤250mg/m2
- doxorubicin <60mg/m2
- daunorubicin
- dactinomycin
- dinutuximab
- epirubicin ≤90mg/m2
- ifosfamide <2g/m2
- idarubicin
- IFN alpha ≥10 million IU/m2
- irinotecan
- melphalan
- MTX ≥250mg/m2
- oxaliplatin
- temozolomide
- trabectedin
what are the chemotherapy agents associated with low emetic risk and what is the frequency of emesis (IV)
frequency 10-30%
- Ado-trastuzumab emtansine
- Aldesleukin ≤12million units
- Amifostine ≤300mg/m2
- Belinostat
- Blinatumomab
- Brentuximab
- Cabazitaxel
- Cytarabine 100-200mg
- Doxorubicin (liposomal)
- Docetaxel
- Gemcitabine
- 5FU
- Etoposide
- Paclitaxel
- Pemetrexed
- Topotecan
what are the chemotherapy agents with minimal emetic risk and what is the frequency of emesis (IV)
frequency <10%
what are the risk groups for IV chemotherapy agents
high, moderate, low, minimal
what are the risk groups for PO chemotherapy agents
moderate to high, minimal to low
what are the chemotherapy agents associated with moderate to high emetic risk and what is the frequency of emesis (PO)
frequency ≥30%
what are the chemotherapy agents associated with minimal to low emetic risk and what is the frequency of emesis (PO)
frequency is <30%
what are the patients risk factors to be assessed
- younger age (<50yo)
- female
- history of low prior chronic alcohol intake (<1 glass)
- history of motion sickness
- history of emesis during pregnancy
- history of previous chemotherapy-induced emesis
- anxiety
what are the antiemetic combinations and elaborate on each combination
for high emesis risk
acute antiemetics: NK1 + 5HT3 + DEXA +/- OLA on d1
delayed antimetics: DEXA on d2-4 +/- OLA on d2-4 (depending if given as acute)
*note NK1 has dosings for d1-3
for moderate emesis risk
acute antimetics: 5HT3 + DEXA on d1
delayed antiemetics: DEXA on d2-3
for low emesis risk
acute antimetics: 5HT3 or DEXA or DOPA
what are the agents used as antiemetics and dosings
NK1 anatagonist
- aprepitant PO 125mg OD on d1 f/b 80mg OD on d2-3
5HT3 antagonist
- ondansetron IV/PO 8-16mg OD on d1
- granisetron IV/PO 1mg OD on d1
NK1- and 5HT3- antagonist combination
- netupitant 300mg + palonosetron 0.5mg (akynzeo) 1 capsule OD on d1
dexamethasone
- IV/PO 12mg OD on d1 f/b IV/PO 8mg OD on d2 onwards
DA antagonsit
- IV/PO metoclopramide 10mg OD-TDS
what is place in therapy of NK1 antagonists
NK1 antagonists like Aprepitant and Netupitant works to prevent acute and delayed CINV by binding to neurokinin-1 receptors and prevent substance P, a nociceptive neurotransmitter, from binding, thus attenuating vagal signals and exert antiemetic effects
- vagal nerve is important in regulation of involuntary bodily functions like HR, digestion and RR
- afferent as the nerve signals are moving towards the brain
dose
- Aprepitant 125mg PO OD on d1 f/b 80mg PO OD on d2-3
- Netupitant 300mg in combination with Palonosetron 0.5mg in a Akynzeo capsule on d1
s/e
- low frequency of nausea, fatigue, weakness and hiccups
drug interactions
- steroids
- warfarin
- BZP (decrease metabolism of BZP)
- ifosfamide (decrease metabolism of ifosfamide)
what is the place in therapy for 5HT3 antagonist
5HT3 antagonists like Ondansetron, Granisetron and Palonosetron works to prevent acute CNIV by binding to and blocking 5HT3 receptors peripherally in the GI tract and centrally in the medulla
dose
- IV/PO Ondansetron 8-16mg OD on d1 f/b 8mg BD on d2 onwards
- IV/PO Granisetron 1mg OD on d1 f/b 1mg OD on d2 onwards
- PO Palonosetron 0.5mg in combination with Netupitant 300mg in an Akynzeo capsule on d1
s/e
- HA, constipation
- may cause QTc prolongation
what is the place in therapy for dexamethasone
dexamethasone prevents acute and delayed CINV by unknown MOA but may be partially due to its activity in the CNS
dose
- IV/PO 12mg Dexamethasone on d1 f/b IV/PO 8mg on d2-3 for moderate emetic risk, d2-4 for high emetic risk
s/e
- more commonly transient elevations in glucose, insomnia, gastric upset, anxiety
- less commonly psychosis and reactivation of ulcers
what is the place in therapy of olanzapine
olanzapine is an atypical antipsychotic useful for prevention of acute and delayed CINV through antagonism of multiple receptors associated with CINV - dopamine, serotonin, histamine, cholinergic
dose
- 5-10mg OD, 2.5mg OD in elderly
s/e
- fatigue, sedation, OH, anticholinergic s/e
what is the place in therapy of metoclopramide
metoclopramide is a dopamine antagonist that works to prevent acute CINV for low emetogenic regimens, and is useful for breakthrough CINV through
- blockade of dopamine receptors in the chemoreceptor trigger zone
- increase forward gut motility
- stimulation of cholinergic activity in the gut
- antagonism of peripheral serotonin receptors in the intestines
dose
- IV/PO Metoclopramide 10mg OD-TDS
s/e
- mild sedation and diarrhea, EPSE (dystonia, akathisia, parkinsonism, tardive dyskinesia)
ddi
- avoid concom olanzapine due to increased risk of EPSE and neuroleptic malignant syndrome
differentiate between the types of EPSE
dystonia
- involuntary muscle contractions that cause repetitive or twisting movements and abnormal postures
akathisia
- inner restlessness and inability to sit still
parkinsonism
- tremor, rigidity, bradykinesia (slowness of movement), postural instability
tardive dyskinesia
- repetitive involuntary movements especially involving the face, tongue and limbs
what is the place in therapy of benzodiazepines
benzodiazepines can be useful for anticipatory CINV by binding to BZP receptors in the postsynaptic GABA neuron to enhance inhibitory effects of GABA, leading to sedation, reduction in anxiety and possibly depression in vomiting centre
dose
- PO Alprazolam 0.5-1mg
- PO Lorazepam 0.5-2mg
s/e
- dizziness, drowsiness, hypotension, anterograde amnesia, paradoxical reactions (hyperactive, aggressive)
caution
- elderly (risk of falls)
what are the place in therapy of adjunctive agents and what are these adjunctive agents
adjunctive agents are not efficacious enough to be used as upfront antiemetic for acute or delayed CINV, and may be considered for refractory CINV
agents include haloperidol, prochlorperazine, chlorpromazine, promethazine
haloperidol belongs to the class of butyrophenones while prochlorperazine, chlorpromazine, promethazine belongs to the class of phenothiazines
all agents work to block dopamine receptors in the chemoreceptor trigger zones
dose of haloperidol
- IV/PO 0.5-2mg q4-6hrs
s/e of haloperidol
- sedation, EPSE
dose of prochlorperazine
- PO 10mg TDS/QDS
s/e of prochlorperazine
- drowsiness, hypotension, EPSE
what are the guiding principles for breakthrough CINV
- general principle is an additional agent of a different drug class is given
- choice should be based on assessment of current prevention strategies used
- consider the use of several agents of different mechanisms if necessary
- if ongoing vomiting and cannot use PO, use IV
- hydration and fluid repletion for losses
- reassess for next cycle’s antiemetics to ensure it is appropriate
what are the non-pharmacological management strategies for CINV
- take small frequent meals and avoid heavy meals
- avoid foods that are greasy, spicy, very sweet or salty, and foods with strong flavors or smells
- sip small amounts of fluid frequently instead of trying to drink a full glass at one time
- avoid caffeinated beveragges
- avoid lying flat for at least 2 hrs after eating
what does a multiday regimen refer to, consider the treatment regimen of 3-day Carboplatin AUC 3 + Etoposide
- guideline suggests giving appropriate prophylactic therapy for the expected emetogenecity on the day of the chemotherapy administration
- continue delayed prophylaxis alone for 2-3d after completion of chemotherapy if indicated
for 3-day Carboplatin AUC3 + Etoposide
- on d1, Carboplatin AUC3 + Etoposide given –> emetogenicity risk is low to moderate –> cover for acute CINV
- on d2 and d3, only Etoposide given –> emetogenicity risk is low –> cover for delayed CINV only as will cover for acute CINV for low risk of emetogenicity
what is the management strategy for anticipatory CINV
- prevention is key, use optimal antiemetic therapy during every cycle
- behavioral therapy (relaxation/ systematic desensitization, hypnosis/ guided therapy, music therapy)
- acupuncture, acupressure
- consider use of BZP before treatment
what are the consequences resulting from CID
- abnormal electrolytes, inappropriate fluid imbalance, malnutrition, renal failure, weight loss, fatigue and dehydration
- often contributes to delays in therapy, dosage reduction and cessation of therapy
what are the potential causative agents of CID
- cisplatin/ oxaliplatin
- cyclophosphamide
- cytarabine
- 5-FU/ capecitabine
- gemcitabine
- MTX
- doxorubicin/ daunorubicin
- irinotecan/ topotecan
- taxanes
- oral targeted therapy
what is targeted therapy and examples of targeted therapy in cancer treatment
targeted therapies are those that specifically target molecules or pathways involved in the growth and survival of cancer cells while sparing normal cells thus potentially leading to fewer s/e compared to traditional chemotherapy
examples of targeted therapy are tyrosine kinase inhibitors and EGFR inhibitors
how do tyrosine kinase inhibitors work
- inhibit the activity of tyrosine kinase, enzymes involved in the regulation of cell growth, proliferation and survival
- TKI interfere with the signalling pathways that are often dysregulated in cancer cells
how do EGFR inhibitors work
- EGFR inhibitors specifically target the epidermal growth factor receptor, a cell surface receptor that plays a roll in cell growth and division
- EGFR is often overexpressed or mutated in certain types of cancer
- EGFR inhibitors block activation of EGFR thereby inhibiting downstream signalling pathways involved in cancer cell proliferation and survival
what are the risk factors of CID
- age >65yo
- female
- eastern cooperative oncology group (ECOG) performance status ≥2
- bowel inflammation and malabsorption
- bowel malignancy
- biliary obstruction
what is ECOG
eastern cooperative oncology group (ECOG) measures functional status and overall wellbeing with higher scores indicating worse functional status
patients with ECOG ≥2 may have reduced physical functioning and may be less able to tolerate s/e of chemotherapy and may also have underlying health issues that predispose them to GI complications
what are the predictive factors of CID
- first cycle (body has yet to adapt to the effects)
- cycle duration >3w (cumulative effect of the drugs in the GIT)
- concomitant neutropenia (low neutrophil count, a WBC, thus increasing susceptibility to infections like GI infections which can contribute to diarrhea)
- other symptoms like mucositis, anorexia, vomiting, anemia
what is CID caused by
CID is caused by inflamm of the intestinal mucosa, leading to an imbalance between absorption and secretion
how is CID severity graded
CTCAE v5.0 grading
grade 1
- increase of <4 stools per day above baseline
grade 2
- increase of 4-6 stools per day above baseline
- limiting ADL
grade 3
- increase of ≥7 stool per day above baseline
- requires hospitalization
- limiting self-care
grade 4
- life threatening
- urgent intervention needed
grade 5
- death
differentiate between the types of CID
complicated vs uncomplicated
uncomplicated
- CTCAE grade 1 or 2
- no complicating s/sx
complicated
- CTCAE grade 3 or 4
- CTCAE grade 1 or 2 with at least one of the following (fever, cramping, sepsis, frank bleeding, dehydration, neutropenia, decreased performance status, CTCAE >grade 2 for nausea and vomiting)
CTCAE grade 2 for N/V
- moderate nausea
- interfere with usual activites
- decreased PO intake w/o weight loss
- 2-5 episodes of nausea within 24hrs period
what are the goals of therapy for CID
- reduce morbidity and mortality from CID
- improve QoL and ADL
- decrease hospitalization
- improve recovery and intestinal mucosa
what is the general management strateiges for CID
uncomplicated
- diet modification
- oral hydration
- loperamide
complicated
- admit to hospital
- octreotide
what is the treatment algorithm for CID
for uncomplicated CID,
1. withdraw chemotherapy –> resume when symptom resolve and consider resuming at lower dose
2. diet modification and oral hydration
- 8-10 large glasses of clear fluid (electrolyte containing fluids are ideal)
- BRAT diet comprising of easily digestible foods that can help firm up stool
- low-fiber foods like white bread, white rice, pasta, well-cooked vegetables, peeled and cooked fruits, lean protein sources
- avoid trigger foods like greasy, spicy and fried foods, dairy products, caffeine, alcohol, high-sugar foods and drinks, and dietary supplements of high osmolality
- small frequent meals
- probiotic rich foods like yogurt and fermented vegetables to restore balance of beneficial bacteria in the gut and improve digestion
3. loperamide
- PO Loperamide 4mg f/b PO 2mg q4hrs or after every loose stool, continue until 12hrs free of diarrhea then stop (max 16mg/day)
4. monitor for improvement or progression
- if diarrhea persists 12-24hrs, schedule for more intensive PO Loperamide 2mg q2hrs
- if diarrhea progresses to severe/ complicated, treat as per
- if diarrhea persists as uncomplicated 12-24hrs after scheduled Loperamide, add Octreotide or any second agent
for complicated diarrhea,
1. withdraw chemotherapy –> resume when all symptoms resolve, restart at decreased dose
2. Octreotide
- SQ Octreotide 150mcg TDS or IV, dose escalation of 50mcg increments up to 500mcg TDS
3. IV fluid hydration
4. IV abx (eg. Ciprofloxacin x7d)
what is the place in therapy of loperamide
loperamide
- works as an opioid to inhibit smooth muscle contraction of the intestines, decreasing motility
- s/e include constipation, dry mouth, abdominal cramp, drowsiness, dizziness, bloating, rash, N/V
- also paralytic ileus associated at higher doses (refer to temporary paralysis of the muscles in the intestine which disrupts the normal movement of food, fluid and air through the digestive tract)
- shown effectiveness in reduction of fecal incontinence, frequency of bowel movement and stool weight (greater efficacy than Diphenoxylate but limited efficacy for grade 3-4 severity)
what is the place in therapy for octreotide
octreotide
- works to decrease hormone secretion which increases transit time within the intestines, decreases fluid secretion and increases absorption of fluid and electrolytes
- s/e include bradycardia, arrhythmia, constipation, abdominal cramp, N/V, dizziness, HA, enlarged thyroid
- found to be beneficial for 5-FU and irinotecan-induced CID
what are the non pharmacological management strategies for CID
- probiotics containing lactobacillus suggested to prevent chemotherapy or radiation induced diarrhea
- avoid trigger foods like spicy, greasy and fried foods, dairy products, high-sugar food and drinks, caffeine, alcohol, dietary supplements with high osmolality
- avoid high fiber foods
- drink 3L of clear fluids (electrolyte containing fluids are ideal)
- small frequent meals
- BRAT diet containing easily digestible foods to firm up stool
why is irinotecan associated with causing diarrhea
irinotecan is a selective reversible inhibitor of acetylcholinesterase leading to cholinergic response whereby there is increased intestinal motility and secretion
what are the types of irinotecan-induced diarrhea and management strategies
early onset (within 24hrs from administration)
- dose dependent
- most become symptomatic during infusion, with mean symptom duration being 30mins
- treat with atropine SQ/IV 0.25-1mg (max 1.2mg) which works to inhibit ACh at muscarinic receptor by acting as a competitive antagonist, causing s/e like blurred vision, constipation, dry mouth, dizziness, insomnia, tachycardia (note c/i in glaucoma)
late onset (after 24hrs from irinotecan)
- can occur at any dose and frequency
- median onset with q3w dosing is 6d vs median onset with q1w dosing is 11d
- treat with loperamide 4mg on first loose stool f/b 2mg q2hrs or 4mg q4hrs at night, until 12hrs free from loose stools
what are the factors that increase risk of developing constipation
- lowered fluid intake or dehydration
- lack of fiber or bulk-forming food in the diet
- low physical activity/ alot of bed rest
- vitamins or mineral supplements like iron and calcium pills
- high serum levels of calcium and phosphate
- thyroid disorder
- depression
- overuse of laxatives
- cancer growing in large intestine or pressing on spinal cord
- medications (pain medications esp opioids like codeine and morphine, chemotherapy agents like vinca alkaloids eg. vincristine/ vinblastine/ vinorelbine, anti-nausea medications like ondansetron/ granisetron/ ASM)
what are the symptoms of constipation
- cramping or pain
- belching
- gas or flatulence
- bloating or feeling of fullness
- loss of appetite
- swollen or distended abdomen
- small hard stools that are hard to pass
- leakage of small amounts of stools that resemble diarrhea
- straining for a bowel movement
- no regular bowel movement for ≥2d
- N/V
- rectal pressure
how can constipation be prevented
- increase fibre intake to add more bulk to stool (but note colorectal cancer pts who underwent surgery and are experiencing constipation may have restrictions on fibre intake)
- increase intake of natural laxatives (vegetables, caffeine, prunes; but prunes are very sweet)
- increase physical activity
- ensure sufficient caloric intake
what are the management strategies for constipation
- stool softeners (dosucate sodium/ calcium)
- help the stool to hold water and keep it soft
- sometimes used together with a laxative - laxatives
- produce or stimulate bowel activity (lactulose, senna, mineral oil, bisacodyl)
- increase fibre or product bulk (psyllium)
- suppository form that promotes bowel activity (glycerine, bisacodyl) - enemas (phosphate enema aka fleet, tap water)
- to clean out the bowel or deliver laxatives by introducing liquid to soften stool, lubricate and stimulate muscles for expulsion of stool
- can also help to relieve severe constipation or fecal impaction
what are the typical dosing of various laxatives
duphalac 10mL TDS
senna 15mg ON
bisacodyl 5mg ON
fybogel 1 sachet BD
what is mucositis
damage to the mucosa of the oral cavity, pharynx, larynx, esophagus and GI tract due to cancer therapy
what is the pathophysiology of mucositis
- chemotherapy and radiation causes direct damage to epithelial stem cells, tissue response varies by seasonal and circadian changes, targeted therapies and small molecule inhibitors have demonstrated the ability to cause a variety of GI toxicities, incl mucositis
- epidermal growth factor plays a role in maintaining mucosal integrity by regulating growth and repair of epithelial tissues, EGFR can be found in the esophagus and levels are increased in an inflamed mucosa (in an attempt to repair damaged tissue by upregulating cell proliferation, survival and differentiation, but this upregulation of EGFR can cause increased sensitivity, enhance inflamm response, delay healing, and altered cell differentiation)
what are the stages of mucositis
- initiation
- chemotherapy and radiation causes direct toxicity
- via generation of oxidative stress and ROS
- increased vascular permeability leads to local accumulation of toxic drugs - upregulation
- ROS damages DNA, leading to epithelial cell death (extent of tissue damage dependent on rate of oral epithelial proliferation)
- nuclear factor KB activation leads to gene upregulation leading to production of pro-inflammatory cytokines and expression of adhesion molecules –> tissue damage, activation of COX2, angiogenesis and apoptosis - signaling and amplification
- pro-inflammatory cytokines (TNFalpha, IL1beta, IL6) are released
- positive feedback, indirectly increasing and extending toxicity to mucosa - ulceration
- prior injury to basal epithelial cells causes atrophy and mucosa breakdown
- oxidative stress increases inflammatory infiltrates
- macrophages are further activated by colonizing bacteria which increases release of pro-inflammatory cytokines - healing
- WBC recovery at d12-16
- proliferation of epithelial cells as chemotherapy gets cleared by liver and kidney
- return of flora
- continuous angiogenesis (formation of new blood vessels from current vasculature) increases risk of future mucositis
what is the typical presentation of mucositis
days 0-5
- often asymptomatic
- redness
- swelling
- burning
- increased sensitivity
days 0-7
- desquamation
- white patches
- often mistaken for candidiasis
days 6-12
- continuous pseudomembranes (layer of fibrin, inflammatory cells and debris covering the mucosal surface)
days 7-16
- painful erosions
- ulcerations
how is the severity of mucositis being graded
grade 0
- WHO: no evidence of mucositis
- NCI-CTCAE: N/A
grade 1
- WHO: erythema and soreness
- NCI-CTCAE: asymptomatic or mild
grade 2
- WHO: ulcers, eating solids
- NCI-CTCAE: moderate pain, modified diet
grade 3
- WHO: ulcers, requires liquid diet
- NCI-CTCAE: severe pain, interferes with PO intake
grade 4
- WHO: ulcers, not able to take PO
- NCI-CTCAE: life threatening
grade 5
- WHO: N/A
- NCI-CTCAE: death
what are the risk factors of mucositis
patient-related factors
- autoimmune disease
- DM
- females (for 5-FU induced)
- Caucasian > African American
- genetic predisposition to tissue damage
- folic acid or vit B12 deficiency
treatment-related factors
[chemotherapy]
- varies by agent and regimen, S-phase specific agents have highest risk
- duration, dose intensity and schedule – repetitive or prolonged lower doses have higher risk than bolus doses, risk increases with number of cycles
- risk increases with reduced CL of chemotherapy due to R/H impairment
- previous therapies that were toxic to mucosa
- risk increases with previous episodes of mucositis
[radiation]
- risk increases when radiation added to chemotherapy
- dependent on radiation source, dosage, dose intensity, volume of mucosa irradiated
- smoking and alcohol consumption increases risk
- risk increases in presence of xerostomia and infection
what are the goals of therapy for mucositis
- prevent or decrease severity of mucositis
- prevent chemotherapy delays or dosage reductions
- manage pain and other symptoms
how to prevent mucositis
- keratinocyte growth factor (KGF): palifermin
- benzydamine HCl mouthwash
- oral hygiene
- low level laser therapy (LLLT)
how to make recombinant KGF
recombinant KGF is produced in e coli
what is the place in therapy of palifermin
palifermin is a keratinocyte growth factor (KGF) that reduces the duration and severity of oral mucositis after intensive chemotherapy or radiotherapy
- dosed at 60mcg/kg/day for three consecutive days before and after myelotoxic therapy
- first three doses are prior to myelotoxic therapy, with third dose given 24-48hrs before therapy begins
- last three doses are after myelotoxic therapy, with first of the three given on the same day of hematopoietic stem cell infusion, ≥4d after most recent dose of palifermin
what is the place in therapy of benzydamine HCl mouthwash
for use after chemotherapy radiation for head and neck cancer
- an NSAID with analgesic, anti-inflammatory and local anesthetic properties thus when used as a mouth wash can help reduce inflammation, relieve pain and promote healing of oral mucositis lesions, and have additional antimicrobial properties which can reduce risk of secondary infections in the oral cavity
what is the place in therapy for LLLT
for use after radiation for HNC
- involves the use of low power lasers or light emitting diodes to stimulate tissue repair, reduce inflammation and relieve pain
what are the pharmacological management for mucositis
- oracare suspension (nystatin 125,000U, tetracycline 62.5mg, hydrocortisone 5mg, diphenhydramine 11.5mg/10mL)
- contains antifungal, antibiotic, steroid, antihistamine
- take after food, must swallow to coat and fully protect gut - mylocaine suspension (diphenhydramine 11.5mg, lidocaine 16.7mg/10mL)
- contains antihistamine and analgesic
- take before food, must swallow - morphine sulfate solution (1mg/mL)
- take before food, wait ~5mins before eating, must swallow
- meant for targeted pain relief - oracort-E (lidocaine, triamcinolone acetate)
- contains analgesic and steroid - soragel (choline salicylate)
- contains an NSAID - medijel (aminacrine, lidocaine)
- contains antiseptic and analgesic - difflam gargle/ spray (benzydamine)
- alcohol as preservative
- difflam-C contains chlorhexidine
what is the non-pharmacological management for mucositis
- oral7
- alcohol free
- natural enzymes
- neutral pH - bioxtra
- alcohol free
- enzymes
- neutral pH
what are the considerations when selecting mouthwashes for non-pharmacological management of mucositis
avoid alcohol-based ones as they can cause further drying effect, causing more xerostomia and leading to mucositis
what is the WHO pain ladder
- non-opioid +/- adjuvant
- if persisting or increasing pain, opioid for mild to moderate pain +/- non-opioid +/- adjuvant
- if persisting or increasing pain, opioid for moderate to severe pain +/- non-opioid +/- adjuvant
what is the key characteristic of morphine
morphine has an active metabolite morphine-6-glucoronide that is renally cleared thus patients with end organ damage of the kidneys are at risk of respiratory depression and extreme somnolenece due to accumulation
what are the considerations when transitioning from short acting opioids to long acting opioids
- for chronic pain, scheduled doses are superior to PRN doses
- add 50-100% of the total amount of SA opioid used as PRN to the scheduled doses of LA opioids to ensure adequate pain control during transition
- rescue PRN doses at 10-20% daily of opioid requirements (calculated based on the new converted scheduled dose)
what is the general opioid conversion guide
[equivalence to 30mg PO Morphine]
PO Codeine : PO Morphine = 10:1
PO Tramadol : PO Morphine = 5:1
PO Hydromorphone : PO Morphine = 1:5
IV/SC Oxycodone : PO Morphine = 1:4
PO Oxycodone : PO Morphine = 1:2
IV/SC Fentanyl : PO Morphine = 1:100
IV/SC Morphine : PO Morphine = 1:3
PO Methadone : PO Morphine
- if PO Morphine daily dose <60mg = 2-7.5mg/day Methadone
- if PO Morphine daily dose 60-199mg and pt <65yo = 10:1 PO Methadone
- if PO Morphine daily dose ≥200mg and/or pt ≥65yo = 20:1 PO Methadone (but max initial dose is 45mg/day)
[conversion equations]
2mg/ 3.6mg PO Morphine = 1mcg/hr Fentanyl patch
what are the considerations for use of fentanyl patches
- patient is opioid tolerant (defined by FDA as ≥60mg Morphine or equivalent)
- absorption can be erratic, increased with heat
- slow onset ~8-12hrs, steady state ~2-3d for full effect
- typically q72hrs but some patients have wearing off effect and will need PRN doses for breakthrough pain
- proper patient administration required eg. do not apply on broken skin
what are the considerations for choice of methadone
- can reverse potential tolerance to other opioids
- even if high baseline opioid use, will be comparatively lesser methadone dose
- does not produce euphoric effect, but benefit is that it saves cost
- very long half life, variations in day-to-day in terms of how pts feel
what are the considerations for use of ketamine
- anesthetic with some interesting properties in patients with opioid hyperalgesia (pts on chronic opioids experiencing increased sensitivity to pain = worsening pain despite continuous opioid use)
- NMDA receptor inhibitor
- some analgesic properties, but more to add to opioids to make them “supercharged” –> thus must decrease baseline opioid dose drastically
- difficult to use, many ADR, questionable efficacy in literature
differentiate between opioid tolerance, opioid dependence and opioid addiction (opioid use disorder)
opioid tolerance
- occurs when a patient using opioids begins to experience a reduced response to the medication, and requires more opioids to experience the same effect
opioid dependence
- occurs when a patient’s body has adjusted its normal functioning around chronic opioid use and will produce unpleasant physical symptoms when medication is stopped
opioid addiction (opioid use disorder)
- occurs when attempts to cut down or control use is unsuccessful or when use results in social problems and a failure to fulfil obligations at work, school or home
- often after patient has developed opioid tolerance and dependence thus making it physically challenging to stop opioid use and increasing risk of withdrawal
what is the relevance of CDC clinical practice guideline for prescribing opioids for pain
- not applicable to (i) management of pain for sickle cell disease (ii) management of cancer-related pain (iii) palliative care or end of life care
- emphasis that opioids should be used only if benefit for pain and functioning outweighs risks
what are the key concepts in the CDC clinical guideline for prescribing opioids for pain
- when initiating, prescribe immediate-release opioids
- prescribe at lowest effective dose
- exercise care when changing opioid dosage (optimize non-opioid therapy while continuing opioid therapy, if benefit does not outweigh risk, gradually taper)
- prescribe at no greater than quantity needed
- evaluate benefits and risks early and regularly
- drug monitoring programme
- evaluate and discuss opioid-related harms and mitigation steps
- consider the benefits and risks of toxicology testing
- use with caution when combining with BZPs or other CNS depressants
- use evidence based medicine to treat opioid use disorder
- if a medical practitioner who attends to a person whom he considers or has reasonable grounds to suspect is a drug addict, shall within 7 days from the date of attendance, furnish to both the director of medical services and director of central narcotic bureau the following information relating to that person (name, identity card number, sex, age, address, drug, grounds to suspect – frequency and dates the medical practitioner or any medical practitioner working in the same hospital has attended to the person, physical symptoms, amounts and types of prescriptions requested by or provided to that person in that hospital)
how does MOH define cancer pain and pain in life-limiting diseases
cancer pain
- defined as pain relating to cancer itself, cancer related treatments or tests
- can be due to the primary tumor or cancer therapies and/or diagnostic procedures
pain in life-limiting diseases
- defined as pain relating to underlying advanced diseases or due to other comorbidities
which opioids do MOH consider to be strong opioids
- buprenorphine
- fentanyl
- hydromorphone
- methadone
- morphine
- oxycodone
- pethidine
- tapantadol
- codeine >60mg TDS
- tramadol >400mg/day
outline how would opioid therapy be initiated in patients with cancer pain, pain in life-limiting diseases as per MOH guidelines
- comprehensive clinical assessment of pain
- onset, frequency, duration, intensity, characteristic, aggravating and relieving factors
- how it impairs one’s ADL
- psychological concerns
- psychiatric history
- history of analgesic and substance use - management of pain
- non-pharmacologicals have increasing evidence of efficacy – reassurance, comfort and support, physical therapy and other complementary therapy
- pharmacological management should be guided by WHO’s sequential three-step pain ladder - recommended opioid dosing and route of administration
- for mild to moderate pain, or pain not relieved by step 1 (non-opioid +/- adjuvant) = weak opioids (codeine, tramadol) w/wo non-opioid analgesics
- for moderate to severe pain, or pain not relieved by step 2 = strong opioids (morphine, fentanyl, pethidine, oxycodone, methadone, hydromorphone, tapentadol, buprenorphine)
- selection of opioids should consider pt’s ability for oral intake and their R/H function – morphine is recommended as it is readily available and is widely used; fentanyl is a safer option for pts with moderate to severe R/H impairment
- if severe pain that requires urgent relief, titrate accordingly to determine parenteral dose for SC/IV route
- dose should be individualised, start low and titrate up as needed to achieve a good balance between adequate pain control and minimal s/e - opioid regimens
- for persistent pain, around the clock regimen required to prevent onset of pain
- rescue doses of immediate release opioids for breakthrough pain - communciations
- indications, effectiveness, s/e, treatment regimen, importance of proper storage
- address concerns from pt/ fam/ caregiver
- explain plain for pain control and s/e review - maintenance of opioids
- assess effectiveness of regimen for pain and s/e (if inadequate, titrate up, taking into account total daily dose and rescue doses)
- consider referral to palliative specialist if pain is not controlled and/or pt is still in severe pain after multiple rounds of medication adjustment
- regularly review pts and indication for opioid use (if no indication, taper and discontinue)
- if indication present, use at lowest effective dose - chronic pain in cancer survivors
- requires multiple modalities management, including non-pharm and pharm
what are the options for oral opioids and relevant dosings and considerations
codeine phosphate 30mg tablet
- 15-30mg q4-6hrs (max 360mg/day)
- low dose for elderly, R/H impairment
- pro drug of morphine
tramadol tablet
- 25-50mg q4-6hrs (max 400mg/day, 300mg/day for elderly, 200mg/day for R impairment, 100mg/day for H impairment)
- avoid in severe H impairment
- low dose for elderly, R/H impairment
morphine IR solution
- 2.5-5mg up to q4hrs (can be used up to q1hrs PRN for breakthrough pain)
- no optimal dose, max dose limited by s/e
- low dose required for elderly, R/H impairment
- start with IR first, consider switching to SR if needed ≥7d, keep IR for breakthrough
morphine SR solution
- dosing based on IR dose, up to q8hrs
fentanyl sublingual tablets
- for breakthrough pain
- max 2 doses for each breakthrough episode, max 4 episodes/24hrs
oxycodone IR capsule/ solution
- 2.5-5mcg q4-6hrs (may be up to q1hr PRN for breakthrough pain)
- no optimal or max dose
- initiate IR first, consider switching to SR if need IR ≥7d, keeping IR for breakthrough
- low dose for elderly, R/H impairment
oxycodone SR tablet
- dosing based on IR, up to q8hrs
methadone
- 2.5mg q8hrs (max 100mg/day)
hydromorphone
- 8mg q24hrs (max 64mg/day)
what are the options for transdermal opioids, and relevant doings and considerations
fentanyl transdermal patch
- dosing based on opioid conversion table (2mg/3.6mg of PO morphine = 1mg/hr of fentanyl patch)
- q72hrs
- not for opioid naive pts (for opioid tolerant pts)
- choice for pts with R/H impairment
- lag time of 8-12hrs after initiation/ removal of patch
what are the options for parenteral opioids, and relevant dosings and considerations
IV/SC morphine
- bolus 1mg q1-2hrs PRN
- infusion 0.2-0.5mg/hr
IV/SC oxycodone
- bolus 0.5mg q1-2hrs PRN
- infusion 0.2mg/hr
- higher risk of respiratory depression
IV/SC fentanyl
- bolus 10mcg q1-2hrs PRN
- infusion 5-10mcg/hr
- opioid of choice in moderate and severe R/H impairment
IV/SC tramadol
- 25-50mg q4-6hrs PRN (max 100mg/dose, max 400mg/day)
- caution is pts w hx of seizures for tramadol
outline the key concepts in referral to palliative services or other services
assessment and review of patients
- started on opioid therapy only after an in-person consult with a trained medical practitioner
- review at appropriate intervals to balance between adequate monitoring and burden of frequent reviews
- home-based palliative service considered for patients with significant disability and have difficulty attending consults in person
referral
- medical practitioner lacks adequate training and/or is unfamiliar with opioid use
- patient has complex needs and require a multidisciplinary team
- patient needs high dose of opioids
- patient’s symptoms are poorly controlled
- patient has aberrant drug behavior
- patient has prolonged use of opioids that does not commensurate with disease condition
what are the adjuvants to opioid therapy
- GABA acting anticonvulsants (pregabalin, gabapentin)
- SNRIs
- tramadol
- lidocaine patches
what are the beneficial outcomes of early palliative care
- improved QoL
- improved mood and depression scores
- lower proportion had aggressive end-of-life care
what are the components of palliative care
- multidisciplinary
- holistic approach
- aka hospice care
- pain and symptom control
- QoL improvement
what are types of palliative care services
- physical, emotional, psychosocial and spiritual care
- grief and bereavement support
- practical helps (financial, counselling, caregiver training, advanced care planning)
- home care, day care, inpatient care and consultative services
who benefits from palliative care
patients with life threatening diseases
- advanced cancer
- end stage kidney, lung, liver, heart, neurological diseases
where can a patient receive palliative care
- at home
- nursing homes
- hospices
- general and community hospitals
- specialists clinics
how is palliative care kept affordable
- government subsidies through means testing
- use of medisave
what are the symptoms to be managed in palliative care
- pain
- dyspnea
- anorexia (loss of appetite or reduced desire to eat)/ cachexia (complex metabolic syndrome characterised by severe weight loss, muscle wasting, weakness, fatigue, loss of appetite; metabolic changes leading to loss of both muscle and fats even with adequate nutritional intake)
- N/V
- constipation
- diarrhea
- malignant bowel obstruction
- fatigue, weakness, asthenia (generalized weakness)
- delirium
- insomnia/ sedation
- lymphedema (edema caused by accumulation of lymphatic fluid in tissues due to dysfunction of the lymphatic system responsible for maintaining fluid balance and filtering of waste products from tissues)
- hormone related symptoms
what are the steps to unclog a feeding tube
- 1/2 tsp (2mL) of baking soda (sodium bicarb)
- level and ensure not to overfill
- dissolve in 15mL of warm tap water
- open one pancrelipase capsule (COTAZYM 8 (10,800 lipase units)) and empty contents into 15mL of warm tap water
- use a small syringe to draw up both the dissolved baking soda and the pancrelipase solution
- use an empty syringe attach to the feeding tube, draw back on plunger of syringe to decompress all air and fluid from feeding tube
- pinch off the tube using your fingers and discard syringe
- attach the syringe containing the baking soda and pancrelipase solution to the feeding tube, push plunger to add the mixture into the feeding tube
- clamp tube (or leave syringe at the end of the feeding tube) and wait 30mins
- after 30mins, flush tube with 30mL of tap water
what are the key features of the GIT
- digestion, absorption, excretion
- secretion of enzymes of fluids
- gut hormone: cholecystokinin (CCK)
- immune function
what are the key functions of the stomach
- acts as a reservoir since it functions as an elastic balloon
- releases intrinsic factor for vitB12 absorption
- produces 1-2L of fluid a day, containing enzymes, gastric acid and electrolytes
what is CCK and what is the role of CCK
cholecystokinin (CCK) is produced in duodenum of small intestine
- to stimulate pancreatic contractions to release pancreatic digestive enzymes (lipases, proteases, amylases)
- and to stimulate liver to produce bile and stimulate gallbladder to release bile, bile digests fats
- CCK also regulates gastric emptying, can inhibit it to slow rate at which food moves from stomach to small intestine which can allow for more time for digestion and absorption of nutrients in the small intestines
- CCK also plays a role in appetite regulation and satiety
what are the likely causes of malnutrition
decreased intake or absorption, increased expenditure losses leads to malnutrition
- advanced abdominal cancer –> ascites –> presses on GIT –> stomach unable to expand as much –> early satiety and feelings of fullness –> decreased intake
- malabsorption after surgery
- chemotherapy induced N/V and taste disturbances –> reduced intake
- bodily stress from burns, trauma, sepsis –> increased bodily expenditure
- protein losses from dialysis
what are the consequences of malnutrition
- increased complications
- poor wound healing
- impaired organ function
- increased mortality
- increased use of healthcare resources
how is nutritional screening and assessment done
- nutritional screening
- refer to dietician/ nutritional specialist
- nutrition assessment (ABCD) – Anthropometric data (height and weight), Biochemical data (electrolytes, serum albumin), Clinical (PMHx, physical examination), Diet history
- formulation of nutritional regimen
what are the possible factors that can affect serum albumin
- inflammation and infection – increased capilary permeability and loss of albumin into interstitial space
- malnutrition – protein deficiency can decrease albumin production by liver
- liver diseases – cirrhosis, hepatitis, liver failure; albumin produced in liver
- fluid status – dehydration can cause relative increase in albumin
- renal diseases – kidney filters albumin; increased urinary loss of albumin
6, trauma and burns – increased capilary permeability, leading to loss of albumin into interstitial space - pregnancy
- chronic diseases
- genetic factors
what are examples of screening tools
3-minute nutrition screening
- validated in outpatient setting
what are examples of tools used for nutritional assessment
seven-point subjecting global assessment
what are the components for 3min-nutritional screening
- weight loss in past 6m
- 3 points if >7kg
- 2 points if 3-7kg
- 1 point if 1-3kg
- 0 point if unchanged or <1kg - nutritional status
- 3 points if starvation or <1/4 of normal portion; tube feeding <1L/day; <1000kcal/day
- 2 points if 1/4 to 1/2 of normal portion; tube feeding 1-1.25L/day; 1000-1250kcal/day
- 1 point if 1/2 to <2/3 of normal portion; tube feeding 1.25-1.5L/day; 1250-1500kcal/day
- 0 points if 3/4 to 1 portion; tube feeding >1.5L/day; >1500kcal/day - muscle wastage
- temporal (3/2 points)
- clavicle (3/2 points)
what are the components of the seven-point subjective global assessment
- weight loss and weight trend
- nutritional status
- GI symptoms that persisted > 2w (N/V/D)
- disease states affecting nutritional requirements (depending on stress levels that affect metabolic demand)
- muscle wastage in at least 3 areas
- fat loss
- edema that is nutritional related
what is the total energy expenditure dependent on
- stress level
- resting/ basal metabolic rate
- physical activity
what are the modes of measuring total energy expenditure
- indirect calorimetry (gold standard)
- measurement of gas exchange durign consumption of substrates required for energy
- C6H12O6 + 6O2 –> ATP + 6CO2 + 6H2O - weight based
- 25-35kcal/kg for general hospitalized patients - predictive equations
- most commonly used
- estimates basal metabolic rate, should be adjusted for physical activity and stress factor
- schofield equation, harris-benedict equation
what are the guide for determining protein requirements
healthy adults
- 0.8g/kg/day
trauma, burns, surgery
- 1.5-2g/kg/day
sepsis, critical illness
- 1.5-2g/kg/day (up to 2.5)
CKD not on dialysis
- 0.6-0.8g/kg/day
CKD on HD/PD
- 1.2g/kg/day
CKD on CRRT
- up to 2g/kg/day
what is the definition of enteral nutrition (ASPEN)
nutrition provided through the GI tract via a tube, catheter or stoma that delivers nutrients distant to the oral cavity
what are the indications for enteral nutrition
for patients who are unable to receive or tolerate adequate nutrition from PO route
- motility disorders
- mechanical ventilation
- altered mental status
- swallowing impairment
what are the various enteral access devices and their pros and cons
- pre-pyloric (NG, PEG)
[nasogastric tube]
- inserted from nose to stomach
- for patients who have functioning stomach and able to tolerate enteral feeding into stomach
- high risk of aspiration in patients with risk of vomiting or reflux
- irritation to nose and throat
- for short term feeding or medication administration
[percutaneous endoscopic gastrostomy]
- directly into the stomach through a small incision in abdomen
- for long term feeding in patients with a functioning GI tract
- lower risk of aspiration
- more comfortable
- requires surgery or endoscopic procedure for placement
- post-pyloric (NJ, PEJ)
[nasojejunal tube]
- from nose down to the jejunum of small intestine
- for short or long term feeding
- lesser risk of aspiration since it bypasses stomach
- used when gastric feeding is c/i due to gastro stasis, gastroparesis, high risk aspiration
[percutaneous endoscopic jejunostomy]
- directly into jejunum through a small incision in the abdomen
- requires surgery or endoscopic procedures for placement
- long term feeding when placement of NJ tube not suitable
PROS
pre-pyloric
- able to tolerate a wider range of enteral products (those of higher osmolality)
- more physiologic since it bypasses less GIT
- higher tolerance to bolus feeding since stomach acts as a reservoir
- may be used for venting (to alleviate pressure or remove excess air or gastric contents from the stomach)
- not to be used in delayed gastric emptying
post-pyloric
- narrower (smaller bore), less discomfort
- may be used in conditions that result in dysfunctionality in proximal GIT
- minimise aspiration risk
what are the modes of administration of enteral nutrition
- bolus
- usually by gravity, mimics oral intake
- more physiologic
- no pump required
- greater freedom for ambulation - continuous
- pump assisted at a constant rate
- better tolerated
- lower risk for aspiration
what are the types of enteral nutrition
- modular
- single nutrient
- used as a fortifier to enhance a specific nutritional component or augment oral diet
- not meant as a meal replacement - semi-elemental
- contains partially or completely hydrolysed nutrients that are easier to digest and absorb
- for patients with impaired GI function or impaired tolerance to standard feed
- but often high in osmolality and thus can lead to diarrhea - polymeric
- contains intact macronutrients
- requires sufficiently functional GIT - immune-modulating or disease-specific
- contains additional or restrictions on specific nutritions to meet needs for disease management
- may or may not meet individual’s full nutritional needs
list commonly seen immune-modulating or disease-specific feeds
- glucerna
- 1kcal/mL
- low glycemic index –> suitable for diabetes - fresubin
- 1.5kcal/mL
- high protein content of 20g/serving –> suitable for conditions requiring increased energy and protein needs - Nepro HP
- 1.8kcal/mL
- high protein content of 18g/serving –> suitable for patients on dialysis - Nepro LP
- 1.8kcal/mL
- low protein, low K, low P –> suitable for patients not on dialysis - Nutrifriend
- 1kcal/mL
- contains omega3 fatty acids (EPA, DHA) which can help to reduce inflammation and modulate immune function –> suitable for inflamm diseases or cancer
what are potential drug-nutrient interactions for consideration and how can this be mitigated
usually not an issue with bolus/ intermittent feeding
administering an incompatible drug may lead to
- precipitation
- curdling, clumping
- alteration of dosage form
mitigate by
- stop feeding, flush access device before and after drug administration
- use therapeutic alternatives available in appropriate dosage forms
what are the possible complications of enteral feeds
- occlusion
- jejunum > gastric (due to diameter)
- incompatible drugs
- formula type (highly concentrated can increase thickness and viscosity; high protein content = contains AA and peptides that can increase viscosity and may denature to form precipitates under certain conditions which adhere to the inner walls of the tube to cause obstruction to flow; high fiber = contain soluble or insoluble fiber sources, soluble can absorb water and form gel while insoluble can aggregate and form clumps, both of which can obstruct, and may also contain particulate matter that accumulate and block) - N/V
- D/C
- tube migration
- infections secondary to microbial contamination
- refeeding syndrome
what are the strategies to maximise tolerance to enteral nutrition
- continuous instead of bolus
- prokinetic agents (metoclopramide, domperidone, IV erythromycin)
- postpyloric feeding if unable to tolerate gastric
- isotonic formulas
- semi-elemental/ elemental for patients with malabsorption issues
why is there an importance on maximising the use of gut function
- maintain functional integrity
- undergo first pass metabolism, promote efficient nutrition utilisation
- maintain normal gallbladder function
- maintain gut associated and mucosal associated lymphoid tissue (important in supporting immune function of GIT)
- less complicated than PN
- less expensive
what is the definition of parenteral nutrition (ASPEN)
refers to intravenous administration of nutrients
what are the indications for parenteral nutrition
patients who are unable to receive or tolerate enteral feeds
- paralytic ileus
- impairment or cessation of normal bowel activity
- resulting from surgery, trauma or certain medications
- intestines unable to effectively contract and propel ingested food or enteral feeds trough the digestive tract, leading to functional obstruction - small bowel obstruction
- mechanical blockage or narrowing in the small intestine, preventing passage of food, fluid and enteral feeds - high output/ proximal fistulas
- can lead to significant losses of fluid, electrolytes and nutrients
- enteral feed can exacerbate fluid and electrolyte imbalances - mesenteric ischemia
- inadequate blood flow to the intestines
- resulting from vascular occlusion or insufficiency
- reduced blood flow compromises delivery fo oxygen and nutrients to the intestine –> ischemic injury and impaired absorption of nutrients
what are high output and proximal fistulas
a fistula is an abnormal connection between an organ, vessel, or intestine and another organ, vessel or intestine, or the skin
high output fistulas refers to fistulas occurring anywhere in the GIT leading to drainage of >500mL of fluid a day
proximal fistulas refers to fistulas in the esophagus, stomach, duodenum, jejunum
what are the general classification of parenteral access devices
peripheral
- position of catheter tip is located outside of central vessels
- requires frequent re-site, approx every 72hrs
- nutrient delivery limited by osmolality (~900mOsmol limit) and concentration, else painful and swelling
central
- position of catheter tip is in large bore blood vessel (distal superior vena cava, inferior vena cava, right atrium)
- can be used for longer term care
what are the types of central peripheral access devices
- non-tunneled central venous catheter
- short tube directly into large vein like internal jugular vein or subclavein vein or femoral vein
- single lumen or multiple lumen for fluid, blood products, hemodynamic montioring, medication adminsitration
- short term access (short lived ≤2w)
- highest risk of infection
- exits skin at insertion site - tunneled central venous catheter
- catheter tip is inserted into a large vessel and tunneled under the skin to a separate exit site usually on chest or upper chest
- long term access
- lower risk of infection and provide better stability than non-tunneled
- single or multiple lumens, often equipped with cuffs to promote tissue ingrowth and secure catheter in palce - peripherally inserted central catheter
- inserted into a peripheral vein usually in upper arm and advanced until the tip rests in a central vein like superior vena cava or cavoatrial junction
- for medium to long term access, weeks to months
- do not need surgical placement and can be done by a trained professional at bedside or in clinic setting - port-a-cath
- implantable venous device useful for chemotherapy patients, used q2w
- implanted beneath the skin, usually in upper chest with catheter inserted into large vein like superior vena cava or jugular vein
- for long term use
- discreet and convenient access
what is the composition of parenteral nutrition
- nutrients in its simplest and most elemental form (dextrose instead of complex sugars, AA instead of protein, TG instead of fats)
- admixture of multiple components (compatibility and stability concerns)
- commercial vs customised formulas (macronutrients in standard formulas in commercial products cannot be adjusted but can adjust electrolytes by adding more)
what are the drug-nutrient concerns for parenteral nutrition and how to mitigate this
less concerned if administering via separate lumens of the same access device
- admixture vs y-site compatibility
- admixture refers to mixing two or more medications or solutions in the same container or infusion bag for simultaneous administration through a single IV line
- Y-site refers to administration intravenously through a Y-shaped injection port whereby medications or solutions flow together briefly before entering IV line then into patient blood stream, ensure do not interact or precipitate when mixed together - TPN vs TNA
- total parenteral nutrition (TPN) refers to separate bags or containers that form a nutritionally complete IV solution to provide all essential macronutrients (carbs, fats, protein) and micronutrients (vitamins, minerals, electrolytes), usually for patients of long term or indefinite IV nutritional support
- TPN is isotonic and sterile
- total nutrition admixture (TNA) refers to a single container admixture combining all essential macronutrients and micronutrients into one solution, often for short term or immediate IV nutritional support, for patients with stable metabolic status
- TNA has a simplified administration process and reduces risk of contamination or errors associated with multiple bag preparations - administration of incompatible drugs
- precipitation
- loss of drug activity
- phase separation of lipid emulsions
- toxicity
mitigation by
- administering via separate peripheral IV cannula
- if needed, pause PN, flush access device before and after medication administration, then resume PN infusion
what are some device related complications relating to parenteral nutrition
- occlusion
- thrombosis/ clotting
- inappropriate flushing technique
- precipitation or crystallisation due to drug incompatibilities
- lipid residues - mal positioning
- catheter related bloodstream infection
what are some metabolic complications relating to parenteral nutrition
- refeeding syndrome
- hyper/hypoglycemia
- fluid overload
- intestinal failure associated liver disease
- metabolic bone disease
why might parenteral nutrition lead to intestinal failure associated liver disease
- due to prolonged NIL BY MOUTH, lack of CCK leads to impaired bile flow, thus causing cholestasis
- may also be due to overfeeding
- may also be due to type of TG fed (MCT and LCT are two essential fatty acids required but LCT is pro-inflamm and is the precursor for inflamm markers thus may cause liver damage if prolonged feeding, newer lipid formulations have SMOF which are soybean (LCT), MCT, olive oil and fish oil with fish oil balancing out LCT since it is anti-inflamm)
why might parenteral nutrition lead to metabolic bone disease
- inadequate amounts of Ca and P in PN which are essential minerals for bone health thus leading to demineralisation of bone and weakening of bone structure
- inadequate amounts of vitamin D
- altered hormone regulation (eg. PTH)
- acid base imbalance
what is the pathophysiology of refeeding syndrome and how to manage it
starvation or malnutrition –> glycogenesis (excess glucose converted to glycogen for storage in liver and muscles), gluconeogenesis (synthesis of glucose from non-carb precursors in the liver) and protein catabolism (breakdown of protein into AA for energy or synthesis of other molecules) –> protein, fat, mineral, electrolyte, vitamin depletion, and salt and water intolerance (body becomes more sensitive to salt and water intake and can cause fluid retention or electrolyte imbalances) –> refeeding = switch to anabolism –> nutrients, fluid and salt –> insulin secretion –> increase protein and glycogen synthesis –> increased glucose uptake, increased thiamine utilisation, increased uptake of K, Mg, P –> hypoK, hypoMg, thiamine deficiency, salt and water retention –> disruption of electrochemical membrane potential and potentially fatal (arrhythmia, cardiac failure, neuromuscular complications)
management
- identify high risk patients
- check baseline serum electrolytes
- replete and correct deficiencies prior to feeding, may supra-correct
- administer vitB1 ie. thiamine (pre-emptive, not routinely checked)
- initiate feeding slowly at~40-50% of nutritional requirements then gradually increase over next few days
- continue monitoring electrolytes as feeding progresses and adjust amounts of replacement as needed
what are the key guiding principles in oral nutritional supplementation, EN, PN
oral nutritional supplements, EN, PN are viewed as artificial nutrition
guiding principles: autonomy, beneficence, non-maleficence, justice
are opioids first line for acute and chronic pain
no, first line pharmacologicals are paracetamol, NSAIDs, COXIBs
- amitriptyline, nortriptyline, duloxetine, ASM may be more effective for neuropathic pain
non-pharmacologicals include cold or heat therapy, physical therapy, exercise, accupunture, relaxation, CBT
what is the significant s/e of opioids
- sedation –> increased fall risk
- respiratory depression
- immunosuppression
- N/V and constipation
- confusion, impaired concentration
- hormonal imbalance
- tolerance, dependence and risk of addiction
what are the signs of opioid overdose
- sedation (sedation score)
- respiratory depression (RR <8bpm)
what are the patient education components with regards to opioid therapy
- treatment plan
- realistic goals for pain and functioning
- avoid consumption of alcohol and other medications that are not part of treatment as may worsen opioid s/e or increase risk of overdose - opioid administration
- educate on how to administer
- patient information leaflet
- explain role of regular interval vs breakthrough analgesic if applicable - opioid s/e
- constipation (occur in almost all patients on strong opioid, to take regular laxative for all patients on strong opioid therapy)
- nausea (may occur during initiation, often transient, if persist, prescribe and optimise antiemetics)
- drowsiness and mental clouding (may occur during initiation and dose increases but often transient, may affect ability to drive and undertake tasks that require concentration. non-compliance can lead to respiratory depression or death, consider dose reduction if moderate to severe or persistent if pain is well controlled else switch opioid if pain not well controlled) - inappropriate medical combinations
- BZP, hypnotics, z-drugs
- anxiolytics
- CNS depressants (incl alcohol) - risks and management of overdose, dependence and addiction
- pre-hospital care for overdose (stage 1: drowsy = monitor and if no improvement in RR or mental status worsens proceed to stage 2 or 3; stage 2: nodding off = call 995 and initiate SAVE protocol; stage 3: unresponsive = call 995 and initiate SAVE protocol)
- SAVE = stimulate patient with physical or verbal stimuli and check for responsiveness; airway control is priority, check for pulse, if none start CPR and AED pads; ventilate patient using bag-valve mask (1 breath every 5 seconds until patient breathing on their own); evaluate patient, if no response after rescue breathing for 2 mins, call 995 while continuing) - opioid storage and disposal
- proper disposal when pain has resolved to prevent non-medical use of medications
- encourage to return any unused opioids to a licensed pharmacy or to the clinic where it was prescribed
