Download Chemotherapy-Induced Peripheral Neuropathy: Why the

Chemotherapy-Induced
Peripheral Neuropathy (CIPN):
Why the complication?
By:
Tiffany Marbach, RN, BSN
Alverno College MSN Student
Spring 2008
[email protected]
Navigating through this tutorial
• To advance to the next slide, click on
the
• To review the previous slide, click on
the
• At any time during the tutorial you wish
to review a different section of the
tutorial, click on the cell at the top of
the screen
Objectives
At the conclusion of this tutorial, the learner should be able to:
• Understand how the peripheral nervous system works, & what
nerves are affected by neurotoxic agents
• Describe the signs and symptoms of Chemotherapy-Induced
Peripheral Neuropathy (CIPN)
• Identify which types of chemotherapeutic agents contribute/cause
CIPN
• Understand who is more at risk for developing this complication
• Describe how patients can have improved health status and
outcomes when educated about how to live with CIPN, as well as
how to prevent it
• Understand ways to treat CIPN once it has developed
Content of Tutorial
Incidence of CIPN
Stress and CIPN
Pathophysiology
Inflammation
Chemotherapy Agents Signs/Symptoms of CIPN
Assessment of CIPN
Patients at risk
Genetics
Pharmacologic Treatment
Nonpharmacologic Treatment
For More Information…
Patient
Teaching
Case Study
References
Incidence of CIPN
• Chemotherapy is prolonging
life
• Cancer is becoming a chronic,
manageable disease
• Many nurses will encounter
those affected by this
common side effect
Microsoft Image Clip Art, 2007
• Estimated to occur in 20% to
nearly 100% of cancer
patients undergoing
chemotherapy (Smith, Beck, & Cohen,
2008).
What is CIPN?
• Characterized as injury,
inflammation, or degeneration
of peripheral nerve fibers
• Can result in loss of motor
and sensory nerve function
• CIPN can result when certain
chemotherapeutic agents are
used to treat cancer (Marrs &
Newton, 2003)
Microsoft Image Clip Art, 2007
• These agents can be referred
to as “neurotoxic”
Why is this important for my practice?
• Encountering more and
more survivors with this
debilitating condition
• Limited research done in
this area
Microsoft Image Clip Art, 2007
Why is this important for my practice?
Incidence increases with:
• Duration of infusion (longer infusion: increased
chance)
• Drugs given
• Previous exposure to neurotoxic drugs
• Combination chemotherapies (in which more
than one neurotoxic drug is given)
• Co-morbidities
Rest and Review!
• Why is CIPN important for all nurses to
learn about?
• A. It isn’t; only oncology nurses need to
care about it
• B. Cancer survival rates are increasing,
so more nurses will have exposure to
patients with this side effect
• C. It is the most common chemotherapy
side effect
Sorry, but that is NOT why it is important
for all nurses to be educated about
CIPN.
Please click on the question mark below
to go back and try the question again!
CONGRATULATIONS!
That is exactly why all nurses should be
educated on CIPN and its effects!
Click on the arrow below to continue with
the tutorial.
Pathophysiology of CIPN
• The Peripheral Nervous
System (PNS) communicates
signals between the central
nervous system (CNS,
composed of the brain and
spinal cord) and the
periphery of the body (Marrs
& Newton, 2003)
Sheffield,
Getbodysmart.com, 2008
Used with permission
• The peripheral nerves
originate from the spinal
cord
• The peripheral nervous
system is made of three
divisions: the sensory
nerves, the motor nerves,
and the autonomic nerves
Sensory nerves
• Sensory nerves are
responsible for
detecting:
• Pain
• Touch
• Temperature
Microsoft Image Clip Art, 2007
• Position
• Vibration
Motor Nerves
• Motor nerves are
responsible for:
• Voluntary
movement
• Muscle tone
• Coordination
Microsoft Image Clip Art, 2007
Autonomic nerves
• Autonomic nerves
are responsible for:
• Intestinal motility
• Blood pressure
Microsoft Image Clip Art, 2007
• Involuntary muscle
movements
Rest and Review!
• Sensory nerves are responsible for
detecting:
• A. Blood pressure
• B. Balance and coordination
• C. Intestinal Motility
• D. Temperature and pain
Sorry,
but that is NOT the function of the
sensory nerves.
Please click on the question mark below
to go back and try the question again!
CONGRATULATIONS!
You are correct.
Sensory nerves are responsible for the
feelings of temperature, pain, touch,
position, and vibration.
Click the arrow below to advance to the
next slide.
Pathophysiology (continued)
• Peripheral nerves are made up
of individual neurons, axons,
cell bodies, and dendrites,
wrapped in a myelin
sheath
Click below for
structure of neuron
diagram!
• Each nerve fiber (neuron), is
made up of single axon
•
• This axon is surrounded by
Schwann cells
• Schwann cells form myelin
sheath
• Dendrites synapse with other
nerves to send a signal across
from one nerve to the next
(Wickham, 2007)
Multiple Sclerosis Resource
Centre , 2008
Used with permission
Pathophysiology (continued)
• Cell body: provides
nourishment and
maintain the nerve
fibers
• Dendrites: extend
from the cell body and
receive/carry stimuli to
the cell body
Microsoft Image Clip Art, 2007
• Axon: then carries the
impulse away from the
cell body
Pathophysiology (continued)
• Peripheral nerve fibers are classified as:
myelinated or unmyelinated
• They are grouped to their size in
diameter (called A, B, and C fibers)
• A Fibers: (motor and sensory fibers),
are largest in diameter, and are
myelinated (allowing for fast impulse
conduction)
Pathophysiology (continued)
• B Fibers: (least common fiber), are smaller in
diameter, and are less myelinated than A fibers
• C Fibers: (some sensory and motor, but
autonomic fibers are most common), smallest
and slowest conducting of the PNS
• Damage to the large fibers (A & B) or small
fibers (C), correspond with the signs/symptoms
of CIPN (Armstrong, Almadrones & Gilbert, 2005)
Sensory nerves are broken down into:
Large fiber nerves:
• Are myelinated
• Sense position, motor control, and
vibration
• Composed of neurofilaments, which act
as framework of axon
Sensory nerves are broken down into:
Small fiber nerves:
• Are unmyelinated
• Include nerves that sense pain and temperature
• Speed of impulse transmission depends on if
neuron is highly myelinated (fast transmission),
lightly myelinated (slower transmission), or
unmyelinated (slowest transmission) (Wickham, 2007)
Rest and Review!
• Highly myelinated nerve cells conduct
impulses:
• A. Fast
• B. Slow
• C. Very slow
Sorry! Wrong answer. Please try again.
Please click on the question mark below
to go back and try the question again!
Nice job!! The highly myelinated nerve
cells are very fast conductors!
Click the arrow below to advance to the
next slide.
Rest and Review!
• The function of the dendrite portion of
the nerve cell is to:
• A. Provide the cell with food and
nourishment
• B. Receive and carry stimuli to the cell
body
• C. Carry the impulse away from the cell
body
OOPS! This is NOT the function of the
dendrites…
Please click on the question mark below
to go back and try the question again!
Excellent answer! The dendrites are
responsible for receiving and carrying
stimuli to the cell body!
Click the arrow below to advance to the
next slide.
Pathophysiology (continued)
• Peripheral neuropathy results
from damage to the axon,
myelin sheath, or cell
body
• Pathogenesis of CIPN is not
completely understood
• It is known that different
sensations arise depending
on chemotherapeutic agent
administered (Wickham, 2007)
Multiple Sclerosis Resource Centre , 2008
Used with permission
Pathophysiology (continued)
• Chemotherapy drugs
are believed to first:
• Damage sensory axons
• Then move on to cause
degeneration and dying
back of axons and
myelin sheaths (Wickham, 2007)
National Resource
Council Canada, 2005
Used with Permission
Pathophysiology (continued)
• CIPN is usually
symmetrical
• Begins in distal end of
longest axons
• Sometimes known as
polyneuropathy:
affects many nerves
Microsoft Image Clip Art, 2007
• Toxins (including
chemotherapy) are
transported along the
axon towards the cell
body (Wickham, 2007)
The stocking/glove phenomena:
Moves distal to proximal
• CIPN usually progresses
from toes to feet to ankles
to lower legs (stocking
distribution)
• Upper extremity damage
usually comes later
Microsoft Image Clip Art, 2007
• Moves from fingertips to
fingers to hands (glove
distribution) (Wickham, 2007)
Rest and Review!
• Nerve cells are damaged by
chemotherapy because:
• A. They aren’t strong enough to handle
the toxicity
• B. The chemotherapy causes
degeneration and dying back of axons
and myelin sheaths
• C. The chemotherapy doesn’t affect the
nerve cells
No…That’s not how nerve cells are
damaged…
Please click on the question mark below
to go back and try the question again!
You’re RIGHT! That is exactly how nerve
cells are damaged!
Click the arrow below to advance to the
next slide.
Rest and Review!
• In a typical pattern of CIPN, the person
experiences neuropathy first in the:
• A. Upper leg
• B. Toes
• C. Hands
• D. Upper arm
Think again. Where does neuropathy
usually show up first in a stocking-glove
pattern?
Please click on the question mark below
to go back and try the question again!
GREAT job! The neuropathies usually
show up first in the lower extremities,
and progress later towards the upper
extremities.
Click the arrow below to advance to the
next slide.
Nerve Growth Factor
• Axons regenerate if toxic
agent removed
• Damage to cell bodies is not
completely reversible
• Nerve Growth Factor
(NGF) plays role in neuron
repair
• NGF is usually reduced after
neurotoxic chemotherapy
• Animal studies show if given
NGF, some neuropathy and
neural structural changes
were prevented or reversed
• Exact mechanism not well
understood (Wickham, 2007)
Microsoft Image Clip Art,
2007
Inflammation and CIPN: What’s the
connection?
• Tissue repair is part of the
inflammatory process
• It is an attempt to maintain
normal body structure and
function
• Cell regeneration can vary
depending on tissue/cell type
• Three types of cells that are
divided according to ability to
undergo regeneration:
labile, stable, or
permanent cells (Porth, 2005)
Microsoft Image Clip Art, 2007
Nerve cells: Permanent/Fixed Cells
• Labile cells: regenerate and
divide throughout life (ex:
Epithelial cells found on skin
or in the mouth)
• Stable Cells: stop dividing
when growth ends, but can
regenerate when confronted
with certain stimuli (ex: liver
cells)
• Permanent/Fixed cells:
cannot undergo mitotic
division, and can’t regenerate
(ex: nerve and cardiac muscle
cells) (Porth, 2005)
Microsoft Image Clip Art,
2007
Nerve cells: Permanent/Fixed Cells
(continued)
• When nerve cell is
damaged (for example,
from a chemotherapy
drug), it can not be
replaced
• It is replaced with scar
tissue
Microsoft Image Clip Art, 2007
• This scar tissue can
not function like the
destroyed cell can (for
example, can’t conduct
impulses) (Porth, 2005)
Rest and Review!
•
•
•
•
Peripheral nerve cells are considered:
A. Labile cells
B. Stable cells
C. Permanent or fixed cells
This is not what nerve cells are classified
as…
Please click on the question mark below
to go back and try the question again!
Right on! Nerve cells are fixed or
permanent cells, that can not
regenerate!
Click the arrow below to advance to the
next slide.
Stress and CIPN: What’s the connection?
• CIPN can often lead to
pain symptoms
• This pain is classified
as acute or chronic
pain
• Acute pain: lasts less
than 6 months
• Chronic pain: lasts 6
months or longer (Porth, 2005)
Microsoft Image Clip Art,
2007
Stress and CIPN: What’s the connection?
(continued)
• CIPN can be considered acute or
chronic
• This depends on length of
treatment, co-morbidities
(pre-existing conditions beside
the CIPN), and disease state
• This can cause physiologic,
psychological, familial, and
economic stress
• Chronic pain can lead to loss of
appetite, sleep disturbance,
and depression (Porth, 2005)
Microsoft Image Clip Art, 2007
Stress and CIPN: What’s the connection?
(continued)
Two factors determine
nature of stress:
• 1. Properties of the
stressor
• 2. The condition of the
person under stress
Microsoft Image Clip Art, 2007
• Severe, prolonged
physical and psychological
distress disrupts health
with chronic stress (Porth, 2005)
Stress and CIPN: What’s the connection?
(continued)
General Adaptation
System (GAS):
• Systemic reaction to
stressor that causes
physical and
psychological
manifestations
• Three stages: Alarm,
Resistance, and
Exhaustion (Porth, 2005)
Microsoft Image Clip Art, 2007
Stress and CIPN: What’s the connection?
(continued)
• 1. Alarm: Stimulation of Sympathetic Nervous
System (SNS)
• Results in release of catecholamines (such as
epinephrine and norepinephrine) and cortisol,
which:
• Increase heart rate, relaxation of bronchial
smooth muscle, decrease insulin release, etc.
• 2. Resistance: Body selects most effective
channel of defense
Stress and CIPN: What’s the connection?
(continued)
• 3. Exhaustion: occurs if stressor is prolonged
• Most common with CIPN
• Resources of the body’s coping mechanisms are
depleted
• Wear and tear on systems is appearing
• Many ailments, including CIPN, begin to show wear
and tear on the person physiologically and
psychologically (Porth, 2005)
Rest and Review!
• The stage in of the General Adaptation
System (GAS) most active in chronic
CIPN is:
• A. Alarm stage
• B. Exhaustion stage
• C. Resistance stage
Wrong stage of GAS…Try again!
Please click on the question mark below
to go back and try the question again!
Correct! The Exhaustion Stage is most
active with chronic CIPN.
Click the arrow below to advance to the
next slide.
Chemotherapeutic agents that induce peripheral
neuropathy
Microsoft Image Clip Art, 2007
• CIPN is a doselimiting toxicity
• This means that
patients could have
chemotherapy dose
reduced, or even
held
• This interrupts normal
chemotherapy cycle
which could affect
outcome
Chemotherapeutic agents that induce peripheral
neuropathy: Platinum Compounds
Cisplatin & Carboplatin:
• Affects 57-92% of patients undergoing
chemotherapy
• Causes axonal swelling and loss
• Progress from sensory, to motor, to (rare)
autonomic symptoms
• Can occur later in treatment course
• 66% of patients have full recovery (if developed)
• Causes loss of sense of position and vibration
• Numbness/tingling (paresthesias)
• Some patients can take two years for recovery to
occur (Armstrong, Almadrones, & Gilbert, 2005)
Microsoft Image Clip Art, 2007
Chemotherapeutic agents that induce
peripheral neuropathy (Platinum
compounds)
Oxaliplatin:
• Alters neuron excitability & interferes
with axon conduction
• Causes sensory neuropathy of large
fibers
• 80% of patients develop
• 40% of those who develop have
resolution of symptoms in 6-8 months
• Can cause acute neuropathy (30-60
minutes after infusion)
• Cramps/spasms in hands and feet
• Aggravated by cold weather
• Causes sensation of loss of breath, jaw
tightness (Armstrong, Almadrones, & Gilbert, 2005)
Microsoft Image Clip Art, 2007
Chemotherapeutic agents that induce
peripheral neuropathy (Taxanes)
Paclitaxel (Taxol) and Docetaxel
(Taxotere):
• Risk depends on dosing & use with other
neurotoxic agents
• Taxol causes CIPN in 60% of patients
• Taxotere causes CIPN in about 49% of
patients
• Affect small fibers, causes axonal injury,
and demyelinization
Microsoft Image Clip Art, 2007
• Altered vibratory sense, loss of deep
tendon reflexes, paresthesias
• Causes progressive neurological
dysfunction (Armstrong, Almadrones, & Gilbert, 2005)
Chemotherapeutic agents that induce
peripheral neuropathy (Vinca Alkaloids)
Vincristine, Etoposide,
Vinorelbine & Vinblastine:
• Greatest potential for CIPN is Vincristine:
Occurs in about 57% of patients
• Degenerates the peripheral nerve fibers
• Affects small and large fibers
• Causes most commonly: motor and
sensory disruption; can cause autonomic
effects
• Paresthesisas, then progresses to muscle
cramping/weakness, constipation,
bladder dysfunction, altered heart rate
(Marrs & Newton, 2003)
Microsoft Image Clip Art, 2007
Chemotherapeutic agents that induce
peripheral neuropathy
Microsoft Image Clip Art, 2007
• Miscellaneous agents
used in oncology
patients that cause
CIPN include:
• Bortezomib (used for
multiple myeloma)
• Methotrexate
• Cytarabine
• Procarbazine
• Interferon
• Thalidomide
• Corticosteriods
• 5-FU
Rest and Review!
• Which chemotherapy agent can cause
prolonged recovery time with peripheral
neuropathies even two years after
discontinuation of the drug?
• A. Cisplatin
• B. 5-FU
• C. Etoposide
• D. Methotrexate
This is not correct. Time to try again!!
Please click on the question mark below
to go back and try the question again!
Good job! Cisplatin can unfortunately be
long-lasting, and take even years to
resolve.
Click the arrow below to advance to the
next slide.
Rest and Review!
• Which chemotherapy agent can be
exacerbated by cold weather and cold
objects, causing the patient to have
sensation of loss of breath?
• A. Carboplatin
• B. Taxol
• C. Taxotere
• D. Oxaliplatin
Wrong drug! Go back and look at the
question a little closer…
Please click on the question mark below
to go back and try the question again!
Excellent! Oxaliplatin can cause coldinduced neuropathies!
Click the arrow below to advance to the
next slide.
Signs and Symptoms of CIPN
Microsoft Image Clip Art, 2007
• Symptoms that patients
may experience depend
on length of infusion,
dose, co-morbidities,
and the drug being
administered
• Symptoms are divided
into sensory, motor,
and autonomic
symptoms, correlating
with which peripheral
nerve is affected
Signs and Symptoms of CIPN
• Sensory Symptoms include:
Microsoft Image Clip Art, 2007
• Paresthesia: feeling of warmth, burning, tingling, cold,
pinprick sensation, numbness
• Hyperesthesia: increased sensitivity to sensory stimulus,
not painful, but can cause cramping, usually worse at
night
• Hypoesthesia: Decreased feeling sensations
• Dysesthesia: Abnormal sensation in skin that feels like
electric sensation, tingling, prickling of the skin
• Hyporeflexia: decreased deep tendon reflexes (Visovsky, Collins,
Abbott, Aschenbrenner, & Hart, 2007)
Signs and Symptoms of CIPN
• Diminished/absent vibration
sensation
• Diminished/absent cutaneous
sensation
• Diminished/absent sense of feeling
object as sharp or dull
• Overall loss of sensation
• Pain: can be burning, shooting,
sharp
• Numbness/tingling
Microsoft Image Clip Art, 2007
(American Cancer Society, 2008)
Signs and Symptoms of CIPN
Motor symptoms include:
• Weakness
• Gait disturbance
• Balance disturbance
Microsoft Image Clip Art, 2007
• Difficulty with fine motor
skills (for example, writing,
buttoning clothing, sewing) (Visovsky
et. al., 2007)
Signs and Symptoms of CIPN
Autonomic symptoms
include:
• Constipation
• Urinary retention
• Sexual dysfunction (erectile
dysfunction in men)
• Blood pressure changes
(Visovsky et. al., 2007)
Microsoft Image Clip Art, 2007
Rest and Review!
• Which of the following describes the
decreased feeling sensation sometimes
experienced with CIPN?
• A. Paresthesia
• B. Hyporeflexia
• C. Hypoesthesia
• D. Hyperesthesia
Try again! There’s a better answer…
Please click on the question mark below
to go back and try the question again!
Awesome! Hypoesthesia is decreased
sensation!
Click the arrow below to advance to the
next slide.
Rest and Review!
• Which symptom is a result of autonomic
nerve damage?
• A. Constipation
• B. Weakness
• C. Numbness and tingling
• D. Balance disturbance
Sorry, but this is not a symptom of
autonomic nerve damage.
Please click on the question mark below
to go back and try the question again!
Nice! Constipation is a common symptom
of autonomic nerve damage!
Click the arrow below to advance to the
next slide.
Assessment of CIPN
Microsoft Image Clip Art, 2007
• Baseline neurological
assessment is key
• Allows nurse/staff to
recognize changes in
peripheral neuropathy
once treatment begins
• Must assess all motor,
sensory, and autonomic
function not only before
start of treatment, but
during and after as well
(Armstrong, Almadrones, & Gilbert, 2005)
Assessment of CIPN
Problems with current assessment
tools:
• Limited because toxicity is
determined subjectively by healthcare
provider
• Broad categories used for scoring
symptoms
• Patients have trouble describing
symptoms
Microsoft Image Clip Art, 2007
• Not much assessment beyond
presence or absence of CIPN is
uniformly performed in most clinic
settings (Wampler, Hamolsky, Hame, Melisko, & Topp,
2005)
Assessment of CIPN
Three problems with measuring
neuropathy:
• 1. Patient difficulty with
describing the uncomfortable
sensations, unless they are painful
• 2. CIPN not always been
considered a pertinent side
effect—usually considered a minor
problem that would eventually
resolve
• 3. Easy, simple, and usefully
comprehensive tool has yet to be
developed (Smith, Beck, & Cohen, 2008)
• These problems lead to unanswered
questions about how to improve CIPN
symptoms
Microsoft Image Clip Art, 2007
Assessment of CIPN
Some assessment tools include:
• Gait: watch patient ambulate,
watch for signs of pain with
ambulation or unbalance
• Motor: watch for signs of
weakness and symmetry
• Reflexes in lower extremity:
achilles and patellar reflexes
Microsoft Image Clip Art, 2007
• Reflexes in upper extremity:
brachioradialis and biceps reflex
(Armstrong, Almadrones, & Gilbert, 2005)
Assessment of CIPN
• Sensory: vibration sense and
position in great toe to ankle
and knee, and finger to wrist
and elbow
• Pinprick sensation from great
toe up each leg to point of
normal sensation; pinprick from
finger up arm to point of
normal sensation
Microsoft Image Clip Art, 2007
• Autonomic: assess bowel
sounds, orthostatic blood
pressures, pulse regularity
(Armstrong, Almadrones, & Gilbert, 2005)
Rest and Review!
• What is a good way to test for motor
disturbance in a person affected with
CIPN?
• A. Vibration sensation testing
• B. Pinprick sensation testing
• C. Assess bowel sounds
• D. Checking reflexes
This is not the best way to test for motor
disturbance…
Please click on the question mark below
to go back and try the question again!
Good job! Testing reflexes is a great way
to assess for motor disturbances.
Click the arrow below to advance to the
next slide.
Assessment of CIPN
NCI-CTCAE (National Cancer Institute
Common Terminology Criteria for
Adverse Effects) assesses from
Grades 1-4 of Sensory and Motor
function:
• Grade 1: Asymptomatic
• Grade 2: Some sensory alteration or
weakness
• Grade 3: Interfering with activities
of daily living
Microsoft Image Clip Art, 2007
• Grade 4: life threatening and
disabling (paralysis) (Wickham, 2007)
Assessment of CIPN
Microsoft Image Clip Art, 2007
• ECOG-CTC tool (Eastern
Cooperative Oncology
Group Common Toxicity
Criteria) also is used to
assess from Grades 1-4 of
Sensory and Motor
function
• Oxaliplatin-Specific
Scale: assesses Grades
1-4 of specific side effects
(Wickham, 2007)
Assessment of CIPN
Total Neuropathy Score:
• Most comprehensive
• Assesses subjective and
objective aspects of
peripheral nerve function
Microsoft Image Clip Art, 2007
• Assesses presence,
characteristics, and location
of symptoms, as well as
physical findings
• Each item scored by doctor
or nurse on 0-4 scale (Smith,
Beck, & Cohen, 2008)
Assessment of CIPN
Total Neuropathy Score:
• Scores summed to obtain total
score
• Higher scores = higher the
degree of neuropathy
• Wide scoring range
• 0=no problems
• 4=severe neuropathy almost
causing disability (Smith, Beck, & Cohen,
2008)
Microsoft Image Clip Art, 2007
Rest and Review!
• Which neuropathy scoring tool is considered
most effective in regards to comprehensive
scoring?
• A. NCI-CTCAE (National Cancer Institute
Common Terminology Criteria for Adverse
Effects)
• B. Total Neuropathy Score (TNS)
• C. ECOG-CTC tool (Eastern Cooperative
Oncology Group Common Toxicity Criteria)
• D. Oxaliplatin-Specific Scale
This is not considered the most
comprehensive CIPN screening tool…
Please click on the question mark below
to go back and try the question again!
YES! The Total Neuropathy Score is
considered one of the most effective
CIPN screening tools!
Click the arrow below to advance to the
next slide.
Patients at risk for developing CIPN
• Some conditions or comorbidities make patients more
prone to developing CIPN
complication than other patients
• The following is a list of other
factors that, if present in a
patient undergoing
chemotherapy with a neurotoxic
drug, may put them more at risk
for developing CIPN
• It’s essential to assess for risk
factors to determine who will
need close monitoring during
treatment!
Microsoft Image Clip Art, 2007
Patients at risk for developing CIPN
Microsoft Image Clip Art, 2007
• Endocrine diseases
include:
• Diabetes mellitus (already
can causes small fiber
injury)
• Hypothyroidism
• Infectious diseases
include:
• HIV/AIDS
• Lyme disease
• Herpes zoster
• Hereditary diseases
include:
• Charcot-Marie-Tooth
syndrome (causes large
fiber injury)
• Freidreich’s ataxia (Wickham,
2007)
Patients at risk for developing CIPN
• Nutritional diseases
include:
• Alcoholism
• Vitamin B12 deficiency
(causes large fiber
injury)
• Thiamine deficiency
• Vitamin E deficiency
• Folate deficiency
• Crohn’s disease (Wickham,
2007)
Microsoft Image Clip Art, 2007
Patients at risk for developing CIPN
Microsoft Image Clip Art, 2007
• Connective tissue
diseases:
• Rheumatoid arthritis
• Lupus
• Metal neuropathy:
• Mercury
• Gold
• Thallium
• Other:
• Amyloidosis
• Atherosclerotic heart disease
• Sarcoidosis
• Biliary cirrhosis
• Uremia
• Vasculitis
• Ischemic lesions (Wickham, 2007)
Patients at risk for developing CIPN
• Medications including:
Microsoft Image Clip Art, 2007
•
•
•
•
•
•
•
•
•
•
Colchicine
Isoniazid
Hydralazine
Metronidazole
Lithium
Phenytoin
Cimetadine
Amiodarone
Pyridoxine
Amitriptyline (Wickham, 2007)
Patients at risk for developing CIPN
• Toxic neuropathy:
•
•
•
•
•
Acrylamide
Carbon disulfide
Ethylene oxide
Carbon monoxide
Glue sniffing (Wickham,
2007)
Microsoft Image Clip Art, 2007
Rest and Review!
• Which vitamin deficiency may
contribute to tendency to develop
CIPN?
• A. Vitamin C
• B. Vitamin D
• C. Vitamin K
• D. Vitamin E
Not the correct Vitamin deficiency…
Please click on the question mark below
to go back and try the question again!
Yes! Vitamin E deficiency is thought to
play a role in development of CIPN!
Click the arrow below to advance to the
next slide.
Rest and Review!
• Which disease or condition may
predispose a patient to developing
CIPN?
A. Atherosclerotic heart disease
• B. Pregnancy
• C. Eczema
• D. Depression
Try again…This condition does not
predispose someone to developing
CIPN…
Please click on the question mark below
to go back and try the question again!
CORRECT! Atherosclerosis can predispose
a person to developing CIPN!
Click the arrow below to advance to the
next slide.
Genetics and CIPN
• Observations strongly suggest
correlation between genetics
and development of CIPN and
pain
• Not many studies done on
development of neuropathic pain
or peripheral neuropathies in
cancer patients
• No common genetic markers have
been satisfactorily identified (Ossipov &
Porreca, 2005)
Microsoft Image Clip Art, 2007
Genetics and CIPN
• One study suggests there may be
genetic component in patients
receiving Taxol for cancer
• ABCB1 is a protein involved in
Taxol elimination and distribution
• Is expressed in the blood-brain
barrier
• It is not detected in peripheral
nerve cells
• However, the cells that make up
blood-nerve barrier express
ABCB1 (Sissung, Mross, Steinberg, Behringer, Figg,
Sparreboom, & Mielke, 2006)
Microsoft Image Clip Art, 2007
Genetics and CIPN
• ABCB1 may protect peripheral
nervous tissue
• It does this by taking toxic
substances away from the
nervous system, and puts it
back into systemic circulation
• Based on expression, it was
hypothesized that patients with
low-expressed ABCB1 gene
variations would be more likely to
experience CIPN (Sissung et. al., 2006)
Microsoft Image Clip Art, 2007
Genetics and CIPN
• None of the patients carrying
the “wild” allele for ABCB1
gene developed CIPN
• Patients carrying different
variations of the gene did
tend to have increased risk
of developing CIPN
Microsoft Image Clip Art, 2007
• Data suggests possible
genetic predisposition to
CIPN with regulation of the
ABCB1 gene (Sissung et. al., 2006)
Genetics and CIPN
• More research needs to be
done in the area of genetics
and CIPN—there could be a
link!
Limitations of the study
include:
• Small sample size
• Taxol-based therapy only
was tested
Microsoft Image Clip Art, 2007
Rest and Review!
• With more research in the area of
genetics, there is a possibility that
genetics may play a role in the
development of CIPN.
• True
• False
Try one more time!
Please click on the question mark below
to go back and try the question again!
Right answer! With more research, they
may find a genetic component to the
development of CIPN!
Click the arrow below to advance to the
next slide.
Prevention of CIPN
• No treatment available to
clinically reverse CIPN!
• As health care professionals, it is
important to educate patients
on ways to prevent CIPN
Ways to prevent include:
• Treating and recognizing preexisting conditions that put
patients at risk
• Frequent assessment during
therapy (Armstrong, Almadrones, & Gilbert, 2005)
Microsoft Image Clip Art, 2007
Pharmacologic treatment of CIPN
•
Amifostine:
Chemoprotectant
• Detoxifies chemotherapy drugs
• Facilitates DNA repair of cells
• Does not interfere with chemotherapy
effectiveness
• In lab animals, shows sparing of nerve
fibers
• In some human trials, it seems
ineffective in preventing or reducing
Taxol-induced PN
• Needs more research with other
chemotherapy drugs (Visovsky et. al., 2007)
Microsoft Image Clip Art,
2007
Pharmacologic treatment of CIPN
Vitamin E:
• Protects against cell damage such as
numbness, tingling, burning, and
pain in periphery caused by Cisplatin
and other chemotherapy drugs
• Studies show those who received
Vitamin E supplementation during
and after chemotherapy reported
less CIPN
• Possibly a relationship between
Cisplatin neurotoxicity and Vitamin E
deficiency (Visovsky et. al., 2007)
Microsoft Image Clip Art, 2007
Pharmacologic treatment of CIPN
Calcium/Magnesium infusions:
• Oxalate, found in Oxaliplatin,
binds to Calcium and Magnesium
• This may deplete these essential
elements and be responsible for
the neurotoxicity of Oxaliplatin
• Patients received 1 gram of both
Magnesium and Calcium before
and after Oxaliplatin infusion
• 65% in infusion group had no
CIPN, compared to 37% in control
(Visovsky et. al., 2007)
Microsoft Image Clip Art, 2007
Pharmacologic treatment of CIPN
Tricyclic antidepressants:
• Analgesic effect in treatment of CIPN
• Been studied as a relief of
paresthesias, including burning,
shooting, or tingling pain
Anticonvulsants:
• Protect against Oxaliplatin-induced
CIPN
Microsoft Image Clip Art, 2007
• Patients who were treated with
Carbamazepine had no CIPN
compared to control group (Visovsky et. al.,
2007)
Pharmacologic treatment of CIPN
Acetyl-L-carnitine:
• Tested in presence of
preexisting Taxol or
Cisplatin-induced CIPN
• Very small studies have been
performed, but look
promising (Visovsky et. al., 2007)
Microsoft Image Clip Art, 2007
Xaliproden:
• Oral neuroprotecive drug,
NGF analog
• Incidence of Grade 3-4 CIPN
was 39% less in patients
who received drug versus
placebo (Wickham, 2007)
Pharmacologic treatment of CIPN
Glutamine:
• Amino acid, may have
neuroprotecive properties
• Upregulates NGF
• In studies, those who take
it for Taxol- preventive
CIPN showed less
weakness, loss of
vibratory sensation, and
toe numbness versus
control group (Visovsky et. al., 2007)
Microsoft Image Clip Art, 2007
Pharmacologic treatment of CIPN
Glutathione:
• May hamper initial accumulation
of platinum agents in peripheral
nerve cells
• Incidence of neuropathy was
greater in placebo than control
group
• In some studies, incidences of no
CIPN were reported with IV
infusion (Visovsky et. al., 2007)
Opioids:
Microsoft Image Clip Art, 2007
• Useful for painful CIPN
• Doses can be titrated to effective
range for CIPN and pain (Wickham, 2007)
Pharmacologic treatment of CIPN
Alpha Lipoic acid:
Microsoft Image Clip Art, 2007
• Been studied in use with diabetic
polyneuropathy
• No studies done yet with
oncology population
• Significantly improved pain,
burning, paresthesias, and
numbness in diabetic patients
Capsaicin ointment:
• Used in diabetic patients
• Decrease in neuropathies in
diabetic patients studied (Visovsky et. al.,
2007)
Rest and Review!
• What class of drugs can be used to
treat pain associated with CIPN?
• A. Tricyclic antidepressants
• B. Beta blockers
• C. ACE inhibitors
• D. Vitamins
These do not treat pain associated with
CIPN!
Please click on the question mark below
to go back and try the question again!
Great! Tricyclic antidepressants show
some analgesic pain relief in patients
with CIPN!
Click the arrow below to advance to the
next slide.
Rest and Review!
• Which amino acid may help prevent
CIPN, especially in patients treated with
Taxol?
• A. Asparagine
• B. Lysine
• C. Glutamine
• D. Valine
Wrong amino acid. Try again!
Please click on the question mark below
to go back and try the question again!
Right answer!! Glutamine shows some
neuroprotective properties in patients
with CIPN!
Click the arrow below to advance to the
next slide.
Nonpharmacologic treatment of CIPN
Acupuncture:
• Shown gait improvement
• Has shown improvement in
sensation and balance
• Patients taking pain
medication for CIPN ended
up decreasing doses
Assistive devices:
• Canes or orthotics
• Help prevent injury related to
CIPN pain and sensory/motor
changes (Visovsky et. al., 2007)
Microsoft Image Clip Art, 2007
Nonpharmacologic treatment of CIPN
Activity and exercise:
• Strengthening programs may be
effective in reversing muscle
strength lost to CIPN
• In severe CIPN, may need
Occupational and/or Physical
Therapy involvement
Microsoft Image Clip Art,
2007
Pulsed Infrared Light Therapy
(PILT):
• Delivers infrared light to improve
foot perfusion
• Not studied in oncology
population, but did show
improvement in sensation in
diabetic neuropathy (Visovsky et. al., 2007)
Nonpharmacologic treatment of CIPN
Transcutaneous nerve
stimulation (TENS):
• Blocks conduction of nerve signal
to brain through electrical impulses
• Improvement in numbness, pain,
prickling sensation
Relaxation breathing:
• Includes deep-breathing exercise,
yoga, meditation, and guided
imagery
• Improves stress and pain related
to CIPN, and helps with
improvement in mood (Marrs & Newton,
2003)
Microsoft Image Clip Art, 2007
Rest and Review!
• Which of the activity can you suggest to
patients as a nonpharmacologic way to
control CIPN symptoms?
• A. Yoga
• B. Heavy lifting
• C. Pursed-lip breathing
• D. Running 4 miles
This IS NOT an appropriate
nonpharmacologic intervention…
Please click on the question mark below
to go back and try the question again!
Good job!! Yoga is a great thing to teach
patients to help control neuropathy and
pain.
Click the arrow below to advance to the
next slide.
Patient Teaching
• Teach signs/symptoms
early on in treatment
• Instruct patients to report
symptoms as soon as they
emerge
Microsoft Image Clip Art,
2007
• Teach strategies for
personal safety (for
example, relying on visual
input to compensate loss of
lower-extremity sensation,
remove throw rugs, use
bath mats, etc) (ONS, 2006)
Patient Teaching
• Teach strategies to prevent
autonomic dysfunction
including postural
• Teach of risk for thermal
hypotension, constipation,
injury due to loss of extremity
& urinary retention by:
sensation by:
• Dangling legs before arising
• Lowering water temperature
in home water heater to avoid • Consuming high fiber diet
burns
• Implementing stool
softener use if needed
• Use bath thermometer
• Use good foot/hand care
• Inspect hands/feet daily for
sores/blisters
• Adequate fluid intake
2006)
(ONS,
Case Study
You are a nurse working in a busy
oncology outpatient clinic. You are
starting a 50 year-old African American
patient named “Joan” on chemotherapy
for Stage III breast cancer. She is in
your chemotherapy chair for the first
time today for teaching and her first
chemotherapy dose…
The oncologist is ordering four cycles of
doxorubicin (Adriamycin), along with
cyclophosphamide (Cytoxan). This will
be given every three weeks for a total
of 12 weeks.
She will then receive four cycles of
paclitaxel (Taxol) therapy…
You decide to first review Joan’s history
with her. You find out she has quite a
few co-morbidities in addition to her
breast cancer, including insulindependent diabetes mellitus for 10
years, a history of alcohol abuse,
depression, and hypothyroidism…
Which of the co-morbidities listed below
does NOT make her more susceptible
to developing CIPN?
A. Hypothyroidism
B. Depression
C. Alcohol use
D. Diabetes mellitus
OOPS! Try again, there is a better answer
as to which disease will not predispose
this patient to developing CIPN…
Please click on the question mark below
to go back and try the question again!
Great job!
Depression is not a co-morbidity associated with
increased risk of developing CIPN. However,
you should continue to watch depressive
symptoms, as they may progress with a
cancer diagnosis and during treatment…
Click the arrow below to advance to the next
slide.
Being the excellent nurse you are, you
assess her baseline neurological
functioning…
She does not have any problems picking
up objects off the floor, buttoning a
shirt, or any feeling of numbness or
tingling in her extremities….
What else should you assess before proceeding
with chemotherapy?
A. Her baseline understanding of CIPN
B. Her understanding of her increased risk of
developing CIPN due to co-morbidities
C. Her ability to understand and comprehend
medical information presented, since she
will most likely need more information
related to CIPN
D. All of the above
There may be more answers to the
question…
Please click on the question mark below
to go back and try the question again!
Excellent job!!
All of the listed statements are correct,
and all of those factors need to be
assessed prior to chemotherapy
initiation!
Click the arrow below to advance to the
next slide.
Joan does very well with her four cycles
of Adriamycin and Cytoxan. She has
now received her first dose of Taxol…
She comes to the clinic and reports that
she is feeling well and has no new
concerns…
Joan states that she has no problems with
her fingers/toes and has no
neuropathies. Which of the following
statements should make you as the
nurse assessing CIPN, investigate more?
A. “I feel like I am forgetting things like
names and faces”
B. “I have been dropping things around the
house a lot more lately”
C. “I have been eating and drinking well”
D. “I have had no fevers or chills”
This is not a statement that warrants
further investigation when assessing for
CIPN, but should be pursued further if
necessary…
Please click on the question mark below
to go back and try the question again!
Way to go!!
You’re correct—if the patient reports she
is dropping objects around the house
for no apparent reason, she may be
showing signs of CIPN.
Click the arrow below to advance to the
next slide.
Since Joan reports she is dropping things
around the house, and after further
investigation, admits her fingers and
toes have become numb and
sometimes painful, you decide to talk
with the MD, who prescribes her to take
Glutamine 10 grams every day for the
first 5 days after chemotherapy, to help
with her neuropathy…
The patient agrees to start Glutamine,
and does take it as directed.
She returns to clinic after her third cycle
of Taxol, and reports that her hands
and feet have now become painful and
she is having difficulty walking…
She is prescribed an analgesic for her
pain, which is only minimally helpful…
What other strategies and nonpharmacologic
ways can you describe for Joan to help her
with her neuropathies and pain?
A. Yoga
B. Light exercise
C. Training for a marathon
D. Relaxation breathing
E. A, B, & D
F. A & B
There may be more answers to the
question…
Please click on the question mark below
to go back and try the question again!
Great answer!!
Yoga, relaxation breathing, and light
exercise are all great ways to try to
combat neuropathies and pain!
Click the arrow below to advance to the
next slide.
Despite your best efforts, as well as the
MD’s recommendations, the patient’s
pain improves only slightly. She starts
to have balance problems and describes
being “very uncomfortable…”
What can you, as the nurse, initiate next?
A. Talk to the MD about a referral to
Physical and Occupational therapy
B. Wait and see if the pain improves
once her chemotherapy is completed
C. Nothing—if the MD doesn’t think it’s a
problem, then there shouldn’t be a
concern
D. None of the above
Not true! There is ALWAYS something you
can do to try and help a patient…
Please click on the question mark below
to go back and try the question again!
You’re right!!
Often times when CIPN has progressed,
physical therapy and/or occupational
therapy can help restore some normal
functioning!
Click the arrow below to advance to the
next slide.
With a referral to physical and
occupational therapy, and a dose
reduction in her final Taxol treatment,
the patient reports better symptom
management. She is also using a cane
as needed to help her balance…
What should you, as the nurse involved in
her case, do now?
A. Nothing—she is improving and
finished with chemotherapy, so she is
no longer your patient
B. Call her on the phone every once in a
while to check in with her
C. Continue to make appointments so
assessment of CIPN can be monitored
Can’t you do a little more to help this
patient?
Please click on the question mark below
to go back and try the question again!
Great answer! By making future
appointments with the patient, you can
continue to assess her progress with
neuropathy…
Click the arrow below to advance to the
next slide.
For more information
• Here are a list of websites that focus on peripheral
neuropathy:
• CancerSymptoms.org: “Peripheral Neuropathy”
www.cancersymptoms.org/peripheralneuropathy/index.sht
ml
• National Institute of Neurological Disorders and Stroke:
“Peripheral Neuropathy Fact Sheet”
www.ninds.nih.gov/disorders/peripheralneuropathy/detail_
peripheralneuropathy.htm
• Cancer Supportive Care Programs: “ChemotherapyInduced Peripheral Neuropathy Fact Sheet”
www.cancersupportivecare.com/nervepain.php
• National Coalition for Cancer Survivorship: “Neuropathy”
www.canceradvocacy.org/resources/essential/effects/neur
opathy.aspx
•
(Wickham, 2007)
References:
•
•
•
•
•
•
•
•
American Cancer Society. (2008, Winter). Side effects of therapy. Cure:
Cancer Updates, Research, & Education, 58-62.
Armstrong, T., Almadrones, L., & Gilbert, M. R. (2005). ChemotherapyInduced peripheral neuropathy. Oncology Nursing Forum, 32(2), 305-311.
Marrs, J., & Newton, S. (2003). Updating your peripheral neuropathy
"know-how". Clinical Journal of Oncology Nursing, 7(3), 299-303.
Microsoft Office clip are available from: http://office.microsoft.com/enus/clipart/default.aspx
Multiple Sclerosis Resource Centre. (2008). Structure of a typical neuron &
Damaged Neuron [Online images]. Retrieved February 27, 2008 from the
Multiple Sclerosis Resource Centre website at:
http://www.msrc.co.uk/images/gallery/nerve1.jpg
Oestreicher, P. (2007). Five minute inservice: Put evidence into practice to
treat chemotherapy-induced peripheral neuropathy. ONS Connect, 24-25.
Oncology Nursing Society (ONS). (2006). Peripheral neuropathy: What
interventions are used to prevent or reduce the effects of peripheral
neuropathy for people with cancer? PEP Card. Pittsburgh, PA.
Ossipov, M. H., & Porreca, F. (2005). Challenges in the development of
novel treatment strategies for neuropathic pain. The Journal of the
American Society for Experimental Neurotherapeutics, 2(4), 650-661.
References (continued):
•
•
•
•
•
•
•
•
•
Porth, C. M. (2005). Pathophysiology concepts of altered health states (7th ed.).
Philadelphia: Lippincott.
Sheffield, S. (2008). Getbodysmart.com (2008). The nervous system: Anatomy and
Physiology [Online image]. Retrieved March 12,2008 from
http://getbodysmart.com/ap/nervoussystem/menu/menu.html.
Smith, E. M., Beck, S. L., & Cohen, J. (2008). The total neuropathy score: A tool for
measuring chemotherapy-induced peripheral neuropathy. Oncology Nursing Forum, 35(1),
96-101.
Sissung, T. M., Mross, K., Steinberg, S. M., Behringer, D., Figg, W. D., Sparreboom, A., et al.
(2006). Association of ABCB1 genotypes with paclitaxel-mediated peripheral neuropathy and
neutropenia. European Journal Cancer, 42(17), 2893-2896.
Turner, H. (2005). Microscopic image of a nerve cell [online image]. Retrieved February 27,
2008 from the National Research Council Canada website at: http://www.nrccnrc.gc.ca/images/education/pl_nerve.jpg
Visovsky, C., Collins, M., Abbott, L., Aschenbrenner, J., & Hart, C. (2007). Putting evidence
into practice: Evidence-based interventions for chemotherapy-induced peripheral
neuropathy. Clinical Journal of Oncology Nursing, 11(6), 901-913.
Visovsky, C., & Daly, B. J. (2004). Clinical evaluation and patterns of chemotherapy-induced
peripheral neuropathy. Journal of the American Academy of Nurse Practitioners, 16(8), 353359.
Wampler, M. A., Hamolsky, D., Hamel, K., Melisko, M., & Topp, K. S. (2005). Case report:
Painful peripheral neuropathy following treatment with docetaxel for breast cancer. Clinical
Journal of Oncology Nursing, 9(2), 189-193.
Wickham, R. (2007). Chemotherapy-induced peripheral neuropathy: A review and
implications for oncology nursing practice. Clinical Journal of Oncology Nursing, 11(3), 361376.
Questions, Comments, or Suggestions?
• Please feel free to email me with any
questions, ideas, suggestions, or
comments regarding this tutorial. I
welcome the correspondence!
• Email: [email protected]
THANK YOU!