Transcript Chemotherapy and Biotherapy Reactions:

Chemotherapy and Biotherapy
Hypersensitivity Reactions
Christine E. Coyle, RN, BSN, OCN
Alverno College MSN Student
Spring 2011
[email protected]
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All images are from Microsoft Clipart, 2007.
Learner Outcomes
At the end of this presentation the
learner will:
• Identify factors that place a patient at risk for
hypersensitivity reactions from cancer therapies,
such as chemotherapy and biotherapy.
• Review pathophysiology of hypersensitivity
reactions, including allergic, anaphylaxis, and
cytokine-release syndrome.
• Discuss the management of hypersensitivity
reactions, emphasizing the oncology nurse’s role.
Clinical Significance
• Almost all cancer therapy infusions have been
reported to cause HSR’s.
• These reactions can be life-threatening and
requires that nurses are prepared to manage
them.
• Encourages the nurse to consider his/her role
in preventing reactions.
Hypersensitivity Reaction
(HSR)
An over expressed immune response that
results in tissue harm or changes throughout
the body in response to an antigen or foreign
substance.
This can include an allergic reaction,
anaphylactic reaction or Cytokine-Release
Syndrome.
Reactions…what’s the
difference?
• Allergic Reaction:
An unpleasant response from exposure to an allergen.
• Anaphylaxis Reaction:
An acute inflammatory reaction which results from the release of
histamine from mast cells, causing a hypersensitivity immune
response. It can presents with shortness of breath (SOB),
lightheadedness, hypotension, and loss of consciousness and can
lead to death.
• Cytokine-release syndrome :
Caused by the release of cytokines- can cause nausea, headache,
tachycardia, hypotension, rash, and SOB. It only occurs with
Monoclonal Antibodies.
National Cancer Institute, 2010
Click on a topic
Immune
Response
Genetics
Risk Factors for
Hypersensitivity
Reactions
Case Study
Management
and Nurse Role
Cytokinerelease
syndrome
Reactions
and Stress
References
Risk Factors
•
•
•
•
•
Type of Chemotherapy/Biotherapy Agent
Previous History with the agent
Allergies
Age
Genetics
Incidence of Reactions
Agent
Overall
Grade 3-4
Carboplatin
(Paraplatin®)
2%
none
Cetuximab (Erbitux®)
15-20%, dependent on 3%
tumor type
Docetaxel (Taxotere®)
5-12%
2%
Eloxatin (Oxaliplatin®)
15-33%
2-3%
Paclitaxel (Taxol®)
41%
2%
Rituximab (Rituxan®)
77% First infusion, 30% 10%
fourth infusion, 14%
eighth infusion
Vogel, 2010
Time out…let’s reflect
Of the drugs previously mentioned, which one
has the highest incidence of HSR’s with the
first infusion?
Correct!
Incorrect
Rituxan
Cetuximab
Incorrect
Incorrect
Paclitaxel
Paraplatin
Review Patient’s History
Assess your patient for
previous reactions and/or
allergies.
Know your patient’s health
history.
Prior history of HSR’s increases
risk to subsequent HSR’s !
Gobel, 2005
Allergies
• Food
• Drugs
• Insect stings
• Latex
• Vaccines
• Anesthesia Medications
Other
• Female gender
• Cardiac, liver, kidney or
pulmonary dysfunction
• Older Age
• Asthma diagnosis
Time out…let’s reflect!
Which is an example of a drug where previous
and/or multiple exposure increases the risk for
reaction?
Incorrect
Docetaxel
Incorrect
Rituximab
Incorrect
Paclitaxel
Correct!
Eloxatin
Is the patient getting Rituximab
for the first time?
CHECK YOUR PATIENT’S LYMPHOCYTE COUNT!
Elevated Lymphocyte count (>40%) =
Increased risk for a reaction
Check your protocol!
Drug Metabolism and Genetics
• Primary site of drug metabolism is the liver
• Cytochrome P450 (CYP450) is a specific
enzyme that is responsible for drug
metabolism
• Some drugs can induce or increase the action
specific to CYP450 which effects how the
drugs work in the body
• Not all CYP450’s are created equal
CYP450
There are genetic differences in the way it works
Possible Genetic
Mutations
CYP450
CYP2D6
Metabolizers
CYP2C19
CYP2C9
Paclitaxel is
metabolized
by the
CYP450
pathway
-Poor
-Intermediate
-Extensive
-Ultra-rapid
This provides a possible explanation as
to why some patients tolerate drugs
better than others
Immune Response
Cytokine-Release
Syndrome, allergic
reaction, and anaphylaxis
reaction all equate to an
Immune Response
Immune Response
-A coordinated response to
cells and molecules in the
immune system
-The body’s protection from
bacteria, viruses and
foreign substances
-Is normally protective but
can cause unfavorable
effects
Porth & Matfin, 2009
Innate Immunity (non-specific)
• The body ’s primary line of
defense
• Contains compliment
proteins, granulocytes, mast
cells, macrophages, dendritic
cells and natural killer cells
Adaptive Immunity (specific)
• Responds less rapidly than innate immunity but
more effectively
• Includes lymphocytes , T cells (in cell mediated
immunity and B cells (in humoral immunity)
• Immunologic memory; more rapid and efficient
with subsequent exposure
Innate and Adaptive Immunity Cells
Click on the pictures to learn more…
Innate
Dendritic cell
Mast Cell
Adaptive
B Cell
Macrophage
Compliment
Protein
T Cell
Natural Killer
Cell
Granulocytes
Adaptive Immunity: Two Types
Cell-Mediated
Immunity
Humoral Immunity
Functions to get rid of
pathogens. T-cells develop
receptors that identify the
viral peptides displayed on
the surface of infected cells
and then turn on the
destruction of infected cells
One of the main parts of the
immune system that triggers
specific B-cells to produce and
secrete large amounts of
specific antibodies. These are
created to fight a particular
microorganism or virus.
Porth & Matfin, 2009
Time out…let’s reflect!
Adaptive immunity has to do with which cells…
Mast Cells
Nope, think
again!
B-Lymphocytes
You’re correct! Is
there another
one?
Macrophages
Sorry, this is r/t
innate
T-Lymphocytes
Way to go! Is
there another
one?
Normal Immune Response vs.
Hypersensitivity Reaction (HSR)
HSR’s are different from the normal immune response. There are
four different types of immune responses. The Type 1 (IgE
response is related to HSR’s.
Type of
Immune
Response
Mechanism of Action
1
Immediate Immunoglobulin E-mediated (IgE)
reaction
2
Antibody-mediated reaction resulting in antibody
–antigen complexes
3
Immune complexes form in the circulation and
deposit in various tissues
4
Delayed reaction which involves activation of Tcells in the immune system
Gobel, 2005
IgE Mediated Response
Allergen
Eosinophils
Histamines
Leukotrienes
Antigen Presenting Cells
Dendritic
cells & B Cells
Present
processed
peptides from
the allergen
Now What!?!?
T
Helper
cells
B
Cells
T cells are
activated and
release IL-4, IL13
Mast
Cells
Isotypes are
induced ,
generates IgE
cytokines
Mast cells bind
to antigen via
IgE antibody
What does this really mean?…your
patient is in TROUBLE!!!
Chemotherapy (Antigen)
Infusing
The body says, “HOLY MOLY, something is not right!”
IgE antibodies
are produced
and bind to
receptors on
Mast cells
Mast
Cells
basophils
Histamines
Leukotrienes, &
prostaglandins
start to circulate
Time out…Let’s reflect
An allergic reaction is caused by an
IgE response in cell-mediated
immunity
True or False?
What’s the problem?
Histamines
The first mediator to be released during and acute
inflammatory reaction. Causes dilation of the arterioles and
increases vascular permeability. Stimulates H1 and H2
receptors.
-trigger contractions in the smooth muscles lining the trachea;
their overproduction is a major cause of inflammation during
a reaction. Leukotrienes are produced in the body from
arachidonic acid. Enhance vasodilatation, increase mucous
production, and contraction of smooth muscle
Prostaglandins
Leukotrienes
Induce vasodilatation, viscous mucous production,
hypotension, increased platelets begin to stick
together
Signs/Symptoms of HSR’s
Chest pain, palpitations,
hyper/hypo-tension,
edema, cardiac arrest
Headache, dizziness,
confusion, LOC, anxiety,
Impending doom
Nausea/Vomiting,
Diarrhea, abd
cramping, bloating
Skin
Quiz yourself by
clicking on the system
to see how each can
be affected
Cough, dyspnea, nasal congestion,
wheezing, bronchospasms,
hypoxemia, chest tightness,
tacypnea
Incontinence, uterine cramping,
pelvic pain, renal impairment
Rash, pruritis, urticaria,
flushing, tearing
“I have a tickle
in my throat.”
“Hey, Nurse could you
get me a blanket, it’s
freezing in here!”
“I don’t know
what is wrong,
I just don’t
feel right.”
Other signs that
your patient may
be reacting…
Confusion
Restlessness
Anxiety
Time out…let’s reflect
Your patient is midway through the infusion on her
ninth cycle of carboplatin for ovarian cancer. She
begins to complain of a “scratchy throat,” palmar
itching and slight shortness of breath. Based on
her symptoms, you would suspect:
A. Paresthesia of her vagus nerve cause by
carbolatin
B. An impending pulmonary embolus
C. An hypersensitivity reaction to carboplatin
Grade Allergic Reaction
Anaphylaxis
1
Transient flushing or rash, drug
fever <38 degrees C (<100.4
degrees F); intervention not
indicated
N/A
2
Intervention or infusion
interruption indicated; responds
promptly to symptomatic
treatment (e.g., antihistamines,
NSAIDS, narcotics);
prophylactic medications
indicated for <=24 hrs
N/A
3
Prolonged recurrence of symptoms
following initial improvement;
hospitalization indicated for
clinical sequelae (e.g., renal
impairment)
Symptomatic bronchospasm, with or
without urticaria; parenteral intervention
indicated; allergy-related edema;
Hypotension
4
Life-threatening consequences;
urgent intervention indicated
Life-threatening consequences;
urgent intervention indicated
5
DEATH
DEATH
National Cancer Institute, 2010
Cytokine-Release Syndrome
(CRS)
A cluster of symptoms associated with the
use of monoclonal antibodies. It results
from the release of cytokines from cells
targeted by the antibody. As tumor cells
are destroyed levels of cytokines and
histamines increase.
Breslin, 2007
Cytokines
• A group of polypeptide proteins that are made
and released by most cells in the body
• Organize communication between cells
• Manage responses among the innate and
mediated immune responses
• Trigger lymphocytes and other immune effector
cells
• Synchronize the damaged of cells targeted by
Monoclonal Antibodies (MOAB’s)
Breslin, 2007
Cytokine-Release Syndrome
Cancer
Cell
Monoclonal
Antibody
Compliment
Immune
effector cells
Cytokines release
into blood stream
Cancer
Cell
Breslin, 2007
Cell Death
Cytokines Release can cause…
•
•
•
•
•
•
•
Fever
Chills
Rigors
Nausea
Vomiting
Dyspnea
Hypotension
Time out…let’s reflect!
True!
True!
True!
True or False, CYTOKINES:
Are a group of polypeptide proteins that
are produced and secreted by
most cells in the body.
Act as chemical messengers, facilitating
communication between cells.
Coordinate responses among the innate
and mediated immune responses.
Clinical Symptoms of CRS
Cytokine-Release
Syndrome can present
almost the same as type
one (IgE) reactions and
can develop into
anaphylaxis-like
reactions…the difference
is the pathophysiology!
Grades of Cytokine-release syndome
Grade 1
Mild reaction; infusion interruption not indicated; intervention not
indicated
Grade 2
Therapy or infusion interruption indicated but responds promptly
to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV
fluids); prophylactic
Grade 3
Prolonged (e.g., not rapidly responsive to symptomatic medication and/or
brief interruption of infusion); recurrence of symptoms following initial
improvement.
Grade 4
Life-threatening consequences; pressor or ventilatory support indicated
Grade 5
DEATH
National Cancer Institute, 2010
What else is going on during a
reaction?
Generalized Adaptation Syndrome
(GAS)
General: the effect has to do with a general
systemic reaction
Adaptation: the response is due to a stressor
Syndrome: the physical manifestations are
dependent on each other.
Porth & Matfin, 2009
GAS and Reactions
Three Stages
Alarm: generalized
stimulation of the
Sympathetic Nervous
System (SNS)
Resistance: the body selects
the most optimal way to
respond
Exhaustion: stressor is
extended, start to see
possible signs of systemic
damage
This response is triggered by
a stressor. For cancer
patients this could be
external or internal factors
such as medication, anxiety,
environment, social support,
&/or life experiences.
Porth & Matfin, 2009
GAS and Reactions
Have you ever thought
that your patient’s stress
or anxiety may have
caused a reaction?
Stress response depends
on what a person
expects to happen in a
given situation based
on previous learning
experiences.
SNS in Stress!!
Adrenal Medula releases
Epinephrine and Norepinephrine
Increased
Blood
pressure
Increased
Heart Rate
Results in
Increased pressure
can damage artery
lining
Glucose, fat, cholesterol
in blood clump together
and create plaque
All can lead to
stroke/ MI
Blood vessels increase
muscle tissue to
control increased
blood flow
Time out…let’s reflect…
What effect does the release of
norepinephrine and epinephrine cause?
Select all that apply:
Correct!
Incorrect
Increase in BP
Decreased in HR
Correct!
incorrect!
Increase in HR
Decrease in BP
Management and the Role
of the Oncology Nurse
Nursing Interventions
Are you ready to
administer the
Chemotherapy or
Biotherapy infusion?
Preventative Measures
• Obtain baseline assessment &
vitals
• Assess for risk factors
• Educate the patient about
signs/symptoms of a HSR?
• Make sure emergency
medication/equipment
supplies are readily available?
• Confirm that the patient took
their pre-treatment
medications if ordered?
• Administer pre-medications as
ordered?
Emergency Supplies
Equipment
Medications
•
•
•
•
•
•
•
•
•
•
•
•
•
Code Cart
Oxygen supplies
Ambu Bag
Stethoscope
Suction set-up
Syringes/Needles
Normal Saline
Epinephrine
Albuterol Inhaler
Diphenhydramine
Famotidine
Dexamethasone
Hydrocortisone
Medications:
Histamine Antagonist
A histamine antagonist, commonly referred to as
antihistamine, is a drug that inhibits action of
histamines by blocking it from attaching to
histamine receptors.
Bind to H1 and H2 receptors and act competitively
to antagonize many effects of the inflammatory
response.
It may be necessary to give H1 and H2 antagonists
may be necessary to counteract the histamine
release.
Medications: IV Fluids
• Maintain IV line with Normal Saline (NS)
• IV fluids should be given to maintain a
systolic BP above 90 mmHg
Watson, 2010
Your patient is reacting!...
now what?
Stay in Control!!!!
-Stop the infusion
-Maintain IV line with NS or appropriate solution
-Stay with the patient and have co-worker activate
emergency team or notify physician
-Maintain Airway (administer O2 if needed)
-Monitor vital signs Q2 minutes until patient the patient
reaches near baseline vital signs
-Administer emergency medications
-Place the patient in supine position (if not vomiting or
SOB)
-Offer emotional support of patient and family
Polovich et al, 2009
Documentation of HSR
• Prompt and accurate
documentation of a HSR
is critical
• Accurate grading will
allow the prescriber to
decide the next
appropriate steps for
treatment
Vogel, 2010
• Pre-infusion assessment
• Initial symptoms and
course of progression
• Timing of reaction and
duration
• Grade and type of HSR
• Timing of interventions
and patient response
• Did the symptoms
resolve?: when/how?
Let’s apply what you’ve learned!
Case Study
Mrs. Jones, age 68, arrives at the Hematology/Oncology
clinic to receive her first chemotherapy for stage IV
ovarian cancer. Her baseline vitals are: BP: 148/62, pulse:
80, respirations: 20, oxygen saturation: 98%. You
administer premedications: dexamethasone 20mg IV,
diphenhydramine, 25mg IV, famotidine, 20 mg IV, and
zofran 8 mg, IV. The following chemotherapy was
ordered: paclitaxel 175mg/m2 infusion over 3 hours and
carboplatin AUC 6 (750 mg) over one hour. Five minutes
after you begin the infusion, Mrs. Jones complains of
itching, SOB and she is nauseated.
Vital signs are now: BP: 92/52, pulse: 120, Respirations:
30 and oxygen saturation is 82%. What is your immediate
response?
Incorrect
Continue to monitor the patient
Incorrect
Slow the infusion down
Incorrect
Assure the patient she will feel better in no time
Correct!
Stop the infusion
Myers, 2000
In conclusion…
• How does this tutorial encourage you to
change your practice when thinking about
HSR’s?
• Nurses play a key role in preventing HSR’s
• Continue to be advocate for your patients!
THANK YOU FOR VIEWING THIS
TUTORIAL!!!
References
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Bonosky, K. (2005). Hypersensitivity reactions to oxaliplatin: what nurses need to
know. Clinical Journal of Oncology. 9 (3), 325-330.
Breslin, S. (2007). Cytokine-release syndrome: overview and nursing implications.
Clinical Journal of Oncology. 11(1), 37-41.
Gobel, B. H. (2005) Chemotherapy-induced hypersensitivity reactions. Oncology
Nursing Forum, 32, 1027-1035.
Gleich, G.J., & Leiferman, K.M. (2009). Oncology infusion reactions associated with
monoclonal antibodies. Oncology. 23 (2), 7-13.
Labovich, T.M. (1999). Acute hypersensitivity reactions to chemotherapy. Seminars
in Oncology Nursing. 15 (3), 222-231.
Lemos, M.L. (2006). Acute reactions of chemotherapy agents. Journal of
Pharmacology Practice. 12, (3), 127-129.
Liebermann, P., Nicklas, R., Oppenheimer, J., Kemp, S., & Lang, D. (2010). The
diagnosis and management of anaphylaxis practice parameter: 2010 update.
Journal of Clinical Immunology. 126 (3), 477-488.
Lenz, H.J. (2007) Management and preparedness for infusion and hypersensitivity
reactions. The Oncologist. 12:601-609
Myers, J.S. (2000). Chemotherapy-induced hypersensitivity reaction. American
Journal of Nursing. 100(4), 53-55.
References
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National Cancer Institute. Common Terminology Criteria for Adverse Events v4.03
(CTAE). Published date June 14, 2010. Available at
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-0614_QuickReference_8.5x11.pdf. Accessed March 9, 2011.
Polovich, M., Whitford, J. M., & Olsen, M. 2009. Chemotherapy and Biotherapy
Guidelines and Recommendations for Practice. 3rd edition. Oncology Nursing
Society.
Porth, C.M., 2009. Pathophysiology, 7th edition. Lippincott.
Scripture, C.D., Sparreboom, A., & Figg, W. (2005). Modulation of cytochrome p450
activity: implications for cancer therapy. The Lancet. 6;780-789.
Timoney, J., P., Eagan, M., M., & Sklarin, N. T., Establishing clinical guidelines for the
management of acute hypersensitivity reactions secondary to the administration
of chemotherapy/biologic therapy. Journal of Nursing Care Quality, 18(1) 80-86.
Vogel, W.H. (2010). Infusion reactions: diagnosis, assessment and management.
Clinical Journal of Oncology Nursing. 14, 10-14.
Viale, P.H., & Yamamoto, D.S. (2010). Biphasic and delayed hypersensitivity
reactions: implications for oncology nursing.
Watson, L.E. (2010). Recognition, assessment and management of anaphylaxis.
Nursing Standard. 24 (46), 35-39.