Christine E. Coyle, RN, BSN, OCN
Alverno College MSN Student
Spring 2011 coylece@alverno.edu

• To move to the next slide click
• To move to the previous slide click
• To go to the home page click
• To go to the last slide viewed
• Click or hover on any underlined words for more information
All images are from Microsoft Clipart, 2007.

• 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.

• 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.

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.

• 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
Risk Factors for
Hypersensitivity
Reactions
Genetics
Case Study
Cytokinerelease syndrome
Reactions and Stress
Immune
Response
Management and Nurse Role
References

• Type of Chemotherapy/Biotherapy Agent
• Previous History with the agent
• Allergies
• Age
• Genetics

Agent Overall
Carboplatin
(Paraplatin®)
2 %
Cetuximab (Erbitux®) 15-20%, dependent on tumor type
Grade 3-4 none
3%
Docetaxel (Taxotere®) 5-12% 2%
Eloxatin (Oxaliplatin®) 15-33%
Paclitaxel (Taxol®) 41%
2-3%
2%
Rituximab (Rituxan®) 77% First infusion, 30% fourth infusion, 14% eighth infusion
10%
Vogel, 2010

Of the drugs previously mentioned, which one has the highest incidence of HSR’s with the first infusion?
Correct!
Incorrect

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 !
Allergies
• Food
• Drugs
• Insect stings
• Latex
• Vaccines
• Anesthesia Medications
Other
• Female gender
• Cardiac, liver, kidney or pulmonary dysfunction
• Older Age
• Asthma diagnosis
Gobel, 2005

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

CHECK YOUR PATIENT’S LYMPHOCYTE COUNT!

• 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

There are genetic differences in the way it works
CYP450
CYP2C19
Paclitaxel is metabolized by the
CYP450 pathway
CYP2D6
Possible Genetic
Mutations
Metabolizers
CYP2C9
-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

-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

• The body ’s primary line of defense
• Contains compliment proteins, granulocytes, mast cells, macrophages, dendritic cells and natural killer cells

• 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

Click on the pictures to learn more…
Dendritic cell Mast Cell
B Cell
Macrophage
Compliment
Protein
T Cell
Natural Killer
Cell
Granulocytes

Cell-Mediated
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
Humoral Immunity
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

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?

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
3
Antibody-mediated reaction resulting in antibody
–antigen complexes
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

Allergen
Now What!?!?
Eosinophils
Antigen Presenting Cells
Dendritic cells & B Cells
Present processed peptides from the allergen
T
Helper cells
T cells are activated and release IL-4, IL-
13
B
Cells
Mast
Cells
Isotypes are induced , generates IgE
Histamines
Leukotrienes cytokines
Mast cells bind to antigen via
IgE antibody

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
Histamines
Leukotrienes, & prostaglandins start to circulate basophils

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
Leukotrienes
Prostaglandins
Induce vasodilatation, viscous mucous production, hypotension, increased platelets begin to stick together

Chest pain, palpitations, hyper/hypo-tension, edema, cardiac arrest
Headache, dizziness, confusion, LOC, anxiety,
Impending doom
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
Nausea/Vomiting,
Diarrhea, abd cramping, bloating
Skin
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.”
Confusion
Anxiety
Restlessness

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
1
2
3
4
5
Transient flushing or rash, drug fever <38 degrees C (<100.4
degrees F); intervention not indicated
Intervention or infusion interruption indicated; responds promptly to symptomatic treatment (e.g., antihistamines,
NSAIDS, narcotics); prophylactic medications indicated for <=24 hrs
Prolonged recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment)
Life-threatening consequences; urgent intervention indicated
DEATH
Anaphylaxis
N/A
N/A
Symptomatic bronchospasm, with or without urticaria; parenteral intervention indicated; allergy-related edema;
Hypotension
Life-threatening consequences; urgent intervention indicated
DEATH
National Cancer Institute, 2010

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

• 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

Monoclonal
Antibody
Cancer
Cell
Compliment
Immune effector cells
Cancer
Cell
Cell Death
Cytokines release into blood stream
Breslin, 2007

• Fever
• Chills
• Rigors
• Nausea
• Vomiting
• Dyspnea
• Hypotension

True!
True or False, CYTOKINES:
Are a group of polypeptide proteins that are produced and secreted by most cells in the body.
True!
Act as chemical messengers, facilitating communication between cells.
True!
Coordinate responses among the innate and mediated immune responses.

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!

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

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

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

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.

Increased
Heart Rate
Adrenal Medula releases
Epinephrine and Norepinephrine
Increased
Blood pressure
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!
Increase in BP
Incorrect Decreased in HR
Correct!
Increase in HR incorrect!
Decrease in BP

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?

• Code Cart
• Oxygen supplies
• Ambu Bag
• Stethoscope
• Suction set-up
• Syringes/Needles
Medications
• Normal Saline
• Epinephrine
• Albuterol Inhaler
• Diphenhydramine
• Famotidine
• Dexamethasone
• Hydrocortisone

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.

• Maintain IV line with Normal Saline (NS)
• IV fluids should be given to maintain a systolic BP above 90 mmHg
Watson, 2010

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

• Prompt and accurate documentation of a HSR is critical
• Accurate grading will allow the prescriber to decide the next appropriate steps for treatment
• 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?
Vogel, 2010

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

• 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!

• 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.

• 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_2010-06-
14_QuickReference_8.5x11.pdf
. Accessed March 9, 2011.
• Polovich, M., Whitford, J. M., & Olsen, M. 2009. Chemotherapy and Biotherapy
Guidelines and Recommendations for Practice. 3 rd edition. Oncology Nursing
Society.
• Porth, C.M., 2009. Pathophysiology, 7 th 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.