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Chemotherapy and Biotherapy Hypersensitivity Reactions
Christine E. Coyle, RN, BSN, OCNAlverno College MSN Student
Spring 2011
coylece@alverno.edu
Navigating through Tutorial
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• Click or hover on any underlined words for more information
All images are from Microsoft Clipart, 2007.
Learner OutcomesAt 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?
National Cancer Institute, 2010
• 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.
Immune Response
Management and Nurse Role
Case Study
References
Cytokine-release syndrome
Risk Factors for Hypersensitivity Reactions
Genetics
Click on a topic
Reactions and Stress
Risk Factors
• Type of Chemotherapy/Biotherapy Agent• Previous History with the agent• Allergies• Age• Genetics
Incidence of ReactionsAgent Overall Grade 3-4Carboplatin (Paraplatin®)
2 % none
Cetuximab (Erbitux®) 15-20%, dependent on tumor type
3%
Docetaxel (Taxotere®) 5-12% 2%
Eloxatin (Oxaliplatin®) 15-33% 2-3%
Paclitaxel (Taxol®) 41% 2%
Rituximab (Rituxan®) 77% First infusion, 30% fourth infusion, 14% eighth infusion
10%
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?
Rituxan Paclitaxel
Cetuximab Paraplatin
Correct!
Incorrect Incorrect
Incorrect
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 !
Allergies• Food• Drugs• Insect stings• Latex • Vaccines• Anesthesia Medications
Other • Female gender• Cardiac, liver, kidney or pulmonary
dysfunction• Older Age• Asthma diagnosis
Gobel, 2005
Time out…let’s reflect!
Which is an example of a drug where previous and/or multiple exposure increases the risk for reaction?
Docetaxel Rituximab Paclitaxel Eloxatin
Correct!Incorrect
Incorrect Incorrect
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
CYP450There are genetic differences in the way it works
CYP450 Possible Genetic Mutations
CYP2C9
CYP2D6
CYP2C19 -Poor-Intermediate
-Extensive -Ultra-rapid
Metabolizers
This provides a possible explanation as to why some patients tolerate drugs
better than others
Paclitaxel is metabolized
by the CYP450 pathway
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
Innate Adaptive
Click on the pictures to learn more…
Dendritic cell
Compliment Protein
Mast Cell
Macrophage
Natural KillerCell
Granulocytes
B Cell
T Cell
Adaptive Immunity: Two Types
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 ImmunityOne 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!
MacrophagesSorry, this is r/t
innate
B-LymphocytesYou’re correct! Is
there another one?
T-LymphocytesWay 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 T-cells in the immune system
Gobel, 2005
IgE Mediated ResponseAllergen
Dendritic cells & B Cells
Antigen Presenting Cells
T Helper cells
BCells
Present processed
peptides from the allergen
T cells are activated and
release IL-4, IL-13
Mast Cells
Isotypes are induced ,
generates IgE
Eosinophils
Mast cells bind to antigen via IgE antibody
HistaminesLeukotrienes
cytokines
Now What!?!?
What does this really mean?…your patient is in TROUBLE!!!
Chemotherapy (Antigen) Infusing
Mast Cells
The body says, “HOLY MOLY, something is not right!”
basophils
IgE antibodies are produced and bind to
receptors on Mast cells
HistaminesLeukotrienes, & prostaglandins start to circulate
Time out…Let’s reflect
An allergic reaction is caused by an IgE response in cell-mediated
immunityTrue or False?
What’s the problem?Histamines
Leukotrienes
Prostaglandins
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
Induce vasodilatation, viscous mucous production, hypotension, increased platelets begin to stick together
Signs/Symptoms of HSR’sChest pain, palpitations, hyper/hypo-tension, edema, cardiac arrest
Headache, dizziness, confusion, LOC, anxiety, Impending doom
Skin Rash, pruritis, urticaria, flushing, tearing
Nausea/Vomiting, Diarrhea, abd cramping, bloating
Cough, dyspnea, nasal congestion, wheezing, bronchospasms, hypoxemia, chest tightness, tacypnea
Incontinence, uterine cramping, pelvic pain, renal impairment
Quiz yourself by clicking on the system to see how each can be affected
Other signs that your patient may
be reacting…
“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.”
“I don’t know what is wrong, I just don’t feel right.”
Restlessness
“I have a tickle in my throat.”
“I have a tickle in my throat.”
Confusion 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, drugfever <38 degrees C (<100.4degrees F); intervention notindicated
N/A
2 Intervention or infusion interruption indicated; responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics);prophylactic medicationsindicated for <=24 hrs
N/A
3 Prolonged recurrence of symptomsfollowing initial improvement;hospitalization indicated forclinical sequelae (e.g., renalimpairment)
Symptomatic bronchospasm, with or without urticaria; parenteral interventionindicated; 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 SyndromeCancer
CellMonoclonal
Antibody
Cancer Cell
Cell Death
Breslin, 2007
Immune effector cells
Compliment
Cytokines release into blood stream
Cytokines Release can cause…
• Fever• Chills • Rigors• Nausea• Vomiting • Dyspnea• Hypotension
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.
True or False, CYTOKINES:
True!
True!
True!
Time out…let’s reflect!
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 promptlyto 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
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.
Three StagesAlarm: 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
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 releasesEpinephrine and Norepinephrine
Increased Heart Rate
Increased Blood
pressure
Results in
Increased pressure can damage artery
lining
Glucose, fat, cholesterol in blood clump together
and create plaque
Blood vessels increase muscle tissue to
control increased blood flow
All can lead to stroke/ MI
Incorrect
Correct! Increase in BP
Decreased in HR
Correct! Increase in HR
Decrease in BPincorrect!
What effect does the release of norepinephrine and epinephrine cause? Select all that apply:
Time out…let’s reflect…
Management and the Role of the Oncology Nurse
Nursing Interventions
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?
Are you ready to administer the
Chemotherapy or Biotherapy infusion?
Emergency Supplies
Equipment• Code Cart• Oxygen supplies• Ambu Bag• Stethoscope• Suction set-up• Syringes/Needles
Medications• 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 familyPolovich 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
• 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
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? Continue to monitor the patient Slow the infusion down Assure the patient she will feel better in no time Stop the infusion
Myers, 2000
Incorrect
Correct!
Incorrect
Incorrect
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• 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• 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. 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.
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