Hypersensi/vity Reac/ons: How To Prepare For The (Not-So) Unexpected. Objec/ves. Defini/on 2/28/16. Kara Thomas, RN BSN OCN Skagit Regional Health

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1 Hypersensi/vity Reac/ons: How To Prepare For The (Not-So) Unexpected Kara Thomas, RN BSN OCN Skagit Regional Health Objec/ves An/cipate and recognize hypersensi/vity reac/ons during chemotherapy and biotherapy administra/on Iden/fy nursing and pa/ent implica/ons in the preven/on and management of hypersensi/vity reac/ons Defini/on Hypersensi)vity (also called hypersensi/vity reac/on or infusion reac/on) is a set of undesirable reac/ons produced by the normal immune system. These reac/ons may be damaging, uncomfortable, or occasionally fatal. Unexpected and excessive responses of the immune system to a foreign substance (an/gen). 1

2 Immune System Review The purpose of the immune system is to protect self from non-self by neutralizing, elimina/ng, or destroying foreign invaders. Immune System Review Major anatomical structures include sites for produc/on, matura/on, prolifera/on, and func/on of the cells of the immune system: bone marrow, thymus, lymph nodes, and spleen. Immune System Review White blood cells are the major cells of the immune system. The various types include granulocytes (neutrophils, basophils, and eosinophils), macrophages, NK cells, and lymphocytes (B and T lymphocytes). 2

3 Immune System Review Immune System Innate Adap/ve Humoral Cell- Mediated Immune System Review Innate Immediate response Involves neutrophils and macrophages Can damage host /ssue Amnesiac Adap)ve Slower response, especially with first exposure (naïve) Specific an/gen recogni/on Memory: rapid recall of an/gen Immune System Review Humoral B lymphocytes are s/mulated to produce an/bodies (immunoglobulins) in response to an an/gen. Plasma cells produce five types of immunoglobulins: IgG, IgA, IgM, IgD, and IgE. Cell-Mediated Involves interac/ons of Helper and Cytotoxic T cells Cytokines: potent glycoprotein mediators that signal between cells and coordinate the immune response 3

4 Types of Hypersensi/vity I: Allergy/anaphylaxis An/gen exposure causes release of vasoac/ve substances (histamine, prostaglandins) from mast cells or basophils. Usually IgE dependent. Bee s/ng II: An/body mediated An an/gen or hapten that is in/mately associated with a cell binds to an/body, leading to cell or /ssue injury IgG or IgM: Rh- mom III: Immune complex mediated Damage is caused by forma/on or deposi/on of an/gen-an/body complexes in vessels or /ssue Lupus, serum sickness IV: Delayed An/gen exposure sensi/zes T cells, which then mediate /ssue injury Contact derma//s, poison ivy Anaphylac/c Reac/on An an/gen is recognized as foreign Body forms an/bodies (part of adap/ve response) Most common an/body formed during an allergic reac/on is IgE IgE promotes histamine release from mast cells Manifesta/on of Anaphylaxis Cutaneous: rash, hives, angioedema GI: nausea, vomi/ng, diarrhea Respiratory: shortness of breath, difficulty breathing, wheezing Circulatory: hypotension, chest pain Sense of impending doom.. 4

5 Anaphylactoid Reac/on An/gen is recognized as foreign T Lymphocytes cause release of cytokines Also called cytokine release syndrome or infusion reac/on Manifesta/on of Cytokine Release Syndrome Fever Chills Headache Nausea Hypertension Fa/gue Can be just as severe as anaphylaxis Anaphylac/c vs. Anaphylactoid Despite the type of reac/on, the symptoms and the treatment may look the same 5

6 Incidence of Hypersensi/vity Overall incidence of hypersensi/vity reac/ons to chemotherapy or biotherapy varies First infusion of rituximab: 50% First infusion of trastuzumab: 40% First or second infusion of paclitaxel: 30% Sixth or seventh infusion of carbopla/n: 12% Risk Factors Chemotherapy Carbopla/n Oxalipla/n Paclitaxel Docetaxel Biotherapy Rituximab Cetuximab Traztuzumab Other Agents Phase 1 drugs Iron Dextran Peglo/case Pa/ent Risk Factors Failure to take prescribed premedica/on for prophylaxis Female First infusion of monoclonal an/body History or allergies (foods, medica/ons, bee s/ngs) History of asthma IV route of administra/on Geographic loca/on (higher rates of rxn to cetuximab in SE states) High lymphocyte counts Higher than normal chemotherapy or biotherapy doses History of autoimmune disease History of pulmonary infiltrates, cardiac or pulmonary dysfunc/on Mul/ple cycles of drugs (pla/num agents) Age (older age) Primary tumor type such as chronic lymphocy/c leukemia and mantel cell lymphoma 6

7 Preven/on Obtain and record baseline vital signs Review allergy history Ensure availability of emergency medica/ons Administer test dose if indicated Slow ini/al infusion rate Administer premedica/ons An/pyre/c An/histamine Cor/costeroid Ra/onale for premeds An/pyre/cs: Prevent and/or mi/gate fever during reac/on An/histamines: H1 blockers mediate tachycardia, pruri/s, rhinnorhea, bronchospasm H2 blockers add media/on of flushing, hypotension & headache Cor/costeroids: Inhibit cytokine release, ameliorate symptoms, an/-inflammatory Emergency Plan If pa/ent exhibits signs/symptoms of HSR: Stop infusion Stay with pa/ent and call for help Maintain open IV line (withdraw causa/ve agent if possible) Assess airway, breathing and circula/on Monitor vital signs If hypotensive, place pa/ent in supine posi/on If vomi/ng, place pa/ent in side-lying posi/on 7

8 Emergency Plan Administer emergency medica/ons as indicated Administer oxygen at high flow rate Provide emo/onal support Document interven/ons and responses Con/nue to monitor as symptoms may recur Pa/ent and Family Teaching Prior to administra/on, discuss possibility of hypersensi/vity reac/on Provide instruc/on on what symptoms to report Aker administra/on, discuss possibility of delayed reac/on and how to manage Illustra/on Immune System: Protect self from non-self Neutralize Eliminate Destroy Non-self Premedicated Immune System: Less responsive More permissive 8

9 Signs and Symptoms of HSR Uneasiness, agita/on Chest /ghtness SOB with or without wheezing Hypotension Tachycardia Headache Itching, local or generalized Abdominal cramping, diarrhea, nausea Periorbital or facial edema Management of Anaphylac/c Reac/on Aker ini/al stabiliza/on is complete, con/nue to monitor pa/ent Provider will formulate plan to con/nue or abort infusion, depending of severity of reac/on May amempt desensi/za/on protocol (necessary for each subsequent infusion of causa/ve agent) Add allergy to EHR Management of Cytokine Release Syndrome Oken managed by short-term cessa/on of infusion Administer addi/onal histamine blocker Restart infusion at slower rate 9

10 Algorithm for Managing Suspected Hypersensi)vity Reac)ons Pa)ent exhibits signs of hypersensi)vity or infusion reac)on (Uneasiness or agita/on, pruritus, ur/caria, dyspnea, bronchospasm, hypotension, itching, facial edema, lightheadedness or dizziness, abdominal cramping, diarrhea, nausea, vomi/ng) Mild Reac)on facial flushing, rash, low back pain, or fall of <30mm Hg in systolic BP 1. Stop infusion and stay with pa/ent. 2. Infuse IV normal saline or fluid as ordered. 3. Monitor VS, O2 sat at least q15min for 1 hour. 4. Administer addi/onal histamine blockers as ordered Response No response or symptoms worsen: Proceed to number 4. Severe Reac)on bronchospasm, hypotension with a >30mmHg drop in systolic BP, respiratory distress, /ghtness in the throat or across the chest 1. Stop infusion; infuse IV normal saline 2. Administer O2 at 2-4 L per NC. No/fy MD. 3. Stay with pa/ent and monitor vital signs. 4. Place pa/ent supine and elevate legs if SBP<60mmHg. 5. Monitor and maintain airway. 6. Administer emergency medica/ons : Histamine blockers Epinephrine--Cor/costeroids 7. Provide emo/onal support. Con/nue to monitor. Discuss plan w/md. Resume infusion rate at 50% of previous rate Pa/ent Improves An/cipate need for CPR. Ac/vate emergency response (911 or code team). Post-Reac/on Decisions Proper documenta/on facilitates informed decision making about the safety of subsequent infusions Overes/ma/ng grade of reac/on may limit further treatment op/ons by denying rechallenge Underes/ma/ng grade of reac/on may lead to inadequate vigilance and preparedness for poten/al emergent situa/on and/or place pa/ent at unnecessary risk if rechallenged NCI CTCAE Grading Adverse Event Infusionrelated reac/on Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Mild transient reac/on; infusion interrup/on not indicated; interven/on not indicated Therapy or infusion interrup/on indicated but responds promptly to symptoma/c treatment Not rapidly responsive to symptoma/c medica/on and/or brief interrup/on of infusion Life-threatening consequences; urgent interven/on indicated Death Na/onal Cancer Ins/tute Common Terminology Criteria for Adverse Events 10

11 Desensi/za/on Different regimens depending on drug Necessary for each subsequent exposure to causa/ve agent Altered infusion rate, concentra/on or both Examples of Desensi/za/on Protocols Carbopla)n 1/1000 of total dose 1/100 of total dose 1/10 of total dose Remainder of dose Carbopla)n Start infusion at 20ml/hr Titrate by 20ml/hr every 15 minutes to maximum rate of 264ml/hr Conclusion Hypersensi/vity reac/ons are frightening. Oncology nurses are uniquely posi/oned to directly influence the management of hypersensi/vity reac/ons. Awareness, prepara/on and close observa/on will aid in minimizing the impact of a reac/on. 11

12 References Eisenberg, S. (2013). Infusion reac/ons. In M. Kaplan (Ed.). Understanding and managing oncologic emergencies: A resource for nurses (pp ). Pimsburgh, PA: Oncology Nursing Society. Infusion reac/ons to systemic chemotherapy. Retrieved from UpToDate.com, 2/4/16. Infusion reac/ons to therapeu/c monoclonal an/bodies used for cancer therapy. Retrieved from UpToDate.com, 2/8/16. Polovich, M., Olsen, M., & Lefebvre, K.B. (Eds.). (2014). Chemotherapy and biotherapy guidelines and recommenda9ons for prac9ce. ( 4 th ed.). Pimsburgh, PA: Oncology Nursing Society. Role of cytokines in the immune system. Retrieved from UpToDate.com, 2/4/16. Viale, P.H. (2010). Dermatologic complica/ons. In J. Eggert (Ed.), Cancer basics (pp ). Oncology Nursing Society: Pimsburgh, PA. Viale, P.H., & Sanchez-Yamamoto, D. (2010). Biphasic and delayed hypersensi/vity reac/ons: Implica/ons for oncology nursing. Clinical Journal of Oncology Nursing, 14(3), Vogel, W.H. (2012). Infusion reac/ons: Diagnosis, assessment, and management. Clinical Journal of Oncology Nursing, 14(2), E10-E21. 12