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SARASOTA MEMORIAL HOSPITAL TITLE: NURSING PROCEDURE DATE: REVIEWED: PAGES: 03/86 7/18 1 of 13 PS1094 ISSUED FOR: Nursing RESPONSIBILITY: RN Chemo Qualified PURPOSE: To provide the RN with specific steps to take if extravasation of a chemotherapeutic agent occurs. If extravasation of a chemotherapeutic agent should occur, contact the physician to obtain orders. OBJECTIVE: DEFINITIONS: The qualified registered nurse (RN) will take all precautions to treat extravasation of chemotherapeutic agents so that the patient will have minimal complications. 1. Extravasation: infiltration of a chemotherapeutic agent into tissues surrounding an intravenous (IV) site. 2. Vesicant: chemotherapeutic agent that produce severe local tissue reaction if extravasated. Tissue reactions may include severe irritation, edema, blisters, and/or necrosis. 3. Extreme irritant: chemotherapeutic agent that produce severe local tissue irritation and edema if extravasated. Tissue necrosis or blisters are possible if large amounts of concentrated doses are extravasated. KNOWLEDGE BASE: 1. Extravasation of vesicants or extreme irritants can cause severe tissue damage if not properly treated. Nerve damage, loss of major joint function, and disfiguring scars have occurred as a result of chemotherapeutic extravasation. 2. The treatment of extravasation can be controversial in terms of how to treat. The physician should always be consulted in conjunction with extravasation management. 3. Available evidence-based extravasation protocols are included in the relevant electronic chemotherapy order sets and are available for use in the event of an extravasation. 4. Extravasation Protocol may include use of the following: a. Administration of an antidote.

PAGE: 2 of 13 b. Cold Pack Kit: topical application of a cold pack: 1) Camptothecins: irinotecan, topetecan 2) Alkylating agents: bendamustine,concentrated carboplatin, concentrated cisplatin, dacarbazine, ifosfamide, mechlorethamine, melphalan 3) Anthracyclines: daunorubicin, doxorubicin, epirubicin, idarubicin 4) Anti-tumor antibiotics: dactinomycin, mitomycin, mitoxantrone 5) Taxanes (classified at SMH as irritants): docetaxel, paclitaxel c. Hot Pack Kit: topical application of a hot/warm pack: 1) Alkylating agents: oxaliplatin (classified at SMH as an irritant) 2) Epipodophyllotoxins: etoposide 3) Vinca alkaloids: vinblastine, vincristine, vinorelbine EQUIPMENT: Equipment will differ for the individual agents. Refer to the procedure/appendix. PROCEDURE: 1. If an RN suspects an extravasation, follow the procedure outlined in Appendix and immediately contact the physician for emergency extravasation orders. 2. Based upon the chemotherapeutic drug administered, the appropriate antidote and kit will be used. 3. The appropriate procedure will be followed per Appendix instructions relative to the drug given. 4. Instill or apply antidote as directed by the physician. Refer to suggested antidotes table in Appendix. 5. If injecting the antidote, inject subcutaneously, in a clockwise fashion into infiltrated area using a 25-gauge (or smaller) needle. Refer to Appendix. Remember to use a new needle with each injection. NOTE: Corticosteroids may be ordered for many drugs as it is believed to reduce complications. 6. Measure and record size and condition of extravasation site every shift or every visit if an outpatient.

PAGE: 3 of 13 PATIENT EDUCATION: Instructions for the patient with an extravasation include (Gonzalez, 2013): 1. Look at the area of extravasation every day. Notify the nurse or physician if you notice: a. Changes in skin color b. Increased redness c. Hand swelling or stiffness d. Appearance of blisters e. Peeling or flaking skin 2. Notify the nurse or physician if the you experience: a. Increased discomfort in the hand or arm b. Increase in pain c. Pain that interferes with exercising the hand and arm d. Fever or chills 3. Elevate the affected arm on a pillow whenever possible. 4. Avoid pressure or friction. Do not rub the area (Gullatte, 2014). 5. Do not apply any other lotions, creams or ointments to the area. 6. After showering, pat the area dry. Do not rub. 7. If taking a bath a home, cover the area with a watertight barrier or dressing. 8. Gently exercise the affected arm or hand, if not contraindicated. 9. Avoid wearing tight clothing around the affected area. 10. Keep the affected area out of strong sunlight. 11. If not contraindicated, after 48 hours use the affected arm or hand normally to promote full range of motion (Gullatte, 2014). DOCUMENTATION: 1. Nursing documentation of the extravasation should be done in the electronic extravasation structured note and include: a. Patency of vascular access (including a description of the quality of the blood return prior to, during, and post extravasation). b. Vesicant administration technique (infusion, IVP, etc.) c. Symptoms reported by patient. d. Assessment of the extremity for range of motion and/or discomfort with movement. e. Patient teaching (including skin assessment and conditions to report). f. Follow-up recommendations (referrals, return appointments). 2. IV/Lines flowsheet documentation:

PAGE: 4 of 13 a. Type, size, location of vascular access. b. Previous number and location of venipuncture attempts. c. Peripheral or central line complication section: 1) Date of the extravasation. 2) Amount and concentration of extravasated agent. 3) Assessment and description of the site appearance (including measurements of edema and/or redness). 4) Immediate nursing interventions (including physician notification, topical interventions, antidote administration, extravasation treatments). REFERENCES: 1. Fidalgo, J. A. P., Fabregat, L. G., Cervantes, A., Marguiles, A., Vidall, C., & Roila, F. (2012). Management of chemotherapy extravasation: ESMO-EONS clinical practice guidelines. Annals of Oncology, 23 (Supplement 7), vii167-vii173. 2. Gonzalez, T. (2013). Chemotherapy extravasation: Prevention, identification, management, and documentation. Clinical Journal of Oncology Nursing, 17(1), 61-64. 3. Gullatte, M. M. (Ed.). (2014). Clinical guide to antineoplastic therapy: A chemotherapy handbook. Pittsburgh, PA: Oncology Nursing Society. 4. Payne, A. & Butler, J. (2017). Extravasation injury from chemotherapy and non-neoplastic vesicants. UpToDate, Inc. Retrieved from https://www.uptodate.com/contents/extravasation-injuryfrom-chemotherapy-and-other-non-antineoplasticvesicants?source=search_result&search=rx%20cytoto xic%20drug%20extravasation&selectedtitle=3~150 5. Polovich, M., Olsen, M., & K. B. LeFebvre. (Eds.). (2014). Chemotherapy and biotherapy guidelines and recommendations for practice (4 th ed.). Pittsburgh, PA: Oncology Nursing Society. 6. Schulmeister, L. (2011). Extravasation management: clinical update. Seminars in Oncology nursing, 27(1), 82-90. 7. Schulmeister, L. (2011). Preventing and managing vesicant chemotherapy extravasations. The Journal of Supportive Oncology, 8(5), 212-215.

PAGE: 5 of 13 8. Truvan Health Analytics Inc. (2016). MicroMedex 2.0: Cytotoxic drug extravasation therapy. Retrieved from http://www.micromedexsolutions.com/micromedex2/libr arian/cs/108cf7/nd_pr/evidencexpert/nd_p/evidenc expert/duplicationshieldsync/d1ffb0/nd_pg/e videncexpert/nd_b/evidencexpert/nd_appproduct/evid encexpert/nd_t/evidencexpert/pfactionid/evidencexpe rt.intermediatetodocumentlink?docid=8808&contents etid=50&title=cytotoxic+drug+extravasation+therapy& servicestitle=cytotoxic+drug+extravasation+therapy 9. Wolters Kluwer. (2017). Lexicomp Online: Management of drug extravasations (Lexi-Drugs). Retrieved from http://online.lexi.com/lco/action/doc/retrieve/docid/patch _f/4111 10. Bragalone, D. L. (2015). Drug information handbook for Oncology: A complete guide to combination chemotherapy regimens. Hudson, OH: Lexi-Comp Inc. REVIEWING AUTHOR (S): Rebecca Kisgen, Clinical Pharmacist, Sarasota Memorial Infusion Deena Damsky Dell MSN, CNS, RN-BC, AOCN, APN Oncology Barbara Poropat BSN, RN, OCN NPD Oncology

PAGE: 6 of 13 Appendix 1. Immediately STOP administering the vesicant/irritant and IV fluids. 2. Disconnect the IV tubing from the IV device. Do not remove the IV device or non-coring port needle. 3. Slowly aspirate as much drug as possible from the IV device needle using a 1-3 ml syringe for peripheral sites and 10 ml syringe for midlines and central line catheters. Do not apply pressure to the area. 4. Temporarily leave IV catheter in place after Cisplatin extravasation to allow for sodium thiosulfate administration. Otherwise, remove the peripheral IV device or port needle. Do not use site for IV access any longer. 5. Notify the physician. 6. Elevate and rest the area for 48 hours to minimize swelling. 7. Initiate substance specific measures. 8. Document all procedures. 9. Provide patient education. 10. Observe region for pain, induration, or necrosis. 11. If pain and/or erythema persist beyond 48 hours or symptoms worsen, notify physician. Surgical debridement may be necessary. SUGGESTED ANTIDOTES FOR VESICANT DRUGS Dactinomycin ---------------- - Apply cold pack for 15 minutes every 6 hours for 48 (see REFERENCES above) Daunorubicin - Initiate dexrazoxane therapy as soon as possible and within 6 hours of the anthracycline extravasation. - Dexrazoxane Infusion Protocol: o Day 1: 1000 mg/m 2 (maximum o Day 2: 1000 mg/m 2 (maximum - Apply cold pack for 30 minutes, then every 15 minutes on day 1 only. Remove at least 15 minutes prior to dexrazoxane treatment. - Avoid cold pack after dexrazoxane administration to - Dose of dexrazoxane should be reduced 50% in patients with a CrCl <40 ml/minute. - Infusion of dexrazoxane should be infused in a large vein in an area other than the extravasation area (e.g. opposite arm).

PAGE: 7 of 13 allow sufficient blood flow to the same arm should o Day 3: 500 mg/m 2 (maximum dose 1000 mg) o Infuse all doses over 1-2 hours area of extravasation. 3 - The be used only when the patient s clinical status (e.g. lymphedema, loss of limb) precludes use of the unaffected arm. A large vein distal to the extravasation site should be used. Doxorubicin - Initiate dexrazoxane therapy as soon as possible and within 6 hours of the anthracycline extravasation. - Dexrazoxane Infusion Protocol: o Day 1: 1000 mg/m 2 (maximum o Day 2: 1000 mg/m 2 (maximum o Day 3: 500 mg/m 2 (maximum dose 1000 mg) o Infuse all doses over 1-2 hours Epirubicin - Initiate dexrazoxane therapy as soon as possible and within 6 hours of the anthracycline extravasation. - Dexrazoxane Infusion Protocol: o Day 1: 1000 mg/m 2 (maximum o Day 2: 1000 mg/m 2 (maximum o Day 3: 500 mg/m 2 (maximum dose 1000 mg) o Infuse all doses over 1-2 hours - Apply cold pack for 30 minutes, then every 15 minutes on day 1 only. Remove at least 15 minutes prior to dexrazoxane treatment. - Avoid cold pack after dexrazoxane administration to allow sufficient blood flow to the area of extravasation. 3 - Apply cold pack for 30 minutes, then every 15 minutes on day 1 only. Remove at least 15 minutes prior to dexrazoxane treatment. - Avoid cold pack after dexrazoxane administration to allow sufficient blood flow to the area of extravasation. 3 - Dose of dexrazoxane should be reduced 50% in patients with a CrCl <40 ml/minute. - Infusion of dexrazoxane should be infused in a large vein in an area other than the extravasation area (e.g. opposite arm). - The same arm should only be used only when the patient s clinical status (e.g. lymphedema, loss of limb) precludes use of the unaffected arm. A large vein distal to the extravasation site should be used. - Dose of dexrazoxane should be reduced 50% in patients with a CrCl <40 ml/minute. - Infusion of dexrazoxane should be infused in a large vein in an area other than the extravasation area (e.g. opposite arm). - The same arm should be used only when the patient s clinical status (e.g. lymphedema, loss of limb) precludes use of the unaffected arm. A large vein distal to the extravasation site should be

PAGE: 8 of 13 used. Idarubicin - Initiate dexrazoxane therapy as soon as possible and within 6 hours of the anthracycline extravasation. - Dexrazoxane Infusion Protocol: o Day 1: 1000 mg/m 2 (maximum o Day 2: 1000 mg/m 2 (maximum o Day 3: 500 mg/m 2 (maximum dose 1000 mg) o Infuse all doses over 1-2 hours Mechlorethamine (Nitrogen Mustard) Isotonic Sodium Thiosulfate - Inject 2 ml of Sodium Thiosulfate solution for each mg of mechlorethamine suspected to have extravasated. - Inject the solution subcutaneously into the extravasation site using a 25 gauge or smaller needle (change needle with each injection). - Apply cold pack for 30 minutes, then every 15 minutes on day 1 only. Remove at least 15 minutes prior to dexrazoxane treatment. - Avoid cold pack after dexrazoxane administration to allow sufficient blood flow to the area of extravasation. 3 - Apply cold pack for 6-12 hours following sodium thiosulfate antidote injection. - Dose of dexrazoxane should be reduced 50% in patients with a CrCl <40 ml/minute. - Infusion of dexrazoxane should be infused in a large vein in an area other than the extravasation area (e.g. opposite arm). - The same arm should be used only when the patient s clinical status (e.g. lymphedema, loss of limb) precludes use of the unaffected arm. A large vein distal to the extravasation site should be used. Pharmacy Instructions: - Prepare 1/6 molar solution. - If 10% Na Thiosulfate: Mix 4 ml with 6 ml sterile water for injection - If 25% Na Thiosulfate: Mix 1.6 ml with 8.4 ml of sterile water for injection - Pharmacy will prepare five(5) 2mL-syringes for nursing use. This will be a combined total dose of 10mL sent to nursing. - Nursing will administer one(1) 2mL-syringe for every mg of mechlorethamine extravasated. - Nursing will only use the number of syringes necessary for the amount extravasated - Reference: 4, 8, 9,10

PAGE: 9 of 13 Mitomycin 50% dimethyl sulfoxide (DMSO) - Apply cold pack for 15 minutes - Reference: 3, 8, 9 - Begin within 10 minutes of extravasation. every 6 hours for 48 - Apply 1-2 ml of DMSO topically to the site using a sterile gauze pad. - Apply to area covering twice the size as the extravasation area. - Allow to air dry. - Do not cover with dressing. - Repeat every 8 hours for 7 days. Vinblastine Vincristine Hyaluronidase - Administer 1 ml (150 units) of hyaluronidase solution as five separate injections, each containing 0.2 ml of hyaluronidase, subcutaneously into the extravasation site using a 25 gauge or smaller needle (change needle with each injection). Hyaluronidase - Administer 1 ml (150 units) of hyaluronidase solution as five separate injections, each containing 0.2 ml of hyaluronidase, subcutaneously into the extravasation site using a 25 gauge or smaller needle (change needle with each injection). - Apply warm pack for 15 - Apply warm pack for 15 - Corticosteroids and topical cooling appear to worsen absorption of the drug - Corticosteroids and topical cooling appear to worsen absorption of the drug Vinorelbine Hyaluronidase - Administer 1 ml (150 units) of hyaluronidase solution as five separate injections, each containing 0.2 ml of hyaluronidase, subcutaneously into the extravasation site using a 25 gauge or smaller - Apply warm pack for 15 - Corticosteroids and topical cooling appear to worsen absorption of the drug

PAGE: 10 of 13 needle (change needle with each injection).

PAGE: 11 of 13 SUGGESTED ANTIDOTES FOR IRRITANT DRUGS Bendamustine Isotonic Sodium Thiosulfate - Apply cold pack for 6-12 hours Pharmacy Instructions: - Inject 2 ml of Sodium Thiosulfate following sodium thiosulfate - Prepare 1/6 molar solution. solution for each mg of bendamustine suspected to have extravasated. antidote injection. - If 10% Na Thiosulfate: Mix 4 ml with 6 ml sterile water for - Inject the solution subcutaneously into injection the extravasation site using a 25 gauge or smaller needle (change needle with each injection). - If 25% Na Thiosulfate: Mix 1.6 ml with 8.4 ml of sterile water for injection - Pharmacy will prepare five(5) 2mL-syringes for nursing use. This will be a combined total dose of 10mL sent to nursing. - Nursing will administer one(1) 2mL-syringe for every mg of bendamustine extravasated. - Nursing will only use the number of syringes necessary for the amount extravasated Carboplatin (concentrated) - Extravasation at concentrations of 10 mg/ml or greater Isotonic Sodium Thiosulfate - Inject 2 ml of Sodium Thiosulfate solution for each mg of carboplatin suspected to have extravasated. - Inject the solution subcutaneously into the extravasation site using a 25 gauge or smaller needle (change needle with each injection). - Apply cold pack for 6-12 hours following sodium thiosulfate antidote injection. Carmustine Notify physician of conflicting recommendations as listed in reference #7: Localization and neutralization through the use of cold compresses and dimethylsulfoxide. Inject 1 to 2 ml SQ 150 international units/ml hyaluronidase, and topical application of dry, warm heat for 1 to 2 - Reference: 8, 9,10 Pharmacy Instructions: - Prepare 1/6 molar solution. - If 10% Na Thiosulfate: Mix 4 ml with 6 ml sterile water for injection - If 25% Na Thiosulfate: Mix 1.6 ml with 8.4 ml of sterile water for injection - Reference: 8 - Reference: 7

PAGE: 12 of 13 Cisplatin (concentrated) - Only extravasations of more than 20 ml of a 0.5 mg/ml. Dacarbazine For greater extravasations, local infiltration of 5 ml: sodium thiosulfate 10%/distilled water 4:6 relation. Ice 20 minutes 4 times a day for 1 to 2 days. Isotonic Sodium Thiosulfate - Apply cold pack for 6-12 hours - Inject 2 ml of Sodium Thiosulfate following sodium thiosulfate solution into existing IV line for each antidote injection. 100mg of cisplatin suspected to have extravasated. - Additionally, inject 1ml as 0.1ml injections subcutaneously into the extravasation site using a 25 gauge or smaller needle (change needle with each injection). Isotonic Sodium Thiosulfate - Inject 2 ml of Sodium Thiosulfate solution for each mg of dacarbazine suspected to have extravasated. - Inject the solution subcutaneously into the extravasation site using a 25 gauge or smaller needle (change needle with each injection). - Apply cold pack for 6-12 hours following sodium thiosulfate antidote injection. Daunorubicin Liposomal -------------------- - Apply cold pack for 15 Docetaxel -------------------- - Apply cold pack for 15 Doxorubicin Liposomal -------------------- - Apply cold pack for 15 Etoposide Hyaluronidase - Administer 1 ml (150 units) of hyaluronidase solution as five separate injections, each containing 0.2 ml of - Apply warm pack for 15 Pharmacy Instructions: - Prepare 1/6 molar solution. - If 10% Na Thiosulfate: Mix 4 ml with 6 ml sterile water for injection - If 25% Na Thiosulfate: Mix 1.6 ml with 8.4 ml of sterile water for injection - References: 3, 8 Pharmacy Instructions: - Prepare 1/6 molar solution. - If 10% Na Thiosulfate: Mix 4 ml with 6 ml sterile water for injection - If 25% Na Thiosulfate: Mix 1.6 ml with 8.4 ml of sterile water for injection - Reference: 8 - Reference: 3, 8 - Reference: 3, 4, 8 - Reference: 3, 8 - Reference: 3, 8

PAGE: 13 of 13 hyaluronidase, subcutaneously into the extravasation site using a 25 gauge or smaller needle (change needle with each injection) Ifosfamide -------------------- - Apply cold pack for 15 - Reference: 3, 8 Irinotecan -------------------- - Apply cold pack for 15 - Reference: 3, 8 Melphalan -------------------- - Apply cold pack for 15 - Reference: 3 Mitoxantrone -------------------- - Apply cold pack for 15 Oxaliplatin -------------------- - Apply warm pack for 1 hour. - Warm pack is preferable and may reduce local pain and inflammation. Paclitaxel (including protein-bound Abraxane ) -------------------- - Apply cold pack for 15 Topotecan -------------------- - Apply cold pack for 15 - May cause blue discoloration of infusion site area 4 - Reference: 3, 4, 8 - Check patient s ordered medications and call MD to discuss corticosteroid order. High-dose dexamethasone (8 mg twice daily for up to 14 days) may be useful to reduce inflammation associated with extravasation. - Reference: 4, 7 - Reference: 3, 4, 8 - Reference: 3, 8