Extravasation Management

Table 2. Vesicant extravasation management guidelines
Drug classification and medication name	Immediate topical therapy	Antidote or treatment	Antidote or treatment administration, patient monitoring, and follow-up
Alkylating agents Mechlorethamine hydrochloride (nitrogen mustard, Mustargen^®)	Apply ice for 6-12 hours following sodium thiosulfate antidote injection (Merck and Co., Inc., 2005).	Antidote Sodium thiosulfate Mechanism of action Neutralizes mechlorethamine to form nontoxic thioesters that are excreted in the urine Preparation Prepare ¹/₆ molar solution. If 10% sodium thiosulfate solution: Mix 4 ml with 6 ml sterile water for injection. If 25% sodium thiosulfate solution: Mix 1.6 ml with 8.4 ml sterile water. Storage Store at room temperature between 15°-30°C (59°-86°F).	Inject 2 ml of the sodium thiosulfate solution for each milligram 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). Assess the extravasation area for pain, blister formation, and skin sloughing periodically as needed or in accordance with institutional policy. Instruct the patient to monitor the extravasation site and report fever, chills, blistering, skin sloughing, and worsening pain. Instruct patients with peripheral extravasations to report arm or hand swelling and stiffness.
Anthracyclines Daunorubicin (Cerubidine^®) Doxorubicin (Adriamycin^®) Epirubicin (Ellence^®) Idarubicin (Idamycin^®)	Apply ice pack (but remove at least 15 minutes prior to Totect^® treatment).	Treatment Totect Note Totect is a patent-protected, U.S. Food and Drug Administration (FDA)-approved treatment for anthracycline extravasation (TopoTarget USA, 2007). Zinecard^® and generic dexrazoxane are neither indicated nor FDA-approved for anthracycline extravasation treatment. There are no therapeutic equivalents to Totect (FDA, 2007). Mechanism of action Unknown Dose The recommended dose of Totect is based on the patient's body surface area: Day one: 1,000 mg/m² Day two: 1,000 mg/m² Day three: 500 mg/m² The maximum recommended dose is 2,000 mg on days one and two and 1,000 mg on day three. The dose should be reduced 50% in patients with creatinine clearance values < 40 ml/minute. Preparation Each vial of Totect 500 mg must be mixed with 50 ml diluent. The patient's dose of Totect is then added to a 1,000 ml normal saline infusion bag for administration. Storage The Totect emergency treatment kit contains 10 vials of Totect 500 mg and 10 vials of 50 ml diluent and is stored at 25°C (77°F).	The first Totect infusion should be initiated as soon as possible and within 6 hours of the anthracycline extravasation. Totect should be infused over 1-2 hours 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, and a large vein distal to the extravasation site should be used for Totect administration. Dimethyl sulfoxide should not be applied to the extravasation area. Assess the extravasation area for pain, blister formation, and skin sloughing periodically as needed or in accordance with institutional policy. Instruct the patient to monitor the extravasation site and report fever, chills, blistering, skin sloughing, and worsening pain. Instruct patients with peripheral extravasations to report arm or hand swelling and stiffness. Instruct the patient about Totect treatment side effects (e.g., nausea/vomiting, diarrhea, stomatitis, bone marrow suppression, elevated liver enzyme levels, infusion site burning). Monitor the patient's complete blood count and liver enzyme levels.
Antitumor antibiotics Mitomycin (Mutamycin^®) Dactinomycin (actinomycin D, Cosmegen^®)	Apply ice pack for 15-20 minutes at least four times a day for the first 24 hours.	No known antidotes or treatments	Assess the extravasation area for pain, blister formation, and skin sloughing periodically as needed or in accordance with institutional policy. In collaboration with the physician or advanced practice nurse, refer the patient for specialized care when indicated or needed (e.g., plastic or hand surgery consult, physical therapy, pain management, rehabilitation services).
Plant alkaloid or microtubular inhibiting agents Vinblastine (Velban^®) Vincristine (Oncovin^®) Vindesine Vinorelbine (Navelbine^®)	Apply warm pack for 15-20 minutes at least four times per day for the first 24-48 hours. Elevate extremity (peripheral extravasations).	Antidote Hyaluronidase Mechanism of action Degrades hyaluronic acid and promotes drug diffusion Preparation Available hyaluronidase preparations are AmphadaseTM [bovine] (hyaluronidase injection (Amphastar Pharmaceuticals, 2005). Vial contains 150 units per 1 ml. Do not dilute. Use solution as provided. Store in refrigerator at 2°-8°C (36°-46°F). Hydase™ (hyaluronidase injection) Vial contains 150 units per 1 ml. Do not dilute. Use solution as provided. Store in refrigerator at 2°-8°C (36°-46°F). Hylenex^® [recombinant] (hyaluronidase human injection (Baxter Healthcare Corporation, 2006) Vial contains 150 units per 1 ml. Do not dilute. Use solution as provided. Store in refrigerator at 2°-8°C (36°-46°F). Vitrase^® [ovine] (hyaluronidase injection (ISTA Pharmaceuticals, 2007) Vial contains 200 units in 2 ml vial. Dilute 0.75 ml of solution with 0.25 ml of 0.9% sodium chloride (final concentration is 150 units per 1 ml). Store in refrigerator at 2°-8°C (36°-46°F).	Administer 1 ml of the 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). Assess the extravasation area for pain, blister formation, and skin sloughing periodically as needed or in accordance with institutional policy. Instruct the patient to monitor the extravasation site and report fever, chills, blistering, skin sloughing, and worsening pain. Instruct patients with peripheral extravasations to report arm or hand swelling and stiffness.
Taxanes Docetaxel (Taxotere^®) Paclitaxel (Taxol^®)	Apply ice pack for 15-20 minutes at least four times a day for the first 24 hours.	No known antidote or treatment. Docetaxel extravasation may cause hyperpigmentation, redness, and tenderness (Sanofi-Aventis, 2007). Paclitaxel is a mild vesicant; extravasation may cause induration, blistering, and rarely tissue necrosis (Bristol-Myers Squibb, 2003; Stanford & Hardwicke, 2003).	Assess the extravasation area for pain, blister formation, and skin sloughing periodically as needed or in accordance with institutional policy. Instruct the patient to monitor the extravasation site and report fever, chills, blistering, skin sloughing, and worsening pain. Instruct patients with peripheral extravasations to report arm or hand swelling and stiffness.