Extravasation 101
Classification
What do I do?!?
Antidote
Anthracycline
100
Define extravasation and give 3 common initial symptoms.
Extravasation is defined as the non-intentional administration of chemotherapy into areas outside the venous system. Common initial symptoms: discomfort or pain ("burning sensation"), ranges from mild-intense and may not always be present; erythema; edema; leaking of fluid around IV device
100
Name a DNA-binding vesicant known to cause a continuing cycle of tissue damage
Anthracyclines: doxorubicin, daunorubicin, epirubicin, idarubicin; Meclorethamine (nitrogen mustard); Bendamustine; Dactinomycin; Mitomycin C
100
BH is a 54 yo male diagnosed with glioblastoma multiforme here for treatment with bevacizumab and carboplatin. At the end of carboplatin infusion, it was noted that there was no blood return from the patient's chest port access. Patient complains of "stinging below port site." The nurse comes to you in a panicked state asking what to do. What do you tell her?
Initial management: Have the nurse immediately stop administration of the chemotherapy and disconnect the infusion, but do not remove the cannula. If it is an imported port, assess needle for correct placement. Inspect the area for skin discoloration, swelling, and tenderness. Avoid applying direct manual pressure to the extravasated site. Note concentration and amount of drug remaining in the infusion bag or syringe. Attempt to aspirate as much drug as possible from cannula. Mark the affected area. Bevacizumab is a non-vesicant (neutral). Carboplatin is an irritant. Apply intermittent cooling and observe.
100
1 mL of this 150 unit/mL antidote solution is administered subcutaneously as 5 separate injections (each 0.2 mL) into the area of a vincristine extravasation.
Hyaluronidase
100
This is the only FDA approved product of dexrazoxane for use in management of anthracycline extravasation in the United States.
Totect. Cost comparison: Totect kit $14,750 (10 vials dexrazoxane 500 mg + diluents) with replacement for expired kit; $6,500 for kit with no replacement program. Zinecard 500 mg: ~$230/vial ($2,300 for 10 vials)
200
This is the most important approach to minimizing the consequences of extravasation
Prevention
200
Vinca alkaloids are considered what type of vesicant
Non-DNA binding vesicant
200
AR is a 35 yo female here for FOLFOX treatment for metastatic colon cancer. Well into the oxaliplatin/leucovorin infusion, the patient rings the call bell complaining of tenderness in her left arm and swelling in the left chest/port area. The nurse immediately stops the infusion as the chemotherapy has infiltrated to the left chest area. There is mild redness at the extravasation site. Port is deaccessed and noted to be dislodged. Nurse aspirates 1/2 mL of fluid from the port. How would you treat AR's extravasation?
Oxaliplatin is an irritant (Fluorouracil and Oxaliplatin are irritants. Leucovorin is a non-vesicant.) Apply warm compress (not cold). Avoid cold compress in this situation because it can exacerbate/precipitate the cold sensitivities/neuropathy associated with oxaliplatin. May give antidote, but there is no known antidote.
200
This antidote is used to treat extravasation of taxanes
No known antidote exists for taxanes or mitomycin. Initial topical therapy involves applying ice pack for 15-20 minutes at least 4 times/day for the first 24 hours.
200
What is the mechanism of action of dexrazoxane in treating anthracycline extravasations?
Reduction of oxidative stress due to complexes of metal ions and anthracyclines by chelating metal ions; Blockade of topoisomerase II poisons by catalytic inhibition of Topo II
300
Chemotherapy agents are grouped into 3 broad categories based on this potential. Name this potential and the 3 categories.
Categorized based on potential for tissue damage. 3 broad categories: vesicant, irritant, non-vesicant (neutral)
300
Cyclophosphamide and fluorouracil are classified as what category
Non-vesicants (neutral) do not impair or destroy tissue. Examples: asparaginase, bleomycin, cyclophosphamide, cytarabine, etoposide, fluorouracil, gemcitabine, methotrexate, rituximab
300
TO, 63 yo male, diagnosed with follicular non-Hodgkin's lymphoma is here for R-CHOP treatment. Patient has a chest port. During vincristine infusion, patient complains of discomfort in chest and redness developing around the port. The nurse stops the infusion and manages to aspirate 1 mL of fluid from the port site. She asks for your advice on how to treat the extravasation. What do you tell her?
Vincristine is a non-DNA binding vesicant. Immediate topical therapy involves applying warm pack for 15-20 minutes at least 4 times/day for the first 24-48 hours. Antidote for vincristine extravasation is Hyaluronidase.
300
Can DMSO be used to treat anthracycline extravasations?
DMSO is a topical solvent that has been used in the past. It is no longer used for anthracycline extravasations because it decreases the efficacy of dexrazoxane.
300
An ice pack is applied at the site of a doxorubicin extravasation. What must the nurse do before administering the antidote dexrazoxane?
Remove the ice pack at least 15 minutes prior to dexrazoxane infusion to allow for sufficient blood flow in the area of extravasation
400
Name 3 determinants of tissue injury severity with extravasation
Volume & concentration of drug; Anatomical site of extravasation; Vesicant potential of drug; Patient factors (older age, comorbidity, immunocompromised)
400
Name two irritants that in high concentrations and large volumes can cause ulcerations
Taxanes (docetaxel, paclitaxel); Platinum agents (cisplatin)
400
Nurse runs in to tell you that mechlorethamine has extravasated. She has already applied a cold pack. What antidote should be used and how should it be administered?
Mechlorethamine is a DNA-binding vesicant. Inject 2 mL of a 1/6 molar sodium thiosulfate solution for every 1 mg of extravasated mechlorethamine, subcutaneously at the extravasation site using a 25-gauge or smaller needle. If using more than one needle, change the needle for each injection. In this example, antidote would be 3 mL of a 1/6 molar sodium thiosulfate solution. Instruct patient to apply ice/cold pack for 6-12 hours following the sodium thiosulfate antidote injection.
400
How would you prepare sodium thiosulfate for treatment of a cisplatin (above concentration considered to be a vesicant) extravasation with sodium thiosulfate 10% and 25% solutions? What molar concentration needs to be prepared?
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 for injection.
400
How is dexrazoxane given? When must it be started? What is the dosing schedule?
The 1st infusion should be given ASAP within 6 hours of extravasation. Dilute dexrazoxane vial with provided diluent and place in 1000 mL NS. Infuse over 1-2 hours in a large vein in an extremity/area other than the one affected by extravasation. Dosing is daily for 3 consecutive days. Day 1 & 2: 1000 mg/m2 (max 2000 mg), Day 3: 500 mg/m2 (max 1000 mg). Reduce dose by 50% if CrCl < 40 mL/min.
500
Name 3 risk factors for extravasation from peripheral veins and 3 risk factors for central venous access devices
*Risk factors for peripheral veins: Small blood vessels (e.g. infants, young children); Fragile veins (e.g. elderly, cancer patients); Obesity; Multiple previous venipunctures; Disseminated skin diseases (eczema, psoriasis); Patient movement; Prior treatment with low pH or caustic drugs (e.g. chemotherapy); Rigid IV devices (butterfly or scalp needles); Inadequately secured IV devices *Risk factors for central venous access devices: Difficulty encountered during insertion of device; Device misplacement or catheter migration; Long dwell time (> 6 mo); “pinch off” syndrome; Fibrin sheath or thrombus at catheter tip; Location of port in area where it is difficult to secure needle (abdomen); Short needles
500
Above what concentration is cisplatin considered a vesicant and not an irritant
Cisplatin concentration >20 mL of 0.5 mg/mL
500
PY is a 69 yo male diagnosed with pancreatic cancer. During his gemcitabine infusion, the nurse notes swelling around the patient's peripheral infusion site and immediately stops infusion. The patient does not complain of pain. The nurse runs to you to tell you that chemo has extravasated! What do you tell her?
Gemcitabine is a non-vesicant (neutral) agent. Attempt to aspirate any extravasated solution. Elevate the limb. Apply a cold pack if local symptoms occur. Otherwise, observe. Arrange for follow up for patient as needed.
500
How does sodium thiosulfate work as an antidote?
Sodium thiosulfate neutralizes agents (mechlorethamine, bendamustine) to form non-toxic thioesters. Decreases production of hydroxyl radicals that cause tissue injury.
500
Can dexrazoxane be used to treat liposomal anthracycline extravasations?
Ulcerative potential of liposomal anthracycline is much less than the non-liposomal formulations. May be a function of amount of drug extravasated. Larger amounts may cause ulceration. There was one case report where patient responded but not as well as patients that got non-liposomal forms.
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