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Intravenous Extravasation of Cytotoxic Drugs

Implementation

Flow chart for treatment of intravenous extravasation of cytotoxic drugs:

Emergency response:

  • Stop the infusion immediately.
  • Allow the needle to remain and aspirate with as much water as possible. Avoid applying direct pressure on the area of extravasation.  
  • The volume, type, and time of extravasation should be recorded.
  • A doctor/plastic surgeon should be called for to examine the patient.
  • The damaged area and skin manifestations should be marked/photographed.
  • The affected area should be kept elevated.
  • The remaining chemotherapy should not be discarded.
  • The patient should be informed about what is happening and what must be done. 
  • The needle is removed while aspirating.
  • Pain medication is administered if necessary.

Based on which medication has leaked extravasally, the doctor or plastic surgeon will decide whether conservative treatment or primary surgery is necessary.

Conservative treatment

Conservative treatment consists of two different treatment strategies to limit the damage by extravasation: localize/neutralize and spread/dilute (2).

Localize and neutralize:

  • Place an ice pack on the area for 15-20 minutes, at least 4 times daily for multiple days. A coldpack is used to limit spreading of the drug. Studies have indicated that there is reduced cellular uptake of drugs at lower temperatures (2).
  • The drug that has leaked extravasally is neutralized by a specific drug if the instructions are followed.
  • The affected area of the body should be kept elevated.

Spread and dilute (applies to vincristine, vinorelbine, vindesine, and vinblastine):

  • Warm compresses are placed on the area for 15–20 minutes, at least 4 times daily, for multiple days.
  • To dilute the drug that has leaked extravasally, many subcutaneous injections are given with hyaluronidase diluted with sterile water.

If the patient has lasting pain or blisters, surgical treatment should be considered by excising the area with direct sutures, skin transplant, or flap reconstruction.

Another type of reconstruction may be necessary at a later time. 

Treatment 

Dexrazoxan (Savene®)

Dexrazoxan is an EDTA analong used to treat extravasation of anthracycline (doxorubicin, daunorubicin, epirubicin, idarubicin). The mechanism of action is not fully understood, but it is believed that it may work through two mechanisms. By chelating iron, the formation of the iron-doxorubicin complex and  iron-mediated hydroxy radicals are hindered, which cause oxidative damage to cell membranes and proteins. Another possible mechanism is inhibition of topoisomerase II (3).

Treatment lasts for 3 days. In all cases of extravasation of anthracycline, this treatment should be assessed by an oncologist and surgeon/plastic surgeon.

  • The first infusion should start as soon as possible and within 6 hours after extravasation. 
  • On the following two days, the infusions should occur at the same time as the previous infusion (+/- 3 hours).
  • If possible, the infusion should be placed in a vein where there is no extravasation.
  • An ice pack or cooling element used on the area must be removed at least 15 minutes before the infusion starts to ensure sufficient blood circulation.

Cost

A package costs about NOK 100,000.-. If the expiration date runs out, the drug is replaced by the pharmaceutical company free of cost.

Dimethylsulfoxide (DMSO)

DMSO (70–90% solution) quenches free radicals and prevents formation of sores. The solution can be used after extravasation of cytotoxic drugs (anthracycline, mitomycin C, doxorubicin, idarubicin, epirubicin andactinomycin D) together with cooling of the area when other treatment methods cannot be used (5, 6). DMSO cannot be used in combination with dexrazoxan (3, 4).

  • An area twice as big as the affixed area is treated with the solution every 8 hours for one week.(6)

Hyaluronidase

Hyaluronidase is an enzyme that breaks down hyaluronic acid found in connective tissue. This leads to permeability and increased diffusion of the drug that is leaking extravasally, and is used only to spread the drug out into the tissue (spread and dilute).  

  • Hyaluronidase is administered subcutaneously or intradermally in 5-10 locations on the border of the area where the drug has leaked extravasally (7).

Surgical treatment

"Wash-out"

The washing out technique can be used with chemotherapy drugs when tissue damage is likely. When used with anthracycline, it is important that this is performed before the chemotherapy drug goes intracellularly.

In most cases, this is a very successful method if it is performed within 6 hours after the extravasation.

  • The patient receives regional anesthesia.
  • Multiple small incisions must be made to ensure sifficient access to the damaged subcutaneous tissue.
  • With an infiltration needle, which is usually used for liposuction, isotonic NaCl is flushed through the tissue and drains through the incisions.
  • The infiltrated fluid is then carefully removed by suction through a small needle used for liposuction.
  • The procedure is repeated until 300-500 ml fluid is used.

References

  1. Ekstravasation Guidelines Implementeringsværktøj [Online] 2007 [hentet 10. mars 2009]; Tilgjengelig fra URL: http://www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=2726
  2. Hasinoff BB. Dexrazoxane use in the prevention of anthracycline extravasation injury. Future Oncol 2008; 2006: 1–15.
  3. Statens legemiddelverk. Preparatomtale. 2008
  4. Langstein HN, Duman H, Seeling D, Butler CF, Evens GR. Retrospective study of the management of chemotherapeutic extravasation injury. Ann Plastic Surg 2002; 49: 369–74. 
  5. Bertelli G, Gozza A, Forno GB, Vidili MG, Silvestro S, Venturini M et al. Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: A prospective clinical study. J Clin Oncol 1995; 13: 2851–5.
  6. Clinical Pharmacology© 2008 database. Hyaluronidase. 2008.

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