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Knowledge is power when treating extravasation reactions
Knowing beforehand the agents that do or may cause an extravasative reaction expedites its management. Have a treatment protocol ready.
An extravasation reaction is one of those situations in oncology therapy that everyone wants to avoid and no one ever feels they have enough information to deal with.
The situations can pass without much harm to the patient, but some can cause devastating injuries. Some, but not all, chemotherapy agents can cause tissue necrosis when the drug solution inadvertently leaks from the vein, a process known as extravasation.
Symptoms
These agents that can cause necrosis after extravasation are called vesicants. Some non-chemotherapy medications can also cause extravasation reactions. Some of these include calcium chloride, phenytoin, TPN solutions, contrast media and vasopressors.
Symptoms of extravasation reactions range from pain and self-limited, localized inflammation to full-thickness necrosis, ulceration and sloughing of skin and underlying structures. Lesions may expand in size over weeks to months. Most heal poorly and slowly. In extensive ulceration, plastic surgery may be needed to remove trapped drug from the tissue, as well as skin grafting. The extent of symptoms also depends on the infusion site, condition of the tissue, concentration and volume of the vesicant and any treatments that may have been applied.
Table 1 lists chemotherapy agents that have the highest potential for tissue necrosis after extravasation. Other chemotherapy agents occasionally associated with vesicant reactions after extravasation are listed in Table 2.
Some chemotherapy agents can cause irritation, pain, phlebitis, aching or tightness at the injection site or along the vein without causing direct tissue destruction or necrosis. These chemotherapy agents, classified as irritants, are listed in Table 3.
Prevention
An extravasation reaction is one of those situations where “an ounce of prevention is worth a pound of cure.”
When chemotherapy is to be given through a peripheral vein, it is best to have a large, intact vessel with good blood flow and a good blood return. Several factors are associated with an increased risk of extravasation: venous fragility, decreased local blood flow, increased venous pressure, like SVC syndrome, previous radiation therapy in the area, recent venipuncture in the same vein and certain injection sites, such as dorsum of hand and antecubial fossa.
Despite careful adherence to proper administration techniques by experienced nurses, extravasations still occur. Peripheral lines should only be used for short infusions of vesicants when a nurse can constantly monitor the line and blood return. When continuous infusions of vesicants are to be given, a central line should be used. Central venous catheters have improved the safety of giving vesicants, since they are less likely to become dislodged than peripheral catheters. However, they are not foolproof in preventing extravasation episodes. Access devices like the Portacath and Infusaport have the potential for extravasations when the needle dislodges from the port (infusing solution into the chest wall tissue). In addition, the catheter can separate from the port or a fibrin sheath can cause enough backpressure to cause extravasation where the catheter enters the vein.
If extravasation occurs, the nurse should immediately stop the infusion, leaving the needle/catheter in place, and without flushing the line. The nurse should attempt to aspirate as much drug and fluid from the bleb or tissue as is possible. Another person should contact the physician immediately. A preauthorized treatment protocol should be followed if one exists.
If appropriate, the antidote should be injected into the same needle and then the needle may be removed. If the needle was already removed, inject the antidote with a 25-gauge needle into the subcutaneous tissue.
Administer any nonpharmocologic treatments (see Table 4) as indicated. The nurse should document the episode and treatments taken in the medical record for future comparison. Photographs should be taken if possible. The affected extremity should be kept elevated on pillows for two days. The patient should be instructed to protect the area from sunlight and to report any change in the area to the physician. A plastic surgery consultation may be necessary.
Specific therapies and antidotes have been suggested for some vesicant extravasations. Unfortunately, proper large-scale comparative trials of these treatments are not possible due to the infrequent nature of these episodes and the unethical nature of a placebo controlled trial in these cases. Therefore, available information is drawn from small, uncontrolled trials, case reports and animal studies. In addition, not all extravasations of known vesicants will produce ulcerations in all cases. The recommended treatments include warm or cold compresses and a few pharmacologic antidotes. Specific treatments/antidotes are not known for all the recognized vesicant chemotherapy agents.
Hot and cold
Warm compresses cause local vasodilation and increased blood flow in the area. This increase in circulation would facilitate drug removal. Warm compresses are only recommended in the extravasation of the vinca alkaloids and possibly for etoposide and paclitaxel. Warm compresses worsen the damage of other vesicants. Apply them 15 to 20 minutes four times daily for 24 to 48 hours.
Intermittent cooling of the tissue can cause vasoconstriction, which tends to restrict the spread of the drug. Cold compresses are recommended for the extravasation of most vesicants except for the vinca alkaloids. Apply without pressure for 15 minutes four times daily, or on/off more frequently, for three days.
Hyaluronidase is an enzyme that breaks down the subcutaneous tissue bonds and thereby promotes drug diffusion through the interstitial space and enhanced systemic drug absorption from the area. It is recommended for extravasations of the vinca alkaloids and possibly paclitaxel and docetaxel. When used, 150 to 300 units of hyaluronidase should be diluted in 1 to 6 mL of sterile water and injected into the extravasation site.
DMSO is a solvent that penetrates rapidly into tissues. It is believed to act as a free radical scavenger and antioxidant. It appears to have activity in the extravasation of many agents (see Table 4).
DMSO is commercially available as a 50% solution, even though most of the trials were conducted which solutions >90%. When used, it should be applied topically with a cotton swab (1.5 mL) to an area of skin twice the size of the infiltration every 6 hours for 10 to 14 days. The skin should be allowed to air dry. DMSO may cause some transient skin redness.
Sodium thiosulfate
Sodium thiosulfate is recommended for the treatment of mechlorethamine and cisplatin extravasations. It is thought to inactivate the drug by providing an alkylation site thereby producing a nontoxic molecule.
When used, 4 mL of a 10% solution should be diluted with 6 mL sterile water to form a 1/6 molar, or 4% solution. It should be injected at the extravasation site at a dose of 2 mL for each mg of mechlorethamine or each 100 mg of cisplatin.
Injections of sodium bicarbonate and corticosteroids are no longer recommended due to their lack of efficacy and potential to cause harm themselves.
Treatment guidelines
Table 4 is a synopsis of currently recommended treatment guidelines for the treatment of extravasation episodes with vesicant chemotherapy agents.
Because of the need for prompt action and the scarcity of good clinical information, hospitals and clinics that administer chemotherapy should have an authorized policy or procedure and treatment algorithm to follow in the case of an extravasation episode. Nurses who administer chemotherapy should be well trained in proper administration techniques. Oncology physicians, nurses and pharmacists should be familiar with the proper actions to take in the treatment of extravasation reactions.
For more information:
- Bertelli G. Prevention and management of extravasation of cytotoxic drugs. Drug Saf. 1995;12:245-255.
- Oncology Nursing Society. Cancer Chemotherapy Guidelines and Recommendations for Practice. 1999.
- Comas D, Mateu J. Treatment of extravasation of both doxorubicin and vincristine administration in a Y-site infusion. Ann Pharmcother. 1996;30:244-246.