The patient, “JB,” is a 68-year-old woman who underwent a right lumpectomy and axillary node dissection for stage II breast cancer. Her oncologist suggested adjuvant chemotherapy (four cycles of cyclophosphamide(Drug information on cyclophosphamide) [Cytoxan] at 600 mg/m2 plus doxorubicin(Drug information on doxorubicin) [Adriamycin] at 60 mg/m2) followed by local radiation therapy. JB agreed to treatment, and had an implanted venous access port (VAP) surgically placed for chemotherapy. She was rather large breasted, and the port was surgically implanted about 3.5 inches below her left clavicle. Cycles one and two of chemotherapy were administered uneventfully.
Mrs. B. was accompanied by her adult daughter, a labor and delivery nurse, when she came to the office for cycle three. Her assigned nurse (nurse 1) tried to cannulate her VAP twice, but was unsuccessful and asked a more experienced nurse (nurse 2) to cannulate the port. Nurse 2 cannulated and flushed the VAP, started the intravenous rider (IVR) of dolasetron(Drug information on dolasetron) (Anzemet), and left the treatment room. After the antiemetic was finished, nurse 2 returned to the treatment room to start an IVR of doxorubicin (105 mg in 53 mL saline) to infuse over a period of 30 minutes by controller pump. Neither nurse stayed with Mrs. B. to observe the infusion or check for blood return.
When nurse 2 returned to start the cyclophosphamide, JB’s daughter told the nurse that her mother was experiencing breast pain. The nurse pulled JB’s shirt down to assess the port site. JB’s entire left breast was ‘angry red,’ swollen, and firm. Nurse 2 stopped the infusion, applied an ice pack to the patient’s left breast, and notified the oncologist, who ordered that JB be sent to radiology for a venogram through the VAP. The radiologist recannulated the port to do the venogram, and phoned the oncologist to report no extravasation of contrast dye. JB returned to the oncologist’s office, where the remaining cyclophosphamide was infused.
Management Issues
JB was sent to a plastic surgeon that same day. He treated her with intravenous antibiotics for presumed infection in the breast and removed the VAP. Over weeks to months, the patient’s breast became more painful as a large area of necrosis progressively worsened. After 10 months without healing, she went to another surgeon, who performed a left total mastectomy with tram-flap reconstruction.
Though vesicant extravasation is uncommon, it has potentially devastating consequences for patients (and the nurses caring for them), because of ensuing local tissue damage. Anthracyclines (doxorubicin, daunorubicin(Drug information on daunorubicin), epirubicin(Drug information on epirubicin), and idarubicin(Drug information on idarubicin)) bind to nuclear DNA of cells in the area of extravasation and cause immediate cell death. Dead cells lyse and release bound anthracycline, which is taken up into surrounding cells. This vicious cycle can continue for months and can lead to progressive destruction of subcutaneous tissues, tendons, and nerves, with this process evidenced by blistering, necrosis, and eschar formation.[1,2]
Naturally, prevention of extravasation is ideal, and many patients now have a VAP placed when vesicant chemotherapy is planned. In the past, extravasation was estimated to occur in 0.3% to 4.7% of VAP infusions,[2] but now the rate is probably lower because oncology nurses have become aware of the risks and adhere to standards of care. The most likely causes of extravasation from ports are incorrect needle placement (not within the port septum) or subsequent needle displacement from the port septum. Other causes are thrombus and fibrin sheath formation around the catheter that leads to backtracking, or catheter fracture secondary to pinch-off beneath the clavicle, which can lead to extravasation with tunneled catheters and VAPs.[3]
Although previous pharmacological antidotes for anthracycline extravasations were largely ineffective, in September 2007 dexrazoxane (Totect) received US Food and Drug Administration approval for treatment of anthracycline extravasation.
Dexrazoxane may prevent damage by interfering with topoisomerase II and by chelating iron, as these effects may prevent formation of iron-doxorubicin complexes and iron-mediated hydroxyl radicals that damage cell proteins and membranes.[3,4] There have been several case reports of successful prevention of anthracycline-related necrosis with administration of dexrazoxane within 6 hours of extravasation and repeated for two more doses, including patients with VAPs.[5]
Approval of dexrazoxane for extravasation was based on two prospective single-arm studies that included a total of 54 evaluable patients who had experienced tissue-confirmed anthracycline extravasation.[6] These patients received 3 days of IV dexrazoxane (at doses of 1000, 1000, and 500 mg/m2) starting within 6 hours of extravasation. Only one patient (1.85%)—who experienced a very large extravasation—required surgery to resect necrotic tissue. Conversely, Kane and others estimate that 10% to 25% of these patients would have required surgery if they had not received dexrazoxane.[7]
Specific Nursing Considerations
Nurses who are unaware of, or do not otherwise implement correct interventions for suspected or actual extravasation may be accused of negligence if subsequent necrosis occurs, and they may be subject to malpractice suit.[8] High concentrations of doxorubicin are usually administered via syringe through the sidearm of a running intravenous infusion (IV) or as a direct IV push (preceded by and followed with normal saline). In either case, close observation of the port site and chest is necessary to detect any new swelling or redness, and appropriate monitoring includes checking for easily obtained vigorous blood return every few minutes and reminding the patient to report any change in sensation during infusion.
Because the extent of anthracycline-induced injury is directly related to the concentration and amount of drug extravasated, the nurse must stop the vesicant infusion or IV push if extravasation is suspected. Applying an ice pack to an anthracycline extravasation site is recommended, to decrease the spread of drug within local tissues. Documentation should include the details of the infusion, as well as the amount of vesicant agent left in the IV bag and tubing and in the IV catheter (to estimate the amount extravasated), the patient reports and site evaluation, nursing measures, physician notification, and follow-up instructions.[9]
