Cases & Commentaries

Chemotherapy Extravasation

Commentary By Lisa Schulmeister, RN, MN, APRN-BC

The Case

A 73-year-old woman with no past medical history
was diagnosed with stage IIIA breast cancer. She and her oncologist
decided to begin systemic chemotherapy that would involve 6 cycles
of treatment, all administered at the outpatient chemotherapy
center located at the local hospital.

The patient arrived for her first day of
treatment. A nurse who was relatively new to the job had difficulty
placing a peripheral IV catheter but was ultimately able to achieve
venous access in the left arm. Despite meeting some resistance when
infusing saline, the nurse proceeded to infuse the first
medication, doxorubicin, a highly toxic chemotherapeutic agent. The
patient immediately began complaining of pain at the infusion site.
Upon closer examination, the nurse noted that the chemotherapy had
infused outside of the vein (extravasated) into the skin.

The nurse removed the IV catheter and placed an
ice pack on the site. She had not been given any information about
how to manage extravasations nor had she been informed of the
location of the "extravasation kit," so she did not know what else
needed to be done. Eventually, the IV site was bandaged and the
patient was sent home to return later in the week. The patient
suffered pain at the site with some mild redness and blistering but
had no long-term side effects.

The Commentary

Intravenous chemotherapeutic agents are
associated with multiple complications, both local and systemic.
Extravasation of the medication into the skin is one of the most
dreaded complications that can occur during chemotherapy
administration (1), as
patients can suffer short-term and long-term consequences.
Fortunately, steps can be taken to reduce the risk of extravasation
and limit the consequences if it does occur.

Vesicant (causing blisters) chemotherapy
agents such as doxorubicin, the agent this patient received, can
cause tissue necrosis if they leak from the vein or are
inadvertently administered into tissue. Doxorubicin and the other
anthracycline vesicants (daunorubicin, epirubicin, idarubicin)
cause cell death (necrosis) by binding to the DNA in healthy tissue
cells when they extravasate. In addition, anthracyclines are not
easily metabolized by the body; they can remain in the tissues for
a substantial period of time. Consequently, these extravasation
injuries often become larger, deeper, and more painful over time.
Other types of vesicant chemotherapy, such as the plant alkaloids
(e.g., vincristine, vinblastine), do not bind to the DNA in healthy
cells and are more easily metabolized in the tissues. Therefore,
extravasation injuries with these agents generally remain
localized, are mildly painful, and improve over time.(2)

Despite the best efforts of nurses and health
care facilities, extravasation of vesicants does occur, albeit
infrequently. Published incidence rates of chemotherapy
extravasation range from 0.01% (3) to
6%.(4)
However, many health care providers realize that even one
extravasation injury is one too many, particularly since most
injuries are preventable.(2)

The severity of a vesicant extravasation
injury is influenced by the type of vesicant that extravasates
(DNA-binding or non-binding [Table
1
]), concentration and amount of vesicant in the tissue, and
location.(5)
Extravasations in the dorsum of the hand or wrist generally cause
more damage than extravasations in other areas, such as the
forearm, which was the site of this patient's extravasation. This
is because the forearm has more overlying tissue and fewer
underlying structures (such as tendons and nerves) than the hand
and wrist.

Unlike the patient in this case, who had a
minor extravasation and no long-term effects (most likely because
the event was detected early), some extravasations may require
hospitalization for wound debridement, skin graft or flap
placement, and IV antibiotics. Scheduled chemotherapy treatment
often must be delayed, which may set back treatment and lead to
psychological distress for the patient. Long-term sequelae may
include chronic infection, disability, and disfigurement.(5)

Prevention (Table 2) is the most important approach to
extravasation management.(1) The
Oncology Nursing Society (6) and
Infusion Nurses Society (7)
have published guidelines for vesicant administration and
extravasation management. Institutional policies and procedures
used in hospitals, clinics, and office settings should be written
in accordance with these guidelines and reviewed annually.

In the case above, the IV device was inserted
with some difficulty, and the nurse proceeded with vesicant
administration despite meeting resistance when infusing saline.
Traumatic IV device insertion can pierce the vein wall and increase
the risk of extravasation. Vesicants should only be administered
after a peripheral IV device is easily inserted, a blood return is
obtained from the IV, saline flows freely, and there is no evidence
of redness or swelling. Even when all signs point to a well-placed
line, extravasation of chemotherapy delivered peripherally remains
a possibility, due to patient movement, inadequately secured IV
devices, and prior venipuncture.(8)

Because of the high risk of extravasation
associated with peripheral vesicant administration, patients often
are advised to have an implanted port placed. Implanted ports
(Figure) are usually placed under the skin on the chest
wall. A non-coring needle is inserted into the septum of the port,
which is connected to tubing that terminates in the superior vena
cava. Implanted ports reduce, but do not eliminate, the risk of
vesicant extravasation. Extravasation from implanted ports may
occur when non-coring needles are incompletely inserted or
dislodged, from thrombus formation at the catheter tip that causes
backtracking of the vesicant to the puncture site, or from device
malfunction or breakage. When a blood return is not obtained from
implanted ports, device patency and placement must be confirmed by
other measures (e.g., dye study, successful instillation of a
declotting agent, etc.) prior to vesicant administration.(6-9)

If an extravasation occurs or is suspected,
steps should be promptly taken to limit the damage. First and
foremost, vesicant administration should immediately be stopped.
The extravasation site should be assessed and measured, and
findings documented. Digital photographs are helpful to assess
changes over time. Local cooling (ice pack) is recommended for
extravasations of DNA-binding agents to constrict blood vessels and
help prevent the vesicant from spreading to adjacent tissues.
Doxorubicin is a DNA-binding agent, so applying ice to the
patient's extravasation—as was done in this case—was an
appropriate action. Local warming (dry heat) is indicated for
non–DNA-binding vesicant extravasations to increase blood
flow to the area, which helps distribute the vesicant and promote
its absorption. Hyaluronidase, an enzyme that degrades hyaluronic
acid and breaks subcutaneous tissue bonds, is used as an antidote
for extravasation of non–DNA-binding vesicants. It is locally
injected to promote drug diffusion and enhance absorption of the
vesicant.(1,8)

Other chemical agents can also be used to
limit tissue damage after extravasation in some circumstances. For
example, dimethyl sulfoxide (DMSO), a free radical scavenger that
is applied topically to an extravasation area, has been used to
treat anthracycline extravasations. In one study, application of a
99% DMSO solution every 6 hours for 2 weeks in patients with
suspected vesicant extravasations prevented tissue necrosis in 16
patients.(10) In
another study, only 1 of 57 patients treated with DMSO (every 8
hours for 1 week) with suspected vesicant extravasations developed
necrosis.(11)
DMSO side effects include mild burning and scaling at the
extravasation site and malodorous breath. The only medical grade
DMSO product available in the United States is a 50% solution,
which may not be as efficacious as the 99% solutions used in many
trials.

In two clinical trials conducted in Europe,
patients with suspected extravasations (confirmed by biopsies
showing that anthracyclines were present) were treated with
dexrazoxane, an agent that is indicated to prevent
anthracycline-induced cardiac toxicity.(12) Dexrazoxane's mechanism of action is unknown, but
some evidence suggests that it inhibits topoisomerase II reversibly
and reduces anthracycline tissue damage.(13) One of 57 patients with biopsy-verified anthracycline
extravasations developed tissue necrosis (overall efficacy 98.2%),
and the majority of the patients were able to continue chemotherapy
as scheduled.(12)
This IV treatment must be initiated as soon as possible and within
6 hours of an anthracycline extravasation. Totect (dexrazoxane for
injection) is packaged as an extravasation treatment kit for single
patient use and recently became commercially available in the
United States.(13,14)

Despite advances in IV device technology, the
risk of extravasation during vesicant administration cannot be
completely eliminated. Patients need to be informed of this risk,
and nurses must implement risk reduction strategies such as those
outlined in Table
2
. In addition, health care providers need to be aware of the
latest advances in extravasation management so they can promptly
initiate appropriate treatment.

Take-Home Points

  • Vesicant chemotherapy agents are known
    to cause tissue necrosis if they leak from the vein or are
    inadvertently administered into the tissue.
  • Extravasation is a known risk of
    vesicant administration.
  • Implanted ports reduce, but do not
    eliminate, the risk of vesicant extravasation.
  • Vesicants should only be administered
    after a blood return is obtained, saline flows freely, and there is
    no evidence of redness or swelling.

Lisa Schulmeister, RN, MN, APRN-BC
Oncology Nursing Consultant
New Orleans, Louisiana

References

1. Schrijvers DL. Extravasation: a dreaded
complication of chemotherapy. Ann Oncol. 2003;14(suppl
3):iii26-iii30.
[go to PubMed]

2. Schulmeister L. Extravasation management.
Semin Oncol Nurs. 2007;23:184-190.
[go to PubMed]

3. Langstein HN, Duman H, Seelig D, Butler CE,
Evans GR. Retrospective study of the management of chemotherapeutic
extravasation injury. Ann Plast Surg. 2002;49:369-374.
[go to PubMed]

4. Barlock AL, Howser DM, Hubbard SM. Nursing
management of adriamycin extravasation. Am J Nurs. 1979;79:94-96.

[go to PubMed]

5. Goolsby TV, Lombardo FA. Extravasation of
chemotherapeutic agents: prevention and treatment. Semin Oncol.
2006;33:139-143.
[go to PubMed]

6. Polovich M, White JM, Kelleher LO, eds.
Chemotherapy and Biotherapy Guidelines and Recommendations for
Practice. 2nd ed. Pittsburgh, PA: Oncology Nursing Society;
2005.

7. Infusion Nurses Society. Infusion nursing
standards of practice. J Infus Nurs. 2006;29(suppl 1):s1-s92.

[go to PubMed]

8. Hadaway L. Infiltration and extravasation. Am
J Nurs. 2007;107:64-72.
[go to PubMed]

9. Schulmeister L, Camp-Sorrell D. Chemotherapy
extravasation from implanted ports. Oncol Nurs Forum.
2000;27:531-538.
[go to PubMed]

10. Olver IN, Aisner J, Hament A, Buchanan L,
Bishop JF, Kaplan RS. A prospective study of topical dimethyl
sulfoxide for treating anthracycline extravasation. J Clin Oncol.
1988;6:1732-1735.
[go to PubMed]

11. Bertelli G, Gozza A, Forno GB, 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;13:2851-2855.
[go to PubMed]

12. Zinecard (Dexrazoxane for injection) [package
insert]. New York, NY: Pfizer Inc; 2005.

13. Mouridsen HT, Langer SW, Buter J, et al.
Treatment of anthracycline extravasation with Savene (dexrazoxane):
results from two prospective clinical multicentre studies. Ann
Oncol. 2006;18:546-550.
[go to PubMed]

14. Schulmeister L. Totect: a new agent for
treating anthracycline extravasation. Clin J Oncol Nurs.
2007;11:387-395.
[go to PubMed]

Tables

Table 1. Vesicant Chemotherapy Agents

Reprinted with permission from Elsevier. In:
Schulmeister L. Extravasation management. Semin Oncol Nurs.
2007;23:184-190.

Classification Examples
DNA Binding  
Alkylating agents Mechlorethamine (nitrogen mustard)
Anthracycline antibiotics Daunorubicin, doxorubicin, epirubicin,
idarubicin
Other anticancer antibiotics Dactinomycin, mitomycin, mitoxantrone
Non-DNA Binding  
Alkylators Amsacrine
Plant alkaloids Vinblastine, vincristine, vindesine,
vinorelbine
Taxanes Docetaxel, paclitaxel (note: considered to be mild
vesicants)


Table 2. Extravasation Prevention
Strategies

Inform the patient that extravasation is a risk of vesicant
administration.
Instruct the patient to avoid movement during vesicant
administration and to immediately report pain, burning, or other
symptoms.
Insert a new IV device immediately prior to peripheral vesicant
administration.
Use a large vein in the forearm for peripheral vesicant
administration.
Do not administer a vesicant in a vein below a recent
venipuncture site.
If insertion of an IV device is difficult, requires probing, or
causes pain, restart the IV in another location.
Refer patients at high risk for peripheral extravasation for
central line placement. High-risk patients include those with
small, fragile veins or limited peripheral access due to
lymphedema, cerebral vascular accident, or other causes;
cognitively impaired patients; and active young children.
Stabilize and secure the IV device and cover the site with a
transparent dressing to aid in visualization of the site.
Obtain a blood return prior to, and during, vesicant
administration.
Immediately stop vesicant administration if there is a loss of
blood return from the IV device, the patient reports stinging or
pain, or redness or swelling develops.

Figure

Figure. Example of Implanted Port.