[doxorubicin] and vincristine, the most commonly used chemotherapy
drugs in the
battle against cancer in pets, are caustic vasosclerotics. If
Adriamycin is extravasated into the perivascular tissues, the results
may turn into one of your worst nightmares.
a few spills go home undetected and untreated only to be noticed
anywhere from 1 -10 days later. The pet owner calls into the office
with complaints that the pet has pain, or is limping or has swelling or
desquamation or is licking the venipuncture site.
notorious vasoclerotic is Adriamycin and its anthracyline relatives,
doxorubicin, daunorubicin, epirubicin and idaruricin. Vincristine,
vinblastine, cis-platin, mitoxantrone, mechlorethamine (Mustargen),
mithramycin and etoposide are also vesicant, but they pale in their
toxicity when compared to the irreversible indolent tissue damage
inflicted by the Adriamycin group... The important
point here is that the attending nurse and clinician must act
immediately and vigorously to literally and totally remove every drop
of the spilled adriamycin from the tissues.
the site may not look dramatic even after the first few days and one
might feel optimistic well into the second week. Vincristine sloughs
show up within the first seven days. The damaged tissue forms crusts,
causing the injured skin to look like leather. When the dead tissue
falls off, it may leave a deeper ulcer that will heal.
sloughs may begin to show only after 7- 10 days. Then, it looks
inflamed for another one to three weeks, then slowly worsens as the
weeks and months wear on. The ulceration and tissue necrosis
from adriamycin will infiltrate and spread deeper and deeper, exposing
muscle, tendons and bone. The area of eshar (a slough produced
by a thermal burn or corrosive agent or gangrene) enlarges and deepens,
forming necrotic sequestration of tissue that may get infected and the
case turns into the worst nightmare that one can imagine. Why the
tissue damage spreads is poorly understood.
In actual fact, the
effects of an Adriamycin extravasation will persist for months and will
involve much more area than the
initial spill touched. The tissue damage seems to worsen over these
months. The injured tissues do not heal or regenerate. There is severe
swelling and corruption of the tissues of the entire limb. In most
cases, amputation is the only option because of the extensive and
irreversible indolent nature of the tissue necrosis. The real nightmare
is deciding whether to amputate the leg of a cancer patient who may die
from its cancer in the near future.
This accident is
like an acid burn
that will continue to eat the tissue relentlessly with no response to
even the best of treatment and, regrettably, may require amputation.
against extravasation of any chemotherapy drug is the best control.
There must be a clean stick into the vein when placing the catheter and
there must be constant monitoring of the injection site to make sure
that one is still in the vein during the entire administration of the
majority of oncologists and oncology nurses seem to feel most
comfortable with direct, close supervision of each drop of Adriamycin.
They use very small-gauge butterfly catheters, no
larger than 23 gauge. The total dose is diluted to 10 ml for a cat and
approximately 1 ml per pound for dogs with sterile saline or water for
Then the butterfly catheter is flushed with saline
and then the Adriamycin solution is administered while frequently
pulling the syringe back just enough to see blood in the hub of the
syringe. This helps verify that the catheter is still well positioned
in the vein and not up against the vein wall. This type of intense,
direct supervision during the administering diluted solutions of
Adriamycin works best to avoid
An excellent suggestion to avoid extravasation
was in the “Tech Talk” section of the latest on line issue of the
Veterinary Cancer Society Newsletter. Jenny Rose, CVT, recommended
using a small gauge butterfly catheter with 12 inch tubing and
attaching a three-way stopcock affixed with a 12 ml luer-lock syringe
of 0.9 percent saline solution at one port and the chemotherapeutic
drug at the other port.
before and after drug administration is easily performed without
switching from one syringe to another. This also allows the continuous
aspirating to see if one is still in the vein during the entire
administration of the drug.
the Site [in case of an extravasation]
references say to act immediately and do not remove the catheter when
extravasation occurs. Use a syringe to remove as much drug as possible
from the catheter, tubing and tissue. Removing 5 to 6 ml of blood in a
cat and 10 ml in a dog is adequate.
Then insert a 27-gauge
needle into the bleb and aspirate as much of the drug as possible. This
is intended to minimize the amount of drug at the site.
references then say to administer the “appropriate antidote” or flush
saline through the catheter to dilute residual drug. Then use ice cold
packs or cold compresses for 6 to10 hours on the Adriamycin,
actinomycin-D or mechlorethamine spills. Place warm compresses on the
vinca alkaloid and etoposide spills for 3-4 hours.
procedures should minimize the vesicant’s toxicity. The idea is to
spread the vinca alkaloid with the warm compresses to help disperse the
drug into the circulatory system. The opposite idea is to use cold
compresses to localize Adriamycin spills to reduce its toxicity.
Confused? The most disheartening thing is to read the literature that
says nothing, including the list of recommended “antidotes,” seems to
“Antidotes” for Extravasations
Adriamycin spills, a compound called DHM3 or the timely use of
(Zinecard) injected directly into the tissue area of the spill within
three hours of the accident may offset the damage.
I could not
find anyone who has used these agents for extravasation in dogs or
cats. The price of Zinecard is $250 and $350 for the 250 mg and 500 mg
Zinecard is used in humans to reduce the
cardiotoxic effects of anthracycline drugs. The use of 1 ml of 1/6
molar isotonic sodium thiosulfate for each ml of extravasated cisplatin
can inactivate it. This antidote is recommended only if a large amount
of cisplatin is extravasated.
Hyaluronidase at 150 units/ml is
recommended at 1 ml for every ml of extravasated vinca alkaloid or
etoposide. This is purported to enhance absorption and disperse the
Topical DMSO or infiltration of the area with 1
mg/kg of hydrocortisone or using intralesional dexamethazone is
considered controversial and probably a waste of time
is only fleeting mention in the literature about flushing with saline
with the caution that this procedure may, indeed, spread the drug to a
deeper or wider area.
In my experience,
there is only one way
that I can sleep at night if adriamycin is extravasated: We treat every
Adriamycin spill like the worst snakebite on earth and we treat it
After the aspirations from the catheter and the bleb
are completed, we infiltrate saline into the site as described above.
Then we prep the leg for surgical incisions. Then I take charge. Using
the bevel of a sterile 18-gauge needle, I make 10 to 30 vertical, deep
skin incisions (slits) that extend into the perivascular SQ tissues in
a lettuce-bag pattern.
The slits extend beyond the entire
extravasation site and 360 degrees around the limb. Then we run copious
amounts of saline or isolyte solution through the entire site and
around the limb with the philosophy of flush, flush and flush, and then
flush some more.
We gently squeeze or “milk” the tissue. I may
poke the 18-gauge needle into the deeper parts of the limb into the
muscle and fat to allow the solution to bathe those tissues and ooze
out. Hopefully every drop of the offending vesicant will percolate out
through the skin slits in a diluted fashion.
On one occasion,
we were pleased to see the distinctive red color of the adriamycin as
it exited the tissue. In a typical 60-pound dog, we may flush one to
two liters through the extravasation site over a 30 to 45 minute
period, depending on what drug was spilled.
We recommend using
nothing short of this extreme measure to get every drop of drug out of
the spill area, especially if it involves Adriamycin.
the pet home with a light wrap and instructions for cold compresses for
the next 24 hours. We recheck the patient weekly for the next 3 weeks
to monitor for tissue damage and healing of the skin slits.
completely avoid the nightmares that are so predictable with
extravasations by using this “Modified Villalobos Snake Bite Slit
Technique” because it works. We hope that by contributing our
successful experience to the profession that the potential for
suffering of patient, pet owner and practitioner can be minimized.
Villalobos owns Animal Oncology Consultation Service in Woodland Hills.
She received the 1999 Bustad Companion Animal Award and is associated
with VCA Clarmar and Coast Animal Hospitals in Torrance and Hermosa