"Oncologic Emergencies"
GULF COAST VETERINARY ONCOLOGY'S TUMOR TIDBITS
Volume 2, Number 3: February 2001
This Month's Feature: Oncologic Emergencies
DON'T FORGET TO VISIT OUR WEB SITE: CARING FOR PETS WITH CANCER, a
comprehensive web site for veterinarians and pet owners caring for pets
with cancer. Drug handouts, tumor handouts, case examples, pet loss
information, and much more at:
Editor: Kevin A. Hahn, DVM, PhD, Diplomate American College of
Veterinary Internal Medicine (Specialty of Oncology) & Overall Nice
Guy;
Gulf Coast Veterinary Oncologists, Houston, TX 77027,
drhahn@gulfcoastvetspec.com
_______________________________________________________________________
ANNOUNCEMENTS
Seeking - Full-time technician (RVT preferred) in Medical Oncology.
Available immediately. Monday-Friday, No Weekend or Overnight Duties.
Good pay/health and retirement benefits. Schedule an appointment with
Dr. Hahn or call 713-693-1166 or fax resume to 713-693-1167.
_______________________________________________________________________
Tidbit Topic : ONCOLOGIC EMERGENCIES
INTRODUCTION
In the cancer patient, emergencies can include those caused by physical
or metabolic derangements from the cancer (ruptured viscous, pericardial
effusion, disseminated intravascular coagulation, hypercalcemia,
hypoglycemia, hyponatremia) or those caused by therapeutic intervention
(sepsis, drug extravasation, diarrhea). Awareness of common
paraneoplastic syndromes, early recognition of signs, and proper medical
or surgical management may improve the prognosis for the patient
arriving in an emergency condition.
METABOLIC COMPLICATIONS OF CANCER
Hypercalcemia is the most common metabolic disturbance associated with
neoplasia. Most commonly the result of parathyroid-related peptides
produced by some tumors, hypercalcemia is usually caused by lymphoma.
Other tumors frequently implicated include anal sac adenocarcinoma,
mammary adenocarcinoma and primary hyperparathyroidism. Emergency care
for the hypercalcemic patient involves a diuresis with 0.9% NaCl for
enhanced calciuresis. Furosemide (2-4 mg/kg BID) will also enhance
calcium elimination. Other drugs used to treat hypercalcemia include
intravenous biphosphonates (etridronate, disodium palmidroate), gallium
nitrate, mithramycin, and salmon calcitonin. Corticosteroids prevent
bone reabsorption, intestinal absorption and increase urinary calcium
excretion. However, because of their rapid antitumor effects,
corticosteroid use should be withheld until a tissue diagnosis is made.
Identification and treatment of the primary disease becomes the highest
priority. Lymph node aspiration/biopsy, chest radiographs, abdominal
ultrasound and bone marrow evaluation should follow physical examination
including lymph node palpation and perianal examination. Every effort
should be made to rule out lymphoma and anal sac adenocarcinoma.
Hypoglycemia associated with neoplasia may be the result of an insulin
secreting tumor, the result of destruction of normal gluconeogenic
tissues or glucose consumption associated with such systemic
complications as bacterial sepsis. The most common tumors associated
with hypoglycemia are insulinoma, hepatoma and carcinoma. Insulinomas
are diagnosed by demonstrating inappropriately high levels of insulin in
the face of hypoglycemia. Animals showing clinical signs of hypoglycemia
(stupor, coma, seizures) can be treated with parenteral dextrose and
dextrose containing fluids. Prednisone (0.5-2 mg/kg divided BID) will
increase hepatic gluconeogenesis and antagonize the effects of insulin
on peripheral tissues. Diazoxide (10-40 mg/kg divided BID) can directly
inhibit insulin secretion and may be useful in the medical management of
insulin secreting tumors. Surgical excision and medical management of
metastatic lesions can lead to the temporary resolution of clinical
disease.
SHOCK AND THE CANCER PATIENT
Animals with large intraabdominal tumors may appear normal to the owner
until such time that these vascular tumors rupture and lead to acute
blood loss, collapse and hypovolemic shock. Acute collapse can also be
seen with pericardial tamponade secondary to vascular tumors on the
heart or at the heart base. Both cases will present with cool
extremities, a rapid heart rate, decreased mentation and hypotension. It
is important to differentiate pericardial tamponade from hypovolemia as
aggressive fluid therapy may actually worsen the patient's condition.
Jugular pulsation, elevated central venous pressure (distension of the
lateral saphenous vein when held above the heart), decreased amplitude
electrocardiogram and a rounded cardiac silhouette are often seen with
tamponade. Tamponade is best treated immediately with
pericardiocentesis. Internal blood loss from a ruptured vascular tumor
should be treated with shock doses of crystalloid fluids. Frequent
rechecks of heart rate, blood pressure and packed cell volume are
mandatory. If the packed cell volume drops precipitously, whole blood,
packed red blood cells or cell free hemoglobin should be used to improve
blood oxygen content. Patients should be carefully evaluated to identify
the source of the hemorrhage. When a patient's condition allows,
radiographs of the chest and abdomen will help stage the disease and
provide the veterinarian and owner with more information on the extent
of the disease. Exploratory surgery will be necessary to remove the
source of blood loss and fully evaluate the extent of the disease. The
acute nature of these cases requires compassion and understanding from
the veterinarian. The diagnosis of "cancer" when the only finding is an
intraabdominal mass can be overwhelming for owners. Clients need to be
informed and given every option. Surgical exploration and biopsy are
the only ways to definitively diagnose and treat these cancers.
SEPSIS AND SHOCK
Sepsis and septic shock are not uncommon in cancer patients. Sepsis can
be the result of the disease itself or a complication of treatment.
Intestinal neoplasia can lead to bacterial translocation and even
rupture of a hollow viscus. These animals will present with signs of
acute abdominal distress and evidence of peritonitis on plain
radiographs (free air, decreased abdominal detail). The diagnosis can be
confirmed with a diagnostic peritoneal lavage. Animals with diffuse
intestinal neoplasia may have a more chronic course of weight loss,
panyhypoproteinemia and non-specific gastrointestinal symptoms, which
may lead to weakened immunity and septic complications. Septic shock is
characterized by fever or hypothermia, leukocytosis or leukopenia and
hypotension associated with the systemic release of local inflammatory
mediators. Emergency management of these cases centers around the quick
identification and removal of the septic focus, appropriate antibiotic
therapy, and cardiovascular support with fluids, colloids, and if
necessary, positive inotropes.
EXTRAVASATION OF CYTOTOXIC CHEMOTHERAPEUTICS
Some of the more common chemotherapeutic agents used in veterinary
medicine cause significant tissue injury when they extravasate into
perivascular tissues. Some of the more serious compounds include the
vinca alkaloids (vincristine and vinblastine) and doxorubicin. Other
agents causing some tissue damage include mithromycin, mitoxantrone and
cisplatin. Every effort should be made to prevent extravasation. Veins
used for chemotherapy should not be used for blood sampling. Multiple
attempts to catheterize one vein or recent venipunctures make it
unsuitable for administration of any cytotoxic drugs. A careful
"first-stick" approach using a small (22-23 g) catheter should be used
to administer large volumes of drugs like cisplatin and doxorubicin.
Small volumes (less than 1cc) can be given through a small (23-25 g)
butterfly catheter. Saline should be flushed before and after
administration of the chemotherapeutic to assess catheter placement and
insure vessel integrity. The earliest sign of extravasation is pain.
Animals will become extremely agitated, even to the point of self-trauma
as these vesicants leak into surrounding tissues. Erythema may develop
quickly or over several days ultimately resulting in tissue necrosis and
open draining wounds. When extravasation is suspected, do not remove
the catheter. Instead, use the catheter to remove as much drug as
possible. Keep in mind that even with the use of antidotes and good
first aid, intense wound management may be required.
ANAPHYLAXIS
Allergic complications are uncommon side effects of chemotherapy.
Reactions range from potentially lethal anaphylaxis to mild delayed type
hypersensitivity reactions. Serious anaphylaxis has been associated with
L-asparaginase. Because L-asparaginase associated anaphylaxis usually
occurs within minutes, it is advisable to observe the patients for no
less than 30 minutes after administration. Giving the drug by
intramuscular injection can minimize the risk of anaphylaxis.
Intravenous and intraperitoneal administration is associated with higher
incidence of anaphylactic reactions. Anaphylaxis causes acute collapse
and hypotension. Emergency management of these patients involves quick
shock therapy. Intravenous access and shock volumes of crystalloid
fluids (up to 90 ml/kg/hour) are given along with 0.1- 0.3 ml of a
1:1000 dilution of epinephrine given IV or IM. Delayed type
hypersensitivity can be seen with any drug but has been most commonly
associated with doxorubicin, etoposide and paclitaxel. These reactions
typically result in erythema and swelling of the ears, face and paw.
Delayed hypersensitivity reactions can be minimized by diluting drugs
such as doxorubicin with 250-500 ml of 0.9% NaCl and administering
slowly over 30 minutes. Hypersensitivity reactions can be treated with
rapid acting corticosteroids (Dexamethasone sodium phosphate (2 mg/kg
IV) and an antihistamine (Diphenhydramine 2-4 mg/kg IM).
ACUTE TUMOR LYSIS SYNDROME
Acute (hours to days) collapse and even death can be seen with the
treatment of extremely chemosensitive tumors. The destruction of large
tumor volumes can lead to massive release of inflammatory cellular
debris. The resulting inflammatory cascade can mimic sepsis and septic
shock, and can best be described as a systemic inflammatory response.
Electrolyte disturbances caused by the release of intracellular
potassium and phosphorous also contribute to cardiovascular problems.
Tumors most frequently associated with acute lysis include lymphoma and
leukemia. Fast recognition of tumor lysis with appropriate
cardiovascular support is required if the patient is to survive.
Bradycardia in the face of shock should alert the clinician to possible
hyperkalemia. Hypocalcemia may result from high phosphorous levels and
can result in impaired cardiac conduction and reduced cardiac output.
Aggressive fluid resuscitation, normalization of electrolytes and
support of cardiac output and vascular tone are necessary to see the
patient through the crisis
NEUTROPENIA
Bone marrow suppression is an expected complication of many
chemotherapeutic protocols. In addition, diseases like leukemia and
lymphoma can invade the bone marrow causing primary granulopoeisis and
even pancytopenia. Drugs that are highly myelotoxic include doxorubicin,
cyclophosphamide, cisplatin and carboplatin. Doxorubicin and
cylcophosphamide usually cause myelosuppression in 7-10 days.
Recognizing the neutrophil nadir and taking steps to prevent bacterial
colonization should help prevent serious complications. Patients should
be closely monitored during this period. Changes in appetite, attitude,
body temperature, mucous membrane color and pulse quality warrant closer
examination. Every effort should be made to prevent bacterial
colonization during periods of neutropenia. Signs of bacterial
colonization will also be affected by neutropenia. Bacterial
colonization of lungs and bladder can result in infection without
suppurative inflammation. Culture of urine, blood and bronchial fluid
can result in the identification of causative organisms without cellular
evidence of inflammation. Treatment of neutropenia and septic
complications is directed at maintaining perfusion through the use of
crystalloid and colloid solutions, and antibiotic therapy with
bactericidal drugs effective against likely organisms. Recombinant human
granulocyte-colony stimulating factor (5 mg/kg/day SQ) can be
administered to neutropenic patients to decrease the duration and
severity of chemotherapy induced neutropenia.
NAUSEA, EMESIS, AND DIARRHEA
Gastrointestinal complications of cancer and chemotherapy are often the
most difficult for owners. When treating the veterinary cancer patient,
the clinician needs to clearly communicate treatment goals with owners.
If animals are apparently made worse by the treatment, owners may be
reluctant to continue. Because anorexia, nausea, vomiting and diarrhea
are obvious outward signs they may be more disturbing than neutropenia,
hypercalcemia, lymphadenopathy or other complications. These signs may
also be due to the tumor itself and distinguishing what is caused by the
treatment and what the disease causes may be difficult. Supportive care
should be timely and aggressive. Goals include maintenance of hydration
with replacement fluid therapy and symptomatic therapy. Upper GI
inflammation can be managed with antacids and GI protectants. Symptoms
of inflammatory colitis can be managed with sulfasalazine 10-30 mg/kg
TID. Many chemotherapeutics stimulate the chemoreceptor trigger zone to
cause a central nausea. Secondarily, the primary disease can cause
stimulation to the gastrointestinal tract and peritoneal cavity
resulting in nausea and vomiting. Early antiemetic therapy should be
considered in anorectic nauseous patients. Chemotherapy induced emesis
is mediated by 5-HT3 -serotoniergic receptors. Antiemetic drugs, which
antagonize this receptor, seem work the best. Metoclopramide (1-2
mg/kg/day) has some partial 5-HT3 antagonist properties and can be given
by continuous infusion. Specific 5-HT3 receptor antagonists such as
ondansetron (0.5 - 1.0 mg/kg) though expensive, work even better.
_______________________________________________________________________
For further information on "Oncologic Emergencies" or about any other
cancer issue, please call us (713-693-1166) or email Dr. Hahn at
drhahn@gulfcoastvetspec.com .
For more information on the web, use Medline at:
=================================================================
Tumor Tidbits, February 2001. Volume 2, Number 3.