"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.