Ferret emergency conditions and critical care (Proceedings)

The ferret patient will often present in an emergency setting with acute presentation of either an acute or chronic disorder. The purpose of this presentation is to review several of the more common ferret emergency conditions, diagnostic modalities, and treatment options. Ferrets as a species are quite amenable to handling, diagnostic testing, surgery and hospitalization. Management recommendations specific for the ferret patient will be discussed.

Hypoglycemia

Hypoglycemia is a common clinical condition in pet ferrets in the United States. Pancreatic islet cell neoplasia (insulinoma) is the most frequent cause of hypoglycemia in the ferret. Other differential diagnoses for hypoglycemia include sepsis, neoplasia, anorexia or starvation, hepatopathy or other metabolic disease.

Ferrets in the age range of two to seven years are most commonly affected. Hypoglycemia related to pancreatic islet cell neoplasia is not common in young ferrets under the age of two years. The initial clinical signs may develop gradually and may not be clinically obvious to the ferret owner. The history may include rear leg weakness, general musculoskeletal weakness, episodes of collapse with hypersalivation, depression, gagging, pawing at the mouth or seizures. Seizures related to hypoglycemia, although quite common in the canine patient, are rare in ferrets. Clinical signs are often intermittent in nature and may not be evident at the time of initial evaluation and physical examination.

A blood glucose level should be measured on any ferret over two years of age presenting to the hospital with the above-mentioned clinical signs. Rapid blood glucose analysis can be performed with either glucose measurement strips or a digital glucometer. It is helpful to also submit part of that same blood sample for evaluation by a clinical pathology laboratory for verification. The normal fasted blood glucose level in the ferret is between 65 mg/dL to 112 mg/dL. A blood glucose level less than 65 mg/dL with accompanying signalment and clinical signs is suggestive of insulinoma. Ferrets with a blood glucose level less than 40 mg/dL may present lethargic, collapsed or comatose. Other blood parameters indicative of insulinoma include an elevated serum insulin concentration (using an assay that has been validated for ferrets) concurrent with hypoglycemia. A definitive diagnosis of insulinoma can only be obtained from histopathological analysis of a surgical pancreatic biopsy.

In cases of hypoglycemic collapse, administer a slow intravenous (IV) bolus of 50% dextrose (0.5 to 2 mL, diluted) to response. The immediate goal of treatment is stabilization and not the complete reversal of the hypoglycemia. Administration of the IV dextrose too rapidly has the potential to stimulate the pancreatic tumor to release large amounts of insulin, resulting in rebound hypoglycemia. After initial stabilization, an intravenous catheter should be placed for fluid support. A constant rate infusion of fluids supplemented with 2.5-5% dextrose should be started. Diazepam can be administered for control of seizures if necessary. Prednisone at a dose of 0.5 to 2 mg/kg PO every 12 hours should be started. The prednisone acts to inhibit peripheral tissue uptake of glucose and stimulate gluconeogenesis . It is best to start with the lowest dose possible to maintain adequate blood glucose level above 70 mg/dL. The dextrose supplementation in the fluids can be adjusted based on regular blood glucose monitoring during hospitalization.

Diazoxide (Proglycem®) is a medication that can also be utilized to treat hypoglycemia secondary to insulin oversecretion2. Diazoxide exhibits hyperglycemic activity by directly inhibiting pancreatic insulin secretion. This action may be a result of the drug's capability to decrease the intracellular release of ionized calcium, thereby preventing the release of insulin from the insulin granules. Diazoxide also enhances hyperglycemia by stimulating the beta-adrenergic system, stimulating epinephrine release and inhibiting the uptake of glucose by cells 3 . Diazoxide can be administered to ferrets orally at a dose of 5 to 30 mg/kg PO every 12 hours 2 . Once clinical signs have resolved, the IV dextrose supplementation can be gradually discontinued. Blood glucose level will need to be monitored after cessation of dextrose supplementation. It is best to keep the ferret hospitalized, if possible, for glucose monitoring at least 24 hours after discontinuation of fluid support. Often, the prednisone dose can be lowered with concurrent administration of diazoxide. Nutritional management is important and should include a high-protein, meat-based ferret or feline diet. Foods high in sugar or carbohydrate content (including treat foods such as raisins) should be avoided. The intake of sugar or carbohydrate based food items could cause an exacerbation of clinical signs by initially causing an increase in blood glucose level and subsequent rebound hypoglycemia.

A small number of ferret patients with seizure activity may be refractory to medical treatment alone. Ferrets unable to maintain normal blood glucose level once dextrose supplementation is discontinued may require surgical intervention. These ferrets, once stabilized, may require surgical debulking of the pancreatic tumors. Debulking may assist with management of this disease, but is not curative. Many ferrets, however, may not have visible pancreatic nodules. There is potential for microscopic disease in the pancreatic tissue. The average life expectancy with medical and/or surgical therapy after the development of persistent hypoglycemia is approximately 8-12 months.

Hematological Emergencies

Anemia is a relatively common clinical condition in the ferret patient. As with other mammals, when evaluating the patient for the anemia, it is important to try and determine if the anemia is regenerative or non-regenerative in nature. Differential diagnoses for anemia in the ferret patient include regenerative anemia due to blood loss or hemolytic disease and anemia of chronic disease.

Potential causes of blood loss in the ferret patient include gastrointestinal ulceration (often due to Helicobacter mustalae infection or trichobezoar), trauma, gastrointestinal polyps, rodenticide ingestion, or hemorrhaging neoplastic mass Estrogen toxicity will lead to profound anemia in the intact female ferret due to persistent estrus in intact females leading to bone marrow suppression. Adrenal disease and ovarian remnants are two other conditions in the ferret, which can lead to blood loss. Neoplasia with bone marrow infiltration (such as lymphosarcoma), chronic renal disease, Aleutian disease (rarely seen clinically) are conditions that can lead to anemia. Autoimmune hemolytic anemia has the potential to cause anemia but is difficult to diagnose in the ferret patient due to lack of ferret-specific anti-antibody reagents.

Clinical signs that may direct the clinician towards an anemia condition include pale mucous membranes, decreased activity level, visible gastrointestinal or other blood loss. Vulvar swelling and alopecia may indicate a hormonal etiology (adrenal disease or ovarian remnant). Organomegaly, pleural effusion, ascites and other systemic signs may suggest neoplastic disease. Diagnostics to confirm anemia are similar to other mammals and include a complete blood cell count with platelet and reticulocyte counts, serum chemistry, radiographs, abdominal ultrasound and/or bone marrow aspirate in cases of nonregnerative anemia. Serum levels of androgens can be measured to aid in the diagnosis of adrenal disease. Treatment for anemia includes immediate support for patient stabilization and treatment for the correction of the underlying etiology contributing to the anemia. Whole blood transfusion or Oxyglobin®(Biopure Corporation,Cambridge, MA) infusion should be considered if the packed cell volume (PCV) is less than 18%. A transfusion may be needed earlier if the blood loss in ongoing.

Whole blood transfusion is required if the ferret needs platelets as well as red blood cells. Blood groups have not been identified in ferrets. Some clinicians consider it safe to transfuse an individual ferret up to three times from the same donor ferret. The volume of blood required for transfusion is calculated as with the dog or cat. A donor ferret should be chosen who is in good body condition and weight, is current on vaccinations and has no history of health problems. The maximum blood volume taken from the donor ferret should not exceed 1% of the ferret's body weight in grams 6. The donor ferret should be anesthetized for the blood collection. Isoflurane anesthesia is the anesthetic of choice for this type of procedure for most ferrets. After the donor ferret is anesthetized, the neck is shaved over the area of the jugular vein. The skin is cleansed and the blood is then collected using a butterfly catheter (22 gauge or larger) pre-flushed with anticoagulant acid-citrate-dextrose (ACD) solution 6. The blood is drawn into a syringe containing 1 mL of ACD per 6 mL blood to be collected for a total of 7 mL. The recipient ferret can be pretreated with dexamethasone sodium phosphate at a dose of 2 mg/kg IV. The whole blood transfusion can then be administered through an intravenous or intraosseous catheter. A transfusion filter should be placed on the line and ideally the catheter should be 22 gauge or larger in order to prevent lysis or disruption of the transfused blood cells 6. Oxyglobin® provides oxygen-carrying function and also has colloidal properties Oxyglobin® has been used in ferret patients with positive clinical effects. Advantages of Oxyglobin® use include the lack of need to find a ferret donor, no blood filter system is required and it can be delivered through a peripheral catheter that is 24 gauge in size.

Additional treatment options for anemic ferrets include fluid therapy if the patient is hypovolemic. Fluid therapy should be exercised with caution to avoid hemodilution. Parenteral or oral iron supplementation if often indicated. Oxygen support should be provided as needed. Other medical management is aimed at treating the underlying cause of the anemia. Ferrets with potential GI blood loss should be placed on gastrointestinal treatment to include anti-ulcer and protectant medications. Surgical intervention may be required in some ferrets if there is a neoplastic mass or specific source of hemorrhage. It is ideal to evaluate the ferret's platelet count prior to surgery. Clotting tests utilized for other mammals can be utilized in the ferret but unfortunately the volume of blood required to run these tests may be prohibitive with an anemia condition.

Dyspnea

There are many potential etiologies for dyspnea in the ferret patient. Differential diagnoses for dyspnea in the ferret include primary cardiac disease, pleural effusion, pneumothorax, influenza, space-occupying thoracic mass, and primary pulmonary disease (rare in ferrets) Ferrets with severe hypoglycemia may present with open-mouthed breathing related to anxiety2. Cardiac disease is a common clinical condition in the ferret patient. Clinical signs include lethargy, exercise intolerance, increased respiratory effort, anorexia, weight loss, coughing and/or ascites. Physical examination may reveal an arrhythmia and/or murmur. Ferrets normally have a pronounced respiratory sinus arrhythmia. Diagnostics should be postponed if the ferret is dyspneic.

A space-occupying thoracic mass can lead to dyspnea. Differentials for thoracic masses in ferrets often include neoplasia (especially lymphoma), abscess or granuloma, megaesophagus can lead to aspiration pneumonia and respiratory signs or distress 6. Pleural effusion is diagnosed as in other mammals. Conditions leading to pleural effusion include cardiac disease, neoplasia, and heartworm disease. Pneumothorax should be ruled out if the ferret has a history of trauma. Radiographs are usually diagnostic and thoracocentesis can be performed. Ferrets tolerate chest tubes and these can be placed similar to the technique used in cats.

As mentioned previously, primary pulmonary disease is not very common in ferrets. Diagnosis can be obtained from a tracheal wash or lung aspirate. If canine distemper is a possibility from the history and clinical signs, the patient should be placed in an isolation area of the hospital. Canine distemper virus is 100% fatal in ferrets.

Urinary Tract Emergencies

Urethral obstruction is most commonly seen in male ferrets greater than two years of age. Urethral obstruction in the male ferret is often secondary to adrenal disease and androgenic stimulation of the periurethral prostatic tissue Enlargement of the periurethral prostatic tissue can lead to compression of the urethra and subsequent obstruction of urine flow. Clinical signs of urethral obstruction may include stranguria, pollakiuria, alopecia and/or pruritis (secondary to adrenal disease), or anuria if the condition progresses to urethral obstruction. Physical examination may reveal a mass dorsal to the bladder, which is often the hypertrophied or cystic prostatic or periurethral tissue.

Diagnostic testing for the ferret with suspected urethral obstruction should include a urinalysis, urine culture and sensitivity testing (collected by cystocentesis), and abdominal ultrasound to evaluate the urinary tract, paraurethral region, and adrenal glands. If cystic areas are visible involving the prostatic tissue, a fine needle aspirate may be obtained of the fluid material via ultrasound guidance. A complete blood cell count and chemistry profile will provide important information to include blood urea nitrogen (BUN), creatinine (Cr) and phosphorus. Creatinine is a more sensitive indicator of renal function in the ferret than BUN and even a mild elevation in creatinine can be a concern.

Treatment of urethral obstruction involves alleviating the immediate obstruction and then treating and correcting the condition leading to the development of the obstruction Urethral catheterization can be performed in ferrets but can be quite difficult due to the small size and location of the urethral opening. The patient should be anesthetized using Isoflurane or other gas anesthesia. There are several options of materials to use for urethral catheterization in the ferret. A red rubber catheter (3.5 Fr), 20-22 gauge 8" jugular catheter, or a specialized ferret urethral catheter (Slippery Sam® , Cook Veterinary Products). A magnifying loupe will help to facilitate visualization of the urethral opening. The urethral opening in ferrets is several mm. proximal to the tip of the penis. Once the catheter is placed it can be sutured and a bandage should be placed around the abdomen to stabilize it. Ferrets are very adept at removing indwelling urinary catheters. A small neck collar may be necessary to prevent removal of the catheter by the ferret. The catheter may be difficult to pass if the prostate is compressing the urethra. In some of these cases, a cystotomy may be required and catheter placement can then be made through the abdominal wall.

If adrenal disease is diagnosed, medical therapy can be initiated. Leuprolide acetate for depot suspension (Lupron® , TAP Pharmaceuticals Inc., Lake Forest, IL) can be administered. Leuprolide acetate is a gonadotropin-releasing hormone (GnRH) analog. Its presumed mechanism in ferrets is to cause a brief rise in LH and FSH and then prolonged reduction of both. Leuprolide acetate is used to decrease androgenic hormone production in some ferrets with adrenal disease. Because the effect of the leuprolide acetate treatment is not going to be immediate, the ferret will need to managed to alleviate the urethral obstruction. Surgical therapy is often required in cases of urethral obstruction. Prostatic marsupialization can be performed to alleviate the pressure on the urethra and allow drainage of the prostatic fluid directly out of the body through the surgically created stoma. In ferrets with adrenal enlargement, surgical resection or biopsy of the affected adrenal gland can be performed during the abdominal exploratory to address the prostatic enlargement. Recurrent obstruction due to cystic calculi or active urinary sediment may require a prescrotal urethrostomy. Urine production should be monitored and the urinary catheter should be maintained for at least 2-3 days after surgery to measure urine production. A broad-spectrum antibiotic should be started pending urine/prostatic fluid bacterial culture and sensitivity results.

Other urologic conditions that can present in the ferret include urolithiasis, urinary tract infection and renal disease/failure. The diagnosis and treatment of these conditions are similar to that in other mammals.

Gastrointestinal Emergencies

Gastrointestinal (GI) foreign bodies are very common in ferrets. Ferrets like to chew on objects and will often seek out rubber or spongy items in the home. In young ferrets the most common type of foreign body tends to be rubber. Older ferrets can develop trichobezoars within the gastrointestinal tract, which can become obstructive. In contrast to cats, linear foreign bodies are rare in ferrets.

Clinical signs of gastrointestinal obstruction in ferrets include anorexia, inappetance, lethargy, and diarrhea. Vomiting often does not occur in ferrets with gastrointestinal foreign bodies. If vomiting is reported, a gastrointestinal foreign body should be considered as a primary differential. Bruxism is a common clinical sign in ferrets with abdominal discomfort. Some ferrets with GI obstruction may present in a weakened, debilitated state.

A presumptive diagnosis of GI foreign bodies or obstruction might be obtained from the physical examination. The small, tubular body shape of the ferret makes the gastrointestinal tract readily palpable. Foreign bodies in the small intestine may be associated with localized discomfort on palpation. Trichobezoars or gastric foreign bodies are more difficult to palpate. Radiography is an important diagnostic tool for a definitive diagnosis. Whole body radiographs are indicated in ferrets suspected to have GI foreign bodies or obstruction. Radiographic findings indicative of GI obstruction may include gaseous distention of the stomach, segmental ileus with dilation of a portion of the intestinal tract. Occasionally the foreign object or trichobezoar may be visible. Abdominal ultrasound can also be utilized in the diagnosis of this condition. Contrast (barium) studies are not usually needed for diagnosis, but can be useful if other imaging tests are not definitive. A minimum data base should include a complete blood cell count and serum chemistry for ferrets that present with clinical signs of several days duration and prior to surgical treatment.

Ferrets can rarely pass gastrointestinal foreign bodies. Because of the small luminal diameter of the ferret small intestine, foreign objects lodges in the small intestinal tract will rarely pass and are usually obstructive. Surgical exploration and removal is usually required. Debilitated ferrets should be stabilized prior to surgery if possible. Many ferrets with GI obstruction will present with some degree of dehydration. Parenteral fluids can be administered via a peripheral intravenous catheter. During the abdominal exploratory surgery for evaluation of the GI tract, it is also indicated to explore the entire abdomen including the liver, pancreas, spleen, adrenal glands and internal lymph nodes. Biopsies can be collected from these structures if enlarged or abnormal at the time of the exploratory. Surgical techniques are similar to those utilized with other mammals. Due to the ferret's small body size, they are more prone to hypothermia during anesthesia than larger species. Sequelae to hypothermia include hypoxia, metabolic acidosis, cardiac arrhythmias, reversible platelet dysfunction, and prolonged drug action. Use of a convective heater during surgery can aid in the maintenance of the ferret's body core temperature.

Recovery from gastrointestinal surgery for ferrets is usually quite rapid. Postoperative supportive care includes continues IV fluid support, analgesia, gastrointestinal protectants and anti-ulcer medications. Most patients are able to eat soft foods 24 hours following surgery. Most ferrets require 24-48 hours of hospital care after a gastrointestinal surgery for foreign body removal. If the ferret patient has other disease conditions the recovery period may be longer. Prevention of trichobezoar formation may be possible with the use of feline laxative during periods of heavy shedding. This author, however, has documented recurrence of trichobezoar formation in a ferret patient within 12 months of the first gastrotomy, even with regular laxative usage.

Vaccine Reactions

A wellness visit for routine vaccinations has the potential to develop into an emergency condition in the ferret patient. Ferrets have a predilection for unpredictable, anaphylactic reaction to vaccines administered. Ferrets should be given a health examination on an annual basis. Once they reach four years of age, twice yearly examinations are recommended because of the high incidence of disease in these older animals. Ferrets should be vaccinated against canine distemper and rabies viruses. Reactions have been documented with both distemper and rabies vaccination, although there is a higher reaction rate with distemper vaccination in the author's practice setting. A vaccine reaction in the ferret patient can be severe and has the potential to be life-threatening if the reaction progresses to a shock state. Unfortunately there has been mortality reported in ferrets with vaccine reactions, despite pre-medication prior to vaccination and immediate post-reaction emergency treatment.

Clinical signs of a vaccine reaction include gagging, vomiting, collapse, cyanotic mucous membranes, tachypnea and/or dyspnea, diarrhea, lethargy, fever, erythematous skin, hypersalivation, and/or tail piloerection. Ferrets should remain in the clinic for at least 30 minutes following vaccination. This allows for monitoring of the ferret during the immediate post-vaccination period and allows for quick assessment and treatment should the ferret develop a reaction. If the client leaves the clinic immediately after the vaccination visit, there is risk of the ferret developing complications if immediate therapy cannot be provided when a vaccine reaction occurs.

A vaccine reaction in the ferret patient can be severe and has the potential to be life-threatening if the reaction progresses to a shock state. Unfortunately there has been mortality reported in ferrets with vaccine reactions, despite pre-medication prior to vaccination and immediate post-reaction emergency treatment.

Treatment for an adverse vaccine reaction is dependent on what, if any, type of premedication treatment was provided prior to vaccination. If an adverse reaction occurs, an antihistamine (diphenhydramine hydrochloride [Benadryl® , Parke-Davis, Morris Plains, NJ] at 0.5-2 mg/kg IV or IM) and epinephrine at 20 ug/kg IV, IM, SC, or intratracheal, and dexamethasone sodium phosphate at 2-4 mg/kg IV If the diphenhydramine or other medications were administered as a premedication prior to vaccination, it should not be administered again. When administering these medications for treatment of a vaccine reaction, it is important to obtain an accurate body weight and dose specifically to the ferret's actual body weight. A ferret that experiences a severe reaction may require hospitalization for intravenous fluid supplementation and monitoring. Gastrointestinal protectant medications may be necessary if severe gastrointestinal symptoms develop.

Trauma

The ferret's compact, tubular body shape, inquisitive personality, and natural burrowing behavior predispose the ferret to accidental trauma. Trauma often occurs in ferrets from accidentally being stepped on, trapped in a confined space or caging. Traumatic conditions can lead to abnormalities involving the thorax, abdomen and orthopedic systems. Diagnosis and treatment of traumatic injury can be approached the same as in feline and canine patients.