Emergency Treatment

All patients with serious neurologic signs referable to hypoglycemia should be treated immediately by intravenous administration of a 50% dextrose solution. Clinicians give 1 to 5 ml slowly over 10 minutes. If the animal responds clinically, continuous intravenous administration of fluids with a 5% dextrose solution should be considered. Some clinicians prefer to dilute the initial dose in 5% dextrose or sterile water to create a 20% to 25% solution before injection and thereby reduce the osmolality of the infused solution.

Regardless of the glucose concentration chosen to be administered in an emergency, the goal of glucose administration is not to establish a normal serum glucose level but to eliminate clinical signs related to hypoglycemia.

When glucose is administered intravenously in patients with insulinoma, the tumor may be stimulated to release massive amounts of insulin, leading to severe hypoglycemia. This may result in a vicious cycle of the patient receiving larger volumes and more frequent dosing of intravenous dextrose even as clinical signs become more severe. In dogs with insulinoma, intravenous glucagon may be considered if the low serum glucose and associated clinical signs are not reversed with infusions of dextrose. Glucagon stimulates hepatic gluconeogenesis and glycogenolysis. According to package directions 1 mg of lyophilized glucagon USP should be reconstituted according to package directions and mixed with 1 L of 0.9% saline solution. This resulting 1 µg/ml solution is given at 5 to 10 ng/kg/min. The dosage is adjusted as needed to maintain the serum glucose at a concentration of 50 to 100 mg/dl. When the dog is able to eat and maintain its own blood sugar and/or other surgical or medical therapy is used to treat the insulinoma, the glucagon infusion may be tapered slowly over 1 to 2 days as the serum glucose and clinical signs are monitored (Fischer et al, 2000).

Owners who witness a hypoglycemic seizure may be instructed to rub a sugar solution (corn syrup) on their pets’ gums. Most animals respond rapidly. Owners should be warned not to place their hands directly into the mouth of an animal having a seizure and not to pour a sugar solution into the mouth of an unconscious pet.

If the animal responds to intravenous or oral glucose administration, it then should be fed a small, high-protein meal and kept as quiet as possible. Owners who notice a pet is becoming weak may prevent a hypoglycemic seizure by feeding.

Prolonged hypoglycemia can cause focal laminar and pseudolaminar necrosis of the cerebral cortex, which can result in an acquired seizure disorder. Anticonvulsants may be required long term for some animals recovering from hypoglycemic seizures.

In an emergency situation, if seizures persist despite the correction of hypoglycemia, cerebral hypoxia and edema may be responsible. Glucocorticoids, mannitol, or both, should be administered. Diazepam and phenobarbital may be required to control the seizures. The clinician also should consider the possibility that a condition other than hypoglycemia may be the cause of the seizures.

Uptake of glucose by cells is accompanied by the intracellular transport of potassium. The serum potassium concentration should be monitored in patients receiving dextrose infusions and supplemented in most cases (e.g., 16 mEq KCl/L of fluid). This is particularly important for animals unable to eat.

Surgery

Surgery is the treatment of choice for the initial long-term management of animals with insulinoma. Exploratory celiotomy is useful in confirming the diagnosis, staging the patient, and removing the neoplastic tissue. All identifiable pancreatic nodules should be removed, and metastatic lesions should be resected whenever possible. When possible, pancreatic masses should be removed by partial pancreatectomy. Survival time for dogs undergoing partial pancreatectomy is longer than that for those undergoing nodulectomy. Partial pancreatectomy can be performed by the suture-fracture technique, the dissection-ligation technique, or through the use of an electrothermal bipolar vessel-sealing device (LigaSure V). The bipolar vessel-sealing device (BVSD) denatures collagen and elastin within vessel walls and thus safely seals tissue and vessels while causing less tissue damage than is seen with the higher temperatures used in traditional cautery. Using the BVSD to perform partial pancreatectomy in dogs results in shorter surgical times and a decreased incidence of postoperative pancreatitis when compared with dogs undergoing the suture fractionation technique. The BVSD is likely more effective in sealing pancreatic ducts during partial pancreatectomy and thus minimized the leakage of pancreatic juices in to the remaining tissue that could cause local or generalized pancreatitis (Wouters et al, 2011). Whether metastatic lesions are visible, biopsy of the liver and mesenteric lymph nodes is recommended for staging.

Localizing a pancreatic nodule can be difficult, especially in dogs. In ferrets, nodules are less challenging to find. In cats with insulinoma, all those reported have had a pancreatic nodule identified. The entire pancreas should be palpated carefully and the liver and mesenteric lymph nodes visualized. Intravenous infusion of methylene blue has been suggested as a means of enhancing the visibility of insulinomas, but this procedure has not been evaluated in a large study, and methylene blue can cause serious Heinz body hemolytic anemia. It is not recommended routinely but can be given intraoperatively if no nodule can be identified. The surgeon must allow 30 minutes for tumor staining to occur. Intraoperative ultrasonography is safe, but the accuracy of this technique depends on the experience of the ultrasonographer. If no mass has been imaged preoperatively and equipment is available, it is prudent to plan for intraoperative ultrasound.

When a nodule cannot be identified intraoperatively, biopsy specimens should be taken from the pancreas, liver, and mesenteric lymph nodes. In dogs, insulinoma develops within the right and left pancreatic lobes with equal frequency, and occult nodules are most common in the body of the pancreas. Thus random removal of pancreatic tissue offers no advantage.

Nodules were identified during surgery in the five cats with insulinoma that have been described. One of these cats had a relapse in clinical signs 6 days after surgery, suggesting that occult nodules were present. A second cat, which had a large tumor, died during the immediate postoperative period. In each of the other three cats, a single nodule was identified and removed.

In ferrets, multiple pancreatic nodules are more common than solitary nodules. Occult insulinoma appears to be rare in ferrets. Full abdominal exploratory celiotomy is recommended in all species but is especially important in ferrets. Nonpancreatic neoplasia has been identified frequently in ferrets undergoing celiotomy for insulinoma. Adrenal tumors are seen most commonly.

The serum glucose concentration should be stabilized before induction of anesthesia and surgery. Although it is not necessary for the serum glucose to be in the normal range, ideally the measured levels should be stable and the patient should have experienced one or more days without seizures before surgery. Frequent feedings, continuous intravenous infusion of dextrose solution (5% dextrose or higher), or both, are the best ways to accomplish this. If these methods are unsuccessful, more aggressive medical management (see section on medical management) should be considered. In dogs, as mentioned above, a constant rate infusion of glucagon can be considered to stabilize refractory patients.

Monitoring the serum glucose concentration throughout and after surgery is important. Surgical manipulation of insulinoma can enhance the release of insulin from the tumor(s). Anesthesia masks the signs of neuroglycopenia; thus the only way of preventing serious hypoglycemia is to monitor the patient carefully and administer dextrose as needed. While the surgeon is manipulating the pancreas and any metastatic lesions, the serum glucose concentration should be evaluated every 10 to 20 minutes. Because the patient may require several different concentrations of dextrose-containing solutions throughout the surgery and postoperative period, such solutions should be prepared in small quantities and supplies should be close at hand.

After surgery, the glucose concentration should be monitored every 30 to 60 minutes for the first 3 to 4 hours, and then every 2 to 4 hours until the glucose concentration has stabilized and the appropriate concentration of dextrose solution has been selected. The patient may have hyperglycemia after surgery, and intravenous fluids without dextrose may be appropriate.

In dogs, the most common postoperative complication is pancreatitis. Documented or suspected pancreatitis has been reported in cats and ferrets as well postoperatively. During surgery, the pancreas should be handled gently, and the surgeon should pay special attention to preserving the blood supply to the pancreas when performing a partial pancreatectomy. Use of an electrothermal BVSD (LigaSure V) may reduce the risk of pancreatitis in dogs undergoing partial pancreatectomy. Intravenous administration of fluids (e.g., lactated Ringer’s solution with 5% dextrose) before, during, and after surgery helps to ensure adequate pancreatic circulation. Dogs should be treated as if they have pancreatitis after pancreatic surgery and held off food and water for 36 to 48 hours after the procedure, or longer if clinical signs of pancreatitis are apparent. Small amounts of water and bland food may be started on the second or third day after surgery.

Postoperative pancreatitis and postoperative hyperglycemia appear to be uncommon complications in ferrets. Ferrets may be fed 24 hours after surgery. The prevalence of postoperative complications in cats undergoing surgery for insulinoma is not known, in part because pancreatitis is difficult to diagnose in cats due to variable clinical signs (see Chapter 138). The conservative postoperative management described earlier also is recommended for cats.

In some animals, the high concentration of circulating insulin secreted by the tumor suppresses the function of normal beta cells, leading to hyperglycemia once the insulin-producing tumor is removed. As function of the beta cells returns, postsurgical hyperglycemia is resolved. If treatment with insulin is required after resection of an insulinoma, the clinician and the owner should be aware that endogenous insulin eventually may be produced either by the normal beta cells or by recurrent tumor cells. The owner should monitor glucose in the urine several times per week, and serum glucose should be checked at least monthly to avoid an iatrogenic hypoglycemic crisis.

When a patient that has previously undergone surgery for insulinoma begins to show signs of hypoglycemia, a second surgery may be attempted or medical management instituted. If all visible tumor can be resected again, animals may remain symptom free for a number of additional months. It appears that ferrets whose first symptom-free interval was several months are most likely to benefit from a second surgery.