Emergency Management of Insulinoma and Other Causes of Hypoglycemia

Karo syrup can be used by owners at home to help control hypoglycemia.
Figure from www.gotoaid.com.

Hypoglycemia is a medical emergency that may result in seizures and permanent brain damage (1-5). Mild cases of hypoglycemia can quickly become serious and life threatening if the low blood glucose concentration continues to fall.

Untreated, severe, prolonged hypoglycemia can lead to stupor, coma, and even death in some animals.

Emergency Management of Hypoglycemia

Oral glucose administration
Owners who witness a hypoglycemic seizure can be instructed to rub a sugar solution (e.g., Karo syrup or honey) on their pet’s gums. Most animals will respond rapidly. However, owners should be warned not to place their hands directly into the mouth of an animal that is having a seizure and not to pour a sugar solution into the mouth of an unconscious pet (2,3,6).

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.

Intravenous glucose administration
All patients with serious neurologic signs referable to hypoglycemia should be treated immediately by intravenous administration of a 50% dextrose solution (1-5 ml is given slowly over 10 minutes).  If the animal responds clinically, continuous intravenous administration of fluids with a 5% dextrose solution should be considered  (2,3,6). Some clinicians prefer to dilute the initial dose in 5% dextrose or sterile water to create a 20-25% solution prior to injection and thereby reduce the osmolality of the infused solution.

Regardless of the glucose concentration chosen to be administered in an emergency, it is important to keep in mind that it is not necessary to completely normalize the serum glucose concentration, but rather, to eliminate the clinical signs related to hypoglycemia.

Intravenous glucagon infusion
When glucose is administered intravenously to a patient with insulinoma, the tumor may be stimulated to release massive amounts of insulin, leading to severe hypoglycemia. This may result in a viscous cycle of the patient receiving larger volumes and more frequent dosing of intravenous dextrose even as clinical signs become more severe (2,3,6,7).

In dogs with insulinoma, intravenous glucagon should be considered if hypoglycemia and associated clinical signs cannot be not stabilized with infusions of dextrose alone. Glucagon stimulates hepatic gluconeogensis and glycogenolysis, thereby raising the circulating glucose concentrations.

One milligram of lyophilized glucagon USP should be reconstituted according to package directions and mixed with 1 liter of 0.9% saline solution. This resulting 1.0 µg/ml solution is given at 5-10 ng/kg/minute (2,6,7). The rate of infusion is adjusted, as needed, to maintain the serum glucose at a concentration of 50-100 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 slowly tapered over 1-2 days as the serum glucose and clinical signs are monitored (6,7).

Complications of Prolonged Hypoglycemia and Its Treatment

Acquired seizure disorder
Prolonged hypoglycemia can cause focal laminar and pseudolaminar necrosis of the cerebral cortex, which can result in an acquired seizure disorder (2-6). Anticonvulsants may be required long-term for some animals recovering from hypoglycemic seizures.

If seizures persist despite the correction of hypoglycemia, cerebral hypoxia and edema may be responsible. Glucocorticoids, mannitol, or both, should be administered to help treat cerebral edema. Diazepam and phenobarbital may be required to control the seizures. However, we should also consider the possibility that a condition other than hypoglycemia may be the cause of the seizures.

Secondary hypokalemia
Uptake of glucose by cells is accompanied by the transport of potassium from the circulation to the intracellular space. This can result in severe hypokalemia in some cases (2,6). Therefore, the serum potassium concentration should be monitored in patients receiving dextrose infusions and animals supplemented with potassium in most cases (e.g., 16 mEq KCl per liter of intravenous fluids). This is particularly important for animals that are unable or refuse to eat.

References:

1. Elie MS, Zerbe CA. Insulinoma in dogs, cats, and ferrets. Compend Contin Educ Vet 1995;17:51-59.
2. Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. 3rd ed. St Louis: Elsevier Saunders; 2004;616–644.
3. Kintzer PP. Insulinoma and other gastrointestinal tract tumours In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;148-155.
4. Goutal CM, Brugmann BL, Ryan KA. Insulinoma in dogs: a review. J Am Anim Hosp Assoc  2012;48:151-163. 
5. Kraje AC. Hypoglycemia and irreversible neurologic complications in a cat with insulinoma. J Am Vet Med Assoc 2003;223:812-814.
6. Meleo KA, Peterson ME. Treatment of insulinoma in the dog, cat, and ferret In: Bonagura JD,Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013 (in press)
7. Fischer JR, Smith SA, Harkin KR. Glucagon constant-rate infusion: a novel strategy for the management of hyperinsulinemic-hypoglycemic crisis in the dog. J Am Anim Hosp Assoc 2000;36:27-32.