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Standards of Care July 2009 (Vol 11, No 6)


by Elke Rudloff, DVM, DACVECC, Rebekah Franklin, DVM

    CETEST This course is approved for 1.0 CE credits

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    Normal resting plasma glucose levels are 53-117 mg/dL in dogs and 57-131 mg/dL in cats. Clinical signs, such as nervousness, tremors, and weakness, can be observed in normal rats, mice, rabbits, cats, dogs, and monkeys when plasma glucose levels approach 64.8-68.4 mg/dL. In veterinary medicine, hypoglycemia is diagnosed when the blood glucose level is <60 mg/dL.

    Hypoglycemia occurs when there is an excess of insulin or insulin analogues, a decrease in glucose production, or an increase in glucose use. Causes of hypoglycemia are listed in (Box 1). Several counterregulatory endocrine mechanisms are triggered when the brain senses a decreasing level of glucose. The release of epinephrine, corticosteroid, and glucagon suppresses endogenous insulin secretion, antagonizes insulin, and, along with the release of growth hormone, increases the production and release of glucose, thereby increasing plasma glucose. These endocrine responses result in sympathoadrenal signs of hypoglycemia, including tremors, nervousness, and hunger. Insulin is not required for glucose transport into neurons; therefore, the increased plasma glucose that results from counterregulatory mechanisms is readily available for important neuronal functions.

    Neuroglycopenia is a syndrome in which hypoglycemia results in neurologic signs. The brain, almost exclusively, uses glucose for energy—it uses 25% of all glucose in the body—but cannot synthesize or store it. Also, the metabolic rate of brain tissue is three times that of peripheral tissues. These characteristics make the brain particularly sensitive to the effects of hypoglycemia. When protracted or severe hypoglycemia exhausts counterregulatory mechanisms, excitotoxin (e.g., glutamate, aspartate) release, apoptosis, and pseudolaminar necrosis can occur in the brain.

    The rapidity and degree of hypoglycemia determine the severity of clinical signs. The most reliable criteria for diagnosing clinically significant hypoglycemia are: (1) clinical signs of hypoglycemia, (2) blood glucose <60 mg/dL, and (3) relief of signs after glucose supplementation. Hypoglycemia requires immediate treatment to prevent development of irreversible neurologic damage, cardiovascular collapse, and death.

    Diagnostic Criteria

    Historical Information

    • Recent ingestion of bread dough or xylitol gum.
    • Extreme exercise associated with onset of clinical signs.
    • Preexisting liver disease.
    • Untreated neoplasia (pancreatic β-cell tumor, large mesenchymal and epithelial tumors).
    • Exposure to glycemic agents such as insulin or glipizide.
    • Exposure to ticks (virulent babesiosis).
    • Time since last meal.

    Gender Predisposition


    Age/Breed Predisposition

    Hypoglycemia can occur in any breed or species. The following are breed- and age-specific syndromes that can be associated with hypoglycemia.

    • Extrahepatic portosystemic shunt: Yorkshire terriers, miniature poodles, miniature schnauzers, Lhasa apsos, shih tzus, dachshunds, Maltese.
    • Intrahepatic microvascular shunt: Maltese, cairn and Yorkshire terriers, retrievers, Irish setters, Irish wolfhounds, Old English sheepdogs, and Persian and Himalayan cats.
    • Neonates lack glycogen stores, making them more dependent on regular caloric intake. Breeds predisposed to neonatal hypoglycemia include toy and miniature breeds such as the Chihuahua, Yorkshire terrier, Maltese, and poodle. Labrador retrievers and pit bulls may also be predisposed.
    • Rarely, hepatic enzyme deficiencies and deficiencies in contra-insulin hormones can result in hypoglycemia in puppies.
    • Hypoglycemia associated with heavy exercise: hunting dogs.
    • Glycogen storage diseases: beagles and Maltese.
    • β-Cell tumors: standard poodles, boxers, fox terriers, German shepherds, and Irish setters.

    Owner Observations

    • Stumbling.
    • Abnormal behavior.
    • Lethargy.
    • Vocalizing.
    • Weakness.
    • Collapse.
    • Tremors.
    • Seizure activity.
    • Excessive hunger.

    Physical Examination Findings

    Sympathoadrenal signs:

    • Tachycardia.
    • Hypothermia.
    • Hypotension.
    • Dilated pupils.

    Signs of neuroglycopenia:

    • Weakness.
    • Tremors.
    • Nervousness.
    • Bradycardia.
    • Vocalizing.
    • Lethargy.
    • Ataxia.
    • Seizure activity.
    • Clinical signs can progress to decerebrate rigidity, loss of spinal reflexes, miotic pupils, and coma.

    Laboratory Findings

    • Blood glucose <60 g/dL.

    Handheld glucometers allow easy and quick determination of blood glucose levels. However, very low blood glucose levels can fail to generate a reading, and falsely low readings can occur when serum is hemoconcentrated, testing is delayed, or serum is not separated from glucose-consuming blood cells. Dry chemistry analyzers provide more consistent results when serum or plasma has been separated from red cells and the sample is immediately evaluated.

    Key To Costs

    Other Diagnostic Findings

    Methods of collecting samples for the following tests are discussed elsewhere in the literature.

    Complete Blood Count $

    • Neutrophilia with left shift, degenerative left shift, neutropenia, or presence of toxic neutrophils may suggest sepsis.
    • Neutropenia with leukocytosis and eosinophilia may be seen with hypoadrenocorticism.

    Serum Biochemical Profile $

    • Decreased blood urea nitrogen, cholesterol, and albumin may suggest hepatic insufficiency.
    • Sepsis can result in increased liver enzyme, total bilirubin, and renal enzyme levels.
    • Hypoadrenocorticism can also result in hyperkalemia, hyponatremia, and azotemia, unless there is a cortisol deficiency without a mineralocorticoid deficiency.

    Urinalysis $

    • Pyuria and bacteriuria can support a diagnosis of urinary tract infection.

    Preprandial and Postprandial Bile Acids $

    • Elevated paired samples support a diagnosis of hepatic insufficiency.

    Adrenocorticotropin Hormone (ACTH) Stimulation Test $

    • Decreased pre- and post-ACTH injection cortisol levels confirm a diagnosis of hypoadrenocorticism.

    Serum Insulin $

    • To measure serum insulin, a blood sample must be taken when serum glucose is <60 mg/mL; monitored fasting may be necessary to identify when serum glucose levels drop to this point.
    • A diagnosis of pancreatic β-cell tumor is suspected when serum insulin is >20 U/mL during a hypoglycemic episode. When insulin levels are normal or seem inappropriately high for the degree of hypoglycemia, an amended insulin:glucose ratio (AIGR) can be calculated:

    If plasma glucose is <30 mg/dL, 1 is used as the denominator. An AIGR >30 supports the diagnosis of insulinoma.

    Serum Fructosamine $

    • A low level may support a diagnosis of insulinoma.

    Thoracic Radiography $

    • Radiographic signs of a mass lesion may support a diagnosis of neoplasia.
    • Radiographic signs of pneumonia or pleural fluid may indicate a septic focus.

    Abdominal Radiography $

    • Radiographic signs of a mass lesion or intraperitoneal fluid may support a diagnosis of neoplasia or infection.

    Abdominal Ultrasonography $$

    • Abnormal fluid structures or pyelectasis may indicate a septic focus.
    • Microhepatia, vascular shunts, or renomegaly can support a diagnosis of hepatic insufficiency.
    • A mass lesion may support a diagnosis of neoplasia or septic focus.

    Summary of Diagnostic Criteria

    • Blood glucose <60 mg/dL accompanied by neurologic signs that resolve with glucose supplementation.
    • Neurologic abnormalities.

    Diagnostic Differentials

    • Artifact hypoglycemia.
      — Can occur if there is a delay between sample collection and analysis.
      — Repeat sample collection and run test immediately, or collect sample in a serum separator tube, immediately removing serum.
      — Hemoconcentration can cause artifact hypoglycemia when handheld glucometers are used to test whole blood samples. Eliminate artifact by testing a serum or plasma sample.
    • Primary neurologic disease.
      — Blood glucose level >60 mg/dL.
      — Central nervous system imaging.
      — Neurotoxicity testing.

    Treatment Recommendations

    Initial Treatment (Figure 1)

    When neurologic signs are apparent:

    • Insta-Glucose (Valeant Pharmaceuticals, Aliso Viejo, CA) is a dextrose gel that can be rubbed on the oral mucous membranes, where it is directly absorbed and immediately available.
    • Corn syrup contains fructose and can also be rubbed on the gums for absorption, but it requires hepatic metabolism to dextrose. Owners of pets at risk for hypoglycemia should keep these products available for immediate administration.
    • In the hospital, an intravenous bolus of 1 ml/kg of 25% dextrose in normal saline (or 0.5 ml/kg of 50% dextrose diluted 1:1 in normal saline) is administered followed by a constant-rate infusion of 1.25%–10% dextrose in a replacement or maintenance solution. When dextrose solutions of 7% or greater are needed for prolonged periods, infusion via a central line reduces the risk of phlebitis.


    • Glucagon: 50 ng/kg/min IV or IM bolus, then 5–40 ng/kg/min IV. $
      — Useful for hypoglycemic patients with adequate glycogen stores (e.g., insulin overdose, insulinoma) that have difficulties maintaining glucose levels with dextrose supplementation.
      — Requires close glucose monitoring.
      — Once clinical signs of hypoglycemia have abated and measures for glucose control have been instituted, administration can be gradually discontinued.
      — Owners of diabetic pets can store and administer IM glucagon injections at home for emergency use before transport.
    • Dexamethasone: 0.5–1 mg/kg IV or PO q24h. $
      — Preferred corticosteroid if testing for hypoadrenocorticism is anticipated.
    • Prednisolone: 0.25–1 mg/kg IV or PO q12h. $
      — Refractory seizures and altered mentation may persist as a result of cerebral edema and neural injury.
      • Mannitol: 100–1000 mg/kg IV as a slow bolus over 20 minutes may improve cerebral blood flow. If positive results are seen, the dose is repeated 2–3 times every 2 hours. Contraindications to mannitol infusion include fluid-intolerant states (e.g., heart dis- ease, oliguric or anuric renal failure), hyperosmolar states (e.g., hypernatremia), and severe dehydration.

    Insulinoma $$–$$$

    Best treated with surgical debulking.

    • Corticosteroids (prednisolone, 0.5–1 mg/kg PO divided q12h) increase insulin resistance and decrease glucose uptake by muscle cells, making glucose available for neurologic tissue.
    • Octreotide (20–40 μg sC q8–12h), a somatostatin analogue, suppresses insulin synthesis and release.
    • Diazoxide (5–30 mg/kg PO q12h) can block insulin release by decreasing intracellular release of ionized calcium. It also stimulates the adrenergic nervous system, gluconeogenesis, epinephrine release, and glycogenolysis. response to this drug is variable.
    • Streptozotocin and alloxan selectively destroy pancreatic β cells and have been used for treating non- resectable β-cell tumors. streptozotocin has been associated with nephrotoxicity, which may be ameliorated with saline diuresis.

    Patient Monitoring

    • Serial measurement of blood glucose level.
    • Neurologic evaluation of level of consciousness and coordination.

    Home Management

    • Recommend frequent small meals that are higher in fat and contain complex carbohydrates and fiber (canned and dry). Avoid monosaccharides, disaccharides, and propylene glycol additives.
    • Counsel owners of diabetic pets about the clinical signs of hypoglycemia and the proper use of insulin, dextrose supplements, and glucagon.

    Treatment Contraindications

    The goal of glucose supplementation is to provide enough glucose for normal body functions. Persistent hyperglycemia caused by oversupplementation can result in osmotic fluid shifts, diuresis, and fluid losses. Oversupplementation of dextrose in patients with insulinoma can result in overstimulation of the pancreas, leading to increased insulin release and exacerbation of hypoglycemia.


    Favorable Criteria

    • Reversible causes, such as sepsis, toxin exposure, and insulin overdose.
    • Neonates and toy breeds with hypoglycemia that responds to increased feeding frequency.
    • Positive response to treatment for hypoadrenocorticism.

    Unfavorable Criteria

    • Patients with β-cell tumors, glycogen storage diseases, or end-stage hepatic failure generally have a poor long-term prognosis.
    • Prolonged neuroglycopenia can result in permanent brain injury.
    • Nonresectable neoplasia.

    Feldman EC, Nelson RW. Beta cell neoplasia. In: Feldman EC, Nelson RW, eds. Canine and Feline Endocrinology and Reproduction. 3rd ed. Philadelphia: WB Saunders; 2004:616-644.

    Koenig A. Hypoglycemia. In: Silverstein D, Hopper K, eds. Small Animal Critical Care Medicine. St. Louis: Saunders Elsevier; 2009:295-299.

    Loose N, Rudloff E, Kirby R. Hypoglycemia and its effects on the brain. J Vet Emerg Crit Care 2008;18(3):223-224.

    McMichael M, Dhupa N. Pediatric critical care medicine: specific syndromes. Compend Contin Educ Pract Vet 2000;22(4):353-360.

    Todd JM, Powell LL. Xylitol intoxication associated with fulminant hepatic failure in a dog. J Vet Emerg Crit Care 2007;17(3):286-289.

    Click here to download this article as a PDF.

    CETEST This course is approved for 1.0 CE credits

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