Endocrine Emergencies.part1.Endocrine Pancreatic Disorders

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Vol. 19, No. 1 January 1997 HEINZ SYMPOSIUM 1996

Continuing Education Article

FOCAL POINT

KEY FACTS

s In diabetic ketoacidosis, serum

potassium is usually elevated but

the body stores of potassium are

typically depleted.

s Hemolysis in diabetic cats

may be caused by Heinz-body

formation.

s Hyperosmolar nonketotic

syndrome is usually preceded by

the classic signs of diabetes

mellitus.

s Attempts to restore euglycemia

in a patient with insulinoma may

result in rebound hypoglycemia.

5Diabetic ketoacidosis is acommon emergency in small

animal practice.

EndocrineEmergencies. Part I.Endocrine PancreaticDisorders

Colorado State University

Deborah S. Greco, DVM, PhD

Pancreatic disorders often cause emergencies in small animal practice.This article reviews the signs and immediate medical management ofemergencies related to high or low blood glucose.DIABETIC KETOACIDOSISPathophysiology

Diabetic ketoacidosis is probably the most common endocrine emergency insmall animal practice. Diabetes mellitus results from impaired glucose utili-zation, increased gluconeogenesis, and increased hepatic glycogenolysis. De-creased peripheral utilization of glucose leads to accumulation of glucose inserum, followed by osmotic diuresis. Osmotic diuresis drives polydipsia, andinadequate intake of fluid results in dehydration.

Insulin is anabolic; therefore, insulin deficiency leads to protein catabolismand contributes to the clinical signs of weight loss and muscle atrophy. As aconsequence of protein catabolism, amino acids are utilized by the liver to pro-mote gluconeogenesis. Stress hormones, such as cortisol and epinephrine, stim-ulate protein catabolism and glycogenolysis, respectively.1

Some of the most profound changes associated with the ketoacidotic diabetic

state occur in lipid metabolism. Because of increased lipase activity, adipose tis-sue is broken down at an accelerated rate into nonesterified fatty acids. Hepaticassimilation of these fatty acids, which depends on the rate of lipolysis, is alsoaccelerated.2 Nonesterified fatty acids are released into the bloodstream and de-livered to the liver for repackaging as triglycerides or are used extrahepaticallyas oxidative fuels.1

With insulin deficiency, lipid metabolism in the liver becomes deranged andnonesterified fatty acids are converted to acetyl coenzyme A rather than beingincorporated into triglycerides. Acetyl coenzyme A accumulates in the liver andis converted into acetoacetyl coenzyme A and then ultimately to acetoaceticacid. Finally, the liver starts to generate large amounts of acetoacetic acid, -hydroxybutyrate, and acetone.1,2

V


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As insulin deficiency culminates in diabetic ketoaci-dosis, accumulation of ketones and lactic acid in theblood and loss of electrolytes and water via urine resultin profound dehydration, hypovolemia, metabolic aci-dosis, and shock. Nausea, anorexia, and vomiting result

when ketonemia and hyperglycemia stimulate thechemoreceptor trigger; they contribute to the dehydra-tion caused by osmotic diuresis. Ketonuria and osmoticdiuresis result in sodium and potassium loss via urine,thus exacerbating hypovolemia and dehydration.Eventually, severe dehydration may result in hypervis-cosity, thromboembolism, severe metabolic acidosis, re-nal failure, and finally death.

DiagnosisThe clinical signs and physical examination findings

in animals with acute diabetic ketoacidosis are dra-

matic. These dogs and cats typically have a history ofanorexia, weakness, depression, and vomiting that waspreceded by polydipsia, polyuria, and weight loss.3,4

Animals suffering from diabetic ketoacidosis are oftenpresented in shock.

Physical examination findings may include depres-sion, tachypnea, dehydration, weakness, and vomit-ing.3,4 Diabetic cats may exhibit clinical icterus as a re-sult of hemolysis, hepatic lipidosis, biliary obstructiondue to pancreatitis, or acute pancreatitis. The gastroin-testinal signs (e.g., vomiting, abdominal distention, andabdominal pain) are similar to those of pancreatitis

(which can occur concurrently with diabetic ketoacido-sis) and peritonitis.1 Diagnosis of diabetic ketoacidosisis based on hyperglycemia, glycosuria, and ketonuria orketonemia.

TreatmentTreatment, as outlined in Treatment of Diabetic Ke-

toacidosis, includes the following steps (in order of im-portance):

s Fluid therapy with 0.9% salines Insulin therapy (low-dose intramuscular or

intravenous)5

s Electrolyte supplementation (potassium chlorideand/or potassium phosphate, magnesium)

s Reversal of metabolic acidosis

Fluid TherapyFluid therapy should consist of 0.9% saline supple-

mented with potassium when insulin therapy is initiat-ed. A large central venous catheter should be used toadminister the fluid because the animals are severelydehydrated and require rapid fluid administration; cen-tral venous pressure may also be monitored via a jugu-

lar catheter to avoid overhydration.Fluid rates depend on the severity of dehydration,

maintenance requirements, continuing losses (vomitingand diarrhea), and the presence of concurrent disease(e.g., congestive heart failure). Use of hypotonic solu-

tions is controversial because serum hyperosmolalityoften causes idiogenic osmoles in the brain, which aretrapped when serum osmolality decreases and rapidlyproduce cerebral edema.5

InsulinInsulin therapy should be initiated as soon as possi-

ble. Either intravenous insulin or low intramusculardoses are given.5 The protocol outlines the intravenousinsulin fluid rate, which should preferably be adminis-tered via a separate peripheral catheter. Approximately50 ml of fluid and insulin is allowed to run through the

intravenous drip set and then discarded because insulinbinds to the plastic tubing.5

The species of regular insulin (beef, pork, or human)does not affect response; however, the type of insulingiven is critical. Regular insulin must be used; insulinzinc suspension, extended insulin zinc suspension, andisophane insulin suspension should never be given intra-venously. Intravenous insulin reduces blood glucose tobelow 250 mg/dl within approximately 10 hours indogs and after about 16 hours in cats.5 Once eugly-cemia has been achieved, the animal is maintained onsubcutaneous regular insulin (0.1 to 0.4 U/kg subcuta-

neously every 4 to 6 hours) until it starts to eat and/orthe ketosis has resolved.An alternative, as shown in the protocol, is to use

low-dose intramuscular insulin. However, blood glu-cose levels may drop precipitously as depots of intra-muscular insulin are absorbed from muscle tissue thathad been poorly perfused.

ElectrolytesElectrolyte (specifically potassium) balance may be

difficult to manage during a ketoacidotic crisis. Potassi-um should be supplemented as soon as insulin therapy

is initiated. Although serum potassium may be normalor elevated in animals with diabetic ketoacidosis, theanimals total body stores of potassium are actually de-pleted.

Metabolic AcidosisCorrection of the metabolic acidosis tends to drive

potassium intracellularly in exchange for hydrogenions. Insulin facilitates this exchange. The net effect is adramatic decrease in serum potassium, which must beattenuated with appropriate potassium supplementa-tion in fluids. Refractory hypokalemia may be compli-

Small Animal The Compendium January 1997

C E N T R A L V E N O U S C A T H E T E R s R E G U L A R I N S U L I N s P O T A S S I U M


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The Compendium January 1997 Small Animal

Treatment of Diabetic Ketoacidosis

Step One: Fluid Therapy

sPlace intravenous catheter, preferably central venous.

Administration rate:

s Estimate dehydration deficit (ml):

Deficit (ml) = Dehydration (%) body weight (kg)

1000 ml

s Estimate maintenance needs:

2 ml/kg/hr hours required to rehydrate (24 hours)

s Estimate losses (vomiting, diarrhea)

Fluid dose = Dehydration deficit + maintenance needs + losses

Hourly fluid administration rate (ml/hr) = Fluid dose (ml) 24 hours

Fluid composition:

Blood Glucose (mg/dl) Fluids Rate Route Monitor Frequency

> 250 0.9% saline Up to 90 Intravenous Packed cell Every 4 hr

ml/kg/hr volume, total

to rehydrate solids, sodium,

potassium,

osmolality

200250 0.45% saline Up to 90 Intravenous Packed cell Every 4 hr

plus 2.5% ml/kg/hr volume, total

dextrose to rehydrate solids, sodium,

potassium,

osmolality

150200 0.45% saline Up to 90 Intravenous Central venous Every 2 hr

plus 2.5% ml/kg/hr pressure, urine

dextrose to rehydrate output

100150 0.45% saline Up to 90 Intravenous Central venous Every 2 hr

plus 2.5% ml/kg/hr pressure, urine

dextrose to rehydrate output


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Step Two: Insulin

Intravenous insulin (regular only) is mixed in 250 ml of 0.9% saline; 50 ml is allowed to run through the administration

set and discarded. See the text for treatment recommendations for hyperosmolar coma.

Blood Glucose (mg/dl) Rate Route Dose Monitor Frequency (U/kg)

Intravenous (regular only)>250 10 ml/hr Intravenous Cats:1.1 Blood glucose Every 12 hr

Dogs:2.2

200250 7 ml/hr Intravenous Cats:1.1 Blood glucose Every 12 hrDogs:2.2



250 mg/dl Initial dose Intramuscular 0.2 Blood glucose Hourly

Every hour Intramuscular 0.1 Blood glucose Hourly


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H E I N Z - B O D Y A N E M I A s H E M O L Y S I S s R E B O U N D H Y P O G L Y C E M I A

Step Four: AcidBase Balance

pH Bicarbonate Concentration Dose of Bicarbonate Rate

(ml)

< 7.1 600 mg/dl),hyperosmolality (>350 mOsm/L), severe dehydration,central nervous system depression, and a paucity of ke-tones or metabolic acidosis.5 Hyperosmolar nonketoticsyndrome in dogs and cats is an unusual syndromecharacterized by neurologic and gastrointestinal abnor-malities (e.g., progressive weakness, anorexia, vomiting,and lethargy). These signs are usually preceded by theclassic signs of uncomplicated diabetes mellitus: poly-dipsia, polyuria, weight loss, and polyphagia.

Physical examination reveals severe dehydration, hy-pothermia, extreme depression, lethargy, and coma.5

Approximately one third of ketoacidotic diabetic catsare presented in recumbency and with a serum osmolal-ity in the range of 388 mOsm/L; this may be a mani-festation of mixed hyperosmolar syndrome.5

Treatment of hyperosmolar coma is difficult. Severalguidelines, which differ from the treatment of diabetic

ketoacidosis, should be followed. First, fluid therapyshould be approached cautiously by estimating the flu-id needs (dehydration deficit) and replacing 80% of thedeficit over a 12- to 24-hour period.5 Isotonic, ratherthan hypotonic, solutions should be used. Hyper-glycemia should also be reversed very slowly. A lowerdosage of insulin (1.1 U/kg over 24 hours) is recom-mended for hyperosmolar animals, and insulin therapyshould be delayed until 2 to 4 hours after fluid therapybegins.5

HYPOGLYCEMIC SEIZURES

Causes of hypoglycemia include iatrogenic insulinoverdose, insulinoma, sepsis, large tumors, hunting dogand puppy hypoglycemia, hypoadrenocorticism, por-tosystemic shunts, hypothyroidism, growth hormonedeficiency, and (rarely) starvation.814 Insulin overdose,hypoadrenocorticism, and insulinoma are the mostcommon endocrine disorders that result in hypo-glycemia.

Treatment should consist of administration of aslow intravenous bolus of 50% dextrose (0.5 g/kg di-luted 1:4). If no vein is readily accessible, corn syrupor pancake syrup may be applied to the oral mucous

membranes with a large syringe. Thereafter, animals with hypoglycemia of any cause should be given acontinuous infusion of 5% dextrose until they can befed.

Veterinarians should avoid the temptation to restoreblood glucose concentrations to the normal range indogs with insulinoma. Administration of higher andhigher doses of 50% dextrose in an attempt to restoreeuglycemia may result in a cycle of rebound hypo-glycemia by provoking insulin secretion. The goal ofintravenous glucose therapy is to stop the seizure ratherthan to normalize blood glucose.


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Long-term management of hypoglycemia depends onthe cause. The veterinarian must therefore use appro-priate diagnostics to identify the cause of the hypo-glycemia.

The immediate therapy for hypoglycemia resulting

from insulin overdose is the same as for other causes ofhypoglycemia. However, endogenous glucose storesmay have been depleted by the insulin overdose; it maytake several days for hyperglycemia to recur.5 In thesecases, insulin therapy should be discontinued until hy-perglycemia recurs. Insulin overdose in animals maylead to cerebral edema and temporary blindness or be-havior changes. These signs are often temporary and re-solve after several weeks or months.

About the Author

Dr. Greco is affiliated with the Department of Clinical Sci-ences, College of Veterinary Medicine and Biomedical

Sciences, Colorado State University, Fort Collins, Col-

orado, and is a Diplomate of the American College of

Veterinary Internal Medicine.

REFERENCES1. Nelson RW: Diabetes mellitus, in Ettinger SJ, Feldman EC

(eds): Textbook of Veterinary Internal Medicine, ed 4. Phil-adelphia, WB Saunders Co, 1995, pp 15101537.

2. Feldman EC: Diabetic ketoacidosis in dogs. Compend Con-tin Educ Pract Vet2(6):456-463, 1980.

3. Schaer M: Insulin treatment for the diabetic dog and cat.Compend Contin Educ Pract Vet 5(7):579590, 1983.4. Ling TV, Lowenstine LJ, Pulley LT, Kaneko JJ: Diabetes

mellitus in dogs: A review of initial evaluation, immediateand long-term management and outcome. JAVMA170:521530, 1977.

5. Macintire DK: Emergency therapy of diabetic crises: Insulinoverdose, diabetic ketoacidosis and hyperosmolar coma. VetClin North Am Small Anim Pract25(3):639650, 1995.

6. Nichols R, Crenshaw KL: Complications and concurrentdisease associated with diabetic ketoacidosis and other severeforms of diabetes mellitus. Vet Clin North Am Small AnimPract25(3):617624, 1995.

7. Christopher MM: Hematologic complications of diabetesmellitus. Vet Clin North Am Small Anim Pract 25(3):

625638, 1995.8. Rogers KS: Hyperinsulinism. Compend Contin Educ PractVet7(10):829841, 1985.

9. Atkins CE: Disorders of glucose homeostasis in neonatal andjuvenile dogs: HypoglycemiaPart I. Compend Contin EducPract Vet6(3):197208, 1984.

10. Atkins CE: Disorders of glucose homeostasis in neonatal andjuvenile dogs: HypoglycemiaPart II. Compend ContinEduc Pract Vet6(4):353366, 1984.

11. Breitschwerdt EB, Loar AS, Hribernik TN, McGrath RK:Hypoglycemia in four dogs with sepsis. JAVMA 178:10721076, 1981.

12. Leifer CE, Peterson ME, Matus RE, Patnaik AK: Hypo-glycemia associated with nonislet cell tumor in 13 dogs.

JAVMA 186:5355, 1985.


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Endocrine Emergencies.part1.Endocrine Pancreatic Disorders