Internal Medicine
April 2008 (Vol 29, No 4)

Understanding and Treating Diabetic Ketoacidosis

  • by
  • Brandy Tabor , CVT , VTS (ECC)

Diabetic ketoacidosis (DKA) is a serious metabolic disorder that can occur in animals with diabetes mellitus (DM).1,2 Veterinary technicians play an integral role in managing and treating patients with this life-threatening condition. In addition to recognizing the clinical signs of this disorder and evaluating the patient's response to therapy, technicians should understand how this disorder occurs.


DM is caused by a relative or absolute lack of insulin production by the pancreatic b-cells or by inactivity or loss of insulin receptors, which are usually found on membranes of skeletal muscle, fat, and liver cells.1,3 In dogs and cats, DM is classified as either insulin-dependent (the body is unable to produce sufficient insulin) or non-insulin-dependent (the body produces insulin, but the tissues in the body are resistant to the insulin).4 Most dogs and cats that develop DKA have an insulin deficiency. Insulin has many functions, including the enhancement of glucose uptake by the cells for energy.1 Without insulin, the cells cannot access glucose, thereby causing them to undergo starvation.2 The unused glucose remains in the circulation, resulting in hyperglycemia. To provide cells with an alternative energy source, the body breaks down adipo­cytes, releasing free fatty acids (FFAs) into the bloodstream. The liver subsequently converts FFAs to triglycerides and ketone bodies. These ketone bodies (i.e., acetone, acetoacetic acid, b-hydroxybutyric acid) can be used as energy by the tissues when there is a lack of glucose or nutritional intake.1,2 The breakdown of fat, combined with the body's inability to use glucose, causes many pets with diabetes to present with weight loss, despite having a ravenous appetite.

If diabetes is undiagnosed or uncontrolled, a series of metabolic events can occur that lead to DKA. Predisposing disease processes (e.g., infection, pancreatitis, heart disease), trauma, or exposure to a stressful situation (e.g., being boarded or relocated) can also lead to this condition. Normally, insulin suppresses hepatic glucose production during a state of hyperglycemia. In the absence of insulin, the liver continues to release glucose, exacerbating hyper­glycemia. At the same time, cellular demand for glucose stimulates the release of glucagon from the pancreas. This hormone, together with the stress hormones cortisol, epinephrine, and growth hormone, triggers the liver to produce even more glucose and ketone bodies.1

When the production of ketone bodies exceeds the body's ability to utilize them, they build up in the circulation, resulting in ketosis.2 Although acetone is chemically neutral, the other two substances (i.e., acetoacetic and b-hydroxybutyric acids) are acidic. Therefore, when these acids accumulate in the blood, they cause the blood pH to drop, resulting in metabolic acidosis.4

At the same time, the rise in glucose levels begins to cause osmotic diuresis.5 The renal tubular threshold for total reabsorption of ketone bodies and glucose is quickly exceeded, causing these substances to spill over into the urine for excretion.2 The negative charge of the ketones draws positively charged ions associated with electrolytes, such as sodium and potassium, into the urine to maintain a neutral state.2 Lack of fluid intake, combined with vomiting, diarrhea, and increased urine production, which commonly occur in patients with DKA, can cause an increased loss of electrolytes and fluid through the urine. This fluid loss can lead to dehydration and decreased tissue perfusion, while at the same time reduce the glomerular filtration rate (GFR), which can cause renal failure.2 As the GFR decreases, so does the patient's ability to excrete glucose and ketones, both of which accumulate in the vascular space.2

Clinical Signs

Patients that present with DKA may have been previously diagnosed with and treated for DM, or clients may have observed clinical signs of DM in their pet. Signs of DM include weight loss, polydipsia, polyuria, and polyphagia. Technicians should obtain a thorough patient history in case owners observed these signs but thought that they were unimportant.1,2 The questions that are asked of the owners should be phrased carefully, and leading questions should be avoided. Although the signs of DM precede the development of DKA, patients that develop this metabolic disorder are seriously ill. They may experience vomiting, anorexia, or lethargy, which are often caused by dehydration, electrolyte abnormalities, and acidemia.1 When a patient presents with vomiting and anorexia, it is likely that ketonemia, ketonuria, and metabolic acidosis have already developed; therefore, severe illness may occur within a week or less.2

On physical examination, the pet may present with a thin body condition, muscle wasting, dehydration, depression, unkempt hair­coat, or hypothermia.1 Other signs of DM, such as cataracts in dogs or plantigrade stance due to diabetic neuropathy in cats, may also be noted.2 Plantigrade stance is characterized by walking on the sole of the foot rather than on the toes, as dogs and cats typically do. Clinicians may detect ketone breath,2 which smells like acetone or nail polish remover. Patients with severe metabolic acidosis may also exhibit slow, deep Kussmaul breathing patterns.2



The four classic laboratory findings consistent with DKA are hyperglycemia, glucosuria, ketonuria, and metabolic acidosis.1 Therefore, if DKA is suspected, a complete blood count, full chemistry profile, urinalysis, urine culture, and blood gas analysis should be conducted.1,2 If possible, urine should be collected via cystocentesis. Urine reagent test strips that measure glucose and ketones should detect glucosuria and ketonuria.1 Since azotemia is a common finding in DKA patients, it is important to assess urine specific gravity before therapy is initiated. A dehydrated patient with a urine specific gravity of greater than 1.030 is most likely exhibiting prerenal azotemia, with normal kidney function. However, patients with a urine specific gravity of less than 1.020 may have primary renal failure.2 Evaluation of renal failure is important not only for fluid therapy but also for monitoring. For patients suspected of having oliguric or anuric renal failure, monitoring of urine output is crucial.2 A urine culture should also be conducted to detect a urinary tract infection, which can complicate treatment. The complete blood count most commonly reveals an elevation in packed cell volume and total protein, due to hemoconcentration caused by dehydration.1,2

Not surprisingly, blood chemistry findings will show an increase in blood glucose level. Although the average blood glucose level for a DKA patient is 500 mg/dl, readings may range from 200 to more than 1,000 mg/dl. Other abnormal findings may include elevated liver values, as well as increased levels of blood urea nitrogen, creatinine, cholesterol, and triglycerides.1 De­creased values for many electrolytes, including sodium, potassium, chloride, phosphorus, and magnesium, are also common.1 Electrolyte abnormalities may also be detected on a lead II electrocardiogram strip. For instance, the most common indication of hypokalemia on an electrocardiogram is a prolongation of the Q-T interval, with a lowering of the ST segment and a decrease in the T wave. Premature atrial and ventricular contractions may occur. Hyperkalemia, on the other hand, can result in a spiking of the T wave, a widening of the QRS interval, and a decrease in the P wave. Patients may exhibit brady­­cardia and ventricular arrhythmias.2


The anion gap, which measures the difference between unmeasured anions and cations, can be calculated from the chemistry panel and electrolyte results (see box below). An elevated anion gap can indicate ketoacidosis. There are other causes, however, of an increased anion gap, in­cluding ethylene glycol toxicity and renal failure.2 An elevated anion gap should be evaluated in conjunction with blood work results and the patient's history to determine the cause of the increase. The anion gap in healthy dogs and cats ranges from 12 to 15 mEq/L, and most animals with ketoacidosis have an anion gap ranging from 20 to 35 mEq/L.2

Arterial blood gas analysis is necessary to document the degree of metabolic acidosis.1,2 The body's buffering system may not be able to maintain a normal pH as the ketones build up in the circulation.2 A pH less than 7.0 can correlate with a grave prognosis.2 If the clinic has limited resources and an arterial blood gas analysis cannot be conducted, treatment can be initiated based on the presence of hyperglycemia, glucos­uria, and ketonuria.2

Treatment of underlying disease processes is essential in order to successfully resolve DKA. For this reason, it is also beneficial to conduct an electrocardiogram, obtain thoracic and abdominal radiographs, and conduct an abdominal ultrasonogram. These diagnostics may reveal heart failure, pancreatitis, or liver disease.


In patients with DKA, treatment should in­clude the following steps in order of importance:

  • Fluid therapy to restore fluid volume and enhance perfusion
  • Insulin therapy to lower glucose and ketone concentrations while reversing metabolic acidosis
  • Correction of electrolyte abnormalities

The goal of treatment is for all parameters to return to normal over 36 to 48 hours.2

Fluid Therapy

Rapid initiation of fluid therapy is a cornerstone of DKA treatment. Placement of a central venous catheter eliminates the need for frequent veni­puncture to monitor blood glucose, electrolytes, and venous blood gases.5 It also allows central venous pressure to be measured to avoid overhydration.

Fluid therapy is geared toward correcting cellular dehydration, poor tissue perfusion, and electrolyte abnormalities.5 Fluids can also de­crease blood glucose levels, even without in­sulin, through dilution and by increasing GFR, which allows for increased secretion of glucose through the urine.5 However, fluid therapy alone cannot reduce the ketone concentration.2

The type of fluid chosen should be based on the patient's electrolyte status.2 Since most pa­tients with DKA have a deficit in total body sodium,2,5 a common fluid choice is 0.9% sodium chloride. Other fluid options include Normosol-R, Plasma-Lyte 148, and Ringer's solution.2,5 Hypotonic fluids (e.g., 0.45% sodium chloride) usually do not provide enough sodium, and rapid infusion can result in cerebral edema, which can lead to coma.2,5 The use of buffer in the fluids is controversial.2

The volume and rate of fluids infused during the first 24 hours should be designed to correct dehydration, while supplying maintenance needs and replacing ongoing fluid losses from vomiting or diarrhea.2,5 There are several methods of determining dehydration, including assessing skin turgor, mucous membrane moisture, and urine specific gravity, as well as monitoring packed cell volume and total protein levels. Dogs and cats with DKA are typically 6% to 12% dehydrated.2 The amount of fluid to be infused can be calculated with the formula in the box above. The initial fluid rate is determined by the clinician based on many factors, including the presence of underlying diseases (e.g., congestive heart failure). If the patient is in shock during presentation, the clinician may choose to administer a crystalloid fluid bolus.6

Because of the high fluid rate required to correct dehydration, replace losses, and maintain normal requirements, the patient should be monitored closely for signs of fluid overload (e.g., nasal discharge, coughing, peripheral edema, ascites, increased respiratory rate and effort). After dehydration has been corrected, the fluid rate can be decreased to a maintenance rate that includes replacement of ongoing losses.2

Insulin Therapy

Insulin therapy is crucial in treating patients with DKA. Insulin has the effect of lowering blood glucose, as well as reducing ketone concentration, which can improve metabolic acidosis. Insulin also decreases serum potassium levels by promoting potassium entry into the liver and skeletal muscle.7 The initiation of insulin therapy is often delayed to allow fluid therapy to correct dehydration and normalize electrolytes.2 The clinician should decide when it is best to start insulin therapy based on the individual patient. Regular insulin, which is short acting and has a fast onset of activity, is the only type of insulin that should be used in the initial treatment of DKA.5


Three protocols for insulin therapy exist: intramuscular insulin injections hourly, intramuscular or subcutaneous injections every 4 to 6 hours, and an insulin constant-rate infusion.2,5 Each protocol has advantages and disadvantages; therefore, the clinician should choose the protocol based on experience.5 A constant-rate infusion is typically preferred.2,5 If the patient is dehydrated or has poor perfusion, intermittent intramuscular or subcutaneous insulin is not recommended. Insulin therapy should be administered in such a way as to lower the blood glucose gradually (50 mg/dl/hr) to 200 to 250 mg/dl over 6 to 10 hours.2 This slow, steady decrease prevents the osmolarity from changing too rapidly.2 Once the blood glucose level has reached 200 to 250 mg/dl, 2.5% to 5% dextrose should be supplemented in the fluids to avoid hypoglycemia while the ketosis resolves.2,5 The reversal of ketogenesis and the subsequent resolution of ketosis can take as long as 48 to 72 hours.2,5 Once the patient is able to eat and drink without vomiting, treatment with a longer-duration insulin, administered as twice-a-day injections, may be used.5

Electrolyte Supplementation

One of the most common electrolyte abnormalities in patients with DKA is hypokalemia. Clinical signs of this imbalance include muscle weakness and cardiac arrhythmias. In cats, cervical ventro­flexion can occur. Even if blood work reveals that potassium is normal, it should be anticipated that the concentration will drop rapidly as dehydration is corrected and as the potassium moves from the extracellular space into the intracellular space in response to insulin therapy and correction of the acidemia.2 Therefore, potassium chloride should be supplemented in the fluids.2,5 Potassium supplementation can be based on the potassium replacement scale (see table below) as long as the potassium supplementation does not exceed 0.5 mEq/kg/hr.2,5 Serum potassium levels should be reevaluated every 6 to 8 hours to allow for adjustments and to avoid oversupplementation.2,5

The patient's serum phosphorus level may also decline after therapy is initiated for the same reason that the potassium level drops.2 Hypophosphatemia typically affects the hematologic and neuromuscular systems, resulting in hemolytic anemia, weakness, ataxia, and seizure activity if phosphorus levels fall to 1.5 mg/dl.2 Potassium phosphate can be added to fluids and given as a constant-rate infusion of 0.01 to 0.03 mmol/kg/hr.2,5 Serum phosphorus levels should be reevaluated every 6 to 8 hours and supplementation adjusted as necessary.2,5 Hyperphosphatemia can cause mineralization of tissue, iatrogenic hypocalcemia, and hypotension2,5; therefore, oversupplementation should be avoided.2,5 If potassium phosphate is added to the fluid regimen, the amount of potassium chloride should be adjusted to account for the additional potassium.


Hypomagnesemia, which is also a common finding in patients with DKA, can be life threatening and cause refractory hypokalemia and cardiac arrhythmias. If the hypomagnesemia is mild, it can usually be resolved by administering a fluid that contains magnesium (e.g., Plasma-Lyte 148).5 However, if it is more severe (<1.2 mg/dl), it should be treated more aggressively with an infusion of magnesium sulfate or magnesium chloride.2,5

Monitoring Response to Therapy

Careful patient monitoring, especially during the first 24 to 48 hours, is vital for successful treatment outcomes. Patients must be kept warm and dry, and they should be turned every few hours to prevent the formation of pressure ulcers. Since hematologic and physical parameters may change quickly, it is important for technicians to monitor the patient for any changes and to alert the clinician as soon as possible if any occur. Blood glucose levels should be checked every 1 to 2 hours until the level is less than 250 mg/dl. As soon as the level is reached, dextrose should be added to fluids to create a 2.5% to 5% dextrose solution in order to prevent hypoglycemia while insulin therapy continues.2,5

Serum electrolyte levels should be measured every 6 to 8 hours.2 When the serum sodium reaches 140 to 155 mEq/L, IV fluid should be changed from 0.9% sodium chloride to Ringer's solution or lactated Ringer's solution, both of which have a lower sodium content.2 Electrolyte abnormalities can be further monitored with lead II electrocardiogram strips.

As insulin lowers the ketone concentration, the anion gap should return to normal, and ketonuria will resolve. Total venous CO2 or arterial blood gases should be monitored every 6 to 8 hours.

It is important to evaluate hydration status every 2 to 4 hours.2 Respiratory and cardiac auscultation should be normal, and mucous membranes should be pink and moist with a normal capillary refill time. Central venous pressure should remain below 10 cm H2O.2 Doppler blood pressure readings should remain within normal limits. A fasted pet should lose about 0.5% to 1.0% of body weight per day.2 Abnormal weight gain may indicate overhydration. Fluids should be adjusted as needed.

Urine output should be monitored every 2 to 4 hours. Technicians should expect a minimum of 1 to 2 ml of urine/kg of body weight per hour.2 Lack of urine output within a few hours of initiating fluid therapy is a medical emergency, and the clinician should be notified immediately. Urine should also be checked for glucosuria and ketonuria.

When patients are hypophosphatemic, packed cell volume should be checked daily for signs of hemolytic anemia.


Complications of therapy for DKA include hypoglycemia, cerebral edema, hemolytic anemia, hypernatremia, hyperchloremia, hypo­kalemia, and hypophosphatemia.2 The best way to avoid these complications is with frequent reassessment of the patient's electrolyte and blood glucose levels during the first 24 hours of treatment and then as the clinician deems necessary.2


The prognosis for patients with DKA depends on response to treatment, the severity of the illness, and any underlying diseases that may exist.5 The high mortality rate seen with patients that develop DKA is most often associated with the underlying disease that caused the animal to develop DKA.2

Role of the Technician


Veterinary technicians play a crucial role in treating patients with DKA. The mortality rate increases in patients that are not intensely monitored.2 Technicians are responsible for alerting the clinician immediately of blood work results and monitoring the patient for signs of neurologic problems, aspiration pneumonia (if vomiting occurs), poor urine production, anemia, and overhydration, including nasal discharge, weight gain above expected, and changes in lung sounds, pulse quality, blood pressure, and mucous membrane color. The patient should be kept comfortable and taken to an appropriate area for voiding because any existing polyuria may not resolve immediately.


The author thanks Missy Jenkins, CVT, and Forest Burkhart, CVT, both of whom are affiliated with the Animal Emergency and Specialty Center in Parker, Colorado, for reviewing and gently critiquing the article.

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1. Kerl ME: Diabetic ketoacidosis: Pathophysiology and clinical laboratory presentation. Compend Contin Educ Pract Vet 23(3):220-229, 2001. 2. Feldman EC, Nelson RW: Diabetic ketoacidosis, in Canine and Feline Endocrinology and Reproduction, ed 3. St. Louis, Saunders, 2004, pp 580-615.

3. Randels A: Diabetic ketoacidosis: Monitoring and management. Proc IVECCS Annu Conf:837-841, 2006.

4. Rose DB, Post TW: Hyperosmolar states: Hyper­glycemia, in Clinical Physiology of Acid-Base and Electrolyte Disorders, ed 5. New York, McGraw Hill, 2001, pp 794-821.

5. Kerl ME: Diabetic ketoacidosis: Treatment recommendations. Compend Contin Educ Pract Vet 23(4):330-340, 2001.

6. Rose DB, Post TW: Introduction to disorders of osmolality, in Clinical Physiology of Acid-Base and Electrolyte Disorders, ed 5. New York, McGraw Hill, 2001, pp 682-695.

7. Rose DB, Post TW: Potassium homeostasis, in Clinical Physiology of Acid-Base and Electrolyte Disorders, ed 5. New York, McGraw Hill, 2001, pp 377-378.

Tags: Internal Medicine Veterinary Technician Journal Canine Feline