Diabetic Ketoacidosis

Also known as: DKA

Introduction

Severe diabetic ketoacidosis is a medical emergency and requires prompt treatment to correct dehydration, electrolyte disturbances and acidosis.

It is a complication of insulin dependent Diabetes Mellitus.

DKA is the result of marked insulin deficiency, and ketonaemia and ketoacidosis occur approximately 15 days after insulin concentrations are suppressed to fasting levels. Marked insulin suppression occurs on average 4 days after fasting glucose levels reach 30mmol/L.

Many cats with DKA have other intercurrent conditions which may precipitate the condition including: infection, pancreatitis or renal insufficiency.

Pathophysiology

Insulin deficiency leads to increased breakdown of fat that releases fatty acids into the circulation. Free fatty acids are oxidised in the liver to ketones that are used by many tissues as an energy source instead of glucose.

This occurs when intracellular levels of glucose are insufficient for energy metabolism as a result of severe insulin deficiency.

In the liver, instead of being converted to triglycerides, free fatty acids are oxidised to acetoacetate, which is converted to hydroxybutyrate or acetone.

Ketones are acids that cause central nervous system depression and act in the chemoreceptor trigger zone to cause nausea, vomiting and anorexia. They also accelerate osmotic water loss in the urine.

Dehydration results from inadequate fluid intake in the face of accelerated water loss due to glucosuria and ketonuria. Dehydration and subsequent reduced tissue perfusion compounds the acidosis through lactic acid production.

There is whole body loss of electrolytes including sodium, potassium, magnesium and phosphate and there is also intracellular redistribution of electrolytes following insulin therapy which may compound plasma deficiencies.

Complications of the disease include: hyperviscosity, thromboembolism, severe metabolic acidosis, renal failure and death.

Differential Diagnoses

These fall in three categories:

1. Diabetic cats with another condition. Cats with DKA which do not respond to therapy within 1-2 days should be suspected of having an underlying condition such as acute necrotising pancreatitis or sepsis.
2. Nonketotic hyperosmolar diabetes. There is extreme hyperglycaemia, hyperosmolarity, depression and dehydration but no ketosis or acidosis.
3. Severe illness resulting in depression and dehydration preceded by polyuria and polydipsia. This may occur when acute renal failure occurs on top of chronic renal failure. There will be no ketonuria or glucosuria and no marked hyperglycaemia.

Clinical Signs

There will be early signs of diabetes mellitus such as: polyuria/polydipsia, polyphagia, weight loss for several weeks prior to presentation.

Acutely, cats will present with depression, weakness, vomiting, diarrhoea, acetone-smelling breath, slow deep breathing.

Mild cases may have a history of diabetes mellitus but may appear bright and alert on presentation.

Diagnosis

Diabetes mellitus may have already been diagnosed previously.

Biochemistry findings:

Marked hyperglycaemia, usually over 30mmol/L

Plasma pH < 7.3

Ketonaemia

Increased liver enzymes (ALP, AST)

Electrolyte changes: levels will guide treatment and should be monitored 2-3 times a day. Potassium and phosphate may be normal or elevated on admission, but drop rapidly once therapy is initiated.

Urinalysis findings:

Glucosuria

Ketonuria: usually there is a positive dipstick reaction. Beta-hydroxybutyrate is the predominant ketone in cats, but it is metabolised to acetoacetate and acetone after several days, and these are the ketones detected by dipsticks.

Signs of a urinary tract infection may be present: pyuria and bacturia

Haematology findings:

Stress leukogram or an inflammatory leukogram if an inflammatory focus is present.

Radiography and ultrasonography: may be indicated to assist in identifying intercurrent conditions such as pancreatitis.

Diagnosis is rarely a problem in the severe form of DKA.

Treatment

Treatment is usually an emergency, and involves several components:

1. Fluids: most cats are moderately to severely dehydrated on presentation, and require fluids. O.9% saline is commonly used, however may worsen a metabolic acidosis and buffered crystalloid such as lactated Ringer's or Hartmann's solution may be a more appropriate choice. Fluid deficits should be corrected over 12 to 18 hours, monitoring for signs of cerebral oedema and hyperosmolarity. High continuing fluid losses are common until glucosuria and ketonuria are reduced, and maintenance fluid requirements are relatively high. The cat must be monitored carefully for adequacy of hydration and urine output. Weight is a useful indicator during hospitalisation.
2. Electrolytes: fluids should be supplemented with potassium if levels are normal or decreased. Phosphate should be supplemented if levels are normal or decreased, as hypophosphataemia leads to Heinz body formation and haemolytic anaemia. Phosphate cannot be added to calcium-containing fluids such as Hartmann's, so it may be necessary to run fluids through two separate intravenous cannulas, or preferably through a multi-lumen central (jugular) catheter. Electrolyte deficits can be addressed by adding Potassium chloride and potassium phosphate to fluids.
3. Acidosis: Fluid expansion, sodium chloride-containing fluids and insulin therapy should correct the acidosis. Bicarbonate administration is only recommended when levels are below 7mmol/L. There are many disadvantages to bicarbonate therapy, including accelerated development of hypokalaemia and hypophosphataemia, and these usually outweigh the advantages.
4. Insulin: this is needed to stop ketone formation and provide glucose to insulin sensitive tissues. Insulin therapy can worsen hypokalaemia and hypophosphataemia, and fluid and electrolyte correction should be started before insulin is administered. Insulin therapy should be commenced 1-2 hours after fluids are started, but no more than 4 hours after fluid therapy is started, ideally when potassium levels are normal. The goal of therapy is to decrease serum glucose by 4mmol/L/hour until 12-14mmol/L. Continuous intravenous protocols and intramuscular protocols are available, depending on the clinical setting. Once serum glucose is maintained at 10-14mmol/L, insulin can be given subcutaneously every 6-8 hours.
5. Food: cats should be encouraged to eat using palatable food, preferable low carbohydrate. However any food is better than no food.
6. Intercurrent disease: this needs an appropriate management plan, such as antibiotics if bacterial infection is present, or treatment for pancreatitis, congestive heart failure, renal failure, dioestrus.

Prognosis

The prognosis is usually guarded to poor, depending on the stage of disease at presentation, and the presence of any concurrent diseases. Delay in seeking treatment and inability to provide intensive care may affect survival.

Diabetic Ketoacidosis Learning Resources
Flashcards Test your knowledge using flashcard type questions	Small Animal Emergency and Critical Care Medicine Q&A 08

References

Pasquini, C. (1999) Tschauner's Guide to Small Animal Clinics Sudz Publishing

Wingfield, W. (2001) Veterinary Emergency medicine secrets Elsevier Health Sciences

Norsworthy, G. (2010) The Feline Patient John Wiley and Sons

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