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Diabetic ketoacidosis: an endocrine emergency

Diabetic ketoacidosis (DKA) is a commonly seen and rapidly life-threatening endocrine emergency. DKA develops in severe uncontrolled cases of diabetes mellitus. A relative or absolute lack of insulin leads to hyperglycaemia due to lack of uptake of glucose into the tissues.

There is also an increased mobilisation of the body’s protein and fat stores. The fatty acids released this way are converted into ketone bodies (acetone, acetoacetate and beta-hydroxybutyrate) which can be utilised extra-hepatically as an alternative source of energy. Unfortunately, insulin deficiency impairs the use of ketones in the peripheral tissues, and together with their increased production causes high concentrations to develop in the blood. These high concentrations of ketones overwhelm the body’s buffering mechanisms, leading to severe metabolic acidosis. The renal threshold for ketone resorption is also exceeded leading to ketonuria. High concentrations of ketones and glucose in the urine cause osmotic diuresis leading to dehydration, which may be worsened by concurrent vomiting and diarrhoea. Dehydration leads to pre-renal failure which means reduced excretion of glucose, ketones and hydrogen ions. This leads to a worsening of acidosis, ketosis and hyperglycaemia.

Diagnosis

Diabetic ketoacidosis should be suspected in any known diabetic patient that becomes acutely ill. However, a high index of suspicion for the condition should be maintained for any acutely ill patient which has a history of polyuria, polydipsia, weight loss and polyphagia. Clinical signs on physical examination include dehydration, weakness and depression.

Diagnosis is confirmed by the presence of a persistent hyperglycaemia, glucosuria and ketonuria. A urine dipstick test should always be performed in a sick animal with hyperglycaemia. Although cats can exhibit stress hyperglycaemia which can reach the mid 20s (mmol/l), this is usually transient, so the presence of glucosuria is highly suggestive of diabetes mellitus. If in any doubt, fructosamine can be measured – however, in DKA there will not be sufficient time to obtain a result before it becomes necessary to institute treatment. In any case, ketonuria is virtually diagnostic for DKA, although other, rarer causes include a low carbohydrate-high fat diet, hypoglycaemic syndromes such as insulinomas and severe trauma leading to lipolysis.

If diabetic ketoacidosis is confirmed then haematology, urinalysis and biochemistry (including urea, creatinine, electrolytes, calcium and phosphate), ECG and blood gas analysis if available should be performed.

Treatment

The aims of treatment are to correct dehydration, electrolyte abnormalities and acidosis; to correct hyperglycaemia and to treat any underlying causes such as infection.

If the animal appears clinically well, then conservative medical management with regular insulin given subcutaneuosly every 8 hours is probably sufficient, provided any underlying causes are addressed. However, if the animal shows signs of systemic illness such as vomiting, diarrhoea, lethargy, anorexia or dehydration, then intensive therapy should be instituted. This consists of fluid therapy, insulin therapy, bicarbonate therapy (if blood gas analysis available) and treatment of complications and concurrent disorders.

Fluid therapy

0.9% saline is the fluid of choice, since most animals with DKA have severely depleted total body sodium, whether or not serum sodium is low. An initial rate of 60 to 100ml/kg/24 hours is recommended, with subsequent adjustments based on hydration status, vomiting and diarrhoea, azotaemia and urine output. However, if the animal is in shock, then more aggressive fluid therapy is indicated. The fluid should be supplemented with potassium based on serum concentration, with half of the potassium supplement being provided as potassium phosphate. If the serum potassium concentration is not known, initially add 20mEq potassium chloride and 20mEq potassium phosphate to each litre of fluid. Potassium concentrations should be reassessed every 6 to 8 hours. Since insulin therapy and rehydration worsen potassium deficits, potassium supplementation may need to be aggressive to prevent life-threatening hypokalaemia. However, some cases of DKA develop hyperkalaemia secondary to oliguric renal failure, so if possible, potassium concentration should be assessed before treatment is started.

Bicarbonate can be added to fluids if the plasma bicarbonate or total venous CO2 are low. If blood gas analysis is not available, then bicarbonate supplementation may be best avoided.

Once a blood glucose concentration of 15mmol/l has been reached, the fluid can be changed to 5% dextrose.

Insulin therapy

The goal of insulin therapy is a gradual decline in blood glucose over 6 to 10 hours. This is probably best achieved by the intermittent intramuscular technique. Regular crystalline insulin is given intramuscularly at an initial dose of 0.2 IU/kg, then 0.1 IU/kg hourly until the blood glucose reaches 12-15mmol/l. Then the insulin is given subcutaneously at an initial dose of 0.25 to 0.5 IU/kg every 6 to 8 hours. In cases of severe hypokalaemia, it may be prudent to reduce the initial dose of insulin to prevent this worsening.

Concurrent diseases

Concurrent diseases can be responsible for insulin antagonism and the precipitation of the condition of DKA. Common concurrent disorders include bacterial infection, pancreatitis, renal failure and congestive heart failure. Hyperadrenocorticism and metoestrus also cause insulin resistance. The fluid therapy regime may need to be adjusted to take these into account. If nil per os is needed for pancreatitis, then 5% dextrose can be given to maintain blood glucose concentration. Antibiotic therapy may be indicated.

Complications

Complications from the treatment of DKA are common, and may result from inadequate patient monitoring or overly aggressive treatment. To decrease the mortality rate from therapeutic complications, it is important that abnormal parameters are corrected slowly. Monitoring should include: blood glucose every 1 to 2 hours initially; hydration, respiration and pulse every 2 to 4 hours; serum electrolytes every 6 to 8 hours; urine output and urine dipstick for ketones and glucose every 2 hours; body weight, PCV, temperature and blood pressure every 24 hours. Common complications of treatment include hypoglycaemia, cerebral oedema, severe hypernatraemia, severe hypokalaemia and hypophosphataemia leading to haemolytic anaemia.

Long term treatment

Blood glucose usually takes 4 to 8 hours to return to near normal levels. Ketone levels take longer to normalise, and as they are converted from acetoacetate to beta-hydroxybutyrate (to which dipsticks are more sensitive) the degree of ketonuria can appear to worsen. The success of treatment can be assessed subjectively by such parameters as demeanour and appetite. Once the animal has stopped vomiting, is eating and is well, long-acting insulin can be used for maintenance as for uncomplicated diabetes.

References/further reading

  • Nelson, R. W., (2000) Diabetes Mellitus. In Textbook of Veterinary Internal Medicine, Eds Ettinger, S. J., and Feldman, E. C. W.B. Saunders, Philadelphia. 1438-1459
  • Bruskiewicz, K. A., (1997) Diabetic ketosis and ketoacidosis in cats: 42 cases (1980-1995) JAVMA 211: 188