Diabetic ketoacidosis (DKA) occurs when a patient with diabetes mellitus is severely uncontrolled, often in cases where diabetes mellitus has not yet been diagnosed. Diagnosis of diabetes mellitus is often made on presentation of a DKA patient. 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, in addition to diabetes mellitus.
One of insulin’s major functions is to modulate glucose levels in the body. In doing so, it has to fight against other hormones whose function is to increase glucose levels, termed hyperglycaemic or diabetogenic hormones. Common examples of these hormones include glucagon, catecholamines, oestrogen, and cortisol. In a DKA patient, not only is there a deficiency of insulin, there may also be normal or increased levels of diabetogenic hormones. Increased levels are usually caused by other disease processes, such as neoplasia, or hyperadrenocorticism. These other disease processes are often enough to cause a patient to become severely uncontrolled and develop into a DKA. Without insulin, the cells cannot access glucose, thereby, undergoing starvation. However, unused glucose remains in the circulation, resulting in hyperglycaemia. To provide cells with an alternative energy source, the body will then break down adipocytes, releasing free fatty acids (FFAs) into the bloodstream. The liver converts these FFAs into triglycerides and ketone bodies, which are used as energy by the tissues when there is a lack of ordinary nutritional sources.
The pancreas releases glucagon, which together with the stress hormones cortisol, epinephrine, and growth hormone, triggers the liver to produce even more glucose and ketone bodies. When the body isn’t able to utilise all of the ketone bodies made, they build up in the circulation, resulting in ketosis. Although acetone is chemically neutral, the other two substances in ketone bodies (i.e., acetoacetic and b-hydroxybutyric acids) are acidic, and cause the blood pH to drop, resulting in metabolic acidosis.
Once all of this has occurred, DKA will progress as the hyperglycaemia and excess ketones worsen. Glucose and ketones will be excreted by the kidneys resulting in the urine becoming hyperosmotic. The hyperosmotic urine causes water to be drawn through the kidneys in an effort to dilute the hyperosmotic fluid. This is termed osmotic diuresis, and causes the patient to lose water, sodium, and potassium in the urine, thus, becoming very dehydrated with substantial electrolyte abnormalities. With increased ketogenesis, the blood becomes more and more acidic, leading to a profound metabolic acidosis. The body’s buffer, HCO3 is gradually used up as the acidosis progresses. In late stages, the patient will begin to breathe very deeply with a normal to very slow rate, in order to lower blood CO2 and compensate for the acidosis (although this can rarely be done completely). This breathing pattern is referred to as Kussmaul respirations and is a characteristic of diabetic coma.
On top of this osmotic diuresis, often these patients will be vomiting and passing diarrhoea, combined with a lack of fluid intake, may cause an increased loss of electrolytes, and further upset the pH. Fluid loss will lead to dehydration, potential shock, and decreased tissue perfusion, reducing the glomerular filtration rate (GFR), which can cause renal failure. As the GFR decreases, so does the patient’s ability to excrete glucose and ketones, both of which will accumulate in the vascular space.
When these patients present as an emergency, they are severely dehydrated, profoundly acidaemic, often very depressed or non-responsive. Ketones, a fruity odour may be evident on the breath; blood gases will reveal several abnormalities including hyperglycaemia, severe metabolic acidosis, hyponatremia, hypokalaemia, hypophosphatemia, and other electrolyte derangements.
The goals of therapy are to rehydrate the patient, volume resuscitate, correct electrolyte abnormalities, correct glucose levels and provide gastroprotection. These cases can be extremely time consuming and often require intensive nursing and the mortality rate increases in patients that are not intensely monitored. Veterinary nurses are responsible for alerting the vet immediately of blood work results and monitoring the patient for signs of neurologic problems, aspiration pneumonia (if vomiting occurs), poor urine production, anaemia, and overhydration, including nasal discharge, weight gain above expected, and changes in lung sounds, pulse quality, blood pressure, and mucous membrane colour.
The fluid dose should be calculated to include maintenance needs, dehydration, and ongoing losses from vomiting or diarrhoea. Hydration should be estimated by physical examination (tachycardia, weak peripheral pulses, prolonged CRT, pale or hyperaemic MM, hypothermia) and more objectively measured by monitoring body weight two or more times a day, and urine output.
Fluid deficits are calculated based on the estimate of dehydration; % dehydration × body weight (kg) × 1000 = ml of fluid deficit. Metabolic acidosis, hyperinsulinemia and hyperglycaemia drive potassium extracellularly, and help mask the potassium deficit. Potassium will be driven back into the cells and be lost in urinary excretion once the metabolic acidosis has been corrected with IV fluid therapy. Furthermore, insulin works to drive potassium intracellularly, meaning that profound hypokalaemia can develop during therapy for DKA. Ideally insulin be withheld until serum potassium exceeds 3.5 mmol/L.
DKA patients will often benefit from the placement of a central venous catheter or a peripherally inserted central catheter (PICC). These catheters will often have multiple lumens to allow for the administration of medications, fluid therapy, and a separate lumen to withdraw blood samples from. This is particularly in DKA patients as they will require multiple blood glucose readings (though the use of continuous blood glucose monitors may eliminate some need for these), as well as frequent monitoring of acid-base status through blood gas measurement. These catheters reduce mounting difficulties seen with multiple sampling, as well as increasing patient comfort. Central lines require some skills to maintain, as they require bandage changes at least twice daily to visualise for phlebitis, extravasation, or bleeding around the site, as well as frequent flushes, protocols for sampling blood, and strict asepsis. Other advantages of placing central lines in DKA patients include the ability to give higher percentage solutions of glucose (anything higher than 5% increases the risk of phlebitis due to the osmolarity), and the ability to measure central venous pressure (CVP).
References
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