Diabetic ketoacidosis (DKA) occurs when a patient with diabetes mellitus is severely uncontrolled; it often occurs in cases where diabetes mellitus has not yet been diagnosed. In addition to the underlying diabetes mellitus, predisposing disease processes (infection, pancreatitis, heart disease, etc), trauma or exposure to a stressful situation (eg being boarded or relocated) can also lead to this condition.
Pathophysiology of diabetic ketoacidosis
One of insulin’s major functions is to modulate glucose levels in the body. In doing so, it has to fight against other hormones – termed “hyperglycaemic” or “diabetogenic” hormones – whose functions are to increase glucose levels. Common examples of these hormones include glucagon, catecholamines, oestrogen and cortisol.
In a patient with DKA, not only is there a deficiency of insulin, but there may also be normal or increased levels of diabetogenic hormones. Increased levels of these hormones are usually caused by other disease processes, such as neoplasia or hyperadrenocorticism, which are often enough to cause a patient to become severely uncontrolled and develop DKA.
Without insulin, the cells cannot access glucose, thereby undergoing starvation; however, unused glucose remains in the circulation, resulting in hyperglycaemia. The body then breaks down adipocytes to provide cells with an alternative energy source, 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. When the body is unable to use 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 (acetoacetic and β-hydroxybutyric acid) are acidic and cause the blood pH to drop, resulting in metabolic acidosis.
Diabetic ketoacidosis will progress as hyperglycaemia and the excess ketones worsen, and glucose and ketones are excreted by the kidneys resulting in the urine becoming hyperosmotic
DKA will progress as hyperglycaemia and the excess ketones worsen, and glucose and ketones are 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 patient is left with a profound metabolic acidosis. Bicarbonate (HCO3), the body’s buffer, is gradually used up as acidosis progresses. In the late stages of DKA, 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 (though this can rarely be done completely).
Clinical presentation and diagnosis
Often, patients suffering with DKA will present with vomiting and diarrhoea, which, combined with a lack of fluid intake, may cause an increased loss of electrolytes and further upset the pH of the body. 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 continue to accumulate in the vascular space.
When these patients present as an emergency, they are severely dehydrated, profoundly acidaemic and often obtunded or stuporous. Ketones – recognisable from their fruity odour – may be evident on the breath. Blood gases will reveal several abnormalities, including hyperglycaemia, severe metabolic acidosis, hyponatraemia, hypokalaemia, hypophosphataemia and other electrolyte derangements.
What do I do when an emergency patient presents with diabetic ketoacidosis?
The goals of therapy for patients presenting with DKA are to:
- Rehydrate the patient
- Volume resuscitate
- Correct electrolyte abnormalities
- Correct blood glucose (BG) levels
- Provide gastroprotection
Cases of DKA can be extremely time consuming and often require intensive nursing as the mortality rate increases in patients not intensely monitored.
Issues associated with DKA include neurological problems, aspiration pneumonia (if vomiting occurs), poor urine production, anaemia and overhydration.
Fluid therapy for diabetic ketoacidosis
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 capillary refill time, pale or hyperaemic MM, hypothermia), urine output and, more objectively, by monitoring body weight two or more times a day.
Fluid dose should be calculated to include maintenance needs, dehydration and ongoing losses from vomiting or diarrhoea
Metabolic acidosis, hyperinsulinaemia and hyperglycaemia drive potassium extracellularly and help mask the potassium deficit. Potassium will be driven back into the cells and lost in urinary excretion once the metabolic acidosis has been corrected with IV fluid therapy. Furthermore, insulin works to drive potassium intracellularly, meaning profound hypokalaemia can develop during therapy forDKA. Ideally, insulin should be withheld until serum potassium exceeds 3.5mmol/l.
Monitoring DKA patients is crucial, and electrocardiograms (ECG) are beneficial for noting any changes to the heart due to increased or decreased potassium. Patients with worsening hyperkalaemia may have spiked T waves, a loss of P waves (atrial standstill) and wide, bizarre QRS complexes evident on their ECGs. Those with hypokalaemia may have a reduction in T wave amplitude and an ST segment depression (Figure 1).
DKA patients often benefit from the placement of a central venous catheter or a peripherally inserted central catheter. These catheters often have multiple lumens to allow for the administration of medications and fluid therapy, and a separate lumen to withdraw blood samples. This is advantageous, as DKA patients require multiple BG readings, as well as frequent monitoring of acid-base status through blood gas measurement. These catheters reduce the mounting difficulties seen with multiple sampling and increase patient comfort.
Central lines require some skill 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 percent increases the risk of phlebitis due to the osmolarity) and the ability to measure central venous pressure (CVP).
Administration of neutral insulin to promote normoglycaemia and eliminate the ketone bodies can be managed either by intermittent intramuscular (IM) injection or intravenously via a constant rate infusion (CRI), before moving onto longer-acting insulin.
Administration of neutral insulin to promote normoglycaemia and eliminate the ketone bodies can be managed either by intermittent intramuscular injection or intravenously via a constant rate infusion
With the first method, IM insulin doses are administered every 15 to 60 minutes based on hourly BG readings until the goal of an 8 to 15mmol/l range is reached. CRI administration is tapered according to the regular BG readings, and the same goal is set for BG levels. If the BG drops below 8mmol/l, a 5 percent dextrose solution should be administered to the patient concurrently with the insulin, where possible, to reverse ketogenesis.
CRI administration has the advantage of fewer injections for the patient, though it is often more costly as neutral insulin binds to plastic giving sets and is also light sensitive. Therefore, CRI-giving sets should be replaced every 24 hours. Preferably, a light-sensitive giving set should be used, and the bag covered with an opaque material.
Finally, consideration for the nutritional status of DKA patients should not be neglected. Many of these patients present with anorexia and vomiting or nausea from pre-renal azotaemia. Appropriate symptomatic treatment, such as anti-emetics, can be instituted, and the patient’s resting energy requirement calculated. Encouragement to eat should still be implemented even if enteral nutritional support has been started.