All about... diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is a serious complication of unregulated or decompensated diabetes mellitus, which is associated with significant morbidity and mortality. DKA patients are challenging but incredibly rewarding to nurse, and VNs play a key role in the management and nursing care of these patients.
Pathophysiology
Diabetes mellitus (DM) results either from an insulin deficiency, or insulin resistance (the impaired action of insulin). Insulin plays many key roles in the body, including promoting glucose uptake by cells, in order to provide cellular energy. When this process cannot occur effectively, two main things result:
1 - glucose remains in the bloodstream as the body cannot utilise it in cells, or effectively convert it to glycogen for storage, resulting in hyperglycaemia;
2 - the body breaks down lipids in the body to provide an alternative energy source.
The metabolism of lipids to provide energy causes free fatty acids to be released into the bloodstream, where they are converted to ketone bodies and triglycerides by the liver. There are three major ketones; acetone, aceto-acetate and beta-hydroxybutyrate (of which the last two are acidic); these can be used as an energy source in short-term situations where there is a lack of usable glucose or a reduced nutritional intake. It is this fat metabolism which makes weight loss a feature of diabetes mellitus, despite polyphagia.
Diabetic ketoacidosis occurs when the process of ketone formation and metabolism becomes unregulated. This occurs due to a lack of insulin, and an increase in counter-regulatory hormones such as adrenaline, growth hormone & cortisol (all of which are released in response to physiological stress) and glucagon (released as the body cannot utilise glucose – and so it naturally tries to increase glucose levels). The combination of reduced insulin levels and increased counter-regulatory hormones cause the liver to produce more glucose and more ketone bodies!
The accumulation of these ketone bodies in the body leads to ketosis. The accumulation of aceto-acetate and beta-hydroxybutyrate, as they are acidic substances, causes metabolic acidosis to develop.
In addition to ketosis and metabolic acidosis, osmotic diuresis occurs due to hyperglycaemia. Here the elevated glucose and ketone levels spill out into the urine from the bloodstream, after crossing the renal threshold (which typically occurs at a blood glucose level of 14-16mmol/L). This draws water and electrolytes into the urine alongside the glucose and ketones, causing increased fluid, sodium and potassium losses. Significant dehydration results from both reduced fluid intake increased urine losses, and vomiting, which is a common clinical sign of DKA.
Clinical Signs
The most common clinical signs of DKA include depression, anorexia and vomiting, but the severity of clinical signs can vary from mild dehydration, polyuria and polydipsia, through to collapse with severe dehydration and hypovolaemia. Patients can develop DKA following previous diagnosis and treatment of diabetes mellitus (e.g. after a concurrent disease such as pancreatitis, on top of an existing diabetes diagnosis) or the client may have not noticed significant changes in their pet, with diabetes going undiagnosed until this point. Clinical signs, therefore, may also include those of diabetes mellitus – PU/PD, polyphagia and weight loss, and potentially other signs such as a plantigrade stance (diabetic neuropathy) in cats, or visual deficits (diabetic cataracts) in dogs.
On physical examination, it may be possible to detect ‘ketone breath’. This occurs as one of the ketone bodies (acetone) has a fruity odour, which can be detected in the breath of some patients, by some individuals (not everyone can detect this). Ketone breath is reported to smell similar to pear drops.
Diagnostics
DKA is characterised by the presence of hyperglycaemia, ketonaemia or ketonuria, glucosuria and metabolic acidosis. A number of diagnostic tests are therefore required to confirm the condition, investigate any concurrent or contributing diseases and assess the patient’s current health status. These include:
Full biochemistry and haematology to detect any contributing diseases, confirm the presence of hyperglycaemia, evaluate the degree of electrolyte disturbance present, detect any inflammation or infection present. Elevations in liver enzymes (ALP and ALT), triglycerides and cholesterol are commonly present, and azotaemia may also be present. Alterations in sodium, potassium, chloride, phosphate and magnesium levels may also be present.
Pancreas-specific lipase to determine whether pancreatitis is present
Urine analysis including dipstick, specific gravity, sediment examination and culture (as UTIs are common in diabetic patients). NB: beta-hydroxybutyrate does not show up on urine dipstick testing, so it is possible for a patient to have a negative urine dipstick and still have ketones present.
Blood gas analysis to confirm whether metabolic acidosis is present
Abdominal ultrasound +/- thoracic radiographs to detect any concurrent/contributing diseases.
Treatment
The goals of DKA treatment are to restore circulating fluid volume, reverse metabolic acidosis, reduce glucose and ketone levels, and correct any abnormalities over a 36-48 hour period.
Fluid Therapy
IVFT should be initiated 1-2 hours prior to insulin therapy and aims to correct dehydration and hypoperfusion, as well as electrolyte abnormalities. A number of fluid choices are available, and the most suitable option should be selected based on the individual patient, and their electrolyte/acid-base status. 0.9% Saline (No. 1) is commonly used (with potassium supplementation) due to the hyponatraemia often present in these patients; alternative fluid choices include Plasmalyte 148 and Ringer’s solution (No. 9).
Electrolyte supplementation is frequently required in these patients, as the insulin treatment required to reduce ketone and glucose concentrations will move potassium (and phosphate to a lesser extent) into cells, reducing circulating levels. Potassium chloride +/- potassium phosphate supplementation should be administered as appropriate.
Administration of Insulin and/or Glucose Preparations
Neutral insulin is administered to promote normoglycaemia and eliminate ketone bodies before the patient is transitioned to longer-acting insulin. Two methods for neutral insulin administration are used; the intermittent intramuscular injection method and the intravenous constant rate infusion method. The intramuscular method begins with a 0.2IU/kg bolus of insulin given as an IM injection; blood glucose measurements are repeated hourly, and additional 0.1IU/kg doses are administered as IM injections every 15-60 minutes, depending on blood glucose results. The goal with the IM method is to maintain blood glucose levels within the 8-15mmol/L range with repeat injections until the patient has stabilised and begins to eat consistently. If at any point during treatment the blood glucose drops below 8mmol/L, glucose should be added to the patient’s intravenous fluids, to make a 5% dextrose solution; blood glucose monitoring should continue hourly and insulin therapy continued wherever possible to reverse ketogenesis. Once the patient’s condition improves and they are eating consistently, they can be transitioned onto longer-acting insulin, given every 12 hours by subcutaneous injection. Insulin should only be administered subcutaneously when the patient’s hydration deficits have been replaced, as malabsorption of subcutaneous insulin is possible in dehydrated patients.
The CRI method involves the preparation of a constant rate infusion of neutral insulin. This is administered at a dose of 0.05-0.1IU/kg/hour depending on the degree of hyperglycaemia; blood glucose levels are monitored one hour after treatment initiation, and 1-2 hourly thereafter. As with the IM protocol, the aim is to maintain the patient’s blood glucose within the 8-15mmol/L range; if the blood glucose drops below 8mmol/L, a separate 5% dextrose solution should be administered alongside insulin therapy. Again, once the patient’s condition stabilises, their dehydration is reversed and they are consistently eating, they are transitioned to longer-acting insulin.
As neutral insulin binds to plastic giving set/syringe driver extension tubing, CRI lines should be replaced every 24 hours, and approximately 50ml of the diluted insulin solution should be run through the giving set/extension line and discarded prior to use. Insulin-containing CRIs also need to be protected from light; this can be achieved via the use of a light-sensitive giving set/extension set if available, or by wrapping the bag/syringe and line with an opaque material.
Nursing Care
DKA patients should be monitored closely, especially in the early stages of treatment. Vital parameters should be regularly assessed and the patient monitored closely for signs of dehydration, hypovolaemia and electrolyte abnormalities (such as neck ventroflexion and muscle weakness in the hypokalaemic patient). Due to the high fluid therapy rates often used, especially in the initial stages of stabilisation, fluid overload is a risk for these patients, and they should be monitored closely for signs such as chemosis, acute weight gain, and respiratory changes.
Patients should be weighed regularly to assess acute fluid loss or gain, and urine output should be measured and compared with fluid input regularly. This can be achieved through placement of a urinary catheter if appropriate to do so, or by weighing bedding and litter trays, or by catching urine in a kidney dish or similar when walking dogs.
Nurses should also consider the sampling requirements of these patients since regular blood glucose assessments (every 1-2 hours) and electrolyte assessments (every 6-8 hours) will be required until the patient’s condition stabilises. Placement of a central venous catheter or peripherally inserted central catheter can be incredibly helpful in these patients and can be performed by nurses. These catheters allow regular blood draws to be performed without repeated venepuncture, as well as the administration of fluid therapy and insulin solutions.
Consideration should also be given to the patient’s nutritional status, as many patients present with anorexia and vomiting. Appropriate symptomatic treatment should be administered, the patient’s resting energy requirement and voluntary food intake should be measured and recorded, and prolonged anorexia should prompt enteral nutritional support.
Following successful treatment of the ketoacidosis, the patient should be transitioned onto longer-acting insulin and managed as a normal diabetic patient.
References
Higgs, P. 2013. Investigating Diabetic Ketoacidosis. Vet Times, available from: https://www.vettimes.co.uk/article/investigating-diabetic-ketoacidosis/
Huang, A & Scott-Moncrieff, C. 2011. Diagnostic Tree: Canine Diabetic Ketoacidosis. Clinician’s Brief, https://files.brief.vet/migration/article/4955/canine-ketoacidosis_handout-4955-article.pdf
Merrill, L. Small Animal Internal Medicine for Veterinary Technicians and Nurses. Iowa: Wiley-Blackwell, 2012.
Nelson, R W. and Couto, C G. Small Animal Internal Medicine. 5th ed. Missouri: Elsevier Mosby, 2014.
Tabor, B. 2019. Understanding and Treating Diabetic Ketoacidosis. VetFolio, available from: https://www.vetfolio.com/learn/article/understanding-and-treating-diabetic-ketoacidosis
