Diabetic Ketoacidosis

Question 1

What is the pathophysiology of diabetic ketoacidosis?

Answer 1

• 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.

Question 2

What are the d/dx of dka?

Answer 2

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.

Question 3

Summarise how dka happens?

Answer 3

A serious and life-threatening complication of diabetes mellitus that results in:

• Ketone body formation in the liver animal enters a metabolic acidotic state.
• Metabolic acidosis
• Severe dehydration
• Shock
• fatal

Occurs due to combined insulin deficiency and excess diabetogenic hormones and/or insulin resistance for other reasons

Question 4

Discuss some triggers of diabetic ketoacidosis?

Answer 4

Commonly identified triggering conditions include:

• infections
• other endocrine disease (e.g. Hyperadrenocorticism)
• and inflammatory disease (e.g. Pancreatitis).
• But any concurrent disease could act as a trigger.

Question 5

Which kbs are a concern in cats and dogs?

Answer 5

• Acetoacetic acid
• Beta-hydroxybutyrate (first one produced)
• (acetone)

Question 6

Do kbs have any beneficial role?

Answer 6

Serve as an energy source when insulin mediated glucose delivery to cells fails/ supply alternative energy source if we don’t have enough insulin to utilise glucose in an effective manner

Question 7

What is the pathophysiology of some of the presenting signs of Dka?

Answer 7

Hyperglycaemia and ketonuria –> causes severe osmotic diuresis

• Renal loss of water and electrolytes
• Dehydration à in SA continues to hypovolaemia

Circulating Ketone bodies –> crtz

• Nausea –> reduces appetite and water intake
• Vomiting –> further fluid loss

Dehydration–> further drop in renal excretion of glucose and ketones

Stress hormones –> further hyperglycaemia

• Cortisol
• Adrenalin

Crtz= chemoreceptor trigger zone (important in some vomiting pathways stimulated by endogenous or exogenous toxins)

Question 8

What are the likely precipitating causes of Dka in dogs?

Answer 8

• Urinary tract infection
• Pyometra /dioestrus
• Pancreatitis
• Endocrine disease
  
  • Hyperadrenocorticism
• Pneumonia
• Corticosteroid treatment
• Neoplasia
• Usually untreated/poorly treated DM

Question 9

What are the likely precipitating causes of Dka in cats?

Answer 9

• Urinary tract infection
• Cholangiohepatitis
• Pancreatitis
• Airway disease +/- rx
• Ckd
• Endocrine disease
  
  • Hypert4
  • Acromegaly??
• Think about an example: airway disease in cats is a common disease associated with inflammation (increased diabetogenic hormones, increased insulin resistance) and is often treated with drugs that are diabetogenic (corticosteroids) leading to increased risk of dka

Question 10

What are clinical signs associated with Dka?

Answer 10

• Lethargy/depression
• Weakness
• Dehydration
• Vomiting
• Tachypnoea
  
  • Reflects the respiratory response to metabolic acidosis
    
    • “blow off” co2
  • Could be associated with aspiration pneumonia as a complication of vomiting/weakness
• Smell of acetone?

Question 11

What can be observed on physical exam with an animal with Dka?

Answer 11

Hepatomegaly:

• Common in diabetic cats and dogs
• Difficult to palpate in many large dogs

Cataracts are commonly observed in dogs

• Associated with the underlying dm

Jaundice can be seen with

• Hepatic lipidosis in cats (hepatic jaundice)
• Underlying pancreatitis (post hepatic jaundice)

Quirky cats: diabetic neuropathy might be seen

• Plantigrade hl stance

Question 12

You have a clinical suspicion of Dka based on vomitting but what could be the d/dx for vomiting?

Answer 12

Primary gi:

• Dietary indiscretion
• Non specific gastritis
• Foreign body
• Intussusception
• Neoplasia
• Infectious e.g. Cpv

Other diseases:

• Dka- but why??
• Pancreatitis
• Pyometra
• Acute kidney injury
• Hepatitis
• Hypoadrenocorticism
• Drugs/toxins
• Cns disease
• Peritonitis

Question 13

What are common lab findings associated with dKa?

Answer 13

Significant hyperglycaemia, often >25mmol/l

Ketonaemia

Azotaemia:

• Likely prerenal due to dehydration
• Might progress to aki due to poor renal perfusion
• Monitor urine output carefully

Metabolic acidosis

Elevated liver enzymes which might reflect

• Underlying lipidosis
• Poor perfusion
• Underlying disease eg pancreatitis, hyperadrenocorticism?

Electrolyte abnormalities

Hyponatraemia

• Increase in water drawn in to the intravascular space by high bg causes dilution of sodium
• May resolve when bg is managed and reduces

Hypokalaemia

• Chronic pu/pd renal loss
• Inadequate intake (anorexia)
• Gi losses due to vomiting and diarrhoea
• Insulin treatment will drive potassium in to cells
• Usually requires supplementation

Hyperkalaemia (less likely more transient)

• If –> extracellular location 2ry to
• Acidosis
• Lack of insulin and
• Plasma hyperosmolarity.
• Could reflect drop in urine output 2ry to oliguric or anuric renal failure.

Question 14

How may haemotology appear with dKa crisis?

Answer 14

• May be normal
• Stress leucogram
• Mature neutrophilia
• Left shift
  
  • Infection?
  • Severe inflammatory disease?
• Heinz bodies in cats?
  
  • Markers for oxidative damage

Question 15

Dka and urinalysis what do we see?

Answer 15

• Glucosuria
• Ketonuria
  
  • Test strips don’t detect b-oh-butyrate
• Variable sg
• Evidence of uti?
  
  • Pyuria
    
    • Can urine sediment exam be misleading?
  • Bacteria
    
    • Is it a cysto sample?
  • Positive culture

Question 16

How is an emergency Dka patient treated?

Answer 16

We need to correct:

• Fluid deficits and restore perfusion
• Electrolyte abnormalities
• Acidosis

We need to provide:

• Insulin
• Carbohydrate substrate when required during insulin therapy

We need to identify and manage

• Precipitating factors (e.g. Uti)

Question 17

How is fluid therapy used to treat dKa?

Answer 17

What do we give?

• Normal (0.9%) saline
  
  • Helps correct fluid and na deficit?
• Hartmanns

How do we give it?

• Iv access is crucial
  
  • Bloods are usually obtained as an iv line is established
• Fluid bolus indicated
  
  • Volume and speed of administration of fluid bolus depends on clinical signs
  • Aim: to normalise perfusion and its associated physical examination parameters
    
    • Give a bolus and then review to see if need to repeat

Question 18

Once hypovolaemia has been addressed how should fluid therapy be continued?

Answer 18

Once hypovolaemia is addressed we need to select an ongoing rate for fluid therapy which depends on

• Fluid deficit ie % dehydration
  
  • Polly: approx. 10% dehydration = 10% x 27kg = 2.7l
  • Replace the deficit in 12-24 hours
  • Sometimes replace half the deficit in 1st 4-6 hours
• And maintenance requirements (2mls/kg/hour)
  
  • Polly: 2 x 27kg x 24 = approx. 1300mls/24 hours
• And ongoing losses “guesstimate” based on monitoring
  
  • Vomiting
  • Diarrhoea
  • Polyuria

Fluid losses can be very significant in an uncontrolled diabetic patient

Question 19

After correcting hypovolaemia and commencing fluid therapy what improvement should be observed?

Answer 19

Improving tissue perfusion

• Starts to manage metabolic acidosis
• Reduces blood glucose by improving gfr

Question 20

What do we need to monitor throughout fluid therapy?

Answer 20

Renal:

• Urine output

Cardiovascular:

• Pulse and hr
• Mm colour
• Peripheral pulse quality

Respiratory:

• Rate, effort
• Auscultation for crackles?
• Tachypnoea occurs due to attempts to correct acidosis- tachypnoea on fluids and pulmonary crackles- more suggestive of fluid overload or aspiration pneumonia.

Question 21

What are the signs of fluid overload?

Answer 21

• Shivering
• Nausea
• Vomiting
• Restlessness
• Tachypnoea
• Coughing
• Chemosis (swelling or oedema of conjuctiva)

Question 22

How should potassium be given/restored to treat dKa?

Answer 22

Potassium supplement

• Restoring renal perfusion –> drop in serum k+ due to increased­ excretion
• Correcting acidosis favours return of k+ in to cells
• Insulin treatment also drives k in to cells
• Significant hypokalaemia can develop in 2-6 hours even if normokalaemic at start of fluid and insulin therapy
• Hypophosphataemia is less common but also a risk within 12-24 hours
• Potassium is usually replaced as potassium chloride but in dka cases if hypophosphataemia becomes a problem then potassium can be supplemented as potassium phosphate.

Question 23

How should insulin therapy be given in dKa?

Answer 23

Insulin treatment

• Rapidly acting insulin is essential
  
  • “neutral” or “regular” insulin
  • Soluble for iv use
• No licenced animal preparation so need to use a human prep
• Different protocols are available- make sure you are happy with the one you choose and carefully follow the “recipe”!

Continuous infusion of soluble insulin. Add 25iu neutral insulin to a 500ml bag of 0.9%nacl or 2.5iu to a 50ml syringe (0.05iu/ml insulin). Infuse at 1ml/kg/hr until the bg is <15mmol/l. Once bg has reduced to this level, reduce the insulin infusion rate to 0.5ml/kg/hr

• This is my preferred protocol and it seems to work very well. Requires one fluid bag for iv fluids +/- potassium and one containing insulin because they run at very different rates!!

Insulin treatment cont’d:

Different protocols are available- make sure you are happy with the one you choose and carefully follow the “recipe”!

• Give an initial dose of 0.2 iu/kg soluble (neutral) insulin i.m followed by 0.1 iu/kg i.m every 1 hour until blood glucose below 15mmol/l
• 0.5iu/kg soluble insulin sc with subsequent adjusted doses every 6 hours

Question 24

How should a CHO source be given during dKa crisis?

Answer 24

Give a CHO source

• Once we give exogenous insulin there is a risk of hypoglycaemia developing.
• Bg will usually fall towards the reference interval long before ketoacidosis resolves
• Dogs/cats may be slow to start eating because of the underlying trigger disease
• Supplementation of fluids with dextrose should start when bg<15mmol/l
  
  • Reduce insulin infusion to 0.5mls/kg/hour
  • Start 2.5% glucose infusion at 6-7 mls/kg/hour
• Offer small volumes of low fat food once we think appetite has returned
• Once blood glucose controlled, and no further vomiting start insulin therapy with a longer acting insulin preparation e.g. Caninsulin

Question 25

What other treatments should be considered during dKa treatment?

Answer 25

Think about other important treatments for the underlying disease, for example….

Analgesia

• If underlying disease might be pancreatitis?

Anti emetics

• Symptomatic treatment?

Antibiotics

• If awaiting culture and suspicious of a uti?

Question 26

What is the prognosis for dKa?

Answer 26

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.

Question 27

How does wiki vet recommend treating a cat with dKa?

Answer 27

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.