Diabetic ketoacidosis (DKA) Flashcards
Pathophysiology
Reduced insulin → Reduced glucose uptake into cells → metabolic deficit
Glucagon → Lipolysis → Fatty Acids → Acetyl CoA → Ketones
Ketones → Acetoacetate, β-hydroxybutyrate, acetone
Acetoacetate and β-hydroxybutyrate are acidic → Metabolic Acidosis
Metabolic acidosis and inadequate cellular energy → inappetence, nausea, reduced mentation, vomiting → dehydration, renal hypoperfusion and electrolyte derangements → Death
Are insulin levels always low in these pts?
- No
- so consider other concurrent disease leading to insulin resistance through increased cortisol, catecholamines or glucagon
History & exam
Often newly diagnosed diabetics (in my experience usually already known i.e. have just started treatment)
Usually middle-aged to older animals.
Since diagnosis – PUPD hasn’t resolved, weight loss has continued. Progressive lethargy, anorexia and vomiting.
Clinically these patients are often dehydrated and hypovolaemic through fluid loss.
Other signs:
- Abdominal pain – pancreatitis common
- Hepatomegaly – Diabetic hepatopathy (dogs), hepatic lipidosis (cats)
- Body condition loss (they may still be obese though)
- Mental dullness – headache
Diagnosis
Usually straight-forward – history and clinical signs are a strong clue.
- Diabetes M → Hyperglycaemia and glucosuria
- Ketones → β-hydroxybutyrate is the most abundant
– Blood ketones is ideal; usually tests for β-hydroxybutyrate
– Urine ketones less ideal; usually tests for acetoacetate so false negatives - Metabolic Acidosis → Blood gas machine e.g. EPOC/iSTAT
Other findings:
- Anaemia and left shift neutrophilia common (cats also have increased Heinz body formation)
- Elevated ALP, ALT due to hepatic effects (cats may be jaundiced)
- Electrolyte derangements
– Pseudohyperkalaemia or hypokalaemia, hypophosphataemia, hyponatraemia, hypochloraemia and hypocalcaemia.
- Bacteriuria – culture and sensitivity is sensible (concurrent UTI 20% dogs)
What is key to treatment? Why?
Fluid Therapy
- Hypovolaemia/dehydration and metabolic acidosis mask the true extent of electrolyte disturbances – in particular potassium and phosphate
- Pseudo-hyperkalaemia
– Acidosis, haemoconcentration, hypo-insulinaemia or reduced sensitivity
– Correction and insulin therapy rapidly reveal true total body hypokalaemia
-> Do not dive in with insulin straight away
Fluid therapy plan
- Hartmanns
- Restore volume status and hydration rapidly – see fluid therapy workshop
– Arguably restore deficit quickly over 6-12 hours. - Reduces glucose significantly alone (mechanism not fully understood)
- Reveals true extent of electrolyte disturbances allowing treatment
– Monitor electrolytes closely (q2-4h)
As hydration restores what can be revealed? What are the signs of these in severe cases?
- hypokalaemia and hypophosphataemia
- Severe hypokalaemia – profound muscle weakness and respiratory arrest when extreme
- Severe hypophosphataemia – weakness, myocardial depression, arrythmias and
haemolysis or seizures in extreme cases
How to treat hypokalaemia
- Potassium supplementation – dose rate dependant on severity (table in
formulary) – CRI or spiked fluids. - High rates can cause bradyarrythmias – at highest doses (>0.5mEq/kg/hr)
consider ECG monitoring (reduce if arrythmias noted) - Monitor and adjust q4-6h
How to treat hypophosphataemia
- CRI of potassium phosphate 0.03-0.12 mM/kg/hr
– Take care as contains potassium too
How to treat hyponatraemia (hypochloraemia)
- Sodium is pushed intracellularly in response to hyperglycaemia
– Maintains normal osmolality - As glucose corrects – sodium should also correct
How to treat hypocalcaemia
- Only correct if clinical signs noted e.g. muscle twitching/tremors
- Usually corrects with fluid therapy and restoration of renal perfusion
- Dose rates in the formulary
How to treat hypomagnasemia
- Rarely done in routine practice as measurement of magnesium is difficult
What is the next step after hydration has been restored?
- switching off ketogenesis
- and as a byproduct, achieved normoglycemia (slight hyperglycaemia) until the pt begins eating, drinking and is BAR
How to treat hyperglycaemia
Via regular neutral insulin administration or insulin CRI
- CRI is considered more effective and titratable
– BG > 15 mmol/L → 0.05IU/kg/hr
– BG 10-15 mmol/L → 0.025IU/kg/hr
– BG <10 mmol/L → 0.025IU/kg/hr and start 5% dextrose supplementation at maintenance
– If BG <7.5 mmol/L → stop insulin and restart once >10 mmol/L again
What to do once the pt is eating and stable?
- slowly switch back to routine insulin regime as per long term DM control
What should you consider if the pt is persistently anorexic?
- tube feeding
Other considerations for tx
- Pain/Headache – analgesia e.g. opiates.
- Nausea/vomiting – anti-emetics
- Consider investigating for concurrent diseases
– In cats:
–> Hepatic lipidosis
–> Chronic renal failure
–> Pancreatitis
–> Bacterial/viral infections
–> Neoplasia
– In dogs:
–> Hyperadrenocorticism
–> Pancreatitis
–> Urinary tract infections – antibiotics
Prognosis
Survival to discharge – 70% (Good but not perfect) <10% dogs relapse
Up to 40% cats relapse
What is eDKA?
- euglycaemic DKA
Use of what drug make a pt at significant risk of developing eDKA? Why? Which animal does this affect?
- sodium-glucose cotransport 2 inhibitors (SGLT2) [Velaglifozin (SenvelgoTM)]
- These promote loss of glucose and sodium into urine – promoting hypovolaemia and reducing glucose available for energy metabolism
- Only used in cats because they are type 2 – so theory is there is still some insulin available. However, some cats can exhaust their islet cells and have no insulin -> severe negative energy balance -> ketogenesis and acidosis
- However, urinary losses of glucose mean they are euglycaemic/normoglycaemic – easy to miss
eDKA diagnosis
- Recent introduction of an SGLT2 inhibitor
– 1/15 risk
– <14d after starting treatment - Clinical signs consistent with DKA e.g. anorexia/vomiting
- Ketones in the blood/urine, acidosis, normoglycaemia.
eDKA tx
- Same principle as DKA, fluid therapy followed by low dose insulin therapy.
– However – glucose supplementation (5%) is immediate as they are euglycaemic.
– Insulin is started despite blood glucose <7.5mmol/l - After cessation of drug – urinary glucose loss continues for 2-3 days, so glucose supplementation must continue
Hyperglycaemic Hyperosmolar Syndrome (HHS) - prevalence
- Rare (<5%) but important
Hyperglycaemic Hyperosmolar Syndrome (HHS) - pathogenesis
Pathogenesis is similar to DKA, but a small amount of insulin and hepatic glucagon resistance reduces lipolysis, so ketones are not elevated. However peripheral insulin resistance in tissues still stimulates gluconeogenesis and glycogenolysis mobilising glucose.
Hyperglycaemia → osmotic diuresis → haemoconcentration → hyperglycaemia..
Hyperglycaemic Hyperosmolar Syndrome (HHS) - diagnosis
- BG > 33.3 mmol/L
- Absence of urinary ketones
- Serum osmolality > 350 mOsm/kg (see PUPD Lecture)
– Alternative version for the calculation: 2 x (Na + K mmol/L) + (glucose in mmol/L) + (BUN in mmol/L)
Hyperglycaemic Hyperosmolar Syndrome (HHS) - tx
- Fluid therapy is key
- however rapid correction of hyperglycaemia (and hypernatraemia) lead to an osmotic gradient across the blood brain barrier
-– rapid cerebral oedema is possible → seizure, coma, death - Therefore; aim to restore deficit over 24-48h, but monitor glucose and sodium very closely. maximum rate of reduction is:
– Glucose <3mmol/L/h
– Sodium 0.5-1mmol/L/h
-Insulin therapy should only be started once normo-volaemic and hydrated as per DKA
– alter insulin doses if glucose is reducing too quickly.
Hyperglycaemic Hyperosmolar Syndrome (HHS) - prognosis
Prognosis in the short term is guarded (~60%) but long-term survival is probably poor (one feline study reported 12% > 2 months)
Monitoring
Blood sampling – Central Venous Catheter
– Requires 24 hour nursing care, so hospitalised setting is ideal
– However, no reason cannot be done in 1st opinion hospital
Glucose monitoring – Freestyle Libra
- Easy to place
- Monitored via an app
- Stops annoying the patient
- Stops you getting bitten
Both of these sets of patients are intensive and require regular blood sampling/glucose monitoring
