Diabetic ketoacidosis Flashcards
Desribe the pathophysiology of diabetic ketoacidosis
- 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
- Insulin levels are not always low in these patients – so consider other concurrent disease leading to insulin resistance through increased cortisol, catecholamines or glucagon.
What is the usual presentation of patients in diabetic ketoacidosis?
- 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!
How would you diagnose diabetic ketoacidosis?
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)
How would you treat diabetic ketoacidosis?
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)
Once hydration is restored, focus switches to switching off ketogenesis and as a by product, achieving normoglycaemia (mild hyperglycaemia) until the patient begins eating, drinking and is BAR.
This is 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.
Once the patient is eating (any food at this point) and stable then slowly switch back to routine insulin regime as per long term DM control.
If the patient is persistently anorexic – consider tube feeding
Pain/Headache – analgesia e.g. opiates.
Nausea/vomiting – anti-emetics
Consider investigating for concurrent diseases:
Dogs:
* Hyperadrenocorticism
* Pancreatitis
* Urinary tract infections – antibiotics
Cats:
* Hepatic lipidosis
* Chronic renal failure
* Pancreatitis
* Bacterial/viral infections
* Neoplasia
- Acromegaly
What will rehydration uncover? What electrolytes will be affected by diabetic acidosis? What should you do?
As hydration restores hypokalaemia and hypophosphataemia may unmask.
* Severe hypokalaemia – profound muscle weakness and respiratory arrest when extreme
* Severe hypophosphataemia – weakness, myocardial depression, arrythmias and haemolysis or seizures in extreme cases.
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
Hypophosphataemia
* CRI of potassium phosphate 0.03-0.12 mM/kg/hr
* Take care as contains potassium too!
Hyponatraemia (hypochloraemia)
* Sodium is pushed intracellularly in response to hyperglycaemia
* Maintains normal osmolality
* As glucose corrects – sodium should also correct
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
Hypomagnasemia
- Rarely done in routine practice as measurement of magnesium is difficult
What is the prognosis for an animal in diabetic ketoacidosis?
- Survival to discharge – 70% (Good but not perfect)
- <10% dogs relapse
- Up to 40% cats relapse
What is an euglycaemic DKA?
- A significant risk with using 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
How would you diagnose an eDKA?
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.
How would you treat eDKAs?
- 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.
What is hyperglycaemic hyperosmolar syndrome?
- Rare (<5%) but important.
- 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
How would you diagnose HHS?
- BG > 33.3 mmol/L
- Absence of urinary ketones
- Serum osmolality > 350 mOsm/kg
- Alternative version for the calculation:
- 2 x (Na + K mmol/L) + (glucose in mmol/L) + (BUN in mmol/L)
- Alternative version for the calculation:
How would you treat HHS?
- Fluid therapy is key again; 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.
- Prognosis in the short term is guarded (~60%) but long-term survival is probably poor (one feline study reported 12% > 2 months)
What are the best ways to monitor patients that require regular blood sampling/glucose monitoring in intensive cases?
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!
