Diabetic Ketoacidosis

Precipitants

• insulin deficiency (unknown or due to mistaken with-holding of insulin)
• excessive glucagon
• excessive glucocorticoids
• infection or other illness
• vomiting
• MI
• trauma, burns, surgery
• stress

Pathogenesis

Lack of insulin means that glucose in the blood cannot be taken up into cells. Therefore the body perceives itself to be in a state of starvation and so begins lipolysis -> ketones and glycerol and gluconeogenesis using glycerol + alanine.

Ketones such as acetoacetate and 3-hydroxybutyrate have 3 effects

• acidosis
• central action -> nausea and vomiting
• ketone excretion in urine (ketonuria) -> osmotic diuresis (losing Na⁺, K⁺, and Cl^-)

Proteolysis occurs to produce the alanine required for gluconeogenesis.

High blood glucose with exacerbation by glucose production -> glycosuria and osmotic diuresis.

Biochemical consequences

• Hyperglycaemia and plasma hyperosmolality -> cellular dehydration
• Metabolic acidosis with low HCO₃^-
• Glycosuria -> hyponatraemia and ketonuria
• May also have
• hyperkalaemia secondary to the metabolic acidosis; however there is an overall lack of body potassium as it is being lost via the osmotic diuresis - therefore give potassium during treatment to prevent severe hypokalaemia
• mild uraemia due to decreased GFR
• hyperlipidaemia (NB this may produce a pseudohyponatraemia)

Clinical consequences

• Dehydration ->
• Hypovolaemia ->
• Renal Hypoperfusion ->
• Acute Tubular Necrosis
• Acidosis ->
• Cardiac arrest, by affecting enzyme function once buffering capacity is exceeded

Clinical features at presentation

• 2-3 day history of gradual deterioration
• Hyperventilation (Kussmaul respiration) - deep and sighing
• Acetone / ketone odour on breath
• Nausea and vomiting
• Hypothermia due to peripheral vasodilatation - may mask pyrexia due to precipitating infection
• Drowsiness and coma - late signs

Investigations

To assess severity of DKA

• venous blood for glucose and U's and E's
• arterial blood for pH and blood gases
• urine for ketones

To assess cause of DKA

• venous blood for FBC, cardiac enzymes, blood cultures
• CXR
• ECG
• urine culture

Management

• 1) Correct dehydration with
• initially isotonic saline until blood glucose < 12 mmol/l
• then 10% dextrose
• 2) Decrease blood glucose with insulin, and monitor blood glucose hourly
• 3) Prevent hypokalaemia with i.v. K⁺ if necessary, monitor K⁺ hourly
• 4) Some doctors correct severe acidosis pH < 7.1 with HCO₃^- ie if cardiac arrest has occurred or is imminent as correction may induce cerebral oedema
• 5) Treat underlying condition - start broad spectrum antibiotics in case of infection
• 6) Be ready for
• shock
• cerebral oedema (treat with mannitol)
• DVT
• DIC

Emergency protocol - as for vivas

• 1) i.v. line for fluid
• usually 90% saline
• >1·5 litres/hr for 2 hrs
• 500ml/hr for 4 hrs
• 500ml/2hr
• 2) Investigations
• blood samples
• glucose
• should be monitored every hour
• once blood glucose < 12mmol/litre change infusion to dextrose saline
• U &Es
• hyponatraemia is common, but if Na+ <120mmol/litre consider another cause eg hypertriglyceridaemia
• if there is hypernatraemia (Na+ >150mmol/l) give first litre of saline as 0.45% instead of 0·9%
• beware the fact that some assays for creatinine cross-react with ketones, so creatinine may not reflect true renal function
• osmolality
• bicarbonate & blood gases
• if acidosis is severe pH < 7·1 some physicians give bicarbonate (100mmol over 1hr); other physicians don't because it affects the oxygenHb dissociation curve
• if there is acidosis without gross elevation of glucose consider overdose (aspirin) or lactic acidosis (esp. if elderly diabetic patients)
• FBC
• patient may have an elevated WCC (even leukaemoid) even in the absence of infection; however even with infection patient may be apyrexial
• blood cultures
• urine tests
• glucose
• ketones
• ketonuria does not equate with ketoacidosis
• normal individuals have ketonuria after a night's fast
• if glucose is normal consider alcohol
• can do test on blood to look for plasma ketonaemia
• MSU (for MC&S)
• 3) Nasogastric tube to prevent gastric dilatation and aspiration
• 4) Detailed Hx (relatives) + examination
• 5) CXR & ECG
• 6) Insulin
• preferably i.v. soluble insulin by pump
• 50u in 50ml 0·9% saline at 6ml/hr (ie 6 units insulin per hr)
• if infection use 10u/hr
• when blood glucose < 14mmol/litre halve infusion rate
• if no pump give 6units/hr i.m.
• 7) Potassium
• monitor serum K+ every hour
• hypokalaemia is likely (since when glucose enters cells it takes K+ with it)
• target range for K+ should be 4-5mmol/litre
• protocol
• if K+ < 3mmol/l give 40mmol K+ over 1 hr by i.v. and then recheck K+
• if K+ 3-4 mmol/l give 30mmol K+ over 1hr
• if K+ 4-5mmol/l give 20mmol K+ over 1 hr
• remember to monitor urine output
• withold K+ if oliguric (rare) or if initial plasma K+ is raised
• 8) If unconsciousness is prolonged give heparin 5000 units/6hr s.c.
• since dehydrated and stationary - to prevent DVT & PE
• 9) Monitor vital signs and glucose every hour, also K+
• 10) Treat any manifest infection - broad-spectrum antibiotics at first, change to more appropriate treatment when organism and sensitivity known
• 11) Be prepared for
• shock
• cerebral oedema (Rx- mannitol 20% 1g/kg = 5ml/kg i.v. over 15 mins)
• DVT
• DIC (Rx - 2 units fresh frozen plasma i.v. immediately, may need platelets and blood so consult expert; maintain accurate fluid balance and monitor urine output with catheter)

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