Diabetic Ketoacidosis

Epidemiology

• New diagnosis of diabetes 10-27%
• Infection ~ 35%, inadequate insulin ~ 30%, surgery, trauma, alcohol, cocaine and drugs such as steroids, thiazides, sympathomimetics.
• No cause found in 19-38%.
• Mortality < 5%. Under 2% in young adults, but > 20% if over 65 years.
• Also high > 15% in patients with hyperglycaemic, hyperosmolar non-ketotic syndrome (HHNS), when BSL usually > 50 mmol/L, and osmolality is > 320 mosm/L – can calculate latter by (2[NA + K] + glucose).

Diagnostic Criteria

• Raised glucose >11.1 mmol/L
• Acidosis with arterial pH < 7.3, or venous bicarb < 15 mmol/L
• Ketonuria (urinalysis may miss 3-hydroxybutyric acid early on); or ketonaemia

Management Complications

• Hypoperfusion
  • Rapid initial crystalloid, especially for significant circulatory insufficiency, at 15-20 mL/kg in first hour ie. 1-1.5 L.
  • Possible role for bicarbonate is in patients with impending cardiovascular collapse, if pH < 6.9. Dilute 100 mmol 8.4% bicarbonate in 250-1000 mL 0.45% NS, and give over 30-60 minutes with 20 mmol K via infusion pump. (Note there are no prospective data concerning bicarbonate use below pH 6.9, and from 6.9-7.1 morbidity and mortality outcomes are equivocal ie. not proven).
• Fluid replacement
  • Total body water deficit 100 mL/kg, and sodium deficit 7-10 mmol/kg.
  • Restore normal hydration with 0.9% NS at 4-14 mL/kg/hr, to correct estimated fluid deficit over first 24 hours, without exceeding change in osmolality greater than 3 mOsm/kg per hour.
  • One regime is NS 1000 mL in first hour, 500 mL/hr next 4 hours, then 250 mL/hr next 4 hours ie. around 4 L in first 9 hours.
  • Aim to restore fluid deficits over 24 hours in adults, or up to 48 hours in children.

Dhatariya K. Diabetic ketoacidosis. BMJ 2007;334:1284-5. [Reference]

• Insulin infusion
  • Insulin infusion at 0.1 units/kg/hr (ie. 5-7 units/hr) short-acting insulin, until BSL < 15 mmol/L, then drop to 3 units/hr.
  • IV bolus short-acting insulin 0.15 units/kg unnecessary.
• Hypokalaemia
  • Total body deficit 3-5 mmol/kg. Give 10-30 mmol K+ per L fluid, as soon as it is known serum K+ level is below 5.0 mmol/L, and urine output is established.
  • Give 40 mmol per L fluid if K+ < 3.5 mmol/L, but must use infusion pump for fluid.
• Hypoglycaemia
  • Adjust insulin rate to drop sugar roughly 5 mmol/L per hour. Avoid BSL dropping below 15 mmol/L.
  • Change to 5% dextrose if BSL < 15 mmol/L, but continue insulin until ketoacids are cleared.
• Hyperchloraemic acidosis
  • Usually related to fluid therapy, but is mild and transient.
  • Change to 1/2 NS (0.45%) if Na > 150 mmol/L. (Remember corrected serum Na level is higher than measured. Add 1 mmol/L to [Na] for each 3 mmol/L rise in BSL above normal).
• Hypophosphataemia / hypomagnesaemia
  • Despite significant depletion up to 5-7 mmol/kg phosphate, and 1-2 mEql/kg magnesium, which may not be reflected by serum levels, replacement of either does not appear to influence clinical course or outcome.
• Cerebral oedema
  • Suspect if sudden headache with neurological deterioration ie. altered level of consciousness and lethargy, usually within 4-12 hours treatment onset (but can occur before initiation of therapy).
  • 0.7 – 1% incidence, usually child / adolescent. Mortality up to 75% with significant neurological morbidity in 25%, once symptoms other than lethargy or behavioural change have occurred.
  • Cerebral vasoconstriction with hypoxic ischaemia and disease severity implicated, plus possibly idiogenic osmoles (taurine, myoinositol) and defective Na/H ion exchange.
  • Relates to a lower PaCO2 at presentation and higher initial serum urea; also smaller increases in serum Na+ and the use of bicarbonate.
  • Rate of change of sugar level, and rates of fluid, sodium, or insulin delivery do not correlate with its occurrence ie. therapy is not responsible.
  • Give mannitol 0.5 – 2.0 g/kg (2.5 – 10 mL/kg 20% mannitol) IV and supplemental oxygen; or consider 3% hypertonic saline 5-10 ml/kg over 30 min instead. Hyperventilation and or dexamethasone appear unhelpful.
• Thromboembolism.
  • Prophylactic low-dose heparin, especially older patients (or if hyperglycaemic, hyperosmolar non-ketotic (HHNS) syndrome).

References

Glaser N, Barnett P et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. NEJM 2001; 344:264-269. [Reference]

Hom J, Sinert R. Is fluid therapy associated with cerebral edema in children with diabetic ketoacidosis? Ann Emerg Med 2008;52:69-75. [Reference]

Kitabchi A, Umpierrez G, Murphy M, Kreisberg R. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2006; 29: 2739-48. [Reference]

Savage M, Kilvert A (on behalf of Assoc British Clinical Diabetologists ABCD). ABCD Guidelines for the management of hyperglycaemic emergencies in adults. Practical Diabetes Int 2006; 23:227-31.

ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child 2004;89:188-94 [or Pediatrics 2004; 113:e133-e140]. [Reference]

Stewart C. Diabetic emergencies: Diagnosis and management of hyperglycaemic disorders. Emergency Medicine Practice: An Evidence based Approach to Emergency Medicine 2004; 6(2): 1-24.