- New diagnosis of diabetes 10-27%.
- Infection ~ 35%, inadequate insulin ~ 30%, surgery, trauma, alcohol, cocaine and drugs such as steroids, thiazides, sympathomimetics, pentamidine.
- No cause in 19-38%, but poor compliance / economic reasons frequent.
- Mortality 1% in adults, but 5% if over 65 years. Also high 15% in patients with hyperglycaemic, hyperosmolar non-ketotic syndrome (HHNS), when BSL usually > 50 mmol/L, more dehydrated with osmolality is > 320 mosm/L – can calculate latter by (2[NA + K] + glucose).
- Raised glucose >11.1 mmol/L
- Acidosis with arterial / venous pH < 7.3, or venous bicarb < 15 mmol/L
- Ketonaemia or ketonuria (urinalysis may miss 3-beta hydroxybutyrate early).
Management / Complications
- 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.
- Aim is to increase venous bicarb by 3 mmol/L/hr; or to drop blood ketone level by 0.5 mmol/L/hr.
- IV bolus of short-acting insulin 0.15 units/kg is unnecessary.
- 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.
- Insulin infusion will drop sugar roughly 3-5 mmol/L per hour, whilst ketones are cleared. Avoid BSL dropping below 15 mmol/L.
- Change to 5-10% dextrose if BSL 15 mmol/L, and continue insulin until ketonaemia is suppressed. Bedside ketone meters now available.
- If volume status is still not optimal, continue the NS together with the 10% dextrose at 125 mL/hr.
- 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 1 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 25 -30% with significant neurological morbidity in 35-40%.
- 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 pH / (PaCO2)and higher K+ and urea at presentation, and smaller increases in serum Na+.
- Also risk is increased with early (in 1st hour) insulin administration (OR 12.7) and large volumes of fluid in first 4 hours (OR 6.55), but not use of bicarbonate (UK case control data).
- Rate of change of sugar level, and rates of fluid, sodium, or insulin delivery after first 4 hours do not correlate highly with cerebral oedema occurrence i.e. later 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.
Edge J, Jakes R, Roy Y. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 2006;49:2002-9. [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]
- Prophylactic low-dose heparin, especially older patients (or if hyperglycaemic, hyperosmolar non-ketotic (HHNS) syndrome).
Joint British Diabetes Societies Inpatient Care Group. The management of diabetic ketoacidosis in adults. March 2010. [Reference]
Kitabchi A, Umpierrez G, Miles J, Fisher J. Hyperglycaemic crises in adult patients with diabetes. Diabetes Care 2009;32:1335-43. [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. [Reference]
ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child 2004;89:188-94 [Reference] [or Pediatrics 2004; 113:e133-e140].