Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis (DKA) is among the most serious acute complications of T2DM

It has a high mortality rate if unrecognised. The overall mortality is <1%, but a mortality rate >5% in the elderly has been reported.502
Mortality in patients with DKA is frequently related to the underlying
aetiological precipitant rather than the metabolic sequelae of hyperglycaemia
or ketoacidosis.502

Principles of management

Correction of dehydration
Correction of electrolyte imbalance
Insulin therapy
Treatment of precipitating factor
Prevention of complications

Assessment

Initial assessment
› History and physical examination
- Look for precipitating causes: infection, missed therapy, non-adherence,
  acute coronary syndrome, cerebrovascular accident, surgery and drugs
  (e.g. steroids).

Investigations

Capillary and venous plasma glucose
Venous blood gas (pH, bicarbonate)
Blood or urinary ketones
BUSE and creatinine
FBC
Urinalysis
If indicated: blood cultures, CXR and ECG

Diagnostic criteria (All 3 criteria must be met)

Capillary plasma glucose >11 mmol/L
Capillary ketones >3 mmol/L or urine ketones ≥2+
Venous pH <7.3 and/or bicarbonate <15 mmol/L

› Patients with high risk for DKA or severe DKA should be admitted to HDU or the ICU. High-risk factors include:

elderly
pregnancy
heart and kidney failure
other serious co-morbidities

Clinical parameters for severe DKA
– Venous bicarbonate <5 mmol/L
– Plasma ketones >6 mmol/L
– Venous pH <7.1 › Hypokalaemia on admission (<3.5 mmol/L)
– GCS <12
– Oxygen saturation <92% on air (via arterial blood gases [ABG])
– Systolic BP <90 mmHg
– Pulse >100 beats/minute
– Anion gap >16 (Anion gap = [Na⁺ + K⁺] – [Cl^– + HCO₃^–])

Treatment

Aims of treatment
– Rate of fall of ketones of at least 0.5 mmol/L/hr, OR
– Bicarbonate rise of 3 mmol/L/hr, AND
– Plasma glucose fall of at least 3 mmol/L/hr, AND
– Maintain serum potassium within normal range.

Precaution during treatment
– Avoid over-correction of hyperglycaemia (within the first 12-24 hours of treatment, avoid lowering glucose to <14.0 mmol/L)

A. Immediate treatment

Correction of dehydration
› Fluid deficits in DKA may be up to 10% of total body weight. Restoration of circulating volume is a priority.
› SBP on admission <90 mmHg (likely due to low circulating volume, but consider other causes such as heart failure or sepsis). Start administration of fluid as shown in Table 4-3.

SBP on admission is ≥ 90 mmHg, start administration of fluid as shown in Table 4-4.

The rate of hydration should be guided by:
- haemodynamic status,
- state of hydration,
- serum electrolyte levels; and
- urinary output.

More cautious fluid replacement in:**
- young people <18 years
- elderly
- pregnancy
- existing heart or renal failure

** In the above instances, consider HDU admission and, insertion and monitoring via central line.

Potassium replacement
› Aim to maintain serum potassium between 4-5 mmol/L.
› Withhold K⁺ replacement if there is no urine output.

Insulin
› Start a fixed rate IV insulin infusion (FRIII): 0.1 unit/kg/hr based on estimate of weight.
› 50 units short-acting human insulin or rapid-acting insulin analogue made up to 50 ml with 0.9% saline solution.
› Delay insulin infusion if the initial potassium <3.5 mmol/L until serum potassium is corrected.
› Basal insulin – may consider continuing patient’s SC long-acting analogue/human insulin while on IV insulin infusion.
› Monitor capillary glucose hourly – if the glucose does not fall by at least 3 mmol/L/hr in the first 2-3 hours despite adequate hydration, increase FRIII by 1 U/hr.

› Once plasma glucose falls below 14 mmol/L:
– add or switch to 5% dextrose and reduce insulin infusion rate by 50%,
– in the presence of persistent ketonaemia, consider maintaining insulin infusion rate and changing to 10% dextrose.

› Beyond 24 hours, maintain plasma glucose at 8-12 mmol/L.503 (Level III)

IV bicarbonate

› The use of IV HCO₃ is not indicated to correct acidosis in DKA due to:
– rise of partial pressure of carbon dioxide (pCO2) in cerebrospinal fluid (CSF) which may lead to a paradoxical increase in CSF acidosis,
– delay in the fall of plasma lactate and ketone level; and
– risk of cerebral oedema especially in younger age group.

› While evidence is lacking, IV HCO3 may be considered if pH is persistently <6.9 despite adequate hydration and insulin treatment.

E.g. 1 ampoule (50 ml) 8.4% NaHCO3 added to 200 ml D5% over 1 hr, repeated every 1-2 hours, until pH is ≥7.0. Each ml of 8.4% NaHCO3 solution contains 84.0 mg NaHCO3 (e.g. 1.0 mmol/ml).

Phosphate
› No evidence to support routine phosphate replacement for DKA.502 (Level III)
› If levels <0.32 mmol/L in the presence of cardiac dysfunction or respiratory depression, consider phosphate replacement.

B. Monitoring

Hourly capillary plasma glucose until it reaches maintenance level of 8-12 mmol/L, then monitor 2-4 hourly.
Vital signs and input-output charting hourly
Venous HCO3 and K+ at 60 minutes, 4 hours and 6-hourly thereafter
6-hourly BUSE and blood/urine ketones
If ketones and glucose are not falling as expected, check if the insulin infusion pump is working and connected, and the correct insulin residual volume is present.
If equipment is working but response to treatment inadequate, increase insulin infusion rate by 1 U/hr increments hourly until targets are achieved.

C. Resolution

Continue IV insulin infusion until resolution of DKA
Resolution is defined as:
› pH >7.3
› Plasma ketone < 0.6 mmol/L

D. Transitioning from IV insulin to SC basal bolus insulin

Patient should be eating and drinking, and back on normal insulin.
Overlap the SC insulin with the insulin infusion for ½ hour (for insulin analogues) or 1 hour (for human insulin).
Calculating a basal bolus regimen (4 times daily)
- Current practice is shifting away from estimating total daily dose (TDD) of SC insulin based on the last 12-24-hour-insulin administered.
- Estimate total daily dose (TDD) of insulin by multiplying the patient’s weight (in kg) by 0.5 U-0.75 U.
- Use 0.75 U/kg for those considered to be more insulin resistant e.g. obese and/or presence of acanthosis nigricans.
- Give 50% of TDD at bedtime in the form of long acting insulin and divide remaining dose equally between pre-breakfast, pre-lunch and pre-dinner meals.
For patients already on insulin before admission, consider resuming previous insulin regimen and adjust dose as needed.
Monitor and adjust insulin doses accordingly.