Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is defined as the presence of a metabolic acidosis (venous bicarbonate less than 15 mmol/L or pH less than 7.3) and significant ketosis (plasma beta hydroxybutyrate greater than 3 mmol/L or ketonuria greater than 2+ on standard urinalysis sticks) in the presence of a random plasma glucose greater than 11 mmol/L or known diabetes. The latter criterion is important as the entity of normoglycaemic DKA is well recognised and is a diagnostic pitfall for the unwary, especially in pregnancy.

Guidelines

New national guidelines on the management of DKA were released in the UK in March 2010. 

Management should be based on the JBDS diabetes DKA algorithm. 

Immediate management

Venous access should be obtained, investigations listed in the preceding Investigations Section should be initiated and 1 litre of normal saline should be administered intravenously.

If the patient is not shocked then the first litre should go in over one hour, otherwise normal saline should be administered as a 500 ml bolus over 15 minutes. This can be repeated once, if the systolic BP is still below 90 mm Hg at the end, then senior help should be sought and the patient transferred to HDU/ITU.

A fixed-dose intravenous insulin infusion should be initiated. Fifty units of soluble insulin such as actrapid is diluted in 50 ml normal saline and given via a syringe driver at a rate of 0.1 units/kg body weight/hour.

Subsequent fluid management

This should always be performed according to clinical assessment, but as a rough guide it is reasonable to expect the average case of DKA to be in a 6-7 litre negative fluid balance and most of this should normally be replaced in the first 24 hours.

Thus, after the first litre, the next should go in over two hours, the next over four, the next over six, the next over eight. But it must be stressed that these figures are only a guide. If there is any significant circulatory compromise, a urinary catheter should also be passed in order to monitor urine output. 

After the first hour, serum K+ should be re-assessed (no K+ should be given in the first bag of fluid). If the serum K+ is greater than 5.5 mmol/L then K+ supplementation should be withheld; if it is between 3.5 and 5.5, 40 mmol K+ should go into each bag; and, if it is less than 3.5 mmol/L, the patient should be transferred to a high dependency clinical area where strong IV K+ can be administered centrally.

Monitoring regimen

It is essential that a monitoring regimen is instituted. The JBDS guidelines recommend hourly assessment of capillary blood glucose levels and blood ketones (if available in your hospital), two hourly assessment of venous blood gases and four hourly Us+Es and lab glucose.

In addition, the patient should be frequently clinically re-assessed, especially with respect to their volume status.

Expectations during clinical management

If treatment is successful it can be expected that ketones will fall by roughly 0.5 mmol/L/hr and/or venous HCO3- will rise by ~3 mmol/L/hr.

If these targets are not being met then consideration should be given to revising the rate of insulin infusion e.g. changing from seven u/hr (for a 70kg patient) to nine u/hr, reassessing in a further two hours and if necessary adding a further two u/hr to the insulin infusion rate.

If the patient is not improving at the anticipated rate, or not improving at all, consideration should also be given to the possibility that there is a pump malfunction, line occlusion, cannula misplacement or other technical problem.

What should the doctor do when the blood glucose level starts to fall?

The rationale of a fixed dose insulin infusion is that it provides more effective suppression of ketogenesis.

However, the practical draw back is that eventually the blood glucose level will fall and the patient may become hypoglycaemic. This is avoided by running 10% dextrose (125 ml/hr) alongside the IV normal saline once blood glucose is less than 12 mmol/L. If the glucose level continues to fall then either the rate of glucose infusion is increased or the strength is increased to 20%.

Continuation of long acting insulin

It is recommended that the long acting insulin (for patients on a basal bolus regimen) should be continued throughout the management of their DKA.

This increases safety by ensuring there is always some insulin onboard and also speeds up conversion back on to their usual subcutaneous insulin.

When should the patient be converted back on to their usual insulin regimen?

This should be undertaken once DKA is resolved and they are eating and drinking normally.

Resolution of DKA is judged to have happened once either the urine is clear of ketones or blood ketones are less than 0.3 mmol/L and venous pH is greater than 7.3.

If the long acting subcutaneous insulin has been continued throughout then stopping IV insulin is a fairly straightforward process of waiting until a mealtime and giving the usual dose of prandial insulin with the meal, overlapping with the IV insulin for two hours and then turning off the IV insulin infusion.

When should intravenous bicarbonate be considered?

The use of IV bicarbonate should be avoided except in extremis - pHs greater than 6.9 will usually respond to fluid resuscitation and effective suppression of ketogenesis by insulin.

However, once the pH is less than 6.8 the situation is dire and, although there is very little evidence to support its use, many would give intravenous bicarbonate at this point. This should always be done on the ITU, under close monitoring.

Should the doctor be wary about the risk of cerebral oedema?

Cerebral oedema is a serious and not infrequent complication of paediatric DKA and this elevated risk extends in to the young adult age range (i.e. early 20s).

In adults, however, it is a very rare complication.

Is there any role for Variable Rate Intravenous Insulin Infusion (VRIII or "sliding scale" insulin) ?

In a minority of cases, the ketoacidosis will resolve but the patient can be too unwell to resume eating and drinking normally and taking subcutaneous insulin. In these instances, the patient can then be switched from a fixed dose insulin infusion to Variable Rate Intravenous Insulin Infusion .

Is 0.9% NaCl really the best intravenous fluid for managing DKA?

This question has been the basis of some debate and other fluids - including Hartman’s - have been proposed as 'crystalloid of choice' in DKA.

However, the wide availability of normal saline, the fact that it comes with either 20 or 40 mmoles of pre-added K+ (unlike Hartman's) and the very low incidence of hyperchloraemic acidosis (one of the theoretical advantages of Hartman's is a lower risk of hyperchloraemic acidosis) associated with its use mean that it is recommended as the first choice intravenous fluid for management of DKA.

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