Anand Swaminathan, MD, MPH (@EMSwami) is an assistant professor and assistant program director at the NYU/Bellevue Department of Emergency Medicine in New York City.

Review questions are available at the end of this post.

Background

Each year, roughly 10,000 patients present to the Emergency Department in diabetic ketoacidosis (DKA). Prior to the advent of insulin, the mortality rate of DKA was 100% although in recent years, that rate has dropped to approximately 2-5%.1 Despite clinical advances, the mortality rate has remained constant over the last 10 years. With aggressive resuscitative measures and appropriate continued management this trend may change.

DKA is defined as:

Hyperglycemia (glucose > 250 mg/dl)

Acid osis (pH < 7.3)

osis (pH < 7.3) Ketosis

In the absence of insulin, serum glucose rises leading to osmotic diuresis. This diuresis leads to loss of electrolytes including sodium, magnesium, calcium and phosphorous. The resultant volume depletion leads to impaired glomerular filtration rate (GFR) and acute renal failure.

In patients with DKA, fatty acid breakdown produces 2 different ketone bodies, first acetoacetate, which then further converts to beta-hydroxybutyrate, the latter being the ketone body largely produced in DKA patients.

With this background in mind, let’s take a look at four urban legends in the management of DKA and the evidence that dispels these legends.

Here’s our case:

45 yo woman w/ DM I presents w/ AMS

Vitals: 73/42, 147, 93%, 96oF, FS > 451



Although this presentation likely represents DKA, a blood gas is typically obtained to confirm the diagnosis. Often, the question arises as to whether an arterial or venous blood gas is adequate.

Urban Legend #1 – An ABG is necessary for the diagnosis and treatment of DKA

ABG gets you pH, PaO 2 , PaCO 2 , HCO 3 , Lactate, electrolytes and O 2 Sat VBG gets all this except for PaO 2 (but we have pulse ox so this isn’t really an issue) – Question is, is it accurate?

There’s a lot of literature on the use of VBG instead of ABG.2-6 Here’s the summary:

pH ABG – VBG: 0.03 – 0.05

HCO 3 ABG – VBG: – 1.5 – 2.0

ABG – VBG: – 1.5 – 2.0 CO 2 ABG – VBG: – 6 mm Hg

The Joint British Diabetes Society 2011 Guidelines endorse the use of VBG instead of ABG for initial assessment of acid/base status as well as continued monitoring during management.7

Bottom Line: VBG just as good as ABG in the diagnosis and management of DKA.

Let’s return to our patient. The VBG: 6.87, 15, Bicarb < 5, K = 2.8. IV fluids have been started and the nurse asks you if you can start the insulin drip.

Urban Legend #2 – After fluids, insulin is the next most critical step in treatment

As discussed earlier, the pathophysiology in DKA involves osmotic diuresis and extensive electrolyte loss. Total body potassium can be severely depleted but extracellular potassium levels can be falsely reassuring as acidosis leads to shift of potassium out of cells. Regardless, hypokalemia is a critical cause of morbidity and mortality and should be immediately addressed.

Insulin administration can exacerbate serum hypokalemia by shifting potassium intracellularly. Thus, potassium should always be repleted prior to starting insulin. About 5-10% of patients with DKA will present with hypokalemia (K < 3.3 mEq/L).8 Insulin therapy should be held until a serum potassium > 3.5 mEq/L is documented. If the potassium is < 5.5 mEq/L but > 3.5 mEq/L, it’s safe to start both IV and PO (if patient tolerates) potassium repletion along with your insulin.

For a review of repletion of severe hypokalemia in DKA, check this post from Reuben Strayer at EM Updates.

Other Electrolytes

Sodium – Serum concentration diluted as a result of osmotic gradient of glucose pulling more water into extracellular space. Phosphate – If < 1.0 mEq/L, start repletion. Magnesium – All patients who are hypokalemic are hypomagnesemic. Replete together as long as kidney function intact.

The Bottom Line: Electrolyte replacement, particularly potassium is more critical early in DKA management than insulin.

In addition to the severe hypokalemia, our patient is markedly acidemic. Guidelines recommend administration of bicarbonate when the pH falls below 7.1 or 7.0.9

Urban Legend #3 – Once the pH falls below 7.1/7.0, bicarbonate infusion is required

A number of studies have retrospectively examined patients with DKA looking for differences in groups that got bicarbonate versus those that did not.10-12 Patients in these studies, some with pH as low as 6.9, had no benefit from bicarbonate therapy. In order for bicarbonate to increase the serum pH, the lungs have to blow off CO 2 . Patients with DKA are already maximally ventilating CO 2 and are not able to increase this rate. Thus, the administration of bicarbonate does not significantly raise the serum pH. Additionally, there is harm to administration of bicarbonate as well. Bicarbonate administration delays the improvement of ketosis13 and worsens hypokalemia and intracellular acidosis.14

Bottom Line: There is no established role for administration of sodium bicarbonate to patients with DKA regardless of their pH.

Back to our patient. Bicarbonate therapy is held and a repeat potassium comes back at 3.9 mEq/L. The insulin drip is ready to hang and the patient’s nurse asks you how much of a bolus you would like to give.

Urban Legend #4 – A bolus of insulin should always be given along with the infusion

Once again, let’s return to pathophysiology. Insulin is administered to stop ketosis and eventually, will aid in “closing the gap.” What we would like to do is to give insulin in a way that leads to near normal circulating levels of around 150 – 200 microunits/ml. Giving a bolus and infusion, however, leads to a high peak insulin level with a low plateau. With an infusion rate of around 0.14 units/kg, the patient will reach a steady plateau state that is near the normal circulating level.15

As far as outcomes, Goyal et al found no difference in glucose change or anion gap change in the patients who received a bolus of insulin followed by an infusion.16 Additionally, the bolus insulin group had longer lengths of stay and a 6-fold increase in hypoglycemic episodes (6% vs. 1%).

Bottom Line: Bolus insulin does not result in a more rapid improvement of the patient and is associated with more episodes of hypoglycemia and a longer length of stay.

Summary

VBG as good as ABG for diagnosis and treatment

for diagnosis and treatment Aggressively replete potassium prior to starting insulin

to starting insulin Bicarbonate is unnecessary in DKA treatment and potentially harmful

in DKA treatment and potentially harmful A bolus of insulin is unnecessary in DKA treatment and potentially harmful

Review Questions

References / Further Reading

Edited by Alex Koyfman, MD