Despite these losses, the increased delivery of potassium to the ECF from the intracellular space usually causes the serum concentration of potassium to be normal and, in some cases, high. This regular concentration of the ECF potassium creates the illusion of normalcy, despite the fact that total body potassium stores are almost always low.

This concept becomes important in understanding the risk of potentially devastating hypokalemia in treating DKA. Insulin administration causes a rapid shift of potassium out of the ECF and into the cells. In addition, fluid resuscitation can be expected to cause a dilutional decrease in serum potassium concentration.

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For this reason, the ADA recommendations encompass a three-tiered approach to potassium regulation during fluid and insulin therapy for DKA:

Patients with a serum potassium concentration >5.2 mEq/L should receive insulin and IV fluid without potassium, but the level should be checked every two hours.3

Patients with a serum potassium concentration between 3.3 and 5.2 mEq/L should have 20-30 mEq of potassium added to each liter of IV fluid with a goal to maintain a level of 4.0-5.0 mEq/L.3 The addition of potassium to the infusion should be delayed until urine output has been established.

Patients with a serum potassium concentration <3.3 mEq/L should receive 20.0-30.0 mEq/hr of potassium until the concentration exceeds 3.3 mEq/L. These patients should not receive IV insulin until the serum potassium concentration is >3.3.3

Other electrolytes. Sodium: Sodium concentration may vary. Both sodium and water are lost during osmotic diuresis; however, water tends to be lost in a proportionally greater amount. As the patient becomes dehydrated, this increases the serum sodium concentration.1

On the other hand, increased serum osmolality draws water out of the cells, which dilutes the sodium and lowers the concentration.5 The sodium and water are replaced with fluid resuscitation.

Phosphate: Phosphate is the most abundant intracellular anion. Like potassium, it is present in small concentrations in the ECF, and its concentration decreases with insulin therapy. However, phosphate concentration is most important inside the cell, where it is involved in energy management and cell membrane maintenance. In DKA, phosphate replacement has not been shown to improve outcomes.3

Because IV phosphate replacement may induce hypocalcemia and hypomagnesemia,5 therapy should be limited to patients with serum concentrations <1.0 mg/dL or such complications associated with severe muscle weakness or cell membrane instability as cardiac compromise, respiratory depression and hemolytic anemia.

When given, 20.0-30.0 mEq/L is added to IV fluids, usually in the form of potassium phosphate, to replace some of the potassium chloride being administered.3

Magnesium: Stored primarily in and on the bone and not hormonally regulated, magnesium may also be depleted due to renal excretion during osmotic diuresis. Levels should be checked and losses replaced.

Bicarbonate: It is tempting, in a case of metabolic acidosis with low bicarbonate, to try to increase both the pH and the bicarbonate level by administering sodium bicarbonate, but no evidence exists to suggest that this improves outcomes. Furthermore, sodium bicarbonate administration may cause physiologic deterioration,3 including hypokalemia attributable to intracellular potassium shift, worsened cerebral acidosis (theoretically caused by decreased respiratory compensation), decreased tissue oxygen uptake and cerebral edema.

The ADA does recommend bicarbonate replacement therapy for patients with a pH <6.9, as this level results in a multitude of deleterious vascular defects. Bicarbonate should be given as 100 mmol (2 amps) in 400 mL H2O with 20.0 mEq potassium chloride over two hours. Repeat this therapy until the pH is >7.0.3

Osmolality. While it varies, osmolality in DKA may be high. Rapid correction of hyperosmolality risks cerebral edema, although in DKA this is primarily a complication seen in children and rarely in patients older than age 20 years.3

Nevertheless, IV fluid and glucose correction goals are geared toward minimizing any risk to the patient. These goals include cautious fluid resuscitation, avoidance of over-correction of hyperglycemia, and the addition of dextrose to the IV fluid when serum glucose concentration decreases to <200 mg/dL.5 In any case, the osmolality should be corrected at a rate not to exceed 3 mOsm/kg/hr.7

Monitoring. Appropriate therapy for DKA brings about remarkable results leading to resolution. But these interventions may cause a variety of dramatic and potentially harmful effects as well. It is important to monitor patients closely to assure steady progress and avoid adverse events:

  • To allow for precise titration of insulin therapy, perform glucose fingerstick checks every hour until stable3
  • To minimize the risk of excessive hemodilution, monitor and document urine output
  • Monitor electrolytes, BUN, and creatinine every two to four hours3

While pH is typically assessed on presentation as part of an arterial blood gas, subsequent checks may be performed every two to four hours3 on venous blood already drawn as part of electrolyte monitoring. The approximate value of the arterial pH can be obtained by adding 0.03 to the value of the venous pH.

If found to be high upon presentation, calculate serum osmolality every two to four hours.

Three types of ketones are produced in the liver in DKA. The first, acetoacetate, is later converted to acetone (which is acid/base neutral) and beta-hydroxybutyrate. The nitroprusside test is used to detect ketones in the serum or urine. However, this method detects only acetoacetate and acetone. It does not detect beta-hydroxybutyrate, the most abundant ketoacid produced.

This leads to two potential misinterpretations: (1) in the initial evaluation of DKA, low or moderate ketone levels do not rule out the possibility of significant ketoacidosis caused by undetected beta-hydroxybutyrate;1 and (2) during insulin therapy, some beta-hydroxybutyrate is converted back to acetoacetate. This may cause the levels of acetoacetate to rise during appropriate therapy. If the nitroprusside test is used as a monitor, it may be misinterpreted as showing a worsening of ketosis.5

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In a patient with functioning kidneys, the administration of appropriate fluids stimulates osmotic diuresis and improvement in serum glucose levels, pH and ketoacid anion levels. In fact, the kidneys can excrete up to 30% of the ketoacid load.1

The addition of insulin stops acid production by inhibiting fatty acid liberation from the adipose tissue and ketogenesis by the liver. It also induces glucose uptake, causing serum glucose concentration to fall.

Phosphate levels can be expected to fall to below normal values, but IV replacement is not usually indicated.

The expectation is that glucose levels will be controlled as a consequence of DKA therapy, but the primary goal is cessation of ketoacid overproduction and elimination of these acids from the blood. The insulin infusion should be continued until the ketoacidois is resolved. This can be expected to occur in 12 to 24 hours.


Resolution of DKA is determined by the ADA to include the following conditions:3

  • Blood glucose <200 mg/dL
  • Two of the following
  • HCO3- ≥15 mEq/L
  • Venous pH >7.3
  • Calculated anion gap ≤12 mEq/L
  • The decreased gap in combination with the normalization of the bicarbonate level indicates the clearing of the ketoacids