Sodium is the primary cation. Chloride and bicarbonate are the primary anions. The anion gap is the numeric result of subtracting the sums of the chloride and bicarbonate concentrations from that of the sodium: Na+ – (Cl– + HCO3-)
This gap becomes important in assessing etiology. In a case of metabolic acidosis attributable to ingestion or endogenous overproduction of an acid, the acid ionizes to form a hydrogen cation and an anion (depending on the type of acid). In a case of aspirin overdose, this could be salicylic acid anions; sepsis produces lactic acid anions; and in DKA, ketoacid anions are produced.
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Multiple sources of measured and unmeasured anions may be present spontaneously. In the end, the total number of anions cannot significantly exceed the number of cations, so the more unmeasured anions that circulate, the less measured anions will be found. The anion gap essentially refers to an estimate of unmeasured anions in the serum.
In DKA, ketoacids are produced that ionize into hydrogen cations and ketoacid anions. These anions are not measured in a basic metabolic panel, so when their levels rise, so does the anion gap. DKA should be part of the differential diagnosis in any patient who presents with constitutional symptoms or positive ketones and a blood glucose concentration >250mg/dL. It should also be considered in any patient with diabetes who presents with any serious illness or stressor.6
The American Diabetes Association (ADA) defines DKA as a combination of hyperglycemia with a blood glucose ≥250 mg/dL, a metabolic acidosis with bicarbonate ≤18 mEq/L, an anion gap >10, and arterial pH ≤7.30 in the setting of moderate ketonemia or ketonuria.3
Hyperosmolar hyperglycemic state (HHS) is another form of hyperglycemic crisis. This condition is more typically found in individuals with severely uncontrolled type 2 diabetes. These patients are insulin-resistant and possess enough circulating insulin to inhibit lipolysis and excess ketogenesis but not enough to stimulate glucose uptake and utilization. They tend to have a more severe degree of volume depletion and impaired renal function, which decreases the ability to excrete excess glucose.
Such individuals present with severe hyperglycemia and its associated hyperosmolality, but they do not have as large an elevation in anion gap or acidosis as seen in DKA.
Management of DKA
Disposition. Generally, patients with DKA will require admission to the hospital in an intensive-care setting. This allows access to cardiac monitoring and close observation while providing aggressive fluid resuscitation and electrolyte replacement. It also allows for the titration of insulin by infusion with frequent blood-glucose monitoring.
The patient’s diet should be designated as nothing by mouth (NPO). Further carbohydrate and/or fat ingestion have the potential for undermining efforts to eliminate ketoacids and control blood glucose levels, and there is an increased risk of vomiting and aspiration in DKA.
Fluid management. Fluid resuscitation is the first step in DKA therapy.3 The total fluid deficit is estimated to be 3.0 to 6.0 L in DKA.5 Fluid is replaced as a crystalloid bolus to improve GFR followed by an infusion to maintain it.
As a rule, a bolus of 15-20 mL/kg (1.0-1.5 L) of normal saline3 is given in the first hour. This may prove overly aggressive for patients with cardiac compromise and should be adjusted accordingly.
The rate and fluid type of initial infusion following the bolus is based on the patient’s hemodynamics, hydration, electrolyte levels, and urinary output. For hemodynamically stable patients with adequate urine output, start with 0.45% NaCl or 0.9% NaCl at 250-500 mL/hr. For patients with normal or high corrected serum sodium, use 0.45% NaCl. For patients with low corrected serum sodium, 0.9% NaCl is advised.3
Hemodynamically stable patients who require 40 mEq/L of potassium supplementation (see Potassium in the next column) should be given 0.45% NaCl, as the added potassium increases the osmolality of the solution.5
Patients with cardiac compromise or poor urine output may become fluid-overloaded or could potentially experience too rapid a drop in serum osmolality and should have a slower infusion.
Regular insulin. Insulin may be given either in an IV bolus followed by infusion or by infusion alone. The ADA recommends a bolus of 0.1 units/kg followed by a continuous infusion of 0.1 units/kg/hr. If no bolus is given, the recommended initial IV infusion rate is 0.14 units/kg/hr.3
Aim to decrease the serum glucose by at least 50-70 mg/dL in the first hour, followed by a steady decline until the level is ≤200 mg/dL.5 Once the glucose level has dropped below 200 mg, the goal is to maintain it between 150-200 mg/dL until the acidosis resolves.
Potassium. Potassium is the primary intracellular cation. About 98% of potassium is stored within the cells of the body. Only 2% is present in the extracellular fluid (ECF).
During the evolution of DKA, potassium is lost in a number of ways. Osmotic diuresis causes potassium loss through renal excretion. Both increased serum osmolality and the lack of circulating insulin cause potassium to move out of the cells and into the ECF, compounding this loss.
In addition, diuresis-induced hypovolemia increases aldosterone levels that promote sodium retention at the expense of potassium.5 Patients experiencing vomiting or diarrhea may also experience GI losses. In total, it is estimated that patients with DKA suffer a 3-5 mEq/kg potassium deficit.7
