Diabetic Ketoacidosis

Posted by • February 6th, 2015

The latest review in the Fluids and Electrolytes series focuses on the safe removal of excess hydrogen ions, the administration of sodium bicarbonate, and the possible contribution of intracellular acidosis to the development of cerebral edema in patients with diabetic ketoacidosis. Several of the issues facing clinicians who care for patients with diabetic ketoacidosis are related to acid-base disorders.

Clinical Pearls

How do changes in extracellular fluid volume affect assessment of the severity of diabetic ketoacidosis?

Because of hyperglycemia-induced osmotic diuresis and natriuresis, patients with diabetic ketoacidosis usually present with a marked contraction of the extracellular fluid volume. This factor affects the assessment of their acid-base status and in some cases their therapy. Determination of the severity of metabolic acidemia is usually based on the extent of the decrease in the plasma bicarbonate concentration. Nevertheless, as shown in the equation below, the plasma bicarbonate concentration may be only moderately reduced when there is both a large deficit of bicarbonate in the extracellular fluid and a severe contraction of the volume of extracellular fluid.

Extracellular fluid bicarbonate concentration [HCO3−] = extracellular fluid HCO3− content (divided by) extracellular fluid volume.

It is important to adjust for changes in the volume of extracellular fluid when using the ratio of the increase in the plasma anion gap to the decrease in the plasma bicarbonate concentration to gauge the magnitude of the acid load.

What subgroups of patients with diabetic ketoacidosis may benefit from treatment with sodium bicarbonate?

Most patients with diabetic ketoacidosis do not require the administration of sodium bicarbonate, since infused insulin will slow the rate of ketoacid production, and bicarbonate ions will be produced when ketoacid anions are oxidized. Although the current consensus opinion is that sodium bicarbonate should not be administered in patients with diabetic ketoacidosis unless the arterial plasma pH falls below 6.90, the authors of this review suggest that this decision in adult patients with diabetic ketoacidosis should be individualized and not based solely on an arbitrary blood pH value. Therapy with sodium bicarbonate may be required in patients in whom a large component of the acidemia is due to hyperchloremic metabolic acidosis, since they may have insufficient circulating anions to metabolize and produce bicarbonate ions, and acidemia may worsen quickly with a rapid infusion of saline. Therapy with sodium bicarbonate may also be considered in the initial treatment of a subgroup of patients who are expected to have a low rate of ketoacid removal (i.e., patients who have marked decrease in their level of consciousness or those with preexisting advanced renal dysfunction [estimated glomerular filtration rate,

Morning Report Questions

Q: How might the sodium-hydrogen ion exchanger in brain-cell membranes contribute to cerebral edema in diabetic ketoacidosis?

A: Brain cells swell when there is a large osmotic force favoring an intracellular shift of water, owing to a higher effective osmolality in brain cells than the effective osmolality in plasma in capillaries near the blood-brain barrier. An increased number of intracellular brain osmoles may occur with an increased influx of sodium ion into brain cells. A high concentration of hydrogen ions in brain cells may activate mechanisms of sodium ion transport in cell membranes, primarily the sodium-hydrogen exchanger 1. The concentration of hydrogen ions in brain cells could increase when beta-hydroxybutyric acid enters cells on the monocarboxylic acid cotransporter. This cation exchanger is also activated by a high insulin concentration in interstitial fluid. If cation exchange through this sodium-hydrogen ion exchanger 1 increases further when the pH in the extracellular fluid increases, that could explain, at least in part, the increased risk of cerebral edema among children with diabetic ketoacidosis when sodium bicarbonate is administered.

Figure 3. Increased Flux through the Sodium-Hydrogen Exchanger 1Leading to an Increase in the Number of Effective Osmoles in Brain Cells.

Q: What measures can be taken to reduce the risk of cerebral edema during treatment?

A: A number of focused measures might be considered in the treatment of patients with diabetic ketoacidosis to reduce their risk of cerebral edema. The effective osmolality in plasma must not be permitted to decrease during the first 15 hours of treatment. When potassium ions are needed, this goal can be achieved if potassium chloride is added to 0.9% saline, at a concentration of 30 to 40 mmol per liter. This solution has an effective osmolality that is reasonably close to that of the urine in these patients at that time. If glucose is to be administered to prevent neuroglycopenia when the plasma glucose concentration decreases, it seems prudent to administer it in a solution that has the smallest possible volume of electrolyte-free water. The clinician should take a detailed history of fluid ingestion and look for signs that indicate recent gastric emptying, with its attendant risk of intestinal absorption of electrolyte-free water. A large bolus of saline should be administered only if there is a hemodynamic emergency.

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