Is There a Risk to Rapidly Lowering the Plasma Potassium in Patients with Hyperkalemia?

Hyperkalemia is one of the most common and serious metabolic complications in patients with chronic kidney disease (CKD) and, in particular, end-stage renal disease (ESRD). Emergent treatment of hyperkalemia by administration of calcium to decrease cardiac repolarization and insulin to shift of potassium into cells is now standard and universally accepted. In most situations, potassium also needs to be removed from the body, either by diuretics, potassium-binding agents, or dialysis. These methods are generally quite effective in lowering plasma potassium levels and may be lifesaving as severe hyperkalemia can cause sudden cardiac death. But, is there also a risk of sudden cardiac death if the plasma potassium is lowered too quickly?

Several factors come into play when making a decision about how and how rapidly to lower plasma potassium in patients with hyperkalemia. First, the etiology of hyperkalemia needs to be considered. Potassium is the most prevalent cation in the body (total body potassium is ˜50 mmol/kg), and most of it is in the intracellular fluid (ICF), with extracellular fluid (ECF) content normally only about 4 mmol/L × 17 L = 67 mmol. Disorders of potassium concentration can be due to an imbalance between intake and output of potassium (external potassium balance), an imbalance in distribution between the ECF and ICF (internal potassium balance), or both (Fig. 15.1). The plasma potassium concentration thus depends on total body potassium as well as its distribution between ECF and ICF. Certain conditions increase the ECF:ICF potassium ratio, leading to hyperkalemia without a change in total body potassium. More
commonly, total body potassium is also increased. If the problem is increased ECF:ICF ratio with normal total body potassium, shifting potassium back into cells may be the only therapy needed (e.g., administration of insulin in hyperglycemic patients). On the other hand, if total body potassium is increased, potassium will need to be removed from the body. Table 15.1 lists common causes of hyperkalemia.

FIGURE 15.1 Internal and external potassium balance. The figure depicts typical potassium balance in a 70-kg man with a total body water of 42 L. (From Moinuddin IK, Leehey DJ. Handbook of Nephrology. Philadelphia, PA: Lippincott Williams & Wilkins; 2013.)

The urgency of treatment of hyperkalemia depends upon its acuity and whether or not there are symptoms and signs attributable to hyperkalemia (EKG changes and/or muscle weakness). One situation in which overly aggressive treatment of hyperkalemia can result in potentially catastrophic results is uncontrolled diabetes, in particular diabetic ketoacidosis. In these patients, lack of insulin leads to decreased cellular potassium uptake, resulting in hyperkalemia even though the total body potassium is often reduced (due to osmotic diuresis from hyperglycemia, poor dietary intake, and gastrointestinal (GI) losses). The increased ECF:ICF ratio in such patients is rapidly reversed by the administration of insulin. Because of whole-body potassium deficiency, hypokalemia frequently ensues during subsequent therapy, and failure to administer adequate potassium can lead to hypokalemia and potentially fatal complications. At the other end of the spectrum, in hyperkalemic patients with marked tissue breakdown (e.g., rhabdomyolysis, hemolysis, tumor
lysis syndrome, shock), release of potassium from damaged cells can raise plasma levels rapidly; such patients generally require urgent therapy.

TABLE 15.1 Etiologies of Hyperkalemia

Normal Total Body Potassium (Increased ECF:ICF Ratio)
Metabolic acidosis (inorganic)
Insulin deficiency
Drugs (digoxin, beta-blockers)
Acute hypertonicity (osmolar water and K shift out of cells)
Hyperkalemic periodic paralysis (very rare)
High Total Body Potassium (Decreased Excretion with or without Increased Exogenous Intake)
Acute or chronic kidney disease
Medications that impair potassium excretion
	Potassium-sparing diuretics
	Renin-angiotensin system (RAS) inhibitors
	Heparin (inhibits biosynthesis of aldosterone)
	Nonsteroidal anti-inflammatory drugs (NSAIDs)
	Calcineurin inhibitors
	Trimethoprim
Adrenal insufficiency
Selective hypoaldosteronism
Hyperkalemic renal tubular acidosis
Salt substitutes (in patients with kidney disease)
High Total Body Potassium (Increased ECF:ICF Ratio Coupled with Decreased Excretion)
Cell breakdown (hemolysis, rhabdomyolysis, tumor lysis, shock)

INSULIN/GLUCOSE

It has now been known for a quarter century that in a normoglycemic patient, the “standard therapy” of 10 units of intravenous regular insulin followed immediately by 50 mL (one “amp”) of 50% glucose (25 g) can result in the development of hypoglycemia in up to 75% of patients (Allon and Copkney, 1990). However, many sources still recommend this regimen (i.e., insulin:dextrose 1 unit:2.5 g). Administration of 10 units of regular insulin with 100 mL (two “amps” or 50 g of glucose, i.e., insulin:dextrose 1 unit:5 g) is a safer alternative. The effect of regular insulin begins in 10 to 20 minutes, peaks at 30 to 60 minutes, and lasts for 4 to 6 hours. Therefore, late hypoglycemia can occasionally occur, leading some to
recommend an infusion of 10% glucose for 4 to 6 hours after the initial bolus, though this is not common practice. The plasma potassium concentration will typically decrease by 0.5 to 1.5 mmol/L with this therapy.

ALBUTEROL

Since activation of the beta-2-receptor also shifts potassium into cells, beta-2-adrenergic agonists such as albuterol can be effective in the acute treatment of hyperkalemia. However, the dose that has been studied is 10 to 20 mg in 4 mL of saline by nebulization over 10 minutes (which is four to eight times the dose used for bronchodilation), which can have cardiac side effects. Insulin and albuterol have additive effects, with the combination reducing plasma potassium concentration by about 1.5 mmol/L (Allon and Copkney, 1990).

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