Susan A. Kecskes
• Serum potassium levels reflect only 2% of total body potassium.
• Therapy for hyperkalemia is aimed at halting intake, stabilizing cellular membranes, intracellular translocation, and enhancing elimination.
• Hypokalemia should be corrected orally, if possible. Extreme caution should be exercised during intravenous replacement to avoid hyperkalemia.
While only 2% of total body potassium is in the extracellular fluid (ECF), potassium is the main cation in intracellular fluid (ICF). Normal potassium concentration in the ECF is 3.5 to 5.5 mEq/L, compared to approximately 160 mEq/L in the ICF. The sodium–potassium ATPase pump in the cell membrane maintains this large concentration gradient.
Potassium homeostasis is managed through the use of both translocation and excretion. The majority of potassium excretion occurs in the kidney. The kidney can adjust urinary potassium excretion from 5 to 1000 mEq/24 h. Approximately 10% of daily potassium intake is lost through the gastrointestinal tract in stool.
As only 50% of a potassium load is excreted in the first 4 to 6 hours, translocation allows the body to maintain stable ECF potassium. In the first hours after ingestion, potassium is translocated into cells, primarily in the liver and muscle. Potassium uptake is regulated by insulin, epinephrine, aldosterone, and acid–base balance.1 Insulin stimulates the sodium–potassium ATPase pump to promote potassium uptake in the liver and muscle. Catecholamines cause an initial rise in serum potassium as it is released from the liver. Subsequently, serum potassium falls as catecholamines promote movement to ICF. Aldosterone acts through both renal and extrarenal mechanisms to reduce serum potassium. Acid–base changes direct potassium shifts. Acidemia promotes movement of potassium to the ECF, whereas alkalosis favors movement of potassium to the ICF.
Hyperkalemia is defined as serum potassium >5.5 mEq/L and can result from increased potassium intake, decreased potassium loss, or from redistribution from the ICF. Increased potassium intake rarely results in an elevation of serum potassium, unless it is iatrogenic or simultaneously associated with decreased excretion. Iatrogenic causes include excessive intravenous administration of potassium, administration of large quantities of cold-stored blood, large doses of the potassium salts of penicillin, or oral intake of potassium-containing salt substitutes. Acute renal failure is the primary cause of decreased excretion. Less commonly, adrenal insufficiency may result in hyperkalemia due to decreased mineralocorticoid activity. Use of potassium-sparing diuretics is also associated with decreased potassium excretion.
Redistribution of potassium from the ICF to the ECF may occur via cell destruction or translocation from intact cells. In patients with trauma, burns, rhabdomyolysis, massive intravascular coagulopathy, or tumor lysis/necrosis, injured cells release stores of intracellular potassium into the circulation. Hematomas in the newborn and gastrointestinal bleeding may result in large volumes of hemolyzing cells and elevated potassium levels. Potassium can be quickly shifted from the ICF to the ECF in response to metabolic acidosis. The ICF is a major part of the body’s buffering system, with extracellular hydrogen ions being exchanged for intracellular potassium ions.
Pseudohyperkalemia is a common occurrence and must be considered in the differential diagnosis of hyperkalemia. It is often associated with hemolysis from the blood draw. Other causes include prolonged tourniquet use, heel squeezing, or use of small-gauge needles. When pseudohyperkalemia is suspected, specimens should be repeated with attention to avoiding such mechanical factors.
Most patients with hyperkalemia are relatively asymptomatic. Neuromuscular symptoms begin with paresthesias and progress to muscle weakness and, ultimately, flaccid paralysis. Cardiac abnormalities are much more likely to produce life-threatening situations. Characteristic changes in the electrocardiogram (ECG) include peaked T waves, prolongation of the PR interval, and progressive widening of the QRS complex. As potassium continues to rise (typically, >8 mEq/L), the classic “sine wave” of hyperkalemia appears (Fig. 82-1). This may rapidly degenerate to asystole or ventricular fibrillation.
FIGURE 82-1. ECG changes in hyperkalemia. A: Normal ECG. B: ECG with peaked T waves, prolonged PR interval, and widened QRS, seen in moderate hyperkalemia (potassium >7.0 mEq/L). (C) “Sine wave” ECG seen at potassium levels >8 mEq/L.
An ECG should always be obtained when hyperkalemia is suspected, to assess the clinical severity. Serum electrolytes, renal indices (BUN, creatinine, and urinalysis), a complete blood count (CBC), and acid–base status should be measured. Urinary potassium levels may help evaluate the cause of the hyperkalemia. All patients with serum potassium levels >6.5 mEq/L should have continuous ECG monitoring and frequent laboratory follow-up.
Treatment of hyperkalemia depends on the level of serum potassium, along with the clinical symptoms and renal status of the patient. In all cases, intake of potassium and potassium-sparing medication should be halted. In asymptomatic patients with intact renal function and modest (<7 mEq/L) levels of serum potassium, halting intake and follow-up of serum potassium levels may be all that is required (Fig. 82-2). For patients with renal dysfunction, the addition of the potassium-binding agent, sodium polystyrene sulfonate (Kayexalate, 1–2 g/kg po, ng, or pr), or dialysis should be considered to enhance elimination.
FIGURE 82-2. Treatment of Hyperkalemia.
Those patients with serum potassium levels >7 mEq/L or who are symptomatic require aggressive intervention to stabilize the cellular membrane, shift potassium intracellularly, and increase potassium elimination. Membrane stabilization is effected by intravenous administration of calcium. Calcium gluconate, 10%, in a dose of 50 to 100 mg/kg, or calcium chloride, 10%, in a dose of 10 to 25 mg/kg, may be administered over 2 to 5 minutes with continuous ECG monitoring. Onset of action is immediate and the stabilizing effects last 30 to 60 minutes. Potassium may be shifted intracellularly to temporarily reduce serum potassium levels. Administration of sodium bicarbonate (1–2 mEq/kg intravenously over 5–10 minutes) has an onset of action of 5 to 10 minutes and duration of 1 to 2 hours. The dose may be repeated if necessary. Insulin administered in conjunction with glucose effectively shifts potassium to the ICF as well. Dextrose (1 g/kg) may be combined with insulin (0.25 units/kg) and infused over 2 hours. Inhalation of α2-agonists is an attractive alternative for patients with delayed intravenous access.2Nebulized albuterol, in a dose of 2.5 mg for patients <25 kg and 5 mg for patients of 25 kg, and above has been reported to reduce potassium in adult patients with chronic renal failure and is likely to have a similar effect in pediatric patients. It should not be a substitute for appropriate intravenous therapy, but may be used while access is obtained. None of these methods alter total body potassium, so the time they buy should be utilized to enhance elimination of potassium from the body. In the absence of renal failure, loop diuretics and/or thiazides will enhance renal elimination of potassium. Sodium polystyrene sulfonate is a resin that exchanges sodium for potassium at a 1:1 ratio. It is administered through the gastrointestinal tract and may be used in patients with and without renal failure. In patients with renal failure or severely symptomatic cases, dialysis is the definitive therapy. Although hemodialysis is more effective than peritoneal dialysis, the peritoneal route may be more readily available in some locations.
Hypokalemia is defined by a serum potassium level <3.5 mEq/L and can result from decreased intake, increased renal excretion, increased extrarenal losses, or a shift of potassium from the ECF to the ICF. A low-potassium diet, eating disorders such as anorexia nervosa, and prolonged administration of intravenous fluids without potassium may all lead to hypokalemia. Increased renal excretion may result from the use of diuretics, osmotic diuresis, hyperaldosteronism, Bartter syndrome, magnesium deficiency, and renal tubular acidosis. Extrarenal losses occur primarily through the gastrointestinal system.1 Vomiting and nasogastric losses may lead to hypokalemia, both from the direct loss of potassium and from secondary hyperaldosteronism associated with hypovolemia. Diarrhea is associated with large potassium losses. Movement of potassium into the cells from the ECF can occur with correction of acidosis, alkalosis, administration of insulin, administration of α2-agonists, or familial hypokalemic periodic paralysis.
Clinical manifestations of hypokalemia are related to its rapidity of onset and degree of severity. Muscle contraction is dependent on membrane polarization and requires a rapid influx of sodium into cells and a comparable efflux of potassium. Hypokalemia impairs this process. The result is alteration of nerve conduction and muscle contraction. Clinical symptoms include muscle weakness, ileus, areflexia, and autonomic instability, often manifested as orthostatic hypotension. Respiratory arrest and rhabdomyolysis can also occur. The ECG can show flattening of the T wave, ST-segment depression, U waves, premature atrial and ventricular contractions, and dysrhythmias, especially in patients who are on digitalis. The kidney has a reduced ability to concentrate urine in hypokalemia, resulting in polyuria. Laboratory data should include serum electrolytes, including magnesium, serum pH, and urine potassium. Urine potassium concentration of <15 mEq/L indicates renal conservation and suggests extrarenal loss. An ECG should be done looking for the alterations just noted.
Since serum potassium levels only measure extracellular potassium concentration, total body concentration may be decreased or normal. Also, potassium must cross the smaller extracellular space to the larger ICF, where the majority of potassium is stored. Both of these factors lead to concern of “overshoot hyperkalemia” during correction. In the patient without life-threatening complications, hypokalemia should be corrected gradually with oral supplementation or, in those patients with a contraindication to oral intake, an increase in the maintenance potassium concentration in the intravenous fluids. Underlying conditions that accompany the hypokalemia, such as alkalosis or hypomagnesemia, should be corrected. Sources of ongoing potassium loss are identified. The loss is then measured and replaced. An effort should be made to determine the cause of the loss and, if possible, treat it. If hypokalemia is associated with digoxin use or life-threatening complications, such as cardiac dysrhythmias, rhabdomyolysis, extreme muscle weakness, or respiratory arrest, intravenous therapy is required. Extreme care should be exercised in the ordering, preparation, and administration of intravenous potassium. Recommendations for dosage of potassium chloride in pediatric patients range from 0.5 to 1 mEq/kg/dose (maximum dose: 40 mEq) to infuse at 0.3 to 0.5 mEq/kg/h (maximum rate: 1 mEq/kg/h).3 Potassium must be diluted prior to intravenous administration. In peripheral lines, the maximum concentration is 80 mEq/L. The maximum recommended central line concentration is 200 mEq/L (usually reserved for severely fluid-restricted patients). Continuous ECG monitoring, along with frequent assessment of serum potassium levels, is essential during intravenous correction of hypokalemia.
1. Gennari FJ. Current concepts: hypokalemia. N Engl J Med. 1998;339:451.
2. Allon M, Dunlay R, Copkney C. Nebulized albuterol for acute hyperkalemia in patients on hemodialysis. Ann Intern Med. 1989;110:426.
3. Taketomo CK, Hodding JH, Kraus DM, eds. Pediatric Dosage Handbook. 19th ed. Hudson, OH: Lexi-Comp; 2012:1390.