60: Hyperkalemia

The serum potassium level is 6.5 mEq/L in an extremely low birthweight infant. Normal potassium levels are generally between 3.5 and 5.5 mEq/L. Definitions can vary by weight, but most define hyperkalemia as >6 mEq/L in newborns. Hyperkalemia is common in extremely low birthweight infants. This is the most serious of electrolyte abnormalities because it can cause fatal arrhythmias. If electrocardiogram (ECG) changes relating to hyperkalemia are present, this is an emergency situation. (See Section V.B.)

1. How was the specimen collected? What is the central serum potassium level? Is it a true level or factitious? Blood obtained by heelstick or drawn through a tiny needle may yield falsely elevated potassium levels secondary to hemolysis. Clot formation can also cause falsely elevated potassium. The blood should not be obtained from a heparin-coated umbilical catheter (release of benzalkonium from a heparin-coated umbilical catheter can elevate the potassium reading). Note: Serum potassium level is 0.4 mEq/L higher than the plasma level.

2. Does the ECG show cardiac changes characteristic of hyperkalemia? This may be the first indication of hyperkalemia. In neonates, serum potassium >6.7 mEq/L is associated with ECG changes. Early cardiac changes include tall, peaked, “tented” T waves, followed by loss or flattened P wave, widening QRS, ST-segment depression, bradycardia, sine wave QRS-T, first-degree atrioventricular block, ventricular tachyarrhythmias, and finally cardiac arrest if the potassium levels continue to increase.

   1. Serum K 5.5–6.5 mEq/L. Tall peaked T waves with a narrow base.

   2. Serum K 6.5–8 mEq/L. Tall peaked T waves, prolonged PR interval, loss or decreased P wave, amplified R wave, widening of QRS.

   3. Serum K >8 mEq/L. Absent P wave, wide bizarre diphasic QRS, progressive QRS widening merging with the T wave, bundle-branch blocks, ventricular fibrillation or asystole.

3. How much potassium is the infant receiving? Normal amounts of potassium given for maintenance are 1–3 mEq/kg/d.

4. What are the blood urea nitrogen (BUN) and creatinine levels? What is the urine output and body weight? Elevated BUN and creatinine suggest renal insufficiency. Another indication of renal failure is decreasing or inadequate urine output with weight gain.

5. Is there associated hyponatremia, hypoglycemia, and hypotension? With low sodium and glucose, high potassium, and hypotension, consider adrenal insufficiency.

6. Does the infant have any of the common characteristics of premature newborns prone to hyperkalemia? These include small for gestational age, female sex, severe respiratory distress syndrome, very low birthweight, requirement of exogenous surfactant, need for inotropic medications, and delayed feeding. Mildly elevated potassium (>5.6 mEq/L) and phosphate levels (>2 mEq/L) within 6 hours of birth may predict the development of hyperkalemia.

True hyperkalemia can be caused by an increase in potassium intake (usually not a problem if kidneys able to excrete potassium), an increase in potassium release, a decrease or inability in potassium excretion by the kidneys, or by a shift of potassium into the extracellular space or an impaired aldosterone activity causing decreased renal excretion.

1. Pseudohyperkalemia is a falsely elevated potassium level (plasma potassium is normal). It can be due to hemolysis (trauma causes destruction of red blood cells [RBCs] with leakage of potassium) during phlebotomy or heelstick or by drawing the sample proximal to an IV site infusing potassium. If an unspun sample is allowed to sit or if there is a delay in processing (after 2 hours), potassium release from the cells increase. Laboratory error (multiple processing variables) can also be a reason. Thrombocytosis and leukocytosis can lead to a false elevation of serum potassium levels because potassium leaks out of an increased number of white blood cells (WBCs) and platelets during clotting. The serum potassium increases by 0.15 mEq/L for every 100,000/mL elevation of the platelet count. Two rare genetic syndromes that can cause pseudohyperkalemia are familial pseudohyperkalemia and hereditary spherocytosis.

2. True hyperkalemia

   1. Common causes of hyperkalemia

      1. Increased potassium intake. From excessive amount in IV fluids, excessive oral supplementation (as in excess KCL supplementation in a bronchopulmonary dysplasia/chronic lung disease infant), or medications containing potassium. Potassium supplements usually are not necessary on the first day of life and often are not necessary until day 3, with the typical requirement of 1–2 mEq/kg/d. This is rare cause because the kidneys usually excrete any excess potassium.

      2. Pathologic hemolysis of RBCs. May be secondary to intraventricular hemorrhage, use of a hypotonic glucose solution (<4.7% dextrose), sepsis (most commonly, Pseudomonas), intravascular hemolysis, cephalohematoma, bleeding, asphyxia, or Rh incompatibility.

      3. Tissue necrosis and breakdown. In certain disease states, such as necrotizing enterocolitis (NEC), tissue necrosis can occur and hyperkalemia may result. Trauma and severe hypothermia can cause rhabdomyolysis.

      4. Renal failure/insufficiency. Impaired kidney function can lead to hyperkalemia. Oliguria can cause decreased potassium clearance and hyperkalemia.

      5. Immaturity-related nonoliguric hyperkalemia (NOHK). Occurs in up to 50% of extremely low birthweight infants and is defined as a potassium level >6.5 mEq/L in the absence of acute renal failure/acute kidney injury or a serum potassium ≥7 mEq/L during the first 72 hours of life with urinary output ≥1 mL/kg/h. This occurs without potassium intake or oliguria. It can result from a shift of potassium from intracellular to extracellular space, immature renal tubular and glomerular functions, and a decreased response to aldosterone. Hyperkalemia is often associated with hyperglycemia as a result of insulin resistance and intracellular energy failure (“hyperglycemia-hyperkalemia syndrome”).

      6. Metabolic acidosis. Causes potassium to move out of cells, resulting in hyperkalemia. For every 0.1-unit decrease in pH, the serum potassium increases ∽0.3–1.3 mEq/L. Respiratory acidosis rarely causes significant hyperkalemia.

      7. Dehydration. Causes hyperkalemia. Volume depletion and congestive heart failure can cause renal hypoperfusion and therefore hyperkalemia.

      8. Medications containing potassium. May elevate the serum potassium level. Digoxin therapy can lead to hyperkalemia secondary to redistribution of potassium. K⁺-sparing diuretics cause decreased potassium losses. Both propranolol and phenylephrine are associated with hyperkalemia. High glucose load can lead to hyperkalemia secondary to increases in plasma osmolality. Other medications, including tromethamine, indomethacin, angiotensin-converting enzyme inhibitors, β-blockers, heparin, trimethoprim, captopril, and nonsteroidal anti-inflammatory drugs are associated with hyperkalemia.

      9. Adrenal insufficiency. Seen in congenital adrenal hyperplasia and bilateral adrenal hemorrhage. In salt-losing congenital adrenal hyperplasia, infants have low serum sodium, chloride, and glucose; elevated levels of potassium; and hypotension. In bilateral adrenal hemorrhage, anemia, thrombocytopenia, and jaundice are seen, and bilateral adrenal masses are palpable. Renal tubular hyperkalemia/hyperkalemic distal renal tubular acidosis type IV occurs secondary to hypoaldosteronism. Infants present with metabolic acidosis and hyperkalemia. It is seen in adrenal disorders (hypoaldosteronism, congenital adrenal hyperplasia) and obstructive uropathy, reduced renal mass, renal reflux, urinary tract infection, and pseudohypoaldosteronism.

      10. Decreased insulin levels. Associated with hyperkalemia. Insulin drives potassium into cells; insulin deficiency can cause hyperkalemia.

      11. Transfusion-induced hyperkalemia. Irradiation accelerates the leakage of potassium out of stored RBCs, which can induce the risk of transfusion-induced arrhythmias from hyperkalemia. Washing of irradiated RBCs reduces potassium and lactate loads. Exchange transfusion can also be a cause.

      12. Hyperosmolality. Caused by inappropriately diluted formula/hyperosmolar amino acid solution/glucose infusions.

   2. Less common causes

      1. Neonatal Bartter syndrome (a variant of this with ROMK mutation presents with early hyperkalemia). It is a group of renal tubular disorders usually characterized by hypokalemic metabolic alkalosis.

      2. Hereditary hyperkalemic disorders. Hereditary pseudohyperkalemia, hereditary hyperkalemic periodic paralysis, various types of hypoaldosteronism, hereditary tubular defects that cause hyperkalemia.

      3. Disorders that cause decreased renal excretion of potassium. Addison disease, mineralocorticoid deficiency, primary hypoaldosteronism, aldosterone synthase deficiency, and pseudohypoaldosteronism.

1. Physical examination. The infant may exhibit no signs or can have bradycardia, ventricular fibrillation or other arrhythmias, or shock. Pay special attention to the abdomen for signs of NEC (ie, abdominal distention, decreased bowel sounds, and visible bowel loops). Evaluate for signs of underlying diseases. It is difficult to state an exact number when clinical signs will appear, but most agree when the serum potassium increases to >7 mEq/L. Signs can be polyuria, abdominal distension, lethargy. Muscle weakness occurs if >8 mEq/L but is hard to evaluate in a newborn. Tendon reflexes can be decreased.

2. Laboratory studies

   1. Immediate tests

      1. Serum potassium level measured by a properly collected venous sample. A repeat serum potassium level is usually recommended before treatment.

      2. Serum and urine electrolytes.

      3. Complete blood count and differential. To rule out sepsis and hemolysis.

      4. Serum ionized and total calcium levels. Hypocalcemia may potentiate the effects of hyperkalemia. Maintain normal serum calcium concentrations.

      5. Serum pH and bicarbonate. To rule out acidosis, which may potentiate hyperkalemia.

      6. BUN and serum creatinine levels. May reveal renal insufficiency.

      7. Urine dipstick and specific gravity. To assess renal status and blood and hemoglobin for tissue breakdown secondary to hemolysis. Examine for casts or sediment.

   2. Further testing

      1. Serum cortisol, 17-OH progesterone 11B-hydroxylase, 21-hydroxylase levels for congenital adrenal hyperplasia.

      2. Serum renin, angiotensin, and aldosterone for hypoaldosteronism.

3. Imaging and other studies

   1. Abdominal radiograph if NEC is suspected.

   2. ECG may reveal the cardiac changes characteristic of hyperkalemia and provides a baseline study (see Section II.B).

First, confirm the potassium level through a repeat STAT serum sample. Document any ECG changes, and if present, this is a medical emergency and needs to be treated immediately (see later).

1. Important considerations

   1. Stop all potassium intake. IV fluids, oral supplements, potassium-containing medications.

   2. Check the calculation of potassium in the IV fluids. Verify that excess potassium was not given.

   3. Correct hypovolemia using isotonic saline. To promote tubular secretion of potassium.

   4. Treat the specific cause. Renal failure can be treated with fluid restriction. If adrenal insufficiency exists, replacement therapy is indicated.

   5. Monitor ECG changes during therapy.

   6. Preterm infants. The combination of insulin and glucose as a treatment has more immediate results and is preferred over the treatment with Kayexalate.

   7. Remember: Calcium prevents cardiac arrhythmias by stabilizing the cell membrane of the myocardium; it does nothing to the serum potassium. Insulin and glucose, albuterol, and sodium bicarbonate decrease the serum potassium level by moving potassium into cells, which reduces the risk of immediate complications but does not remove potassium from the body. Furosemide, sodium polystyrene (Kayexalate), and dialysis (exchange transfusion, peritoneal dialysis) remove potassium from the body by renal excretion, gastrointestinal loss, or removal by dialysis.

2. Hyperkalemia with ECG changes. Arrhythmia from hyperkalemia is difficult to treat. The usual steps of defibrillation, epinephrine, or even antiarrhythmic drugs will not work without lowering the potassium level. Note: Calcium only protects the myocardium and does not decrease the serum potassium. First, give calcium to protect the heart, and then give medications to lower serum potassium levels but not total body stores, and then give medications to cause potassium excretion and lower total body stores.

   1. Stop administration of potassium in IV fluids. Consider stopping any potassium-containing medications or medications known to induce hyperkalemia (see Section III.H).

   2. Protect the heart from the toxic effects of potassium with calcium (does not lower potassium). It stabilizes the myocardium and lowers the threshold potential to protect against arrhythmias. Administer slow IV infusion over 10 minutes, optimally through a central line, not a scalp IV. Observe the ECG while infusing the medication. Improvement in the ECG should occur within 1–5 minutes. Once the arrhythmia or ECG changes disappear, the bolus can be stopped. This only decreases myocardial excitability. It is necessary to give a medication immediately that will begin to decrease potassium. If the infant is on digoxin therapy, remember that calcium therapy can worsen digoxin toxicity and a slower infusion may be necessary. Calcium gluconate 10% (100–200 mg/kg/dose) IV diluted in appropriate fluid and given over 10–30 minutes can be used.

   3. Start a medication to reduce serum potassium levels. Sodium bicarbonate, glucose and insulin, and β-adrenergic agonists cause cellular intake of potassium. Sodium bicarbonate has an immediate onset; glucose, insulin, and albuterol take a minimum of 15 minutes to work. Deciding which one to use depends on your unit's preference. For premature infants, most agree that insulin and glucose is the first-line therapy. One recommendation is to give sodium bicarbonate or insulin and glucose or albuterol until the potassium is down, then give either Lasix or Kayexalate.

      1. Sodium bicarbonate can be used even when blood pH is normal (controversial). Use debated and not recommended as monotherapy or with caution in premature infants. Cochrane review stated that results are equivocal (buffers acid by raising pH). Some suggest using only in life-threatening hyperkalemia or not at all. Correct the base deficit by using the following formula:

         

         Or give 1–2 mEq/kg over 10–30 minutes intravenously (works in 5–10 minutes). Inducing alkalosis drives potassium ions into the cells. In very tiny infants, sodium bicarbonate may have associated risks. Avoid rapid infusion of sodium bicarbonate to decrease the risk of intraventricular hemorrhage. If the infant is intubated, hyperventilation can cause respiratory alkalosis (0.1-unit pH increase causes a 0.6-mEq/L decrease in serum K). This may decrease cerebral perfusion.

      2. Insulin and glucose. Insulin drives potassium into the cells. Insulin must be given with glucose to avoid hypoglycemia. The usual dose is 0.1–0.2 U/kg/h insulin in combination with a continuous infusion of 0.5 g/kg/h of dextrose. Adjust infusion rates based on serum glucose and potassium concentrations. Time to onset 15–30 minutes. Monitor the glucose levels.

      3. β-Adrenergic agonists (controversial). Drive potassium into the cell. They have a rapid onset of action. The most commonly used medication is albuterol nebulized 0.1–0.5 mg/kg/dose (minimum dose 2.5 mg) every 2–6 hours as needed. Nebulized albuterol is effective in premature neonates.

3. Hyperkalemia without ECG changes. Treatment is recommended when serum potassium is >6–6.5 mEq/L (controversial). Deciding which medication to use is dependent on your institution.

   1. Stop administration of potassium in IV fluids. Consider stopping any potassium-containing medications or medications known to induce hyperkalemia (see Section III.H).

   2. Cardiac monitoring with frequent ECGs.

   3. Check the serum potassium frequently (ie, every 1–2 hours) until stable.

   4. Furosemide (Lasix). Enhances potassium excretion in the urine and can be given if renal function is adequate; the usual dose is 1 mg/kg IV every 12 hours (controversial). It takes 5–10 minutes to work. Value is limited in renal failure, with higher doses required. Useful in hyperkalemia associated with congestive heart failure and hypoaldosteronism.

   5. Inhaled albuterol (controversial). See Section V.B.3c.

   6. Sodium polystyrene sulfonate (Kayexalate), a potassium-exchange resin, can be given. It removes potassium from the gut (1 g of resin removes ∽1 mEq of potassium) in exchange for sodium. (Sorbitol free is recommended in neonates as sorbitol can cause bowel necrosis and sodium retention.) The usual dose is 1 g/kg/dose orally every 6 hours or rectally every 2–6 hours. Rectal route is preferred as it has faster onset of 1–2 hours (not effective by 4 hours in a Cochrane review). Administered orally, it lowers the potassium level slowly and therefore is of limited value acutely. This therapy should not be used in extremely low birthweight infants because of risk of irritation, concretions, hemorrhagic colitis, gastrointestinal hemorrhage, colonic necrosis, sodium overload, and NEC. This treatment can cause an increase in sodium and calcium. Repetitive rectal use can cause local bleeding. Do not use with obstructive bowel disease and infants with decreased gut motility (risk of intestinal necrosis).

4. Persistent hyperkalemia. Continuous infusion of insulin with glucose is recommended. Infants with chronic kidney disease may require low potassium diet, alkali treatment, exchange resins, and peritoneal dialysis.

5. Refractory hyperkalemia. If all of these measures fail to lower the potassium level, other measures, such as exchange transfusion with freshly washed packed RBCs reconstituted with plasma or peritoneal dialysis, must be considered. These methods work immediately and are very effective but are limited by the time and complexity involved. If hyperkalemia is secondary to cell breakdown, exchange transfusion is preferred.

6. Treatment and prevention of nonoliguric hyperkalemia of extremely low birthweight infants. Potassium should not be administered in the first days of life until good urinary output is established and serum potassium is normal and not rising. Potassium levels should be monitored every 6 hours in the first few days of life. Early administration of amino acids (first day of life) may stimulate endogenous insulin secretions and prevent the need for insulin infusion. Continuous insulin IV infusion may be necessary. Cochrane review has no recommendations for treatment of hyperkalemia in nonoliguric hyperkalemia in preterm infant, except that insulin and glucose is preferred over Kayexalate.