63: Hypokalemia

The nurse reports a serum potassium of 2.8 mEq/L. Normal serum potassium values vary with technique used by the laboratory but are usually between 3.5 and 5 mEq/L. Hypokalemia is defined as a serum potassium <3.5 mEq/L. Mild hypokalemia is 3.0–3.5 mEq/L. Moderate hypokalemia is 2.5–3.0 mEq/L; severe hypokalemia is <2.5 mEq/L. Severe hypokalemia can cause cardiac arrhythmias.

1. What is the central serum potassium? If a low value is obtained by heelstick, central values should be obtained because they may actually be lower than values obtained by heelstick because of the hemolysis of red blood cells. Was the sample sent immediately to the lab? If a sample sat for hours in a warm area, pseudohypokalemia can occur.

2. Is the infant on diuretics? Are potassium-wasting medications or digitalis being given? Hypokalemia in a neonate usually occurs from chronic diuretic use. Hypokalemia may cause significant arrhythmias if digitalis is being administered.

3. How much potassium is the infant receiving? Normal maintenance doses are 1–2 mEq/kg/d.

4. Are there any gastrointestinal (GI) losses from diarrhea, a naso-gastric/orogastric (NG/OG) tube, or ileostomy? Loss of large amounts of GI fluids can cause hypokalemia. Severe vomiting can also cause hypokalemia such as in infantile hypertrophic pyloric stenosis.

5. What is the infant's magnesium level? Hypomagnesemia can cause hypokalemia. Consider this diagnosis if the hypokalemia does not correct despite potassium supplementation.

Hypokalemia can be caused by a prolonged inadequate intake of potassium, gastrointestinal losses, renal losses, and transcellular shifts or redistrubution. GI and renal losses are more common. Medications (diuretics) are the most common cause in the neonatal intensive care unit (NICU).

1. Pseudohypokalemia can occur if the blood sample sits too long in a warm environment, with a very high white blood cell (WBC) count (uptake of potassium by abnormal WBC), or from a heelstick sample.

2. True hypokalemia (total body deficit)

   1. Inadequate intake (rare) of either maintenance infusion or oral intake of potassium. For a further discussion, see Chapter 9.

   2. Gastrointestinal losses

      1. Loss of fluid via nasogastric tube (common). Unreplaced electrolyte loss from NG tube or excess drainage from ileostomy.

      2. Diarrhea. Congenital chloride diarrhea, any gastrointestinal fistula, short bowel syndrome.

      3. Vomiting. May cause hypokalemia such as infantile hypertrophic pyloric stenosis with vomiting.

      4. Medications. Kayexalate causes fecal potassium loss.

   3. Renal losses

      1. Medications

         1. Diuretic use especially long-term therapy with any thiazide or loop diuretic is the most common medication-related cause.

         2. Steroids and steroid-like medications.

         3. Antibiotics. High-dose penicillin, ampicillin, carbenicillin, vancomycin. Combined treatment of aminoglycosides and vancomycin can cause tubular disturbances in extremely low birthweight (ELBW) infants with renal tubular wasting of potassium.

         4. Magnesium depletion medications such as amphotericin B and aminoglycosides. Amphotericin B can cause direct renal tubular damage with potassium loss.

      2. Any cause of polyuria

      3. Renal tubular losses

         1. Renal tubular acidosis (RTA). Type 1 and 2.

         2. Hypomagnesemia. Exacerbates potassium loss by increasing distal potassium secretion.

         3. Bartter syndrome (neonatal). A rare form of potassium wasting, secondary to chloride channel abnormality. Pseudo-Bartter syndrome presents with the same clinical and biological characteristics as Bartter syndrome but without the primary renal tubule abnormalities. Congenital hypokalemia with hypercalciuria resembles Bartter syndrome.

         4. Other syndromes. Liddle, Gitelman, and Fanconi syndromes.

   4. Transcellular shifts of potassium from serum to cells

      1. Alkalosis (metabolic or respiratory) drives potassium into cells, causing hypokalemia. An increase in pH by 0.1 unit causes a decrease in the serum potassium by 0.6 mEq/L. The decrease is less in respiratory than in metabolic alkalosis.

      2. Insulin therapy causes intracellular uptake of potassium.

      3. Medications that cause an increase in intracellular uptake of potassium include β-adrenergic agonists (such as epinephrine, decongestants, bronchodilators, tocolytic drugs) and xanthine derivatives (theophylline, caffeine). Overdose related: insulin, verapamil.

      4. Hypothermia can drive potassium into cells and lower the plasma potassium concentration.

      5. Endocrinopathies causing potassium loss (less common)

         1. Congenital adrenal hyperplasia. 11B-hydroxylase deficiency accounts for ∼5–10 % of cases and causes hypertension, hypokalemic alkalosis, and salt retention.

         2. Primary hyperaldosteronism/Conn syndrome. Hypertension, hypokalemia, and suppressed renin activity are the 3 laboratory hallmarks of this disease. Secondary hyperaldosteronism can occur from renal artery stenosis, renin-secreting tumors, and coarctation of the aorta.

         3. Cushing syndrome. Hyperfunction of the adrenal cortex in infants is usually caused by a functioning adrenocortical tumor.

         4. Syndrome of apparent mineralocorticoid excess (AME). This can be congenital and causes hypokalemia.

         5. Hyperthyroidism.

1. Physical examination. Mild hypokalemia may not cause any signs. Symptoms of low potassium can include musculoskeletal (weakness, decreased tendon reflexes, paresthesias, paralysis), GI (nausea, vomiting, diarrhea, ileus), and central nervous system (CNS) signs (lethargy). These are difficult to evaluate in an infant. In severe hypokalemia, the infant can have lethargy; an ileus (abdominal distension and hypoactive bowel sounds); cardiac arrhythmias (rare unless <2.5 mEq/L); flaccid or diaphragmatic paralysis; and bradycardia with cardiovascular collapse. In hypertrophic pyloric stenosis in infants, an enlarged pylorus, or “pyloric olive” may be felt 23% of the time (best felt during or at the end of a feeding).

2. Laboratory studies

   1. Repeat the serum potassium level to confirm value.

   2. Spot-check urinary electrolytes. Perform periodic spot-checks of urinary potassium levels to determine whether urinary losses are high. Not accurate with recent diuretic use.

   3. Serum electrolytes and creatinine. To evaluate renal status and other electrolyte abnormalities.

   4. Blood gas levels. An alkalosis may cause or aggravate hypokalemia (ie, as hydrogen ions leave the cells potassium ions enter the cells, causing decreased serum potassium levels). Treatment of acidosis may worsen hypokalemia.

   5. Serum magnesium. To rule out hypomagnesemia.

   6. Drug screen. If the infant is on any medication that can cause hypokalemia it is best to check the levels. Check digoxin level if the patient is on a digitalis preparation. Hypokalemia can potentiate digitalis-induced arrhythmias.

   7. Serum adrenocorticotropic hormone (ACTH), cortisol, renin activity, and aldosterone levels. To evaluate for Cushing, adrenal hyperplasia, and Conn syndromes.

   8. Serum insulin and C-peptide tests. To evaluate for hyperinsulinism.

3. Imaging and other studies

   1. Abdominal radiograph. If ileus is suspected.

   2. Abdominal ultrasound. In infants in whom pyloric stenosis is suspected, the diagnostic procedure of choice. Also check for adrenal tumor or hyperplasia.

   3. Electrocardiography (ECG). The ECG may appear normal in hypokalemia or may show conduction defects. If hypokalemia is present and the infant is unstable, an ECG may show conduction defects such as prominent U wave with prolonged QT interval, flattening or biphasic of the T wave, and a depressed ST segment. Ventricular and atrial arrhythmias may also develop. The U-wave appearance may mimic atrial flutter. Note that these ECG findings are also seen in hypomagnesemia. Digitalis toxicity is increased with low potassium.

   4. Magnetic resonance image (MRI). MRI of the head to rule out pituitary tumor if indicated.

1. General measures. Hypokalemia is increasing in neonatal intensive care units because of the widespread use of diuretics. The goal of treatment is to increase the potassium intake so that normal blood levels are maintained. Short-term intravenous (IV) potassium administration may cause damage to the veins and occasionally hyperkalemia, as potassium does not rapidly equilibrate. Rapid correction is not recommended because of hyperkalemia risk with potential cardiac complications. Corrections are given slowly, often over 24 hours. If too large a bolus is given, cardiac arrest may result. Serum potassium levels should be monitored every 4–6 hours until correction is achieved. Once levels reach high normal, decrease the amount of potassium given. The majority of cases can be corrected by increasing daily potassium intake by 1 or 2 mEq/kg/d.

   1. If alkalosis is present, correct before potassium correction (see Sepsis).

   2. If the infant is acidotic, potassium acetate or citrate salts can be given. Treatment of acidosis may worsen hypokalemia.

   3. Correct low magnesium, see Adverse Effects.

2. Emergency treatment of life-threatening cardiac arrhythmias or potassium <2.5 mEq/L. IV potassium accompanied by ECG monitoring. Never give a bolus; only in extreme emergencies consider giving 0.5–1 mEq/kg/dose over 1 hour in a central line with continuous ECG monitoring (maximum dose rate: 1 mEq/kg/h).

3. Symptomatic hypokalemia. (Not life threatening.) Should be treated with IV potassium. This can be done by increasing the amount in the IV fluids (preferred) or a correction over 24 hours:

4. Mild hypokalemia. May resolve without treatment. If the infant is on oral feeds, oral supplementation with potassium chloride may be given, usually 2–3 mEq/kg/d in 3 to 4 divided doses (diluted with feedings), adjusted depending on serum potassium levels.

5. Hypokalemia with hypovolemia. IV fluid with potassium chloride (KCL) is indicated.

6. Specific measures. Any specific defects (ie, renal defects, adrenal disorders, and certain metabolic problems) require specific evaluation and therapy.

   1. Inadequate maintenance infusion of potassium. Calculate the normal maintenance infusion of potassium that should be given and increase the amount accordingly (normal maintenance infusion is 1–2 mEq/kg/d, usually only necessary after the first day of life).

   2. Abnormal potassium losses

      1. Medications. If the infant is receiving potassium-wasting medications, increase the maintenance dose of potassium (eg, patients with bronchopulmonary dysplasia on long-term furosemide therapy). Oral supplementation with potassium chloride may be given, 1–2 mEq/kg/d in 3 to 4 divided doses (with feedings), adjusted depending on serum potassium levels. It was once thought that a potassium-sparing diuretic decreased the amount of potassium supplementation; however, a randomized study showed that serum electrolytes sodium and potassium were not affected by the addition of spironolactone.

      2. Gastrointestinal losses

         1. Severe diarrhea correction. Withhold oral feedings to allow the gut to rest and give IV potassium (initial dose of KCl, 1–2 mEq/kg/d). Serum potassium levels are monitored, and the IV dose is adjusted.

         2. Nasogastric drainage/severe vomiting. This amount should be measured each shift and replaced mL/mL with 1/2 normal saline with 10–20 mEq of KCl/L.

         3. Pyloric stenosis. Correct dehydration if present and if surgery is indicated.

7. Renal loss of potassium. Other than induced by medications.

   1. Bartter syndrome. Potassium supplementation is given orally with a starting dosage of 2–3 mEq/kg/d, which is increased as necessary to maintain a normal serum potassium level. Certain forms respond to indomethacin.

   2. Hyperaldosteronism. Surgery and dexamethasone therapy may be indicated.

   3. Cushing syndrome. Medication and possible surgery.

   4. Renal tubular acidosis types 1 and 2. Alkaline therapy and potassium supplementation if needed.

8. Redistribution of potassium

   1. Alkalosis. Determine the cause of metabolic or respiratory alkalosis and treat the underlying disorder. Treat the alkalosis before increasing potassium intake.

   2. Medications. Should be discontinued if possible or alternatives used that do not affect potassium (see Section III.B.3a).