OVERVIEW: What every practitioner needs to know

Are you sure your patient has hypokalemia or hyperkalemia? What are the typical findings for this disease?

Potassium is the predominant intracellular cation. Normal serum potassium levels are between 3.5 and 5.5 mEq/L. This is much less than intracellular levels that range between 140 and 150 mEq/L. The distribution of potassium levels across cellular membranes helps determine the resting membrane potential as well as the timing of membrane depolarization. Therefore, organ systems largely dependent on membrane depolarization for function are most affected by changes in serum potassium levels.

In hypokalemia, the resting membrane potential is increased. Both action potentials and refractory periods are prolonged. Symptoms do not generally develop unless potassium levels are less than 3.0 mEq/L. The following signs and symptoms should raise the concern for hypokalemia:

Cardiac manifestations:

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  • -T wave flattening

  • -ST depression

  • -Appearance of U wave

  • -Arrhythmias

Skeletal and smooth muscle manifestations:

  • -Hypotonia and muscle weakness

  • -Respiratory depression

  • -Muscle cramps

  • -Constipation and/or ileus

  • -Rhabdomyolysis and myoglobinuria

In hyperkalemia, the resting membrane potential is decreased, and the membrane becomes partially depolarized. Initially, this increases membrane excitability. However, with prolonged depolarization, the cell membrane will become more refractory and less likely to fully depolarize. The following signs and symptoms should raise the concern for hyperkalemia:

Cardiac manifestations:

  • -Peaked T waves

  • -Shortened QT interval

  • -Prolonged PR interval

  • -Flattening of P wave

  • -Widened QRS interval

  • -Bundle branch and atrioventricular conduction blocks

  • -Arrhythmias

Skeletal muscle manifestations:

  • -Ascending muscle weakness

  • -Flaccid paralysis

What caused this disease to develop at this time?

The causes of both hypokalemia and hyperkalemia can be classified into causes related to changes in intake, changes in excretion, and shifts between the intracellular and extracellular spaces.

Causes of Hypokalemia:

Decreased Intake: Daily potassium intake is 2 to 4 mEq/Kg/day up to 40-120 mEq/day in adults. Because the kidneys are able to significantly limit the excretion of potassium, hypokalemia rarely develops exclusively from decreased potassium intake.

Increased Urinary Excretion:

Increased mineralocorticoid activity: Aldosterone increases urinary sodium reabsorption, thereby promoting passive excretion of potassium into the urine.

Polyuria: While the kidneys are generally able to reduce potassium concentrations to 5 to 10 mEq/L, high urine output may still lead to excessive potassium losses.

Diuretics: Loop diuretics, thiazides, and carbonic anhydrase inhibitors can all cause urinary potassium loss.

Metabolic alkalosis: States that lead to increased bicarbonate and therefore increased delivery of bicarbonate to the distal tubules can lead to passive excretion of potassium.

Renal Tubular Acidosis (RTA): RTA leads to shifting of potassium from the intracellular to the extracellular space and resultant total body depletion of potassium even when serum potassium levels may remain normal. Once treatment is begun with bicarbonate replacement, the true hypokalemic state may be realized as increased bicarbonate delivery to the distal tubules will lead to increased excretion of potassium.

Hypomagnesemia: While mechanisms are unclear, hypomagnesemia alone can cause increased potassium loss in the urine.

Bartter Syndrome: Bartter syndrome is an autosomal recessive condition leading to failure to thrive, developmental delay, increased renin levels, hypokalemia and alkalosis. In Bartter syndrome, there is impaired sodium chloride absorption in the ascending limb of the loop of Henle.

Gitelman Syndrome: Gitelman syndrome is a genetic condition characterized by mutations in the thiazide sensitive sodium chloride co-transporter. The syndrome leads to electrolyte wasting of sodium, potassium, chloride and magnesium. Unlike Bartter syndrome, there is generally not growth failure or developmental delay.

Increased Losses other than urinary:

Potassium levels in stool can range between 10 and 80 mEq/L. Prolonged or severe diarrhea can lead to clinically significant potassium losses and hypokalemia.

Sweat: Potassium levels are 5 to 10 mEq/L in sweat. Circumstances that can lead to clinically significant potassium losses from sweat include very hot environments, strenuous exercise, and cystic fibrosis.

Shifting of potassium into the intracellular space:

Alkalosis: With the rise in serum pH, intracellular hydrogen ions will pass into the extracellular fluid in order to minimize the extracellular increase in pH. To maintain electroneutrality, potassium ions will enter the intracellular space to replace the exiting hydrogen ions.

Insulin: Insulin increases the transport of potassium into skeletal muscle and hepatocytes.

Beta-adrenergic activity: Both endogenous and exogenous catecholamines can increase the transport of potassium into cells. Aerosolized albuterol therapy for asthma exacerbations is a common cause of mild hypokalemia in children, although this rarely leads to clinical significance.

Hypokalemic periodic paralysis: A rare genetic disorder that is characterized by sudden and rapid shifts of potassium into cells, leading to very low serum potassium levels. Attacks are manifested by muscular weakness or generalized paralysis that lasts less than 24hrs.

Causes of Hyperkalemia:

Decreased Urinary Excretion:

Renal Failure: Impaired potassium regulation and excretion most often arises in oliguric states and when distal renal tubular flow is compromised.

Hypoaldosteronism: Low levels of aldosterone will result in increased sodium excretion and potassium retention.

Distal renal tubular acidosis: In type I RTA, impaired reabsorption of sodium will lead to decreased potassium excretion.

Other drugs: Spironolactone and ACE inhibitors both can decrease the renal excretion of potassium.

Shifting of potassium into the extracellular compartment:

Metabolic Acidosis: With the decrease in serum pH, extracellular hydrogen ions will pass into the intracellular fluid in order to minimize the extracellular decrease in pH. To maintain electroneutrality, potassium ions will leave the intracellular space to replace the entering hydrogen ions.

Beta-adrenergic Blockade: Nonselective beta-blockers can decrease the transport of potassium into cells.

Insulin: In diabetes, decreased insulin will lead to reduced transport of potassium into cells.

Increased Tissue Breakdown: Injuries and conditions that lead to cellular breakdown can increase serum potassium levels. Such conditions include crush injuries, rhabdomyolysis, and tumor lysis syndrome.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

  • Confirmation of hypokalemia and hyperkalemia is made by analysis of serum potassium levels.

    When serum potassium level results indicate hyperkalemia (serum potassium > 5.5 mEq/L), consideration must be taken for pseudohyperkalemia. Pseudohyperkalemia occurs when intracellular potassium is released into the serum at the site of the blood sampling. This will lead to a falsely elevated potassium level. The chances of this occurring are raised with increased trauma during venipuncture, hemolysis of the sample, use of a tourniquet, and drawing blood over a high resistance catheter or needle.

  • Other diagnostic studies that may help identify the underlying cause or guide management include:

    Basic metabolic panel: Helpful for identifying impaired renal function, aldosterone or cortisol derangements, and acid-base abnormalities.

    Serum Glucose: Hyperglycemia may suggest diabetes.

    EKG: Important in assessing clinical urgency of hyperkalemic states.

    Urinalysis: Can be helpful in identifying renal tubular acidosis, myoglobinuria or systemic hemolysis.

    CK: May be helpful if there is concern for rhabdomyolyisis.

    Serum magnesium level.

If you are able to confirm that the patient has hypokalemia or hyperkalemia, what treatment should be initiated?

  • If the patient has symptomatic paralysis or there are EKG changes consistent with hypokalemia, treatment should be initiated immediately. Intravenous potassium replacement should also be considered for serum potassium levels less than 2.5 to 3.0 mEq/L.

    Intravenous potassium chloride replacement should be started at 0.5mEq/Kg in non-dextrose containing fluid given over 1 to 2 hours (up to 10 to 20 mEq/hr).

    Caution must be taken when replacing potassium in renal disease. Aggressive intravenous replacement should be avoided unless hypokalemia is severe (<2.5 mEq/L) or resulting in EKG changes or paralysis. If replacement is needed, consideration should be given to administering a smaller replacement (0.25 to 0.5 mEq/Kg) over 1 to 2 hours.

    Replacement may need to be at higher doses (1 mEq/Kg) over 1 hour if the patient is on digoxin or has a cardiac condition predisposing to arrhythmias.

    Intravenous replacement should be given through a central venous catheter or multiple peripheral intravenous catheters since potassium infusions greater than 0.5mEq/Kg/Hr can be very irritating to peripheral veins.

    The patient should be closely followed during treatment with cardiorespiratory monitoring.

    Repeat serum potassium levels should be evaluated after each replacement (initially every 2 to 4hrs). If there is not a significant response to the initial replacements, a magnesium level should be evaluated as hypomagnesemia may be contributing to an intractable hypokalemic state.

  • If the patient does not have EKG changes or clinical manifestations of hypokalemia, and the serum potassium level is 3 mEq/L to 3.5 mEq/L, it is generally safe to treat hypokalemia through enteral replacements or through maintenance intravenous fluid solutions.

    If the patient is not critically ill, does not have symptoms of hypokalemia, and has no reason for ongoing potassium losses, mild hypokalemia is likely to self-resolve simply by ensuring adequate potassium intake in diet. Providing 2 to 3 mEq/Kg/Day (up to 20mEq per dose) of enteral KCl divided into 2 to 4 doses is usually all that is necessary to correct mild hypokalemia. Enteral replacement is less likely to lead to overtreatment and resultant hyperkalemia, and should always be considered if there is no urgency for treating mild hypokalemia.

    If the patient is on parenteral fluids, replacement may be provided initially by adding potassium to the parenteral fluids at 20 to 30mEq/L if the fluids are infusing at maintenance needs. It is generally not necessary to exceed these concentrations under normal circumstances for mild hypokalemia.

    If there are ongoing losses, scheduled enteral KCl replacement may need to be continued at a dose that is based on calculated losses estimated.

  • Some circumstances may need consideration for ongoing potassium losses. These situations include: treatment of diabetic ketoacidosis, polyuric states such as diabetes insipidus, or severe diarrhea.

    Diabetic Ketoacidosis: In diabetic ketoacidosis, total body potassium levels are depleted due to extracellular movement of serum potassium levels, and resultant increased renal excretion of potassium. Initially, serum potassium levels will be elevated on presentation. But once treatment with an insulin infusion is initiated, serum potassium levels will fall, and potassium replacement will often be necessary. Serum potassium levels should be monitored every 2 to 4 hours at the onset of treatment. Once serum potassium levels fall below 4.5 to 5.0 mEq/L, potassium is added to the intravenous fluid replacement solutions at about 40 mEq/L. The potassium added is generally a combination of potassium chloride and potassium phosphate divided evenly (20 mEq/L each). Potassium levels are continued to be monitored every 4 to 6 hrs depending on the response. Once the insulin infusion is complete, and the patient is stabilized out of diabetic ketoacidosis, further potassium replacement is not necessary provided the serum potassium level is normalized.

    Polyuria and diabetes insipidus: The kidneys are generally able to limit potassium excretion to 5 to 10mEq/L. This may lead to clinically significant potassium loss with high levels of urine output. Most of the time, close monitoring with potassium replacements as needed is sufficient. However, with very high levels of urine output, replacement fluids with potassium included at 10 mEq/L may be necessary.

    Diarrhea: Severe diarrhea may lead to profound potassium losses, where potassium concentrations in the stool can be as high as 10 to 80 mEq/L. If stool output is substantially large (>10ml/kg every 2 to 4 hours), stool replacement with IVF may be necessary. Including potassium in IVF replacement should be considered if above IV replacement strategies are unable to keep up with potassium losses.

  • If the serum potassium level is 6.0 to 6.5 mEq/L, obtain a 12 lead EKG.

    If there are no EKG changes, eliminate all potassium from diet and intravenous fluid replacement. If there are no risk factors for potassium levels to continue increasing (e.g. renal failure, rhabdomyolysis, acidosis), this is usually all that is needed. The patient should be followed on cardiorespiratory monitoring to watch for rhythm changes or changes in T waves. Repeat potassium levels should be performed at least every 12 to 24 hours to ensure resolution of hyperkalemia.

    If there are risk factors for potassium levels to continue increasing, such as in renal failure, additional measures should be taken to eliminate potassium. Begin Sodium polystyrene (Kayexalate) at 1g/Kg per dose (up to 15g PO, 30-50g PR in adults) every 6hrs PO or every 2 to 4hrs PR. Recheck serum potassium levels every 6 hrs or sooner if there signs of EKG changes on cardiorespiratory monitoring.

    If the serum potassium level is greater than 6.5 mEq/L, or there are EKG changes, more aggressive management is indicated.

    Administer Calcium gluconate 100mg/kg (max: 3g/dose) IV peripherally over 3 to 5 minutes or Calcium chloride 10 mg/kg (max: 1g/dose) IV centrally over 1 to 5 minutes to stabilize cardiac membrane and reduce risk of further arrhythmias.

    If EKG changes improve, but do not normalize, may repeat calcium infusion in 10 minutes. Expect that EKG changes will return in 15 to 30 minutes if other measures are not taken to reduce serum potassium levels quickly.

    Administer sodium bicarbonate 1 to 2 mEq/Kg (max: 50-100 mEq/dose) IV over 5 to 10 minutes. Do not administer with calcium gluconate as is not compatible. Flush IV well between infusions.

    Administer insulin 0.1U/Kg combined with 2ml/Kg of D25W (0.5g/Kg/dose) infused over 30 minutes. May repeat dose 30 to 60 minutes after first dose. Monitor glucose hourly. May also consider infusion of insulin at 0.1U/Kg/Hr with D25W at 1 to 2 ml/Kg/hr if hyperkalemia persists.

    Administer sodium polystyrene as described above.

    Hemodialysis should be considered if EKG changes continue with refractory hyperkalemia or hyperkalemia remains severe (>7 mEq/L).

What are the adverse effects associated with each treatment option?


The most important adverse effect for the management of hypokalemia is overtreatment and iatrogenic hyperkalemia. To avoid this, one must carefully consider the urgency of treating hypokalemia, risk factors for an overresponse to intravenous replacement (e.g., rhabdomyolysis, renal failure), and if intravenous therapy is truly needed over the generally safer enteral therapy.


Calcium chloride or Calcium gluconate: Can cause ventricular arrhythmia and cardiac arrest if given too fast. Calcium solutions must be given slowly over 3 to 5 minutes. Calcium chloride replacement is contraindicated in ventricular fibrillation. Both calcium solutions can cause significant tissue necrosis if extravasated. Do not use Calcium chloride peripherally. Ensure the peripheral IV is working properly and is not infiltrated prior to administration.

Sodium bicarbonate: Can cause hypernatremia, hypokalemia, hypocalcemia, and hypomagnesemia. Can also cause tissue necrosis with extravasation. In infants and neonates, use 4.2% solution and lengthening infusion time as 8.4% solution is very hyperosmolar and may not be tolerated.

Insulin and glucose: Can cause hypoglycemia or hyperglycemia. Blood sugars should be checked after each dose, or hourly if on infusion.

Sodium polystyrene: Can cause iatrogenic hypokalemia requiring potassium replacements if too much is given. Can also cause hypernatremia, hypocalcemia, and hypomagnesemia. There have been reports of colonic necrosis, gastrointestinal bleeding, colitis and perforation when used with sorbitol in patients with underlying gastrointestinal risk factors. Use with caution in patients with prematurity or evidence of gastrointestinal compromise.

Hemodialysis: Carries substantial risks from both the procedure of intermittent hemodialysis as well as the procedure of catheter placement necessary for performing dialysis. Should be used as last resort if above treatments fail.

What are the possible outcomes of hypokalemia and hyperkalemia?

If left untreated, both severe hypokalemia and severe hyperkalemia can lead to paralysis, cardiac arrhythmias, and cardiac arrest. Hyperkalemia, generally carries a higher risk of morbidity and mortality if left untreated. Severe hypokalemia may also cause respiratory failure, constipation and ileus.

How can hypokalemia or hyperkalemia be prevented?

The most important aspect of prevention is consideration of comorbidities or medical therapies that may increase or decrease serum potassium levels, and then adjusting potassium intake as necessary.

To prevent hypokalemia, consider adding enteral potassium replacement to patients on a substantial amount of diuretics, patients with diarrhea or polyuria, or patients who may have heightened mineralocorticoid activity. Also consider replacement of magnesium sulfate in conditions that can cause depletion of magnesium.

To prevent hyperkalemia, consider restricting potassium replacement or eliminating potassium from intake in patients with renal disease, anuria, on ACE inhibitors, or with conditions with increased tissue breakdown such as rhabdomyolysis, burn injuries or crush injuries.

What is the evidence?

Aune, GJ, Custer, Rau. “Fluids and Electrolytes”. (A practical outline for managing fluid and electrolye disorders in children.)

Wood, EG, Lynch, RE, Fuhrman, Zimmerman. “Electrolyte management in pediatric critical illness”. (A practical outline for managing fluid and electrolye disorders in children.)

Kelly, A, Moshang, T, Nichols, DG. “Disorders of Water, Sodium, and Potassium Homeostasis”. (A general review of fluid and electrolyte physiology, derangements and management.)