Hyperkalemia refers to excess potassium in the serum or plasma with potassium ion concentration greater than the upper limit of normal. The normal concentration of potassium in the serum ranges between 3.5-5.2 mEq/L with slight reference range variability among different clinical laboratories. Hyperkalemia is a common occurrence in hospitalized patients, ranging from 1-10% of patients in the hospital.
II. Potassium Homeostasis
Potassium is a major intracellular cation with 98% of total body potassium being intracellular and only 2% being extracellular. For example, a 70kg person has roughly 4200 mEq of intracellular potassium and only 60 mEq of extracellular potassium. Maintaining a close degree of homeostasis between intracellular and extracellular potassium concentrations is crucial for normal function of all cells in the body including nerve cells, cardiac cells and muscle cells. The kidneys play a major role in maintaining this homeostasis; 90% of ingested potassium is excreted in the urine while the other 10% is excreted in the GI tract.
In the kidneys, potassium excretion is achieved though active secretion in the distal collecting ducts. The increase in serum potassium concentration leads to release of aldosterone from the adrenal glands. Aldosterone increases the number of sodium channels in the principal cell of distal collecting ducts and leads to direct reabsorption of sodium and indirect secretion of potassium in order to maintain the electrochemical gradient. Through this mechanism, the kidneys are able to maintain homeostasis by matching intake of potassium with active secretion of potassium.
III. Mechanisms of Hyperkalemia
A. Increased Potassium Intake:
Average adult daily potassium intake in the United States varies from 60mEq to 120 mEq per day. In patients with normal kidney function, this level of intake does not cause hyperkalemia since the kidneys are able to match the increased consumption of potassium with increased urinary excretion of potassium. However, patients with renal impairment, including those with advanced CKD and ESRD, are not able to increase their urinary excretion of potassium and are more prone to developing hyperkalemia with increased dietary intake of potassium. Examples of foods with high potassium content include an average size banana, which contains approximately 10 mEq of potassium, and 1 cup of orange juice, which contains approximately 12 mEq of potassium. Therefore, patients with advanced CKD or ESRD should receive regular counselling on minimizing high potassium diet to avoid hyperkalemia.
Patients who are on diuretics and take potassium supplementation to avoid hypokalemia are also at risk for developing hyperkalemia if their kidney function worsens. These patients require regular monitoring of their kidney function.
B. Decreased Renal Excretion of Potassium:
Decreased urinary excretion of potassium results from either a decrease in GFR or impairment in mineralocorticoid activity. Patients who suffer for acute kidney injury or chronic kidney disease are at risk for developing hyperkalemia due to decrease in potassium filtration.
Since aldosterone is the main hormone responsible for potassium excretion through the kidneys, patients with aldosterone deficiency such as in Addison’s disease or hypoaldosteronism can experience hyperkalemia. However, most commonly, hyperkalemia results from introduction of medications that blocks the Renin-Angiotensin-Aldosterone System (RAAS). Examples of such medications include Angiotensin Converting Enzyme inhibitors (e.g., Lisinopril), Angiotensin Receptor Blockers (e.g., Losartan), Aldosterone Receptor Blockers (e.g., Spironolactone), ENaC Channel Blockers (e.g., Triamterene, Bactrim), and medications that interfere with the release of renin (e.g., Tacrolimus).
C. Transcellular Shift:
Potassium imbalance is found when intracellular potassium moves to the extracellular fluid. Because 98% of total body potassium is intracellular, even small shifts in potassium can elevate extracellular levels. One example can be found in conditions that lower blood pH. The excess hydrogen ions associated with an acidotic environment move into cells causing potassium to move out of the cells into the extracellular space. Another example of transcellular shift happens in patients with hyperglycemia or decreased body insulin. Insulin normally increases the activity of Na-K ATPase which promotes net potassium entry into cells; therefore, insulin deficiency causes hyperkalemia by decreasing the activity of this pump.
Finally, since cells are the major reservoir of potassium ions, direct cell injury, such as seen in hemolysis, rhabdomyolysis, or tumor lysis syndrome, can lead to a significant shift of potassium out of cells and cause significant hyperkalemia.
Pseudohyperkalemia refers to rise in extracellular potassium that occurs either during blood collection or after blood is drawn and therefore is not reflective of true serum potassium levels. The most common scenario occurs when a specimen is hemolyzed during venipuncture. Prolonged clenching of fist during blood drawing can also falsely elevate extracellular potassium levels. Finally, blood from patients with thrombocytosis can exhibit artifactual hyperkalemia. In this instance potassium moves out of cells after clotting has occurred in the collection tubes.
IV. Diagnostic Approach
A. Diagnostic approach to a patient with this problem
After finding hyperkalemia, return to your history, physical, and labs for clues to the underlying etiology which will ultimately guide management.
1. Historical information important in the diagnosis of this problem.
Key questions to consider include: Does the patient have a history of advanced chronic kidney disease or ESRD? Is the patient on hemodialysis and recently missed any sessions? Does the patient have a new AKI? Was the patient recently started on any new medications or increased dose of medications that can cause hyperkalemia? As mentioned above, these include potassium supplements, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), and aldosterone antagonist. Other less common causes include beta blockers and non-steroidal antiinflammatory drugs (NSAIDS).
2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.
Hyperkalemia can be asymptomatic with little physical exam findings. Physical examination should focus on findings that may lead to the underlying cause. Physical examination findings in hyperkalemia can be divided into three main categories: cardiovascular, neurological, and musculoskeletal:
Cardiovascular findings include bradycardia, tachycardia, premature beats, sinus pauses, conduction blocks and other cardiac arrhythmias including ventricular tachycardia and ventricular fibrillation.
Neurologic findings include decreased deep tendon reflexes.
Musculoskeletal findings include global decreased muscle strength or ascending flaccid paralysis. A focal weakness should prompt looking for a different diagnosis.
3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.
Other labs to focus on include the bicarbonate level which will help in assessing for acidosis as a potential cause for hyperkalemia through transmembrane shift. If acidemia is suspected, obtaining arterial or blood gas sampling may be useful.
All patients with hyperkalemia should receive an electrocardiogram (EKG) as the findings will help guide the urgency of treatment. Patients with EKG findings attributable to hyperkalemia should be placed on continuous telemetry monitoring.
EKG changes seen with hyperkalemia include peaked T Waves, widening of QRS duration, prolongation and then finally loss of P waves with a sinusoidal pattern. Peaked T waves start to be seen with a potassium above 6.0. QRS changes are seen when potassium reaches 8.0 or above.
B. Criteria for admission to the hospital include:
Severe hyperkalemia with K > 6.0 mEq/L
EKG changes consistent with hyperkalemia
Worsening renal dysfunction
Serious comorbid conditions (e.g., cellulitis)
C. Over-utilized or "wasted" diagnostic tests associated with the evaluation of this problem.
Be careful when evaluating a patient for hyperkalemia to exclude artifactual hyperkalemia due to hemolysis. Hemolysis of a blood specimen can falsely elevate the potassium concentration. Causes of hemolysis include thrombocytosis, leukocytosis, and mechanical breakdown (tight tourniquet, tube shaking).
V. Management of Hyperkalemia
The urgency to treat hyperkalemia depends on the cause and on the associated signs and symptoms. The first thing to consider prior to treatment of hyperkalemia is whether there are associated EKG changes, which will necessitate emergent treatment. At the same time, it will be important to figure out if hyperkalemia is the result of excess total body potassium or the result of transcellular shift since treatment can be different for each of these etiologies.
While the diagnostic process is proceeding, treatment needs to be triaged into three categories. These categories include protecting the heart, driving potassium into cells, and finally eliminating it from the body.
A. Stabilizing the cardiac membrane
If there are EKG changes suggestive of hyperkalemia then the initial treatment should focus on protecting the heart to treat and potentially prevent lethal arrhythmias. The main treatment is iv calcium. Calcium’s role in treating hyperkalemia is mainly to stabilize the cardiac membrane. It does not have any effect on serum concentration of potassium. Calcium can be give as iv calcium chloride or iv calcium gluconate. The recommended dose of iv calcium chloride is 1g infused over 5 minutes to prevent vein irritation. The recommended dose of iv calcium gluconate is 2g infused over 5 minutes. If EKG changes persist despite receiving iv calcium chloride or iv calcium gluconate then the dose can be repeated every 5-10 minutes. It is also important to keep in mind that the duration of action of these medications is only 30 to 60 minutes; therefore a repeat EKG should be obtained every 1 hour to make sure EKG changes do not recur after initial treatment.
B. Shifting potassium into cells
The next step in treating hyperkalemia involves driving excess potassium into the cells. This is especially true if hyperkalemia is being caused by transmembrane shift, such as in case of diabetic ketoacidosis or similar conditions. This can be accomplished by giving insulin and activating Na-K ATPase. Insulin should be given with glucose to prevent hypoglycemia, unless the patient has significant hyperglycemia with finger sticks greater than 250mg/dl. The usual dose is 10 units of regular insulin with 1 amp of D50 given over 5 minutes. The effect should be seen in around 15-30 minutes and lasts for 4-6 hours. Patients should be monitored for hypoglycemia.
Albuterol treatments including nebulized albuterol also increase the uptake of potassium into cells by increasing activity of Na-K ATPase. Patients should receive 20mg of nebulized albuterol in order to effectively lower potassium levels. This dose is four to eight times more than the dose normally given to patients with COPD or asthma exacerbations. The onset for nebulized albuterol is also around 30 minutes and last 2-3 hours.
Sodium bicarbonate also increases the transmembrane shift of potassium into cells. Its onset is quicker but only lasts for 30-45 minutes. The usually dose is 50mEq (1 amp) over 5 minutes. Sodium bicarbonate is more effective with an acidotic environment. The data on routine use of sodium bicarbonate for treatment of hyperkalemia is lacking. Most often it is used if patients have severe acidemia as the cause of their hyperkalemia.
C. Eliminating potassium from the body
The last step in treating hyperkalemia is elimination from the body. These treatments should be reserved for hyperkalemia in the setting of true total body excess. Eliminating potassium from the body can be done by diuretics, intravenous fluids, exchange resins, and dialysis. Diuretics increase distal delivery of water and sodium in the distal collecting ducts, which indirectly results in urinary potassium excretion. Loop diuretics are the most effective; furosemide, bumetanide, and torsemide are loop diuretics that are effective in increasing potassium excretion. Dose should be based on kidney function, where the higher the creatinine, the higher the dose needed. However, if a patient is on dialysis and does not make urine, this treatment would be ineffective. Additionally if the cause of the hyperkalemia is pre-renal AKI then diuretics should not be used. Hyperkalemia in this scenario can be treated with administration of intravenous normal saline, which similarly to diuretics will increase urinary flow of water as well as distal delivery of sodium and therefore increase active secretion of potassium. In other instances of hyperkalemia, such as those caused by active hemolysis or tumor lysis syndrome, diuretics and intravenous normal saline can be used simultaneously to help in potassium excretion.
Sodium polystyrene sulfonate (Kayexalate) exchanges sodium for potassium in the colon. Kayexalate should only be used when there is a total body excess of potassium in the body. The usual dose is 15-30g given orally. The onset on action varies from 4-6 hours. Multiple doses may be required in order to decrease serum potassium.
The gold standard for definitive treatment for hyperkalemia is hemodialysis. Hemodialysis should be reserved for acute life-threatening hyperkalemia that has not responded to other measures. Hyperkalemia is also an indication for hemodialysis in patients who present with progressive AKI and oliguria that does not quickly reverse with above measures or with the treatment of the underlying cause.
D. Common Pitfalls and Side-Effects of Management of this Clinical Problem
Several points not to be missed when dealing with hyperkalemia:
Be cautious of IV calcium in the setting of digitalis toxicity. IV calcium increases the effects of digitalis as well as its unwanted side effects.
Kayexalate can increase total body sodium levels and lead to volume overload.
As discussed above, hyperkalemia is very common in hospitalized patients, especially in those patients with CKD who may not be adherent with low potassium diet or in patients taking RAAS blockade medications. Unfortunately, hyperkalemia places significant constraints on the use of ACEi, ARBs, and aldosterone antagonists in patients with baseline hyperkalemia despite their overall mortality benefits. Most of the current treatments mentioned above for treatment of acute hyperkalemia have short duration of action and limited evidence for their use. For example, use of insulin and dextrose along with use of albuterol is indicated as temporizing measure for treatment of hyperkalemia with effects lasting for only a few hours. Additionally, repeated use of such medications on the same patient can introduce adverse side effects. Use of Kayexalate on the other hand is based on anecdotal evidence or very small observational studies. Kayexalate has also been shown to cause intestinal necrosis in select group of patients, especially those with intestinal obstruction, ileus or recent abdominal surgeries. Therefore, use of Kayexalate for patients with these conditions is discouraged.
Recently there have been trials on the use of very strong highly selective potassium trapping resins, which have been very effective in lowering serum potassium levels without significant adverse events although long term safety data is lacking. Sodium Zirconium Cyclosilicate (ZS-9) and Patiromer in randomized controlled trials were shown to be effective in lowering serum potassium levels by as much as 1 mEq/l in patients with advanced CKD who were also taking RAAS blockade medications. So far, these randomized controlled trials have been limited to the ambulatory settings. However, given the steepest decline in potassium concentration in these trials happened within the first few hours of receiving these medications, these medications have the potential for use in the inpatient setting. If the results of the prior trials are confirmed in hospitalized patients, these medications will be of value for the acute treatment of hyperkalemia.
Giebisch, GH,, Wang, WH.. “Potassium transport–an update.”. J Nephrol. vol. 16. 2010. pp. S97
Kovesdy,, C.P.. “Management of hyperkalemia in chronic kidney disease.”. Nat Rev Nephrol.. vol. 10. 2014. pp. 653-662.
Fordjour,, K. N.,, Walton,, T. &, Doran,, J. J.. “Management of hyperkalemia in hospitalized patients.”. Am. J. Med. Sci.. vol. 347,. pp. 93-100.
Montague, BT,, Ouellette, JR,, Buller, GK.. “Retrospective review of the frequency of ECG changes in hyperkalemia.”. Clin J Am Soc Nephrol. vol. 3. 2008. pp. 324
Allon, M,, Copkney, C.. “Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients.”. Kidney Int. vol. 38. 1990. pp. 869
Watson,, M. A.. “Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study.”. Am. J. Kidney Dis.. vol. 60. 2012. pp. 409-416.
Packham, DK,, Rasmussen, HS,, Lavin, PT. “Sodium zirconium cyclosilicate in hyperkalemia.”. N Engl J Med. vol. 372. 2015. pp. 222
Weir, MR,, Bakris, GL,, Bushinsky, DA,. “Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors.”. N Engl J Med. vol. 372. 2015. pp. 211
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- I. Definition
- II. Potassium Homeostasis
- III. Mechanisms of Hyperkalemia
- A. Increased Potassium Intake:
- B. Decreased Renal Excretion of Potassium:
- C. Transcellular Shift:
- D. Pseudohyperkalemia:
- IV. Diagnostic Approach
- A. Diagnostic approach to a patient with this problem
- 1. Historical information important in the diagnosis of this problem.
- 2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.
- 3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.
- B. Criteria for admission to the hospital include:
- C. Over-utilized or "wasted" diagnostic tests associated with the evaluation of this problem.
- V. Management of Hyperkalemia
- A. Stabilizing the cardiac membrane
- B. Shifting potassium into cells
- C. Eliminating potassium from the body
- D. Common Pitfalls and Side-Effects of Management of this Clinical Problem