fbpx

Hyperkalemia

Updated : January 12, 2024





Background

Hyperkalemia is a condition that occurs when the levels of potassium in the blood rise above normal levels, typically greater than 5.5 mEq/L. Mild hyperkalemia may not have noticeable symptoms, high potassium levels can cause serious complications such as paralysis, life-threatening cardiac arrhythmias, or muscle weakness, The symptoms of hyperkalemia usually appear when potassium levels reach 6.5-7 mEq/L, but the rate at which potassium levels increase is also an important factor to consider. Infants tend to have higher baseline potassium levels compared to adults.

It is important to note that pseudohyperkalemia, a misleading elevation in evaluated potassium levels due to specimen collection or handling is quite common. Therefore, hyperkalemia should always be confirmed through additional tests before aggressive treatment is initiated in cases where serum potassium levels are elevated without any clear explanation. True hyperkalemia can be caused by several factors, such as increased potassium intake, the progress of intracellular potassium into the extracellular space, or diminished renal excretion.

The necessity of treatment depends on several factors, including the presence of symptoms, serum potassium levels, and the underlying causes of hyperkalemia. Patients with chronic hyperkalemia may not experience symptoms even at increased levels, while those with sudden, acute potassium shifts may experience severe symptoms even at lower levels. Treatment for hyperkalemia typically involves identifying and addressing the underlying cause and may include medications to lower potassium levels or other interventions, such as dialysis in severe cases.

Epidemiology

Hyperkalemia is a condition where there is an excessive level of potassium in the blood. It is a relatively uncommon condition in the general population, affecting less than 5% of people worldwide. However, in hospitalized patients, it may affect up to 10% of patients due to factors such as medications and renal insufficiency. Other significant causes of hyperkalemia in inpatients include diabetes, malignancy, extremes of age, and acidosis.

In contrast, hyperkalemia is rare in children, but premature infants may experience it in up to 50% of cases. Interestingly, hyperkalemia is more commonly reported in men than women, likely due to increased muscle mass and higher rates of rhabdomyolysis, and the prevalence of the neuromuscular disease. Other risk factors for hyperkalemia include non-Black patients and older age.

However, the empirical use of ACE inhibitors is a significant risk factor for hyperkalemia, especially in high-risk populations such as individuals with diabetes, heart failure, and peripheral vascular disease. This is a cause for concern, as hyperkalemia can have severe consequences, including arrhythmias and cardiac arrest. Therefore, it is essential to monitor the potassium levels of patients taking ACE inhibitors, especially in high-risk populations.

Anatomy

Pathophysiology

Potassium is an important mineral for maintaining various physiological processes, including the normal functioning of the heart, kidneys, and other organs. In healthy individuals, most potassium is stored within the cells, with only a small amount in the extracellular fluid. The sodium-potassium pump maintains this intracellular/extracellular potassium balance by pumping sodium out of and potassium into the cell in a 3:2 ratio. This results in an intracellular potassium concentration of approximately 140 mEq/L, much higher than the extracellular concentration of 4-5 mEq/L.

The kidneys play a vital role in regulating potassium levels in the body. Most of the potassium in the body is excreted through the urine, with about 10% eliminated through sweat and stool. The kidneys’ distal convoluted and cortical collecting ducts are responsible for excreting potassium. The amount of potassium excreted by the kidneys is influenced by several factors, including aldosterone, diuretics, WNK1 and WNK4, high serum potassium levels, and high urine flow (osmotic diuresis), and the presence of negative ions in the distal tubule (bicarbonate).

Aldosterone regulates the excretion of potassium and sodium in the kidneys. It promotes sodium excretion and potassium retention, leading to increased potassium levels in the body. Conversely, when aldosterone levels are low, potassium excretion is reduced, leading to higher serum potassium levels. Diuretics are medications that increase urine output by promoting sodium excretion in the distal tubule of the kidneys. This increased delivery of sodium to the distal tubule leads to increased potassium excretion, which can lead to low potassium levels in the body.

WNK1 and WNK4 are kinases that regulate potassium excretion in the distal tubule. These kinases play a crucial role in regulating potassium homeostasis, and mutations in these genes can lead to various kidney disorders. High levels of serum potassium can stimulate the release of aldosterone, leading to increased potassium excretion in the kidneys. High urine flow, also known as osmotic diuresis, can increase kidney potassium excretion. Finally, negative ions such as bicarbonate in the distal tubule can also influence potassium excretion. The negative charge of bicarbonate can attract positively charged potassium ions, leading to increased potassium excretion.

Etiology

Hyperkalemia refers to a condition where there is an unusually high level of potassium in the bloodstream. Pseudohyperkalemia, a common cause of hyperkalemia, occurs due to the breakdown of red blood cells during blood sampling, which releases potassium into the serum. This can happen more frequently when a syringe is used instead of a vacuum device or when excessive pressure is applied during blood collection. Patients with high levels of white blood cells or platelets can also experience a false elevation of potassium levels.

In individuals with normal kidney function, high potassium intake from food is not a common cause of hyperkalemia, but it can be a concern for people with kidney disease. Patients with severe kidney disease or medications that can cause hyperkalemia should avoid consuming foods such as dried fruits, nuts, seaweed, avocados, spinach, and red meat. Hyperkalemia can also result from cellular damage, such as rhabdomyolysis from excessive exercise or crush injury, which can cause potassium to move from the cells into the bloodstream.

Metabolic acidosis resulting from dehydration or sepsis can also lead to hyperkalemia. Medications such as succinylcholine can cause an acute increase in potassium levels in patients with neuromuscular diseases. Tumor lysis syndrome, which occurs during chemotherapy for hematogenous malignancy, can also cause acute hyperkalemia due to the massive release of potassium from dying cancer cells. Chronic or acute kidney disease is a common cause of hyperkalemia.

Reduced filtration rates and primary renal dysfunction can contribute to this condition. Other factors such as dehydration, bleeding, cirrhosis, or heart failure can lead to acute volume depletion and hyperkalemia. In addition, aldosterone deficiency or insensitivity can cause hyperkalemia due to tubular dysfunction. Finally, hyperkalemic periodic paralysis is an inherited condition that can cause potassium to move from the cells into the bloodstream due to compromised skeletal muscle function.

Genetics

Prognostic Factors

Patients with mild transient hyperkalemia have a positive outcome if the underlying cause is identified and treated appropriately. However, suppose hyperkalemia unexpectedly occurs and reaches critical levels.

In that case, it can result in potentially fatal cardiac arrhythmias, which can prove lethal in nearly two-thirds of cases if not promptly managed. It is important to note that hyperkalemia is a risk factor for mortality among patients admitted to the hospital.

Clinical History

Clinical History

Hyperkalemia is a condition in which there is a higher-than-normal level of potassium in the blood. Most patients with mild to moderate hyperkalemia may not show any noticeable symptoms. It is usually detected during routine screening or laboratory tests for patients with suspected electrolyte imbalances due to dehydration, infection, or hypoperfusion.

Hyperkalemia can be caused by factors such as renal disease, diabetes, chemotherapy, major trauma, crush injury, or muscle pain suggestive of rhabdomyolysis. Certain medications can also contribute to the development of hyperkalemia, including potassium-sparing diuretics, NSAIDs, ACE inhibitors, potassium penicillin, succinylcholine, or recent intravenous potassium administration.

Symptoms of hyperkalemia may include fatigue, palpitations, or syncope. However, these symptoms may not always be present or nonspecific, making it difficult to diagnose hyperkalemia based on clinical symptoms alone.

Physical Examination

Physical Examination

During a physical examination, doctors can observe certain signs indicating a patient’s health condition. For example, the renal disease can be indicated by hypertension and edema, while hypoperfusion can be seen through pale skin or reduced capillary refill time. Conditions like rhabdomyolysis and hemolytic disorders can also be identified by observing muscle tenderness and jaundice.

In some cases, physical examination findings may reveal vague symptoms such as muscle weakness, fatigue, or depression. Cardiac examinations may reveal pauses, extrasystoles, or bradycardia in patients with respiratory muscle weakness due to tachypnea or heart block. In severe cases, patients may exhibit skeletal muscle weakness, depressed deep tendon reflexes, or flaccid paralysis.

It should be noted that physical examination results alone may not provide a definite diagnosis. However, they can assist in determining the cause of hyperkalemia or identifying potential causes of muscle tenderness accompanying muscle weakness, such as rhabdomyolysis. Similarly, ileus patients may exhibit hypoactive or absent bowel sounds, which can aid in diagnosis.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential Diagnoses

  • Acute tubular necrosis
  • Head trauma
  • Congenital adrenal hyperplasia
  • Hypocalcemia
  • Metabolic acidosis
  • Thermal burns
  • Tumor lysis sundrome

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Managing hyperkalemia depends on various factors, including the rate of onset, serum potassium levels, symptoms, and underlying causes. If a patient has a neuromuscular weakness, paralysis, or ECG changes with potassium levels exceeding 5.5 mEq/L, confirmed hyperkalemia of 6.5 mEq/L, or is at risk of ongoing hyperkalemia, prompt treatment is required.

The first-line approach to stabilize the cardiac response in hyperkalemia-related arrhythmias and ECG changes is calcium therapy, which does not impact potassium serum concentration but is critical in managing cardiac toxicity. Calcium gluconate is typically the initial drug of choice for patients with evidence of cardiac toxicity.

Albuterol, a beta-2 adrenergic agent, can cause a shift of potassium inside cells but requires higher doses than those typically used for bronchodilation to achieve this effect. For patients with metabolic acidosis, sodium bicarbonate infusion may be beneficial, but it is less effective in a bolus dose. Intravenous epinephrine should not be used to treat hyperkalemia since it could lead to angina.

Loop or thiazide diuretics may be prescribed to aid potassium excretion but should not be used alone for symptomatic patients. For hypervolemic patients with normal kidney function, intravenous furosemide is given every 12 hours or as a continuous infusion. An isotonic saline infusion may be necessary before administering intravenous furosemide every 12 hours or continuous furosemide infusion to euvolemic or hypovolemic patients with normal kidney function.

In hyperglycemic patients, administering insulin and glucose, or insulin alone can help move potassium back into cells, which lowers serum potassium levels. Close monitoring is necessary to detect the onset of hypoglycemia. A 10% dextrose infusion administered at 50 to 75 ml/hour is associated with a lower risk of hypoglycemia than administering D50 as a bolus dose.

by Stage

 

 

by Modality

 

 

Chemotherapy

 

 

Radiation Therapy

 

 

Surgical Interventions

 

 

Hormone Therapy

 

 

Immunotherapy

 

 

Hyperthermia

 

 

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

 

 

Palliative Care

 

 

Medication

 

 

 

dextrose 

25-50g along with 10 units of regular insulin intravenously for 30-60min



sodium bicarbonate 

Starting dose of 1 milliequivalent/kg intravenously once and adjust subsequent doses based on arterial blood pH and PaCO2 results, as well as base deficit calculation



calcium gluconate 

(Off-label)
1.5-3 gm intravenously infused for 2-5 minutes



sodium polystyrene sulfonate 


Indicated for Hyperkalemia
15 gm orally one time a day or two-four times a day
30 gm-50 gm through the rectal route four times a day
Lithium Overdose as Off-label
30 gm in sorbitol six times a day



instant glucose/intravenous dextrose 

(off-label use)
Administer dose of 25 to 50 g intravenously of dextrose over 5 minutes



 

insulin regular human 

0.1

unit/kg

Solution

Intravenous (IV)



sodium polystyrene sulfonate 


Indicated for Hyperkalemia
Oral route:
1 gm/kg orally four times a day as needed
Or
For lower doses, use the exchange ratio of the 1 mEq K+ to 1 gm of resin
Age <1 month
An oral dose is not recommended
rectal route:
1 gm/kg through the rectal route 4-12 times a day as needed
Or
For lower doses, use the exchange ratio of the 1 mEq K+ to 1 gm of resin



instant glucose/intravenous dextrose 

For Infants, Children, and Adolescents:
Administer dose of 0.5 to 1 g/kg intravenously combined with insulin over 15 to 30 minutes
Glucose tolerance test
For Children and Adolescents:
Take dose of 1.75 g/kg orally as a single dose
Maximum dose not more than 75 g and evaluate plasma glucose in two hours after dose



 

Media Gallary

References

 

 

Hyperkalemia

Updated : January 12, 2024




Hyperkalemia is a condition that occurs when the levels of potassium in the blood rise above normal levels, typically greater than 5.5 mEq/L. Mild hyperkalemia may not have noticeable symptoms, high potassium levels can cause serious complications such as paralysis, life-threatening cardiac arrhythmias, or muscle weakness, The symptoms of hyperkalemia usually appear when potassium levels reach 6.5-7 mEq/L, but the rate at which potassium levels increase is also an important factor to consider. Infants tend to have higher baseline potassium levels compared to adults.

It is important to note that pseudohyperkalemia, a misleading elevation in evaluated potassium levels due to specimen collection or handling is quite common. Therefore, hyperkalemia should always be confirmed through additional tests before aggressive treatment is initiated in cases where serum potassium levels are elevated without any clear explanation. True hyperkalemia can be caused by several factors, such as increased potassium intake, the progress of intracellular potassium into the extracellular space, or diminished renal excretion.

The necessity of treatment depends on several factors, including the presence of symptoms, serum potassium levels, and the underlying causes of hyperkalemia. Patients with chronic hyperkalemia may not experience symptoms even at increased levels, while those with sudden, acute potassium shifts may experience severe symptoms even at lower levels. Treatment for hyperkalemia typically involves identifying and addressing the underlying cause and may include medications to lower potassium levels or other interventions, such as dialysis in severe cases.

Hyperkalemia is a condition where there is an excessive level of potassium in the blood. It is a relatively uncommon condition in the general population, affecting less than 5% of people worldwide. However, in hospitalized patients, it may affect up to 10% of patients due to factors such as medications and renal insufficiency. Other significant causes of hyperkalemia in inpatients include diabetes, malignancy, extremes of age, and acidosis.

In contrast, hyperkalemia is rare in children, but premature infants may experience it in up to 50% of cases. Interestingly, hyperkalemia is more commonly reported in men than women, likely due to increased muscle mass and higher rates of rhabdomyolysis, and the prevalence of the neuromuscular disease. Other risk factors for hyperkalemia include non-Black patients and older age.

However, the empirical use of ACE inhibitors is a significant risk factor for hyperkalemia, especially in high-risk populations such as individuals with diabetes, heart failure, and peripheral vascular disease. This is a cause for concern, as hyperkalemia can have severe consequences, including arrhythmias and cardiac arrest. Therefore, it is essential to monitor the potassium levels of patients taking ACE inhibitors, especially in high-risk populations.

Potassium is an important mineral for maintaining various physiological processes, including the normal functioning of the heart, kidneys, and other organs. In healthy individuals, most potassium is stored within the cells, with only a small amount in the extracellular fluid. The sodium-potassium pump maintains this intracellular/extracellular potassium balance by pumping sodium out of and potassium into the cell in a 3:2 ratio. This results in an intracellular potassium concentration of approximately 140 mEq/L, much higher than the extracellular concentration of 4-5 mEq/L.

The kidneys play a vital role in regulating potassium levels in the body. Most of the potassium in the body is excreted through the urine, with about 10% eliminated through sweat and stool. The kidneys’ distal convoluted and cortical collecting ducts are responsible for excreting potassium. The amount of potassium excreted by the kidneys is influenced by several factors, including aldosterone, diuretics, WNK1 and WNK4, high serum potassium levels, and high urine flow (osmotic diuresis), and the presence of negative ions in the distal tubule (bicarbonate).

Aldosterone regulates the excretion of potassium and sodium in the kidneys. It promotes sodium excretion and potassium retention, leading to increased potassium levels in the body. Conversely, when aldosterone levels are low, potassium excretion is reduced, leading to higher serum potassium levels. Diuretics are medications that increase urine output by promoting sodium excretion in the distal tubule of the kidneys. This increased delivery of sodium to the distal tubule leads to increased potassium excretion, which can lead to low potassium levels in the body.

WNK1 and WNK4 are kinases that regulate potassium excretion in the distal tubule. These kinases play a crucial role in regulating potassium homeostasis, and mutations in these genes can lead to various kidney disorders. High levels of serum potassium can stimulate the release of aldosterone, leading to increased potassium excretion in the kidneys. High urine flow, also known as osmotic diuresis, can increase kidney potassium excretion. Finally, negative ions such as bicarbonate in the distal tubule can also influence potassium excretion. The negative charge of bicarbonate can attract positively charged potassium ions, leading to increased potassium excretion.

Hyperkalemia refers to a condition where there is an unusually high level of potassium in the bloodstream. Pseudohyperkalemia, a common cause of hyperkalemia, occurs due to the breakdown of red blood cells during blood sampling, which releases potassium into the serum. This can happen more frequently when a syringe is used instead of a vacuum device or when excessive pressure is applied during blood collection. Patients with high levels of white blood cells or platelets can also experience a false elevation of potassium levels.

In individuals with normal kidney function, high potassium intake from food is not a common cause of hyperkalemia, but it can be a concern for people with kidney disease. Patients with severe kidney disease or medications that can cause hyperkalemia should avoid consuming foods such as dried fruits, nuts, seaweed, avocados, spinach, and red meat. Hyperkalemia can also result from cellular damage, such as rhabdomyolysis from excessive exercise or crush injury, which can cause potassium to move from the cells into the bloodstream.

Metabolic acidosis resulting from dehydration or sepsis can also lead to hyperkalemia. Medications such as succinylcholine can cause an acute increase in potassium levels in patients with neuromuscular diseases. Tumor lysis syndrome, which occurs during chemotherapy for hematogenous malignancy, can also cause acute hyperkalemia due to the massive release of potassium from dying cancer cells. Chronic or acute kidney disease is a common cause of hyperkalemia.

Reduced filtration rates and primary renal dysfunction can contribute to this condition. Other factors such as dehydration, bleeding, cirrhosis, or heart failure can lead to acute volume depletion and hyperkalemia. In addition, aldosterone deficiency or insensitivity can cause hyperkalemia due to tubular dysfunction. Finally, hyperkalemic periodic paralysis is an inherited condition that can cause potassium to move from the cells into the bloodstream due to compromised skeletal muscle function.

Patients with mild transient hyperkalemia have a positive outcome if the underlying cause is identified and treated appropriately. However, suppose hyperkalemia unexpectedly occurs and reaches critical levels.

In that case, it can result in potentially fatal cardiac arrhythmias, which can prove lethal in nearly two-thirds of cases if not promptly managed. It is important to note that hyperkalemia is a risk factor for mortality among patients admitted to the hospital.

Clinical History

Hyperkalemia is a condition in which there is a higher-than-normal level of potassium in the blood. Most patients with mild to moderate hyperkalemia may not show any noticeable symptoms. It is usually detected during routine screening or laboratory tests for patients with suspected electrolyte imbalances due to dehydration, infection, or hypoperfusion.

Hyperkalemia can be caused by factors such as renal disease, diabetes, chemotherapy, major trauma, crush injury, or muscle pain suggestive of rhabdomyolysis. Certain medications can also contribute to the development of hyperkalemia, including potassium-sparing diuretics, NSAIDs, ACE inhibitors, potassium penicillin, succinylcholine, or recent intravenous potassium administration.

Symptoms of hyperkalemia may include fatigue, palpitations, or syncope. However, these symptoms may not always be present or nonspecific, making it difficult to diagnose hyperkalemia based on clinical symptoms alone.

Physical Examination

During a physical examination, doctors can observe certain signs indicating a patient’s health condition. For example, the renal disease can be indicated by hypertension and edema, while hypoperfusion can be seen through pale skin or reduced capillary refill time. Conditions like rhabdomyolysis and hemolytic disorders can also be identified by observing muscle tenderness and jaundice.

In some cases, physical examination findings may reveal vague symptoms such as muscle weakness, fatigue, or depression. Cardiac examinations may reveal pauses, extrasystoles, or bradycardia in patients with respiratory muscle weakness due to tachypnea or heart block. In severe cases, patients may exhibit skeletal muscle weakness, depressed deep tendon reflexes, or flaccid paralysis.

It should be noted that physical examination results alone may not provide a definite diagnosis. However, they can assist in determining the cause of hyperkalemia or identifying potential causes of muscle tenderness accompanying muscle weakness, such as rhabdomyolysis. Similarly, ileus patients may exhibit hypoactive or absent bowel sounds, which can aid in diagnosis.

Differential Diagnoses

  • Acute tubular necrosis
  • Head trauma
  • Congenital adrenal hyperplasia
  • Hypocalcemia
  • Metabolic acidosis
  • Thermal burns
  • Tumor lysis sundrome

Managing hyperkalemia depends on various factors, including the rate of onset, serum potassium levels, symptoms, and underlying causes. If a patient has a neuromuscular weakness, paralysis, or ECG changes with potassium levels exceeding 5.5 mEq/L, confirmed hyperkalemia of 6.5 mEq/L, or is at risk of ongoing hyperkalemia, prompt treatment is required.

The first-line approach to stabilize the cardiac response in hyperkalemia-related arrhythmias and ECG changes is calcium therapy, which does not impact potassium serum concentration but is critical in managing cardiac toxicity. Calcium gluconate is typically the initial drug of choice for patients with evidence of cardiac toxicity.

Albuterol, a beta-2 adrenergic agent, can cause a shift of potassium inside cells but requires higher doses than those typically used for bronchodilation to achieve this effect. For patients with metabolic acidosis, sodium bicarbonate infusion may be beneficial, but it is less effective in a bolus dose. Intravenous epinephrine should not be used to treat hyperkalemia since it could lead to angina.

Loop or thiazide diuretics may be prescribed to aid potassium excretion but should not be used alone for symptomatic patients. For hypervolemic patients with normal kidney function, intravenous furosemide is given every 12 hours or as a continuous infusion. An isotonic saline infusion may be necessary before administering intravenous furosemide every 12 hours or continuous furosemide infusion to euvolemic or hypovolemic patients with normal kidney function.

In hyperglycemic patients, administering insulin and glucose, or insulin alone can help move potassium back into cells, which lowers serum potassium levels. Close monitoring is necessary to detect the onset of hypoglycemia. A 10% dextrose infusion administered at 50 to 75 ml/hour is associated with a lower risk of hypoglycemia than administering D50 as a bolus dose.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

dextrose 

25-50g along with 10 units of regular insulin intravenously for 30-60min



sodium bicarbonate 

Starting dose of 1 milliequivalent/kg intravenously once and adjust subsequent doses based on arterial blood pH and PaCO2 results, as well as base deficit calculation



calcium gluconate 

(Off-label)
1.5-3 gm intravenously infused for 2-5 minutes



sodium polystyrene sulfonate 


Indicated for Hyperkalemia
15 gm orally one time a day or two-four times a day
30 gm-50 gm through the rectal route four times a day
Lithium Overdose as Off-label
30 gm in sorbitol six times a day



instant glucose/intravenous dextrose 

(off-label use)
Administer dose of 25 to 50 g intravenously of dextrose over 5 minutes



insulin regular human 

0.1

unit/kg

Solution

Intravenous (IV)



sodium polystyrene sulfonate 


Indicated for Hyperkalemia
Oral route:
1 gm/kg orally four times a day as needed
Or
For lower doses, use the exchange ratio of the 1 mEq K+ to 1 gm of resin
Age <1 month
An oral dose is not recommended
rectal route:
1 gm/kg through the rectal route 4-12 times a day as needed
Or
For lower doses, use the exchange ratio of the 1 mEq K+ to 1 gm of resin



instant glucose/intravenous dextrose 

For Infants, Children, and Adolescents:
Administer dose of 0.5 to 1 g/kg intravenously combined with insulin over 15 to 30 minutes
Glucose tolerance test
For Children and Adolescents:
Take dose of 1.75 g/kg orally as a single dose
Maximum dose not more than 75 g and evaluate plasma glucose in two hours after dose