Hyperkalemia

Hyperkalemia (high serum potassium) is a common and potentially life-threatening disorder of potassium balance. The most common cause is decreased kidney function. It can also be caused by acidosis, cell breakdown, endocrinological disturbances (e.g., hypoaldosteronism, hypocortisolism), and drugs such as potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), and digoxin. Serum potassium (K⁺) is often falsely elevated due to the method of sampling and levels should be confirmed with repeat testing. To determine the underlying cause of hyperkalemia, it is essential to review the patient's medications, check kidney and endocrine function, and screen for cell lysis (e.g., hemolysis, rhabdomyolysis) and acid-base disorders. Acute increases in serum K⁺ are very dangerous, as they influence the resting membrane potential and thus the electrical excitability of cells. These changes can lead to life-threatening cardiac arrhythmias. It is, therefore, essential to obtain an ECG to determine the level of cardiotoxicity. Management depends on the severity of the hyperkalemia and includes restriction of dietary K⁺, as well as medications to bind, shift, or eliminate K⁺, or to stabilize the cardiac membrane (e.g., calcium gluconate) if necessary. In refractory cases, dialysis may be required. Serum K⁺ should be monitored closely until it is corrected.

See also “Hypokalemia.”

• Hyperkalemia: Serum potassium level > 5 mEq/L
• Acute hyperkalemia: Abnormal ↑ K⁺ not known to be chronic
• Chronic hyperkalemia: Recurrent episodic ↑ K⁺ that require ongoing treatment

References: ^[1][2]

1. Potassium excess
   • Reduced excretion: acute and chronic kidney disease ^[3]
   • Endocrine causes: hypocortisolism, hypoaldosteronism
   • Drugs: potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers, NSAIDs, and trimethoprim-sulfamethoxazole ^[4]
   • GI absorption: increased intake of high-potassium foods (e.g., fresh fruits, dried fruits and legumes, vegetables, nuts, seeds, bran products, milk, and dairy products)
   • Type IV renal tubular acidosis
   • Release from cells: myolysis, tumor lysis, hemolysis
2. Extracellular shift
   • Acidosis → ↑ extracellular H⁺ → inhibition of the Na⁺/H⁺ antiporter → ↓ intracellular Na⁺ → ↓ sodium gradient inhibits the Na⁺/K⁺-ATPase → ↑ extracellular K⁺ concentration
     • Hyperkalemia → ↑ extracellular K⁺ concentration → ↑ potassium gradient stimulates the Na⁺/K⁺-ATPase → ↑ extracellular Na⁺ → ↑ sodium gradient stimulates the Na⁺/H⁺ antiporter → ↑ extracellular H⁺ → acidosis
     • Exception: In renal tubular acidosis, findings include hypokalemia and metabolic acidosis.
   • Hyperosmolality
   • Insulin deficiency (manifests with hyperglycemia)
   • Release from cells: rhabdomyolysis, tumor lysis syndrome, hemolysis
   • Drugs
     • Beta-blockers
     • Succinylcholine: (esp. when given with preexisting burns and/or muscle trauma) ,
     • Digoxin: inhibits the Na⁺/K⁺-ATPase → ↑ extracellular K⁺ concentration
3. Pseudohyperkalemia: due to the release of potassium from red blood cell lysis
   • Blood drawn from the side of IV infusion or a central line without previous flushing
   • Prolonged use of a tourniquet
   • Fist clenching during blood withdrawal
   • Delayed sample analysis

Errors in blood-drawing technique may lead to red blood cell lysis and a falsely elevated serum potassium concentration (pseudohyperkalemia)!

When K⁺ shifts out of the cell, it's a BAD LOSS! – Beta-blockers, Acidosis, Digoxin, Lysis, hyperOsmolality, high Sugar, Succinylcholine

References:^{[1][3][4][5][6]}

• Potassium is an important factor in maintaining the resting membrane potential
• ↑ Extracellular K⁺concentration → ↓ resting membrane potential (less negative than -90 mV) → ↑ excitability

Particularly acute extracellular changes in concentration influence excitability! Chronic changes lead to intracellular compensation!

Symptoms usually occur if serum potassium levels are > 7.0 mEq/L or they change rapidly.

• Cardiac arrhythmias (e.g., atrioventricular block, ventricular fibrillation)
• Muscle weakness, paralysis, paresthesia
• ↓ Deep tendon reflexes
• Nausea, vomiting, diarrhea

Hyperkalemia (and hypokalemia) can cause cardiac arrhythmia and lead to ventricular fibrillation!

References:^[1][7][8][9]

All patients require an ECG and routine laboratory studies to confirm the diagnosis and assess the need for urgent treatment. Further diagnostic testing depends on the suspected underlying etiology. Inquire about last renal replacement therapy for patients with ESRD (e.g., screen for missed hemodialysis appointments, adherence to peritoneal dialysis)

Laboratory studies ^[10][11]

Routine studies

• BMP
  • Glucose: If very high, consider spurious hyperkalemia secondary to hyperglycemic crisis.
  • Serum electrolytes
    • Na⁺: normal or can be ↓ in adrenal insufficiency (see “Diagnostics” in “Adrenal insufficiency”)
    • K⁺: Repeat to confirm the diagnosis and rule out pseudohyperkalemia (see “Etiology”).
  • Kidney function tests: often show renal impairment ^[12]
• CBC: can show hemolytic anemia or thrombocytosis ^[13]
• Liver chemistries: may be abnormal in hemolysis or tumor lysis syndrome
• Blood gases: (venous or arterial): often show metabolic acidosis ^[14]

An inverse relationship between serum K⁺ and pH (e.g., ↓ pH → ↑ K+) has previously been observed in specific types of metabolic acidosis. However, the underlying mechanisms are complex and this association is inconsistent in clinical practice. ^[10][14]

Investigation of underlying causes ^[15][16][17]

Depending on symptoms and risk factors, further testing may be appropriate, particularly if renal function is normal.

• Creatine kinase: ↑ in rhabdomyolysis
• LDH: ↑ in tumor lysis syndrome or hemolysis
• Renin-angiotensin-aldosterone system
  • ↑ Aldosterone: suggests e.g., pseudohypoaldosteronism, nephropathy due to sickle cell disease, and type 1 RTA
  • ↓ Aldosterone: Assess renin.
    • Normal or ↑ renin; : suggests e.g., hypoaldosteronism (e.g., due to Addison disease) or congenital adrenal hyperplasia
    • ↓ Renin: suggests e.g., AIN, diabetic nephropathy
• Cortisol: can be ↓ in primary adrenal insufficiency
• Urine electrolytes: rarely indicated ^[18]

ECG findings in hyperkalemia ^[19][20][21]

The correlation between serum K⁺ levels and the severity of ECG changes is loose. Findings are more likely to occur with rapid-onset hyperkalemia.

• Mild hyperkalemia: 5.5–6.4 mEq/L
  • Tall, peaked T waves
• Moderate hyperkalemia: 6.5–8.0 mEq/L
  • Lengthening of QRS interval (QRS complex widening)
  • Widening and flattening of P wave, which eventually disappears
• Severe hyperkalemia: > 8.0 mEq/L
  • Absent P wave
  • Intraventricular conduction block
  • Unusual QRS morphology
  • Sine wave pattern: a sinusoidal pattern with absent P waves and a wide QRS complex that merges with the T wave; a marker of impending V-Fib and asystole
  • Cardiac arrhythmias (e.g., V-tach, V-fib), asystole

Urgent K⁺-lowering treatment may be necessary even in the absence of ECG changes.

Approach ^{[2][10][15][22]}

• Risk stratification ^[23]
  • The risk of hyperkalemic emergency (acute severe elevation requiring urgent lowering) is elevated if any of the following are present:
    • Clinical manifestations: e.g., cardiotoxicity (see “ECG changes in hyperkalemia”), muscle weakness, paralysis
    • Serum K⁺ > 6.0–6.5 mEq/L ^[24]
    • Comorbidities that affect ongoing K⁺ influx and elimination: e.g., AKI, ESRD, GI bleeding, rhabdomyolysis, TLS
  • Less urgent hyperkalemia (typically chronic elevations that can be lowered more slowly) is more likely in the following cases:
    • Asymptomatic patient
    • Serum K⁺ = 5.5–6.0 mEq/L
    • No high-risk comorbidities

Cardiac arrhythmias due to hyperkalemia can cause sudden death.

To remember K⁺-lowering treatments, think C BIG K Die (if you see a big serum K⁺, your patient may die!): Calcium salts, Beta-agonists/Bicarbonate, Insulin + Glucose, Kation exchange medication, Dialysis/Diuretics.

Cardiac membrane stabilization ^[22]

Calcium salts reduce cardiac irritability.

• Indication: signs of cardiotoxicity (see “ECG changes in hyperkalemia”)
• Options
  • 10% calcium gluconate ^[23]
  • 10% calcium chloride (preferably given in a central or deep vein) ^[15]
• Considerations ^[10]
  • Ensure continuous cardiac monitoring throughout to detect potential arrhythmias.
  • Effects last only 30–60 minutes; additional dosing may be required.

Calcium salts have no influence on serum K⁺ levels and therefore should be paired with another K⁺-lowering agent.

Intracellular potassium shifting ^[10][23][25]

These drugs should be given in tandem with calcium salts (if calcium is indicated).

• Insulin and glucose: preferred acute noninvasive K⁺-lowering treatment; short-acting insulin combined with 50% dextrose
  • Patients with glucose levels > 250 mg/dL should not receive D50W.
  • Monitor all patients for hypoglycemia hourly for at least 2 hours after administration.
• Inhaled SABAs: e.g., nebulized albuterol (off-label) ; to consider as an adjunct to insulin (not effective as a monotherapy) ^[22][27]

Enhanced potassium elimination ^[2][22]

Hemodialysis is the most effective definitive therapy for refractory hyperkalemia. However, it is not a first-line option because of its invasive nature and adverse effects. It is the treatment of choice for patients already receiving regular renal replacement therapy.

Cation-exchange medications ^[23][28]

• Mechanism of action: These drugs release Na⁺ or Ca²⁺ ions in the gut, which are exchanged for K⁺, thereby enhancing enteral K⁺ elimination.
• Clinical applications: nonurgent lowering of K^{+ [10]}
• Options
  • Cation-exchange resins
    • Sodium polystyrene sulfonate : falling out of favor due to adverse effects
    • Sodium zirconium cyclosilicate
  • Cation-exchange polymers, e.g., patiromer ^[29]
• Considerations
  • Avoid simultaneous administration with other oral medications, as resins may bind them, reducing absorption.
  • Give with a laxative (avoid sorbitol). ^[30]

Sodium polystyrene sulfonate carries a risk of intestinal necrosis (especially if combined with the laxative sorbitol) and should be avoided in patients with abnormal bowel function. ^[30]

Additional medications ^[10][25]

The following medications are typically reserved to treat refractory hyperkalemia and only in specific circumstances.

• Diuretics: Consider loop diuretics, e.g., furosemide , in patients with volume overload.
  • Effects are unpredictable and significant side effects can occur.
  • Consider adding normal saline infusion for euvolemic patients to avoid iatrogenic AKI, however this approach can be harmful in patients with risk factors for fluid overload.
  • Close electrolyte and fluid balance monitoring are recommended.
• Sodium bicarbonate: : Consider in patients with metabolic acidosis.
  • Indicated only in patients with severe metabolic acidosis (i.e. pH < 7.2)
  • There is no evidence to support using bicarbonate in the management of hyperkalemia in nonacidotic patients.