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
Potassium excess: due to altered K+ metabolism or intake
- Reduced excretion: acute and chronic kidney disease 
- Endocrine causes: hypocortisolism, hypoaldosteronism
- Drugs: potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers, NSAIDs, and trimethoprim-sulfamethoxazole 
- Type IV renal tubular acidosis
- Increased intake
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
- Exceptions: In renal tubular acidosis and acetazolamide toxicity, findings include hypokalemia and metabolic acidosis.
- Insulin deficiency (manifests with hyperglycemia)
- Beta blockers
- Succinylcholine: (esp. when given with preexisting burns and/or muscle trauma) ,
- Digoxin: inhibits the Na+/K+-ATPase → ↑ extracellular K+ concentration
- Acidosis → ↑ extracellular H+ → inhibition of the Na+/H+ antiporter → ↓ intracellular Na+ → ↓ sodium gradient inhibits the Na+/K+-ATPase → ↑ extracellular K+ concentration ; 
- Pathological cell lysis
- High blood cell turnover: e.g., thrombocytosis, erythrocytosis, leukocytosis
Pseudohyperkalemia: resulting from iatrogenic 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
- Potassium is an important factor in maintaining the resting membrane potential
- ↑ Extracellular K+concentration → resting membrane potential becomes 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:
- Obtain routine laboratory studies to:
- Confirm hyperkalemia and severity.
- Assess renal function.
- Evaluate etiology of hyperkalemia.
- Check ECG: Urgent treatment is required for ECG changes in hyperkalemia.
- Inquire about last renal replacement therapy for patients with ESRD (e.g., screen for missed hemodialysis appointments, adherence to peritoneal dialysis).
- Send further diagnostic laboratory testing depending on the suspected underlying etiology.
Laboratory studies 
- 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”).
- Renal function tests: often show renal impairment 
- CBC: can show hemolytic anemia or thrombocytosis 
- Liver chemistries: may be abnormal in hemolysis or tumor lysis syndrome
- Blood gases: (venous or arterial): often show metabolic acidosis 
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. 
ECG findings in hyperkalemia 
There is a weak correlation between serum K+ levels and the severity of ECG changes. 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
Investigation of underlying causes 
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
- ↑ Aldosterone: suggestive of, e.g., pseudohypoaldosteronism or nephropathy due to sickle cell disease
↓ Aldosterone: Assess plasma renin activity or plasma renin concentration (see also “Hypoaldosteronism”).
- 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 (see “Endocrine testing for adrenal insufficiency”)
- Urine electrolytes: rarely indicated 
Review the patient's medical history and medication list to help identify potential causes of hyperkalemia. 
Therapeutic approach to hyperkalemia 
- Determine severity: See “Risk stratification.”
Hyperkalemic emergency: Patients require immediate management.
- Start continuous cardiac monitoring.
- If there are ECG changes: Stabilize the cardiac membrane first, e.g., with IV calcium gluconate.
- Initiate treatment to shift potassium intracellularly, e.g.:
- Consider nephrology and critical care consults.
- Admit to hospital for ongoing monitoring and treatment.
- Repeat serum K+ at minimum 1, 2, 4, 6, and 24 hours after treatment.
- Identify and treat underlying causes.
Review medications and discontinue or modify dosing of medications that may be contributing to hyperkalemia.
- Decrease dose (or consider discontinuation) of drugs required to treat underlying conditions, e.g., RAAS inhibitors.
- Avoid nonessential drugs associated with hyperkalemia (e.g., NSAIDs, over-the-counter supplements such as milkweed).
- Start a low potassium diet and avoid salt substitutes (consider nutrition consult). 
- Consider treatment to remove potassium from the body, e.g., cation-exchange resins, diuretics, hemodialysis.
- Repeat potassium regularly until it is within normal range, e.g., within 1–3 days. 
Urgent K+-lowering treatment may be necessary even in the absence of ECG changes.
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.
The effects of calcium salts, insulin/glucose, and inhaled SABAs on serum K+ are temporary. Repeat doses may be required while waiting for interventions to remove K+ from the body to take effect.
Risk stratification 
Hyperkalemic emergency is an acute severe elevation that requires urgent lowering and occurs if any of the following are present:
- Clinical manifestations: e.g., ECG changes in hyperkalemia, muscle weakness, paralysis
- Serum K+ > 6.0–6.5 mEq/L 
- 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)
- Patient is asymptomatic
- Serum K+ is 5.5–6.0 mEq/L
- Patient has no high-risk comorbidities
Cardiac arrhythmias due to hyperkalemia can cause sudden death.
Cardiac membrane stabilization 
Calcium salts reduce cardiac irritability.
- Indication: ECG changes in hyperkalemia
- 10% calcium gluconate 
- 10% calcium chloride (preferably given in a central or deep vein) 
- Ensure continuous cardiac monitoring throughout to detect potential arrhythmias.
- Effects last only 30–60 minutes; additional dosing may be required.
Calcium salts should result in normalization of the ECG appearance within 5 minutes; observe the cardiac monitor following initial treatment and repeat the dose if the ECG tracing still appears abnormal.
Calcium salts have no influence on serum K+ levels and therefore should be paired with a K+-lowering agent.
Intracellular potassium shifting 
These drugs should be given in tandem with calcium salts (if calcium is indicated).
Insulin and glucose
- Preferred acute noninvasive K+-lowering treatment
- Sample agent: 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
- Consider as an adjunct treatment 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.
- Recommended concentration is IV 8.4% sodium bicarbonate 
Avoid administering calcium carbonate and sodium chloride through the same IV line without extensive flushing in between because of the risk of calcium precipitation. 
Enhanced potassium elimination 
- Not required for all patients; treatment of the underlying cause may be sufficient.
- The choice of treatment depends on underlying medical conditions and volume status.
Cation-exchange medications 
- 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+ 
- Sodium polystyrene sulfonate : falling out of favor due to adverse effects
- Sodium zirconium cyclosilicate
- Cation-exchange polymers, e.g., patiromer 
- Cation-exchange resins
- Gastrointestinal upset
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. 
- Most effective definitive therapy for refractory hyperkalemia
- Preferred option in patients with end-stage renal failure ; (particularly if already receiving renal replacement therapy), or oliguria.
- For all other patients, avoided as a first-line option because of its invasive nature and adverse effects
Loop diuretics 
- Consider loop diuretics, e.g., furosemide for patients with volume overload
- Closely monitor fluid balance and electrolytes due to unpredictable effects and risk of adverse events.
Acute management checklist
- Determine the severity of hyperkalemia.
- Identify and treat underlying causes.
- Review medications and discontinue or adjust dosing of medications that may be contributing to hyperkalemia.
- Consider starting medication to enhance K+ elimination, e.g., cation-exchange medication, diuretics for patients with volume overload.
- Repeat K+ levels to assess response to treatment.
- Start a low K+ diet.
- Consult nephrology for patients with ESRD or refractory hyperkalemia, e.g., for consideration of hemodialysis.
Patients with hyperkalemic emergency
- Consult critical care.
- Start continuous cardiac monitoring.
- If there are ECG changes: Start IV calcium chloride or calcium gluconate to stabilize cardiac membranes.
- Start short-acting insulin PLUS glucose with or without inhaled SABAs to shift potassium intracellularly.
- Admit to hospital for further management.