Eric E. Bondarsky1, Aloke Chakravarti2, and Paru S. Patrawalla2
1 NYU Langone School of Medicine, New York, NY, USA
2 Icahn School of Medicine at Mount Sinai, New York, NY, USA
Definition of disease
Hyperkalemia is defined as a serum potassium level that is above the upper limit of normal (usually 5.0–5.2 mmol/L).
The prevalence of hyperkalemia in hospitalized patients has been reported to be between 1% and 10%.
The etiology of hyperkalemia can be broken down into causes due to potassium release and causes due to impaired renal excretion of potassium.
Excessive potassium release can be due to phlebotomy, hyperosmolality, acidosis, direct tissue injury, or drugs.
Renal causes of hyperkalemia include renal insufficiency, reduced aldosterone secretion or response, and reduced effective arterial blood volume.
Use of ACE inhibitor or angiotensin receptor blocker
Use of trimethoprim/sulfamethoxazole (TMP‐SMX)
Obtain thorough medication history.
Assess for muscle weakness, especially in the lower extremities.
Auscultate for cardiac arrhythmias.
Obtain serum potassium and magnesium concentrations as well as renal function.
Obtain a 12‐lead ECG.
Respiratory and cranial nerve involvement are rare in hyperkalemia
Spinal cord compression
Cord compression will have an abnormal sensory exam and bowel/bladder dysfunction
The clinician should inquire about typical manifestations of hyperkalemia such as muscle weakness and palpitations and investigate medication use that may cause renal insufficiency or hyperkalemia.
Physical examination is often unremarkable in patients with hyperkalemia but in severe cases can reveal ascending muscle weakness or an irregular heart rhythm.
Diminished or absent deep tendon reflexes can be present.
Physical manifestations of renal failure such as altered mental status, uremic frost, and edema can be encountered. If signs of trauma or prolonged immobility are found, rhabdomyolysis can be suspected as a cause of hyperkalemia.
Disease severity classification
Mild hyperkalemia: serum potassium 5.5–6 mmol/L.
Moderate hyperkalemia: serum potassium ≥6 mmol/L.
Severe hyperkalemia: serum potassium ≥6.5 mmol/L.
Serum potassium, BUN, and creatinine levels for degree of hyperkalemia and renal failure.
Urinalysis for causes of renal insufficiency.
Glucose level to evaluate for diabetes mellitus.
Blood gas for presence and degree of acidosis.
Calcium level to evaluate for hypocalcemia which can lead to arrhythmias.
Digoxin level to assess for digitalis toxicity as an etiology for electrolyte disturbance.
Serum cortisol and aldosterone levels to assess for mineralocorticoid insufficiency as a cause for hyperkalemia.
Electrocardiogram for potentially life‐threatening arrhythmias and for early changes of hyperkalemia such as peaked T‐waves, short QT interval, and depression of the ST segment.
Potential pitfalls/common errors made regarding diagnosis of disease
A hemolyzed sample can falsely elevate the potassium level.
Repeated fist clenches can falsely elevate potassium levels.
Prolonged storage of serum sample can lead to pseudohyperkalemia.
Extremely high leukocyte or platelet counts can lead to pseudohyperkalemia.
For mild hyperkalemia (5.5–6 mmol/L), remove potassium with potassium exchange resins (sodium zirconium cyclosilicate 10g PO), diuretics (furosemide 1 mg/kg IV), or dialysis.
For moderate hyperkalemia (≥6 mmol/L), use above strategies and shift potassium into cells with insulin (10 units IV) and dextrose (50 g IV).
For severe hyperkalemia (≥6.5 mmol/L) without ECG changes, use above strategies and add albuterol (5 mg inhaled, may repeat) and sodium bicarbonate (50 mmol IV).
For severe hyperkalemia (≥6.5 mmol/L) with ECG changes, use above strategies but first stabilize the myocardial cell membrane with calcium chloride (10 mL IV of 10% solution).
In postoperative patients, who are at a presumed risk for ileus, sodium polystyrene sulfate has been reported to cause intestinal necrosis and should be avoided in this population. This also applies to patients with obstructive bowel disease.
Natural history of untreated disease
Untreated, the ECG will evolve with worsening hyperkalemia:
Early changes include peaked T‐waves, short QT, and depression of the ST segment.
This will evolve into bundle branch blocks, prolonged PR, and smaller P‐waves which will eventually disappear.
The QRS complex will widen to form a sine wave.
Ventricular fibrillation or asystole will eventually result.
Prognosis for treated patients
All changes will reverse with treatment of the hyperkalemia.
Definition of hypokalemia
Hypokalemia is defined as a serum potassium level that is below the lower limit of normal (usually 3.5–3.6 mmol/L).
Hypokalemia occurs in up to 21% of hospitalized patients.
Hypokalemia occurs in up to 2–3% of outpatients.
Causes of hypokalemia can be divided into abnormal losses, transcellular shifts, and inadequate intake.
Abnormal losses can be due to medications, gastrointestinal losses, urinary losses, hypomagnesemia, and hemodialysis.
Transcellular shifts can be due to medications, refeeding syndrome, adrenergic stimulation, alkalosis, or thyrotoxicosis.
1.3 for each decade
Parenteral loop diuretics
The clinician should inquire about typical manifestations of hypokalemia such as muscle weakness and palpitations and investigate the medications that are known to cause hypokalemia.
Inquire about gastrointestinal symptoms such as vomiting or diarrhea.
A physical examination is often unremarkable in patients with hypokalemia but in severe cases can reveal flaccid muscle weakness or an irregular heart rhythm.
Check blood pressure as hypertension can be a clue to hyperaldosteronism or Cushing’s syndrome.
Assess respirations, as Kussmaul breathing can be present in diabetic ketoacidosis.
For mild hypokalemia with an evident cause, no further investigation is necessary.
For unclear causes or more severe hypokalemia, a full chemistry panel including magnesium level should be obtained. Consideration should be given to obtaining an arterial blood gas.
If cause remains unclear, assessing urinary excretion of potassium can be helpful. Urine potassium, osmolality, and creatinine levels as well as plasma osmolality levels should be added to the diagnostic investigations.
If a cause remains elusive, a plasma aldosterone : renin ratio should be obtained to rule out primary hyperaldosteronism, especially in the setting of hypertension. A dexamethasone suppression test should be considered to rule out Cushing’s syndrome, especially with typical clinical features of steroid excess. Serum TSH and thyroxine should be obtained to rule out thyrotoxic periodic paralysis.
Under the care of a specialist, adrenal imaging will sometimes be indicated to assess for congenital adrenal hyperplasia.
Under the care of a specialist, duplex ultrasonography or renal artery angiography may be indicated to assess for renal artery stenosis.
In the presence of hypomagnesemia, magnesium should first be repleted.
Once hypokalemia is identified, its cause should be investigated. In the meantime, potassium should be repleted.
In the setting of hypophosphatemia, such as with diabetic ketoacidosis or Fanconi’s syndrome, potassium phosphate can be used as repletion.
In the setting of metabolic acidosis, potassium bicarbonate or one of its precursors (acetate or citrate) can be used to balance the pH.
In almost all other settings, potassium chloride should be used since there is often an element of metabolic alkalosis with most causes of hypokalemia.
Table of treatment
Suitable for patients with no clinical manifestations and mild hypokalemia
Potassium chloride 40 mEq IV/PO Potassium phosphate 1 mmol/kg IV Potassium citrate 10 mEq PO three times daily Potassium acetate 40 mEq IV
Prevention/management of complications
Prevention of hypokalemia in patients at high risk (e.g. patients receiving chronic diuretics) includes regular potassium supplementation in the form of potassium chloride or providing a list of high potassium foods to supplement the diet.
In patients with hypertension, potassium levels less than 3.5 have been associated with a hazard ratio of 2.8 for 90 day mortality, when correcting for covariates.
The prevalence of hyperphosphatemia is low in patients without renal disease.
Hyperphosphatemia has been reported to occur in almost 70% of patients on chronic hemodialysis.
Increased phosphate load.
Shift of phosphate into the extracellular space.
Tumor lysis syndrome.
Hyperphosphatemia causes symptoms due to calcium phosphate crystals forming in the blood leading to symptoms of hypocalcemia.
Limiting dietary phosphate can be helpful even in early chronic kidney disease.
Trending tubular reabsorption of phosphate (TRP) can he be helpful in deciding when to initiate phosphate‐lowering therapies (see later).
Phosphate binders can be used in the prevention of hyperphosphatemia.
A typical presentation of hyperphosphatemia will be a patient with either acute or chronic renal dysfunction who was found on blood tests to have elevated phosphate levels.
In taking a history, the clinician should inquire about common medications that contain phosphate (such as phosphate enemas and fosphenytoin).
If the patient was immobile or crushed, attention should be paid to rhabdomyolysis as a potential cause for the phosphate disturbance.
In a patient with a history of recent chemotherapy, tumor lysis syndrome should be on the differential.
Otherwise, other causes of renal failure should be elucidated, as this is the most common scenario for a presentation of hyperphosphatemia.
The physical exam should focus on clinical manifestations of hypocalcemia, which often accompanies hyperphosphatemia. Assessing muscle twitching, spasms, as well as extrapyramidal signs and parkinsonism can all be useful in the physical exam.
Useful clinical decision rules and calculators
TRP can be determined by calculating the ratio of phosphate clearance to creatinine clearance as follows: %TRP = 1 − [(UP/PP) × (PCr/UCr)] × 100, where UP and PP are plasma and urine phosphate and UCr and PCr are plasma and urine creatinine.
When TRP falls below normal (<80), it may be beneficial to initiate interventions to limit phosphate retention and avoid the ensuing elevation of serum phosphorus.
Serum phosphate, urea nitrogen, creatinine, calcium, and remainder of electrolytes are helpful.
Urine phosphate, creatinine, and remainder of urine electrolytes are helpful for TRP calculation.
Potential pitfalls/common errors made regarding diagnosis of disease
A falsely elevated phosphate level can be encountered in cases of hyperglobulinemia, hyperlipidemia, hemolysis, and hyperbilirubinemia.
Administration of liposomal amphotericin B can also lead to pseudohyperphosphatemia.
Treatment of acute hyperphosphatemia usually revolves around treatment of the associated hypocalcemia.
Treatment of chronic hyperphosphatemia most often occurs in patients with renal dysfunction and revolves around dietary phosphate restriction (<900 mg/day) and phosphate binder therapy to decrease intestinal absorption.
Phosphate binder therapy is primarily chosen based on calcium status. Hypercalcemic patients should take non‐calcium‐containing binders such as sevelamer or lanthanum while hypocalcemic or normocalcemic patients should take calcium‐containing binders such as calcium acetate or calcium carbonate.
Longer or more frequent dialysis sessions can be useful for refractory hyperphosphatemia in patients who are dialysis dependent.
Table of treatment
Dietary phosphate restriction for patients with chronic kidney disease
Phosphate binders: Calcium acetate 1334 mg with each meal Sevelamer 800–1600 mg with each meal Lanthanum 500 mg with each meal
Prolonged or more frequent hemodialysis sessions
The prevalence of hypophosphatemia depends on the definition of the lower range of normal and the population being studied.
Hypophosphatemia has been reported to occur in 3% of hospitalized patients and up to 80% of patients with sepsis.
Decreased absorption of phosphate.
Increased excretion of phosphate.
Shift of phosphate to the intracellular space.
Hypophosphatemia causes symptoms due to depletion of intracellular ATP and 2,3‐DPG. Symptoms usually will not develop unless levels are below 1 mg/dL. Depletion below this level will affect the musculoskeletal, cardiovascular, pulmonary, neurologic, and hematologic systems.
Acute respiratory disease
Use of dopamine
Treating electrolyte abnormalities prior to initiating feeding in malnourished patients may decrease complications related to refeeding syndrome.