Potassium

Mechanism of Action

As a major intracellular cation, potassium preserves acid-base balance and maintains isotonicity and electrodynamic cellular function. Potassium activates many enzymatic reactions within our body and plays an essential role in the transmission of nerve impulses, contraction of cardiac muscles, skeletal and smooth muscles, tissue synthesis, gastric secretion, and renal function. Potassium reduces mean systolic and diastolic blood pressure.[2]

Normal serum potassium values are between 3.5 and 5.0 mmol/L. Levels outside this range correlate with increased rates of death from several causes.[8][9]

Pharmacokinetics

Absorption: When administered orally, potassium chloride is well-absorbed from the upper gastrointestinal tract.

Distribution: Potassium enters cells through active transport from extracellular fluid.

Elimination: Potassium is excreted primarily through urine, with small amounts excreted in skin and feces; most intestinal potassium is reabsorbed.

Administration

Available Dosage Forms and Strengths

Potassium is available in multiple salt formulations, some administered orally (chloride, acetate, bicarbonate, gluconate, and citrate) and some intravenously (chloride and acetate). Certain potassium-containing compounds (eg, potassium chloride) can be injected subcutaneously (hypodermoclysis).[10] Oral administration is always preferable to intravenous injection, except for patients with critical hypokalemia. This is because the relatively slow process of gastrointestinal absorption of potassium salts limits the likelihood of an acute increase in serum potassium concentration.

Oral potassium chloride:

• Extended-release capsule: 8 mEq, 10 mEq
• Extended-release tablets: 8 mEq, 10 mEq, 15 mEq, 20 mEq
• Package: 20 mEq
• Solution: 20 mEq/15 mL (10%), 40 MEQ/15ML (20%), 40 mEq/15 mL (20%)

Intravenous potassium chloride: 

This is available as a single ingredient and can be combined with dextrose and sodium chloride, as listed below.

• Potassium 10 mEq/100 mL; 10 mEq/50 mL; 20 mEq/100 mL; 20 mEq/50 mL; 20 mEq/1000 mL; 40 mEq/100 mL; 2 mEq/mL in 5 mL and 10 mL
• Potassium 10 mEq/L, dextrose 5%, and sodium chloride 0.45% 
• Potassium 20 mEq/L and sodium chloride 0.45% 
• Potassium 20 mEq/L and sodium chloride 0.9% 
• Potassium 20 mEq/L, dextrose 5%, and sodium chloride 0.2% 
• Potassium 20 mEq/L, dextrose 5%, and sodium chloride 0.225%
• Potassium 20 mEq/L, dextrose 5%, and sodium chloride 0.45%
• Potassium 20 mEq/L, dextrose 5%, and sodium chloride 0.9%
• Potassium 30 mEq/L, dextrose 5%, and sodium chloride 0.45% 
• Potassium 40 mEq/L and sodium chloride 0.9%
• Potassium 40 mEq/L, dextrose 5%, and sodium chloride 0.45%
• Potassium 40 mEq/L, dextrose 5%, and sodium chloride 0.9%

Potassium citrate: 

• Extended-release tablets: 5 mEq (540 mg), 10 mEq (1080 mg), and 15 mEq (1620 mg)

Potassium gluconate: 

• Capsule: 595 mg
• Tablets: 2 mEq, 2.5 mEq, and 80 mg

Potassium bicarbonate: 

• Tablets: 10 mEq, 20 mEq, and 25 mEq

Potassium acetate:

• IV solution: 2 mEq/mL of 20 mL, 50 mL, 100 mL

Adult Dosage 

Supplemental potassium doses are usually calculated in mEq. Depending on the potassium supplement formulation being used, the amount of a particular oral supplement that will provide a specific effective dosage of potassium in mEq will vary. The normal adult daily potassium requirement is 40 to 80 mEq; infants and children require 2 to 3 mEq/kg up to a maximum of 40 mEq/m daily.

As a general consideration, the following values are equal:

• Potassium 10 mEq = potassium 10 mmol = elemental potassium 390 mg = 750 mg potassium chloride 

Oral: To reduce gastrointestinal irritation and cathartic effects, oral potassium supplements should be administered with or after meals. Oral potassium salts are usually administered in 1 to 4 doses daily. With a relatively high daily dosage (greater than 20 mEq), drug administration should be divided into doses. Extended-release potassium chloride preparations are useful for patients who cannot tolerate or are non-compliant with multiple daily doses of potassium preparations.

• Mild-to-moderate hypokalemia (3 to 3.4 mEq/L): 10 to 20 mEq potassium twice to 4 times daily.

• Severe hypokalemia (<3 mEq/L): Initiate at 40 mEq 3 to 4 times daily or 20 mEq every 2 to 3 hours. The dose should be adjusted based on serum potassium levels, which should be rechecked every 2 to 4 hours.

IV: Administered via central-line infusion. Continuous ECG monitoring is required for infusions of more than 10 mEq/hr. Dosing adjustments are based on potassium levels.

• Mild-to-moderate hypokalemia (3 to 3.4 mEq/L): Based on serum potassium level and clinical factors, potassium should be initiated at 20 to 60 mEq, with a maximum infusion rate of 10 to 20 mEq/hr.

• Severe hypokalemia (2.5 to 3 mEq/L): 10 to 20 mEq/hr, with a maximum infusion rate of 20 mEq/hr.

• Severe, life-threatening hypokalemia (<2.5 mEq/L): 10 to 40 mEq/hour; adjusted based on serum levels to a maximum infusion rate of 40 mEq/hr with continuous ECG monitoring and central line.[11]

Specific Patient Populations

Hepatic impairment: Patients with cirrhosis should start treatment at the lower end of the dosing range. Frequent monitoring of serum potassium levels is essential.

Renal impairment: Starting at the lower end of the dosing range is recommended for patients with reduced renal function, especially those on RAAS inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs), due to the increased risk of hyperkalemia. Serum potassium levels should be monitored regularly, and renal function should be assessed periodically.[12]

Older patients: These patients may receive potassium per adult dosing guidelines. Treatment should be initiated cautiously, beginning with the lowest recommended dose.

Pediatric patients

Oral: Mild-to-moderate hypokalemia can be treated with 1 to 2 mEq/kg/day in divided doses. Dose adjustments should based on clinical response. The typical range is 1 to 5 mEq/kg/day. No more than 2 mEq/kg should be administered per dose, with a maximum of 40 mEq per dose. Serum potassium levels should be checked at least 2 hours after dosing. Repeat doses as necessary based on laboratory results.[13]

Intermittent IV Infusion: Severe hypokalemia should be treated with 0.5 to 1 mEq/kg per dose, with a maximum of 40 mEq per infusion. Continuous ECG monitoring should be performed for infusion rates exceeding 0.5 mEq/kg/hour. Serum potassium levels should be evaluated 1 to 2 hours after the infusion is complete, and repeat dosing should be performed if needed based on laboratory results.[14]

Adverse Effects

Hyperkalemia is the most common and life-threatening adverse effect of potassium administration and can develop rapidly.[15] This condition can manifest as potentially fatal bradycardia, asystole, and ventricular fibrillation.

Oral preparations commonly cause gastrointestinal side effects, such as nausea, emesis, diarrhea, and abdominal pain.

Extravasation, local irritation, and phlebitis may occur due to improper dilution of intravenous preparations or administration through a peripheral vein.[12]

Hypersensitivity reactions may occur from the use of potassium iodide as well as chronic iodine poisoning (iodism).[16]

Contraindications

Hyperkalemia is an absolute contraindication for potassium replacement. Relative contraindications include inadequate or absent urine output and severe renal impairment. Systemic acidosis and states of dehydration require correction before potassium administration. Potassium administration requires caution in states of significant tissue breakdown (eg, burns or post-operative conditions), adrenal insufficiency, and concomitant administration of potassium-sparing diuretics.

Oral potassium supplements should be used cautiously in patients who have delayed gastrointestinal transit due to structural or functional causes. Potassium iodide should not be given to patients with known sensitivity to iodides.

Precautions 

IV infusion: Potassium should be infused slowly (≤20 mEq/hour), including boluses for hypokalemia. When potassium is included in the long-term or maintenance fluid administration, the concentration should not exceed 40 mEq/L. Exceptions include severe hypokalemia associated with cardiac arrhythmias or diabetic ketoacidosis, where higher concentrations of 60 to 80 mEq/L require caution. 

Potassium IV solutions should only be administered to well-hydrated patients with adequate urine flow (especially post-surgical patients). Potassium dosage selection requires caution in patients with renal impairment and older patients.[17]

Potassium acetate and potassium chloride are concentrated solutions that require dilution before intravenous administration. Local vascular intolerance may be a limiting factor in the ability to administer concentrated solutions. Infusions should occur via a large, high-flow vein (eg, femoral vein), or lower-concentration solutions may be administered in divided doses via peripheral veins.

Monitoring

Fluid balance, hydration, and acid-base status must be monitored periodically in patients receiving potassium replacement. Serum potassium levels require frequent monitoring in patients with renal impairment or intravenous bolus potassium replacement. Regular potassium checks are also necessary when patients receive drugs that increase the risk of hyperkalemia (eg, ACE inhibitors, potassium-sparing diuretics).[18] Continuous ECG monitoring and serial measurements of plasma potassium concentrations are essential during IV administration of potassium, particularly when the rate of administration is greater than 20 mEq/hr.

If refractory hypokalemia is not responding to potassium treatments, consider checking magnesium levels.

Toxicity

Hyperkalemia is the most prevalent and life-threatening hazard of potassium therapy. ECG changes are the most critical indicator of asymptomatic potassium toxicity. They include tall, peaked T waves, ST-segment depression, the disappearance of the P wave, QT interval prolongation, and widening the QRS complex with slurring. Clinical signs and symptoms of hyperkalemia include paresthesias, drowsiness, mental confusion, flaccid paralysis, gray pallor, cold skin, peripheral vascular collapse with a fall in blood pressure, critical cardiac arrhythmias, and heart block.

Treatment of hyperkalemia depends on its severity, and multiple regimens are available.[15] However, rapidly lowering plasma potassium concentrations in digitalized patients can result in cardiac glycoside toxicity. Administration of potassium-rich foods and potassium-sparing diuretics require prompt discontinuation. In patients with severe hyperkalemia, immediate measures that allow an intracellular shift of potassium (eg, administration of sodium bicarbonate, a calcium salt, or insulin-dextrose) have been recommended. Patients with absent P waves or a broad QRS complex and not receiving cardiac glycosides should immediately be given calcium gluconate or another calcium salt IV with continuous ECG monitoring to antagonize the cardiotoxic effects of potassium. If abnormalities on the ECG persist, repeated doses of the calcium salt may be given.

After the ECG normalizes, subsequent efforts should focus on removing potassium from the body. Some potassium adsorption can be accomplished by administering sodium polystyrene sulfonate orally or as an enema. Hemodialysis or peritoneal dialysis will reduce plasma potassium concentrations and may be necessary for patients with renal insufficiency.

Enhancing Healthcare Team Outcomes

Managing low and high potassium levels requires an interprofessional team of healthcare professionals, including nurses, laboratory technologists, pharmacists, and clinicians from various specialties. Without prompt and proper management, the morbidity and mortality from potassium overdose remain high. Cardiovascular mortality from hyperkalemia increases, particularly in patients with chronic kidney disease and those on dialysis.[19] When hyperkalemia results from potassium administration, the patient requires ICU admission for monitoring and treatment. The ICU clinician coordinates care, including the following:

• Ordering serial blood potassium levels
• Monitoring for signs and symptoms of cardiac arrhythmias and continuous EKG monitoring
• Performing various maneuvers to limit drug absorption
• Administering sodium bicarbonate, calcium gluconate, or calcium chloride rapidly to limit cardiotoxicity
• Consulting with the pharmacist about using polystyrene sulfonate and glucose-insulin
• Consulting with a nephrologist for further management, which may include dialysis
• Consulting with a cardiologist for managing life-threatening arrhythmias

Existing treatment protocols for critical hyperkalemia resulting from potassium administration lack solid evidence and are institution-specific.[20] Definitive clinical trials are needed to address practice gaps regarding when and how to treat.[20] The management of potassium overdose does not stop with the resolution of hyperkalemia. Following stabilization, clinicians must determine how and why the patient became hyperkalemic. The nursing and pharmacy teams help identify whether the intended dose was administered or if a medical error led to potassium toxicity. The nephrologist detects any baseline decreased renal function that contributed to the hyperkalemia. Only by working as an interprofessional team can the morbidity and mortality associated with inadvertent potassium overdose be reduced.