Potassium Replacement Therapy
Action And Clinical Pharmacology: Potassium is the principal intracellular ion of body tissues. Potassium ions are involved in a number of essential physiological processes, such as the maintenance of intracellular acid-base balance and tonicity. Other functions include the transmission of nerve impulses, contraction of cardiac, skeletal and smooth muscle, gastric secretion, normal renal function, tissue synthesis and carbohydrate metabolism.
Hypokalemia: Potassium depletion may occur whenever the rate of loss exceeds the rate of intake. Causes of hypokalemia include: inadequate intake, diuretic therapy, diabetic ketoacidosis, metabolic alkalosis, potassium-losing nephropathy, severe diarrhea, prolonged vomiting, drainage of gastrointestinal fluids, hyperaldosteronism, hepatic cirrhosis with ascites, Bartter’s syndrome and long-term corticosteroid therapy. The need for potassium supplementation in patients taking potassium-depleting medications may sometimes be avoided by increasing dietary intake of potassium. For information on food sources of potassium, see Mineral Food Sources in the Clin-Info section.
Potassium deficiency may cause vomiting, abdominal distention, paralytic ileus, acute muscular weakness, paralysis, paresthesia, polydipsia and an inability to concentrate urine, hypotension, cardiac arrhythmias, and coma. Hypokalemia may also potentiate digoxin toxicity.
Hyperkalemia: Manifestations of hyperkalemia include ECG changes which ultimately may progress to complete heart block, ventricular arrhythmias or cardiac arrest. Symptoms of hyperkalemia may or may not be present and include weakness, parasthesias, confusion and muscular or respiratory paralysis (see Overdose).
Pharmacokinetics: Potassium is readily absorbed from the gastrointestinal tract. Potassium is actively transported into cells from the extracellular fluid. Dextrose, insulin and bicarbonate facilitate movement of potassium into cells. Normal adult values for serum potassium range from 3.5 to 5.0 mmol/L. Serum potassium concentrations may not be an accurate indicator of total body stores, as intracellular potassium accounts for 98% of total body amount. Excretion is mainly in the urine (85 to 90%) and closely follows potassium intake. Potassium is readily removed by peritoneal dialysis or hemodialysis.
Slow-Release Preparations: Expanded wax matrix may be seen in stools; it is not an indication of poor bioavailability.
Indications And Clinical Uses: The prevention of potassium depletion when dietary intake of potassium is inadequate for this purpose; the treatment of potassium depletion in patients with hypokalemia; treatment of digitalis intoxication. The i.v. route is indicated when the patient is unable to take potassium orally or if hypokalemia is severe.
Contra-Indications: In hyperkalemia; renal impairment with oliguria, anuria or azotemia; ventricular fibrillation; untreated Addison’s disease; salt-losing adrenal hyperplasia; in extensive tissue breakdown as in severe burns, acute dehydration and heat cramps; increased sensitivity to potassium administration (e.g., in congenital paramyotonia or adynamia episodica hereditaria) and hyperadrenalism associated with adrenogenital syndrome.
All solid dosage forms of potassium supplements are contraindicated in any patient in whom there is cause for arrest or delay in tablet passage through the gastrointestinal tract. In these instances, potassium supplementation should be with a liquid preparation.
Slow-release potassium chloride preparations have produced esophageal ulceration in certain cardiac patients with esophageal compression due to an enlarged left atrium. The administration of these preparations is contraindicated in such patients as well as in patients with dysphagia.
Manufacturers’ Warnings In Clinical States: In patients with impaired mechanisms for excreting potassium, (e.g., renal function impairment), administration of potassium salts can produce hyperkalemia and cardiac arrest. This is of particular concern in patients receiving i.v. potassium but may also occur in patients taking oral potassium. Potentially fatal hyperkalemia can develop rapidly and may be asymptomatic. Careful monitoring of the serum potassium concentration and appropriate dosage adjustment is required.
The concomitant use of potassium supplements and drugs which increase serum potassium may result in severe hyperkalemia (see Precautions, Drug Interactions).
Slow-release preparations should be avoided in patients at high risk for potassium chloride-induced gastrointestinal lesions, i.e., patients with cardiomegaly, esophageal stricture or compression, dysphagia, recent gastric surgery, delayed intestinal transit, ulcerative bowel disease or diverticulitis. Enteric coated tablets have an unacceptably high rate of gastrointestinal symptoms (40 to 50 incidents per 100 000 patient years) and should not be used.
Administration of concentrated potassium injection can be fatal. Parenteral potassium chloride solutions must be well diluted, thoroughly mixed and administrered by slow i.v. infusion. Pain at the injection site and phlebitis may occur. Extravasation is to be avoided.
Precautions: The treatment of potassium depletion, particularly in the presence of cardiac disease, renal disease or acidosis, requires careful attention to acid base balance and appropriate monitoring of serum electrolytes, the ECG and the patient’s clinical status.
Use potassium with caution in diseases associated with heart block since increased serum potassium may increase the degree of block.
Potassium balance is markedly altered in patients with diabetic ketoacidosis. Generally, total potassium is depleted and patients present with potassium deficits of 3 to 5 mmol/kg or greater; however the serum potassium concentration may be high, normal or low depending on the degree of acidosis and volume depletion. Following insulin administration, monitor serum potassium concentrations closely as hyperkalemia can be rapidly converted to hypokalemia.
In patients on a low salt diet, hypokalemic hypochloremic alkalosis is a possibility that may require chloride as well as potassium supplementation. Salt substitutes which primarily contain potassium chloride may result in hyperkalemia especially in renal patients. Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing potassium salt such as the acetate, bicarbonate, gluconate or citrate.
Drug Interactions: Extreme caution is advised with concomitant administration of potassium and potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride) or angiotensin converting enzyme (ACE) inhibitors (e.g., benazepril HCl, captopril, cilazapril, enalapril maleate, enalaprilat, fosinopril sodium, lisinopril, quinapril HCl and ramipril) since the simultaneous administration of these agents can produce severe hyperkalemia.
Adverse Reactions: Nausea, vomiting, diarrhea, unpleasant taste (liquids) and abdominal cramps have been reported. Severe adverse effects reported with potassium preparations have been hyperkalemia and arrhythmias (see Overdose); intestinal, esophageal and gastric ulceration (see Warnings).
Symptoms And Treatment Of Overdose: Symptoms: If excretory mechanisms are impaired or if potassium is administered too rapidly i.v., potentially fatal hyperkalemia can result. Paresthesia of the extremities, listlessness, mental confusion, gastrointestinal symptoms, weakness, heaviness of legs, paralysis, hypotension, cardiac arrhythmias, heart block and cardiac arrest may occur. Frequently hyperkalemia is asymptomatic and may be manifested only by increased serum potassium concentration and characteristic electrocardiographic changes.
Progressive ECG changes occur with increasing serum potassium levels and indicate the need for immediate treatment. ECG changes include increased amplitude and peaking of the T waves, depression of the ST segment, reduction in the amplitude of the R wave, widening of the QRS complex, prolongation of the PR interval, and a decrease in the amplitude and ultimately disappearance of the P wave. Widening of the QRS complex is one of the most ominous signs and indicates the need for aggressive treatment.
Treatment: Discontinue administration of potassium-rich foods, medications and i.v. solutions containing potassium, or medications which can induce hyperkalemia.
In patients with severe hyperkalemia (e.g., serum potassium exceeds 7 mmol/L) or if any ECG manifestations of hyperkalemia exist, immediate treatment is required. The plasma potassium concentration and ECG must be monitored, as well as serum electrolytes, creatinine, glucose and arterial blood gases. I.V. calcium may be administered to antagonize the cardiotoxic effects of potassium, e.g., 1.125 to 7 mmol elemental calcium (1.7 to 10.3 mL calcium chloride 10% or 4.8 to 30 mL calcium gluconate 10%) i.v. over 1 to 5 minutes; this may be repeated after 5 to 10 minutes. The use of i.v. calcium is not recommended in patients receiving digoxin. To promote a shift of potassium from the extracellular to the intracellular compartment, agents such as dextrose and insulin or sodium bicarbonate may be used. 300 to 500 mL of dextrose 10% containing 10 to 20 units of regular insulin per litre may be infused over a 1-hour period. Alternately, give 25 g of dextrose i.v. (e.g., 50 mL of a dextrose 50% prefilled syringe) accompanied by 5 to 10 units of regular insulin i.v. over 5 minutes. To correct acidosis and to promote intracellular potassium shift, sodium bicarbonate 50 mmol (e.g. 50 mL of a sodium bicarbonate 8.4% prefilled syringe) may be given i.v. over 5 minutes and repeated every 5 to 10 minutes as necessary. Bicarbonate must be used with caution in patients at risk for fluid overload.
When ECG approaches normal, measures to reduce body stores of potassium such as cation exchange resins (e.g., sodium or calcium polystyrene sulfonate) may be employed. Hemodialysis or peritoneal dialysis should be considered if the above measures fail or the patient is in renal failure.
In treating hyperkalemia in patients receiving digoxin, too rapid a lowering of the serum potassium concentration can produce digoxin toxicity.
Dosage And Administration: The usual dietary intake of potassium by the average adult is 40 to 80 mmol/day. For information on food sources of potassium, see Mineral Food Sources in the Clin-Info section.
Potassium depletion sufficient to cause hypokalemia usually requires the loss of ³200 mmol of potassium from the total body store.
Dosage must be individualized according to the patient’s needs. Whenever possible, potassium supplementation should be given orally (or via nasogastric tube). Dosage must be reduced in patients with renal failure and administered with great caution, if at all.
Potassium chloride is generally the salt of choice in treating hypokalemia, as hypochloremia is usually an accompanying factor. However, metabolic acidosis may rarely coincide with hypokalemia, in which case an alkalinizing salt may be preferable, e.g., bicarbonate, citrate or gluconate.
Oral: Adults: Tablets should be administered whole with a full glass of water, and should not be broken or chewed. Oral liquids, soluble powders and effervescent tablets should be mixed or dissolved completely in 100 to 200 mL of cold water, juice or other liquid and drunk slowly. Administer with or after meals in 2 or 3 divided doses/day to minimize gastric irritation and too rapid absorption.
Prevention of Hypokalemia: supplementary, approximately 20 to 40 mmol/day.
Treatment of Depletion: approximately 40 to a maximum of 100 mmol/day. In general a daily dose exceeding 60 mmol should not be required.
Parenteral: For i.v. administration only; dilute concentrated solutions before infusing. The dose and rate of infusion are dependent on the individual patient’s condition.
Adults: Generally, potassium concentrations in peripheral i.v. solutions should not exceed 40 mmol/L. Higher concentrations (e.g., 60 mmol/L) may be needed in cases of severe hypokalemia and should be administered via a central line. Care must be taken to avoid extravasation.
In patients whose serum potassium concentration is above 2.5 mmol/L, the rate of infusion should not exceed 10 mmol/hour. The total dose should not exceed 200 mmol/24 hours.
For urgent treatment (serum potassium concentration
Children: 2 to 3 mmol/kg/day or 40 mmol/mday with serum level monitoring.
POTASSIUM SALTS General Monograph, Potassium Replacement Therapy