on 27-Feb-2021 (Sat)

Stable patients with chronic diuretic therapy (at a fixed dose), primary aldosteronism (unless aldosterone secretion increases), or Gitelman or Bartter syndrome typically do not develop progressive hypokalemia because the increased urinary potassium losses are balanced by hypokalemia-induced potassium retention. The net effect is a new steady state in which potassium intake and output are in balance, with a lower-than-normal serum potassium concentration. A potassium-sparing diuretic is usually required in such patients who do not respond adequately to potassium supplementation.

There are two classes of potassium-sparing diuretics: blockers of the cortical collecting tubule sodium channels (amiloride and triamterene); and the aldosterone (mineralocorticoid receptor) antagonists (spironolactone and eplerenone). With respect to treating hypokalemia, these drugs are used in patients with renal potassium wasting in whom, as noted in the preceding section, potassium supplements may not be sufficiently effective

Amiloride is usually preferred to a mineralocorticoid receptor antagonist because it is better tolerated (see "Triamterene nephrotoxicity"). Primary aldosteronism is an important exception since spironolactone or eplerenone is preferred to block apparent adverse effects of excess aldosterone on the heart and vascular system in patients diagnosed with this disorder.

Among patients with heart failure, mineralocorticoid receptor antagonists should be given only if the serum creatinine is less than or equal to 2.5 mg/dL (221 micromol/L) in men and 2.0 mg/dL (177 micromol/L) in women and the serum potassium is less than 5.0 mEq/L.

Most hypokalemic patients have a serum potassium concentration of 3.0 to 3.4 mEq/L. This degree of potassium depletion usually produces no symptoms. Exceptions include patients with heart disease (particularly if they are taking digitalis or certain other antiarrhythmic drugs or are undergoing cardiac surgery [50,51]) and patients with cirrhosis, in whom hypokalemia can increase ammonia generation and promote the development of hepatic encephalopathy

Patients with gastrointestinal losses are treated with potassium chloride if they have metabolic alkalosis (as usually seen with vomiting) or a normal serum bicarbonate concentration, and with potassium bicarbonate (or potassium citrate or acetate) in the presence of metabolic acidosis (as seen with diarrhea or renal tubular acidosis). Treatment is usually started with 10 to 20 mEq of potassium given two to four times per day (20 to 80 mEq/day), depending upon the severity of the hypokalemia.

By contrast, potassium supplements at usual doses produce only modest elevations in serum potassium in patients with hypokalemia due to renal potassium wasting (eg, chronic diuretic therapy, primary aldosteronism). As soon as the serum potassium rises, there is less hypokalemia-induced potassium retention and most of the administered potassium is excreted in the urine. Thus, a potassium-sparing diuretic is likely to be more effective. Amiloride is usually preferred to a mineralocorticoid receptor antagonist because it is better tolerated. Primary aldosteronism is an important exception since spironolactone or eplerenone is preferred to block apparent adverse effects of excess aldosterone on the heart and vascular system

Potassium must be given more rapidly to patients with hypokalemia that is severe (serum potassium less than 2.5 to 3.0 mEq/L) or symptomatic (arrhythmias, marked muscle weakness, or rhabdomyolysis)

A potential diagnostic and therapeutic problem in patients with hypokalemia-induced rhabdomyolysis is that the release of potassium from the muscle cells can mask the severity of the underlying hypokalemia or even lead to normal or elevated values at presentation or after potassium supplementation. If the serum potassium is normal or elevated at baseline, it will not be possible to be certain that underlying hypokalemia was responsible for the rhabdomyolysis and initial potassium therapy in such patients is not warranted and may be dangerous

Particular caution must be exercised when repleting potassium in patients with a concurrent disorder that, when treated, will tend to drive potassium into the cells and worsen the hypokalemia. The two main examples are insulin therapy in diabetic ketoacidosis or nonketotic hyperglycemia, and bicarbonate therapy in metabolic acidosis with a normal anion gap

Potassium repletion is most easily accomplished orally but can be given intravenously. The serum potassium concentration can transiently rise by as much as 1 to 1.5 mEq/L after an oral dose of 40 to 60 mEq, and by as much as 2.5 to 3.5 mEq/L after 135 to 160 mEq [52,53]. The serum potassium concentration will then fall back toward baseline over a few hours, as most of the exogenous potassium is taken up by the cells [54]. A patient with a serum potassium concentration of 2.0 mEq/L, for example, may have a 400 to 800 mEq potassium deficit [39]. In patients with severe hypokalemia, potassium chloride can be given orally in doses of 40 mEq, three to four times per day or, particularly in patients also treated with intravenous potassium, 20 mEq every two to three hours.

Careful monitoring is essential in patients treated with potassium. We suggest that the serum potassium should initially be measured every two to four hours to ascertain the response to therapy. If tolerated, this regimen should be continued until the serum potassium concentration is persistently above 3.0 to 3.5 mEq/L and symptoms or signs attributable to hypokalemia have resolved. Thereafter, the dose and frequency of administration can be reduced to that used in mild to moderate hypokalemia since aggressive repletion is no longer required and gastric irritation can be avoided.

A saline rather than a dextrose solution should be used for initial therapy since the administration of dextrose stimulates the release of insulin which drives extracellular potassium into the cells. This can lead to a transient 0.2 to 1.4 mEq/L reduction in the serum potassium concentration, particularly if the solution contains only 20 mEq/L of potassium [3,55]. The transient reduction in serum potassium can induce arrhythmias in susceptible patients, such as those taking digitalis [55].

Furthermore, treatment with insulin and intravenous fluids will exacerbate the hypokalemia and minimize the efficacy of potassium repletion. Thus, insulin therapy should be delayed until the serum potassium is above 3.3 mEq/L to avoid possible complications of hypokalemia such as cardiac arrhythmias, cardiac arrest, and respiratory muscle weakness.

Although isotonic saline is often the initial replacement fluid used in treating diabetic ketoacidosis or nonketotic hyperglycemia, the addition of potassium will make this a hypertonic fluid (since potassium is as osmotically active as sodium), thereby delaying reversal of the hyperosmolality. Thus, 40 to 60 mEq of potassium per liter in one-half isotonic saline is preferred.

In contrast to patients with marked potassium depletion, patients with hypokalemia due to potassium redistribution (eg, hypokalemic periodic paralysis) have no potassium deficit and even low rates of potassium administration can result in hyperkalemia once the redistributed potassium returns to the extracellular fluid. In a report of patients with hypokalemic thyrotoxic periodic paralysis (baseline serum potassium concentration 2.0 mEq/L), administration of potassium at a rate of 10 mEq/hour (80 mEq/L) resulted in hyperkalemia (>5.5 mEq/L) in 40 percent of patients, one-half of whom had ECG changes [30]. Appropriate therapy in these patients is discussed separately

Pain and phlebitis can occur during parenteral infusion of potassium into a peripheral vein. This primarily occurs at rates above 10 mEq/hour, but can be seen at lower rates. If pain occurs, either the infusion rate or, preferably, the potassium concentration should be reduced.

Rates above 20 mEq/hour are highly irritating to peripheral veins. Such high rates should be infused into a large central vein or into multiple peripheral veins.

For patients with severe hypokalemia due to gastrointestinal or renal losses, the recommended maximum rate of potassium administration is 10 to 20 mEq/hour in most patients.

● In any 1000 mL-sized container of appropriate non-dextrose fluid, we suggest a maximum of 60 mEq of potassium.

● In a small-volume mini-bag of 100 to 200 mL of water that is to be infused into a peripheral vein, we suggest 10 mEq of potassium.

● In a small-volume mini-bag of 100 mL of water that is to be infused into a large central vein, we suggest a maximum of 40 mEq of potassium.

Intravenous potassium is most often infused in a peripheral vein at concentrations of 20 to 60 mEq/L in a non-dextrose-containing saline solution. Use of an infusion pump is preferred to prevent overly rapid potassium administration in any intravenous container with more than 40 mEq of potassium or if the desired rate of potassium administration is more than 10 mEq/hour. For patients with severe hypokalemia, administration in a large central vein is preferred if this access is available.