Diuretic Induced Hypokalemia


DIURETIC INDUCED HYPOKALEMIA

INTRODUCTION

Hypokalemia is a comparatively frequent drawback with diuretic remedy. Profound hypokalemia (serum potassium concentrations ≤2.5 to three.zero meq/L), nevertheless, is comparatively uncommon, described in fewer than 10 to 15 p.c of sufferers receiving excessive doses of diuretics, and customarily solely in these not receiving potassium supplementation.

The lower in plasma focus following extended administration of 50 mg of hydrochlorothiazide per day is roughly zero.5 meq/L, whereas the identical dose of long-acting chlorthalidone causes a larger fall in serum potassium focus (zero.eight meq/L) [1] . In distinction, short-term administration (three days) of 50 mg of chlorthalidone and 40 mg of furosemide ends in a fall in serum potassium focus of solely zero.four and zero.2 meq/L, respectively.

The incidence and severity of hypokalemia are dose-dependent, occurring a lot much less continuously with decrease doses [5,6] . Thus, decrease doses of thiazides (eg, 12.5 mg/day of hydrochlorothiazide or chlorthalidone) or loop diuretics are actually broadly used within the therapy of hypertension as a result of they’re as efficient in blood strain discount with a lesser impact on electrolyte stability.

MECHANISMS

Two components seem like liable for the urinary potassium losing :

  • Elevated supply of sodium and water to the aldosterone-sensitive potassium secretory website within the amassing tubules; and
  • Elevated secretion of aldosterone on account of diuretic-induced quantity depletion or on account of an underlying illness equivalent to coronary heart failure (present determine three) [7] .

TIME COURSE

In secure sufferers on a set diuretic dose, potassium loss, like different diuretic-induced fluid and electrolyte issues, happens solely in the course of the first two weeks of remedy earlier than a brand new regular state is established. Thus, a secure affected person with a traditional serum potassium focus at three weeks isn’t vulnerable to late hypokalemia except the diuretic dose is elevated, extrarenal potassium losses enhance, or dietary potassium consumption is diminished.

CLINICAL SIGNIFICANCE

The event of hypokalemia is of biggest concern in sufferers with underlying coronary heart illness, cirrhosis, or hypertension:

* Potassium depletion can result in cardiac arrhythmias, significantly within the presence of concurrent digitalis remedy or a serum potassium focus ≤three.zero meq/L [1] . As well as, hypokalemia could contribute to an elevated incidence of sudden dying in sufferers with hypertension and left ventricular hypertrophy.

* Hypokalemia (serum potassium lower than three.5 meq/L) can precipitate hepatic coma in some sufferers with superior cirrhosis, due not less than partially to elevated renal ammonia synthesis. The latter impact is mediated partially by a transcellular potassium-hydrogen trade.

* Potassium depletion could have two extra deleterious results in sufferers with hypertension: it might probably increase the blood strain by a imply of 5 to 7 mmHg (in all probability due partially to concurrent sodium retention); and it might probably enhance the incidence of stroke, impartial of different cardiovascular threat components. Alternatively, potassium supplementation can decrease the blood strain by a median of 6/three mmHg.

TREATMENT

All sufferers handled with a diuretic must be monitored for the event of hypokalemia in the course of the first two to a few weeks of remedy. In secure sufferers on a set dose of a diuretic (eg, for hypertension), potassium loss happens solely in the course of the first two to a few weeks of remedy earlier than a brand new regular state is established.

As soon as a gradual state is reached, additional monitoring isn’t required, except the diuretic dose is elevated, extrarenal potassium losses enhance, or dietary potassium consumption is diminished. For example, elevated losses and decreased consumption could also be seen with gastroenteritis. In such sufferers, short-term cessation of diuretic remedy for a number of days could also be acceptable.

The easiest way to deal with diuretic-induced hypokalemia is prevention through the use of the bottom efficient dose. Not surprisingly, the danger of hypokalemia (in addition to different diuretic-induced metabolic issues) is dose-dependent. Therapeutic points differ with the underlying situation being handled.

Hypertension — In most hypertensive sufferers, 12.5 to 25 mg of hydrochlorothiazide (or its equal) produces as nice a fall in blood strain as increased doses, however a a lot smaller discount within the serum potassium focus.

The frequent lack of improved blood strain management with increased diuretic doses could also be associated to activation of the renin-angiotensin-aldosterone system: angiotensin II is a potent vasoconstrictor that can are likely to counteract the antihypertensive impact of extra fluid loss, whereas hyperaldosteronism will improve urinary potassium losses.

Low-dose thiazide remedy isn’t typically utilized in sufferers with resistant hypertension, underlying renal insufficiency, or an edematous state. Loop diuretics are most well-liked within the latter two settings. (See “Optimum dosage and unwanted side effects of loop diuretics” and see “Resistant hypertension”).

Given the usually small discount in serum potassium with low-dose thiazide remedy, prophylactic remedy to keep away from hypokalemia isn’t warranted. If hypokalemia does happen, there are two primary choices: change to a different antihypertensive drug; or deal with the hypokalemia with potassium chloride dietary supplements (starting with 40 meq/day) or with a potassium-sparing diuretic equivalent to amiloride, triamterene, or spironolactone. Among the many potassium-sparing diuretics, we choose amiloride as a result of it has the fewest unwanted side effects.

Potassium-sparing brokers additionally spare magnesium [1,9,11] . This can be a fascinating impact since diuretic-induced magnesium depletion could also be instantly arrhythmogenic and can also trigger hypokalemia that’s refractory to potassium repletion alone.

Correction of hypokalemia has the added benefit of manufacturing a small additional discount in blood strain

Coronary heart failure and cirrhosis — Prophylactic remedy to forestall hypokalemia is a crucial subject in sufferers with coronary heart failure and cirrhosis:

* Amongst sufferers with coronary heart failure, hypokalemia could precipitate critical arrhythmias. It’s endorsed that the serum potassium focus be maintained between four.zero and 5.zero meq/L. As well as, hyperaldosteronism itself seems to contribute to hostile cardiac occasions in sufferers with average to extreme coronary heart failure on account of mineralocorticoid receptors within the coronary heart and vasculature. In such sufferers, outcomes could also be improved with a mineralocorticoid receptor antagonist (spironolactone or eplerenone) (present determine 5). Thus, sufferers who want continual remedy for a beneath aim serum potassium focus must be handled with a mineralocorticoid receptor antagonist fairly than potassium dietary supplements.

The info supporting the cardiac and vascular toxicity of hyperaldosteronism are mentioned individually. (See “Use of diuretics in coronary heart failure”, part on Improved survival with aldosterone antagonism, and see “Scientific options of main aldosteronism”, part on Cardiovascular threat).

* Amongst sufferers with cirrhosis, hypokalemia can promote the event of hepatic encephalopathy, maybe partially by rising ammonia manufacturing. The serum potassium focus must be maintained above three.four meq/L. Most sufferers with cirrhosis are already being handled with spironolactone, since it’s a part of the really helpful diuretic routine. (See “Preliminary remedy of ascites in sufferers with cirrhosis”, part on Considerations with diuretic remedy and part on Diuretic routine).

As talked about above, potassium-sparing brokers additionally spare magnesium [1,9,11] . This can be a fascinating impact since diuretic-induced magnesium depletion could also be instantly arrhythmogenic and can also trigger hypokalemia that’s refractory to potassium repletion alone. (See “Indicators and signs of magnesium depletion”).

PROPHYLAXIS

A separate subject from potassium alternative is the attainable function of prophylactic potassium supplementation in sufferers with coronary heart failure who want aggressive diuresis and have a borderline serum potassium focus (eg, four.zero to four.2 meq/L for the reason that aim is to take care of the serum potassium at a minimal of four.zero meq/L). There are two approaches in such sufferers: extra frequent monitoring, which we choose, or prophylactic potassium supplementation.

MONITORING

After initiation of both potassium-sparing diuretics or potassium dietary supplements, potassium ranges should be monitored. As with the event of hypokalemia, the rise within the serum potassium focus with a set dose of both potassium chloride or a potassium-sparing diuretic in a secure affected person will typically be full throughout the first two to a few weeks of therapy. Ongoing periodic monitoring is required in sufferers with coronary heart failure or cirrhosis, who could have progressive illness.

SUMMARY AND RECOMMENDATIONS

Hypokalemia is a comparatively frequent drawback with diuretic remedy, with the danger rising at increased doses. Marked hypokalemia (serum potassium concentrations ≤2.5 to three.zero meq/L) is rare, being described in fewer than 10 to 15 p.c of sufferers receiving excessive doses of diuretics.

The event of hypokalemia is of biggest concern in sufferers with underlying coronary heart failure or cirrhosis, as it might result in arrhythmias and hepatic coma, respectively. As well as, it might result in a modest elevation in blood strain in hypertensive sufferers.

In sufferers with hypertension who develop diuretic-induced hypokalemia, both one other agent can be utilized, or the hypokalemia might be handled with a potassium-sparing diuretic or potassium supplementation. If a potassium-sparing is chosen, we advise amiloride, because it has the fewest unwanted side effects.

In sufferers with coronary heart failure or cirrhosis who develop hypokalemia on diuretic remedy, remedy ought to embody a mineralocorticoid receptor antagonist since these medicine are used for causes apart from hypokalemia:

* In sufferers with coronary heart failure, we advocate a mineralocorticoid receptor antagonist (spironolactone or eplerenone) due to improved survival due partially to blockade of mineralocorticoid receptors within the coronary heart and vasculature (Grade 1B).

Such advantages of mineralocorticoid receptor blockade haven’t been evaluated in sufferers with important hypertension in whom hyperaldosteronism isn’t a typical function. Nevertheless, mineralocorticoid receptor blockers are necessary in sufferers with main aldosteronism.

* We advocate a mineralocorticoid receptor antagonist (spironolactone or, if not tolerated, eplerenone) in sufferers with cirrhosis and ascites on account of elevated diuretic efficacy in comparison with amiloride (Grade 1B).

After initiation of potassium sparing brokers or potassium dietary supplements, potassium ranges must be monitored, significantly in the course of the first two to a few weeks of therapy and after dose changes.

Diuretic-induced hypokalemia is greatest prevented by use of the bottom efficient dose.

We advise not routinely offering prophylactic remedy to forestall hypokalemia (Grade 2C). That is significantly true in sufferers with hypertension on low-dose thiazide remedy. Sufferers with coronary heart failure who’re present process a fast diuresis require extra frequent monitoring of the serum potassium focus.

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