Tom G. Bartol, MN, NP DISCLOSURES

July 10, 2019

Loop diuretics are widely used in the management of edema and heart failure. They are also widely misunderstood.

The reason is this: Loop diuretics are often prescribed in a dose-dependent strategy. Looking for gentle diuresis? Prescribe a low dose. For a more dramatic response, use a higher dose.

But loop diuretics (eg, furosemide, torsemide, bumetanide) don’t work that way. Loop diuretics are “all-or-none” drugs; they are either “on” or “off.” There is no dimmer switch.^[1]

This was the main message in a recent review from Anisman and colleagues,^[1]about the use of loop diuretics in the management of edema. The authors (a cardiologist, a nephrologist, and a primary care physician) not only conducted an exhaustive literature search, but they also consulted with patients who had experience taking chronic loop diuretics to ensure that their recommendations were practical and patient-centered.

The somewhat unusual pharmacokinetics of loop diuretics explain their all-or-nothing binary clinical response.^[1] Loop diuretics accumulate in the renal tubules, and when the threshold for intratubular concentration of the drug is reached, diuresis occurs. In that case, increasing the dose of loop diuretic won’t increase diuresis further and will only expose the patient to more adverse effects. But if the patient doesn’t respond (frequent urination within 4-6 hours after an oral dose), then the threshold wasn’t reached and a higher dose may be required. The activation threshold is patient-specific; it differs from one patient to the next.

What about the patient who reports voiding frequently, all day and night? The dose is probably sub therapeutic and should be increased. Nocturia usually indicates sub threshold dosing rather than an excessive response.

Other key findings of this review:

• Moderate evidence suggests that torsemide may have advantages over furosemide, including higher potency, longer duration of action, and possibly better symptom control.
• Once the patient is euvolemic after diuresis, use as-needed dosing of the loop diuretic, based on daily weight. The patient takes the therapeutic dose on days when there is a certain amount of weight gain or edema and otherwise foregoes it (the authors provide sample language to instruct patients on as-needed dosing).
• Certain concomitant medications can reduce the effect of loop diuretics(eg, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs).
• Common errors in loop diuretic use include prescribing different doses for morning and evening, prescribing subtherapeutic doses in an effort to achieve gentle diuresis, and prescribing variable doses depending on weight and degree of edema.
• A larger dose of loop diuretic may be needed to achieve the same effect as renal function declines or proteinuria rises. Mild tolerance to loop diuretics can develop over time, requiring a higher dose.
• Common myths about loop diuretics include avoidance in sulfa allergy and discontinuation if the creatinine level rises.