Managing Hypervolemia: Is More Diuretic Better?

In medicine, we're often led to believe that "more is better." More interventions will result in better outcomes. More monitoring will result in earlier detection. More education will improve adherence. But our acceptance of the "more is better" philosophy as a universal truth could lead us astray.

For example, in hypervolemic patients, our referring colleagues urge us to diurese these patients as quickly as possible, using all available methods at our disposal. Once the diuresis has begun, we're often cajoled into increasing its frequency and/or intensity. More diuretics archives euvolemia faster and results in better outcomes for the patient, right?

Let's look at this more closely by analyzing two randomized trials on loop diuretic administration in acute decompensated heart failure: DOSE and DRAIN.

In DOSE, which was published at the beginning of the last decade, nearly 300 symptomatic patients received either continuous infusion or intermittent bolus of furosemide (every 12 hours) and either high- or low-dose furosemide to see whether a particular mode and/or dose of loop diuretic would achieve clinical improvement after 72 hours of therapy. The investigators included two primary endpoints: efficacy based on patient global assessment of symptoms (a survey) and safety based on the change in serum creatinine level.

The somewhat similar DRAIN study was published at the end of the last decade. It randomly assigned 80 patients to receive continuous infusion or intermittent bolus of furosemide. Then patients were subdivided on the basis of whether they received higher or lower doses of the loop diuretic; this dosing was at the treating physician's discretion. The primary efficacy endpoint was freedom from congestion, and safety was a secondary endpoint (measured as change in serum creatinine level).

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How do these two studies compare, and what can they tell us about more exposure versus greater intensity of the diuretic regimen? As is often the case in nephrology, the results of DOSE and DRAIN seemingly contradict one another. Continuous loop diuretic exposure did not yield quicker symptom improvement in DOSE, and there was a trend toward improvement with the higher diuretic dose. Although that result was not statistically significant, the associated worsening in kidney function in the high-dose arm was (23% vs 14% in the low-dose arm). In DRAIN, there was a better chance of reaching the primary outcome with continuous loop diuretic exposure and no statistically significant worsening of kidney function (18% in both arms).

These contradictions may reflect key structural differences between the trials. For example, the patients in DOSE had higher ejection fractions, and the study used a subjective survey to measure efficacy. DRAIN was a smaller study, and it enrolled patients at high risk for diuretic resistance. A strength of DOSE over DRAIN is that it included safety (rise in creatinine) as a primary endpoint.

Does more exposure (ie, continuous infusion) or greater intensity (ie, a higher dose of furosemide) result in faster diuresis and a quicker return to euvolemia? The data are not convincing to me that more is better in these patients. I think we should rely on our personal experience to guide our recommendations. Share your experiences in the comments below.

Tejas P. Desai, MD, is a practicing nephrologist in Charlotte, North Carolina. His academic interests include the use of social media for physician, student, and patient education. He is the founder of NOD Analytics, a free social media analytics group that serves the medical education community. He has two wonderful children and enjoys spending time with them and his wife.

Follow Tejas P. Desai, MD, on Twitter: @nephondemand

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