Salt Loading in Diuretic-Resistant ADHF -- Really?

Tejas P. Desai, MD


March 31, 2020

The premise of acute decompensated heart failure (ADHF) management has been to increase natriuresis, primarily by decreasing sodium reabsorption in the nephron. Salt-loading of patients with ADHF through hypertonic saline is both counterintuitive and a source of legitimate anxiety for many physicians. However, a new study rekindles the idea of promoting natriuresis through increasing renal plasma flow by salt "loading."

Hypertonic Saline: Help or Harm?

How can promoting the very thing that we are trying to treat (symptomatic volume overload) be therapeutic? Yale University investigators who have been using hypertonic saline under strict observation report their findings from 40 patients with diuretic-resistant ADHF—defined as a decompensated state despite a median daily furosemide dose of 400 mg. These patients were given two to seven "doses" of 3% saline infusion, administered over 30 minutes and continued at the discretion of the physician. Both urine output and daily weight were measured 3 days before initiation of hypertonic saline (when patients received only high-dose diuretic) and 3 days after. Because infusion of hypertonic saline is somewhat anxiety-provoking, the treating physician monitored both supplemental oxygen use and fraction of inspired oxygen (FIO2) levels before and after initiation.

This retrospective study showed a greater daily weight reduction and greater urine output with hypertonic saline. Most of the patients in the chart review did not experience an adverse event when given hypertonic saline; there was no increase in the number of patients who needed supplemental oxygen (43% pre- and post-saline), and the FIO2 remained constant during the saline infusion period.

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I was initially impressed by these results, until I dug a bit deeper and was puzzled at the high number of patients receiving inotropic support (64%). If the therapeutic effect of hypertonic saline in ADHF is to increase renal blood flow and thereby increase sodium excretion, why wouldn't a similar result be seen with inotropic support alone? Is hypertonic saline influencing natriuresis by a mechanism other than altering renal blood flow alone? Is the larger weight loss due to enhanced salt or free water excretion? Urine electrolyte values were not reported, making it difficult to ascertain the "quality" of urine. With these limitations, I would not be surprised if most readers move hypertonic saline to the back of the treatment line for ADHF. A randomized trial of hypertonic saline in ADHF, however, may change that.

Studied Before

As it happens, two decades ago, investigators in Italy randomly assigned 60 patients with ADHF to continue high-dose loop diuretic alone or in combination with hypertonic saline. The patients had New York Heart Association (NYHA) class IV heart failure and were refractory to high-dose diuretics. Those in the hypertonic saline arm were dosed on the basis of their degree of hyponatremia: the more severe the hyponatremia, the greater the salinity infused. Hypertonic saline was administered twice daily until NYHA class IIb and ideal body weight were achieved, after which therapy was converted to oral furosemide in all patients. None of the patients was maintained on an inotropic agent.

The patients with ADHF who received hypertonic saline lost more weight, made more urine, and excreted more sodium than those maintained on high-dose diuretic only. And they spent fewer days in the hospital. Despite being small, this randomized study suggests that hypertonic saline without inotropic support is safe and can improve diuretic-resistant ADHF. So why aren't we using it?

A common misperception is that peripheral vein infusion is an absolute contraindication or that administration can be done only in an intensive care unit. Make no mistake, indiscriminate and unmonitored infusion of hypertonic saline is dangerous and ill-advised, but that doesn't mean we can ignore its potential benefit in treating patients with ADHF. We need more randomized trials, like the one performed in Italy two decades ago, to get us more comfortable using hypertonic saline in patients with ADHF.

Do you have experience with hypertonic saline in patients with ADHF? Share your insights 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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