Equation may help guide diuretic therapy in acute decompensated heart failure

The newly developed and validated equation predicts sodium output based on a spot urine sample collected two hours after administration of loop diuretics.


An equation that predicts natriuretic response based on a spot urine sample after diuretic administration could help improve diuretic therapy in patients with acute decompensated heart failure, a recent study found.

Researchers developed a natriuretic response prediction equation (NRPE) to predict sodium output using a spot urine sample collected two hours after administration of loop diuretics and created cohorts to validate it and to evaluate its effectiveness in clinical practice. In the first cohort, patients were given IV loop diuretics followed by timed, supervised six-hour urine collection that included spot urine samples at hours 1, 2, and 6. Sodium output was defined as poor (<50 mmol/L), suboptimal (<100 mmol/L), or excellent (>150 mmol/L). The NPRE was used to predict natriuretic response versus the reference value, which was directly measured six-hour cumulative sodium output. The second cohort, the Yale Diuretic Pathway (YDP) cohort, used the equation to guide titration of loop diuretics with a nurse-driven automated protocol. The study results were published Feb. 8 by the Journal of the American College of Cardiology.

In the first cohort, which included 409 patients and 638 cases in which loop diuretics were administered, the NPRE had excellent discrimination for predicting poor, suboptimal, and excellent natriuretic response, with an area under the curve greater than or equal to 0.90. It also outperformed clinically obtained net fluid loss (P<0.05 for all cutpoints). In the second cohort, the YDP was initiated in 161 patients. The protocol called for 2 to 12.5 mg of IV bumetanide to be administered up to three times daily, with spot urine sodium and creatinine levels checked one to two hours after each dose. Spot urine data were automatically sent to the electronic health record, where a computerized decision support tool calculated the predicted natriuretic response using the NPRE and provided the next recommended IV bumetanide dose to the nurse. Mean daily urine output (1.8 ± 0.9 L vs. 3.0 ± 0.8 L), net fluid output (−1.1 ± 0.9 L vs. −2.1 ± 0.9 L), and weight loss (−0.3 ± 0.3 kg vs. −2.5 ± 0.3 kg) all improved after the protocol was initiated (P<0.001 for all comparisons).

The authors noted that the study was done at two hospitals in the same health system and that the protocol should be tested in other settings. Among other limitations, they said that no specific inclusion or exclusion criteria were used for the second cohort, that it had no control group, and that the protocol was not started at hospital admission in all patients. They concluded that the NPRE can be used to rapidly and accurately predict natriuretic response and guide IV diuretic therapy in patients with acute decompensated heart failure. “Incorporating the NRPE into an automated, nurse-driven diuretic titration protocol resulted in rapid diuretic titration and what appeared to be safe and effective decongestion,” the authors wrote. “Further research is warranted to understand if this strategy can improve post-discharge outcomes.” They plan to evaluate their approach in a blinded randomized trial.

An accompanying editorial pointed out additional limitations of the study, including substantial resistance in the second cohort to diuretics at baseline and the fact that the study did not address continuous infusions of loop diuretic agents or thiazides. “Likewise, the YDP prioritizes upfront escalation to maximal loop diuretic therapy before considering adjunctive diuretic agents, but the utility of this approach versus early introduction of thiazide and other diuretics is unclear,” the editorialists wrote.

However, the editorial noted that despite these limitations, the proposed protocol is practical, may improve efficiency of care, and allows objective grading of diuretic response and dose selection. “For patients hospitalized for HF [heart failure], multiple stakeholders continue to emphasize the post-discharge phase following hospitalization; yet, we must not let these initiatives distract from obvious knowledge gaps regarding best upstream inhospital management,” the editorialists wrote. “High-quality evidence to guide in-hospital management of congestion and use of diuretic agents is long overdue, and carries significant potential to fundamentally change HF care delivery.”