A Randomized Trial of Protocolized Diuretic Therapy Compared to Standard Care in Emergency Department Patients with Acute Heart Failure

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Of the one million emergency department (ED) patients hospitalized with acute heart failure (AHF), loop diuretics are the only IV treatment used over 80% of the time, although only with level of evidence C. Prior studies have focused on the initial dose of IV diuretic and failed to find one strategy with maximal efficacy. Diuretic dosing and response vary widely, leaving many patients inadequately treated. Some have a clinical response to diuretic therapy resulting in symptom improvement and discharge from the hospital within 3-5 days.

However, despite apparent symptom improvement, 50% of these patients experience no weight loss and up to 50% leave the hospital with residual congestion. Patients with residual congestion and minimal weight loss at hospital discharge experience a disproportionately high number of readmissions. Up to 20% of hospitalized patients have a poor initial response to IV loop diuretics, and are considered diuretic “non- responsive”.

As a result of untreated fluid and sodium retention, worsening heart failure (WHF) occurs frequently during their inpatient stay. Patients who develop WHF experience prolonged hospital lengths of stay (LOS), increased mortality, and consume significantly more resources. There is an unmet need to individualize diuretic therapy to improve decongestion and subsequently reduce adverse events. Yet, even knowing the fundamental role of congestion in AHF, there is little consensus among clinicians about how to optimize diuretic responsiveness. Despite multiple clinical trials aiming to clarify the ideal approach to loop diuretics in the management of congestion, the appropriate selection of dose and route, as well as determination of effectiveness of diuretic therapy remains largely empirical.

A standardized, protocol-driven treatment pathway for hospitalized patients started in the first two hours of ED evaluation and utilizing objective measures of diuretic response is needed. This would maximize diuretic efficiency, facilitate quicker resolution of congestion, avoid WHF and prolonged LOS, and reduce AHF readmissions. Our strong preliminary data suggests low urine sodium predicts length of stay and outcomes after initial diuretic dosing in the outpatient and inpatient setting, and can be used to titrate diuretics. Our preliminary use of spot urine sodium to titrate loop diuretic doses and maximize response in inpatients with AHF has shown compelling improvements in congestion and weight loss.

We propose to begin this protocol in the ED and hypothesize it will improve AHF outcomes relative to structured guideline-based usual care. Specifically, we hypothesize use of spot urine guided diuretic therapy will: 1) result in significant improvement in global clinical status at 5 days relative to structured guideline-based usual care, and 2) result in significant improvement in congestion at 5 days and in global rank at 30 days relative to structured guideline-based usual care. Early protocolized treatment of patients with AHF will more rapidly improve dyspnea, avoid development of in-hospital WHF, result in greater decongestion at hospital discharge, and therefore prevent HF-related readmissions and CV death.