This systematic review aims to analyze the safety and efficacy of administering IV diuretics in the outpatient setting to patients with an acute heart failure exacerbation when compared to traditional management with inpatient hospitalization. Our search included studies that examined patients with both heart failure with reduced ejection (HFrEF) and heart failure with preserved ejection fraction (HFpEF) that presented with symptoms consistent with worsening heart failure, and that were treated with intravenous diuretics in an outpatient setting. The outcomes of interest were efficacy, measured by readmission rates and average reduction in weight, as well as safety, measured by mortality rates and incidence of adverse events, specifically hypotension, hypokalemia, and acute kidney injury.

A search was performed in the electronic databases MEDLINE, SCOPUS, CINAHL Complete, and Cochrane Central using non-controlled vocabulary search terms and the following controlled vocabulary indexation terms (MeSH and textwords for MEDLINE, Search codes for SCOPUS, and textwords for CINAHL Complete and Cochrane Central): Diuretics, Outpatients, and Intravenous. The search strategy was developed with the support of an information specialist to ensure a comprehensive approach incorporating all key search terms. An overview of the complete search strategy is available upon request. Selection criteria included full-text articles written in English, studies conducted in human adults, and included patients with heart failure and the use of IV diuretics outside of a hospital/inpatient setting. Review studies, case reports, case series, abstracts, studies examining the treatment with intravenous diuretics in the emergency department, or use of subcutaneous or oral diuretics were excluded.

A total of 801 titles and/or abstracts of studies retrieved using the search strategy were independently screened by three reviewing authors to identify studies that potentially met the inclusion criteria. Full texts of relevant studies were retrieved and independently assessed for eligibility. Of these, 786 articles were excluded, and 15 studies were selected to be included in this systematic review for data extraction. See Figure 1 for a flowchart of article selection on eligibility and inclusion of studies for data extraction. Data from selected studies were extracted manually by two authors. Patient characteristics, selection criteria, study protocol and treatment regimens, treatment outcome (all-cause mortality, re-hospitalizations for HF, efficacy, cost, and adverse events), and the limitations of these studies were examined. 30-day all-cause mortality and readmission rates were compared to patients hospitalized for decompensated heart failure and treated with IV diuresis from the 2021 Medicare database. Statistical analysis was conducted using a Chi-square test with Yates' correction.

Based on this evidence, the reviewed studies suggest that outpatient treatment with intravenous diuretics of patients with worsening HF has a low risk of adverse events, primarily AKI (2.3%), hypotension (0.7%), and hypokalemia, with hypokalemia being the most common (4.5%). Almost all studies included regular vital signs and laboratory monitoring before and after the administration of IV diuretics. Adverse events were typically reported as mild and transient. No patients in these studies required escalation of care due to an adverse event. The minority of patients who required readmission shortly after treatment had worsening HF refractory to IV diuresis rather than complications from treatment. Most patients required frequent clinic follow up visits after IV diuresis administration for additional safety monitoring. One study (13) focused exclusively on patients with cardiac amyloidosis and found that outpatient IV diuresis was similarly safe and effective in this population.

The selected studiesprovide evidence for reduction in rates of 30-day readmissions when compared to 2021 Medicare data (20.0% vs. 22.6%, p = 0.0401This suggests that outpatient IV diuresis is an acceptable alternative to manage acute heart failure, sparing patients an admission without leading to a rise in the need for readmission. Prior studies, such as the systematic review conducted by Wierda, et al. (2) did not demonstrate any significant reduction in readmission or mortality rates. This suggests that the many advances in heart failure management over the last decade have improved our ability to care for these patients outside of the hospital. Among the individual studies, there has been mixed evidence on the ability of transitional care models to reduce readmission rates for patients with heart failure. Further randomized trials are needed to better elucidate why readmissions occur, and how to prevent them with outpatient interventions.

Interestingly, our collective data also demonstrated a statistically significant decrease in 30-day mortality rates when compared to the 2021 Medicare data of patients hospitalized for heart failure exacerbations (5.6% vs. 10.7%, p = 0.0003). This may be explained by limited data and power, with this review incorporating additional studies. Additionally, many selected studies had strict exclusion criteria, which indicates a sampling bias towards patients that have milder disease being selected for outpatient diuresis. Another explanation is that routine complications of hospitalization are being avoided in the outpatient setting such as hospital-acquired pneumonia, venous thromboembolism, line-associated infections, delirium, and other iatrogenic insults. Lastly, advances are being made in the safety and treatment of heart failure itself such as the development of mortality-reducing medications and advanced monitoring techniques. The inability to control the baseline demographics and co-morbid conditions between the studies, and also among patients included in 2021 Medicare data, is a limitation of this study. Further studies are needed to directly compare outpatient and inpatient IV diuresis while controlling for variables such as age, gender, ejection fraction, and co-morbid conditions.

Cost was also analyzed in the majority of studies. The average cost savings per patient ranged from $839.4–$10,395. Based on median data, HF hospitalizations contributed to 65% of all medical HF costs over a 1-year treatment period post hospitalization (19). In addition to readmission, decreasing the incidence of emergency room visits may also play a crucial role in driving cost down. While operating an outpatient clinic requires significant financial resources and staffing, these studies demonstrate a cost benefit when compared to the traditional model of care.

There are many socioeconomic factors that influence whether a patient is hospitalized, regardless of HF severity such as patient preference, access to transportation, caregiver support, and other comorbid conditions that require a higher level of care. In certain patient populations, most often patients in the beginning stages of HF, intravenous diuretics administered in an outpatient setting is a reasonable alternative to traditional inpatient intravenous diuresis. This is also particularly important in a rural healthcare system where improving access to and quality of care are of significance due to costs and time associated with travel (4).

In order to determine which patients would benefit the most from outpatient treatment, further studies are needed to assist in establishing risk stratification and clinical decision making. One potential area of development is to create a risk stratification system to classify patients as low, intermediate, or high-risk based on their co-morbidities, initial vital signs, laboratory values, and severity of heart failure. One study (16) incorporated utilization of spot urine sodium as a triage tool in determining appropriateness of ambulatory IV diuresis. They found that high spot urine output was a useful indicator in generating an acceptable response to outpatient diuresis. These tools may help to triage patients in a more standardized way across institutions. It would also be beneficial to incorporate travel distance and time in considering the most ideal candidates for outpatient IV diuresis.

Prior studies have demonstrated that patients prefer outpatient treatment when compared to inpatient treatment (20). As our healthcare shifts to a more patient-centered approach, we have learned that matching patients' preferences to treatment options and settings may raise treatment adherence and outcomes. Outpatient diuresis also aims to reduce broader costs associated with inpatient hospitalization, and minimize delays in care that are due to over-saturation of emergency departments and inpatient units. Many of the studies included in this review did report cost-associated outcomes, and the general data represents an overall cost improvement with outpatient treatment. It is estimated that in the United States, savings of 650 million to more than 2 billion dollars is possible with a shift towards outpatient treatment for HF (2). This is becoming increasingly important in maintaining access to care as the estimated population of heart failure continues to rise.

Notably, there are logistical challenges related to running outpatient diuresis clinics such as staffing, space, access to diuretic infusions, and equipment needed for close monitoring of vital signs and laboratory values. Further advanced ambulatory techniques mentioned above would also incur further costs for the patients and healthcare systems. Other alternatives to intravenous diuresis are currently being explored, with subcutaneous diuretics as an area of potential interest. This has been shown to have increased bioavailability when compared to oral diuretics, and may be a suitable alternative when outpatient intravenous diuresis is not an option (21). Further studies are ongoing to better elucidate the role of subcutaneous diuretics in the management of acute decompensated heart failure. Randomized control trials with an inpatient IV diuresis control group are needed to more accurately compare safety and outcomes between the outpatient and inpatient setting.