The 2022 American College of Cardiology/American Heart Association heart failure (HF) guideline indicated that IV loop diuretic therapy provided the most rapid and effective relief for signs and symptoms of congestion leading to hospitalization for HF. It also stated that no changes in patients’ global assessment of symptoms or in renal function had been observed when diuretic therapy was administered by continuous infusion (CInf), by bolus injection (BInj), at a high dose, or at a low dose; however, that observation was based on one study. The guideline falls short of making specific recommendations as to dose and mode of administration of loop diuretics in HF.

The researchers conducted a meta-analysis to compare the effects of IV loop diuretics administered by CInf versus BInj in patients with acute decompensated HF. They searched PubMed and EMBASE databases for randomized, controlled trials published between January 1, 2001, and July 31, 2022, comparing CInf with intermittent BInj furosemide in patients with congestive HF. They excluded studies involving patients with chronic stable HF, case reports, case series, observational studies, nonrandomized studies, review articles, and those involving patients with valvular heart disease, postcardiac surgical patients, or congenital heart disease.

The primary outcome of the meta-analysis was all-cause mortality and loss of body weight. Secondary outcomes included length of hospital stay (LOS), brain natriuretic peptide (BNP) reduction, occurrence of hypokalemia, and urine output at 24 hours.

Nine studies involving 786 patients were included in the meta-analysis. The mean age was 66.86 years (range 55.5-82 years), with nearly three-quarters of patients being male. Study populations ranged in size from 14 to 156 patients.

Fewer than one-half (44.4%) of studies compared all-cause mortality among patients receiving CInf or BInj of furosemide within 6 months of the acute severe inpatient hypertensive episode. While the incidence of all-cause mortality was higher in the CInf group (14.69%) versus the BInj group (9.34%), it did not achieve statistical significance (relative risk [RR] 1.51; 95% CI, 0.94-2.43). Almost 90% of studies assessed LOS in a total of 713 patients and did not find a difference between the two treatment groups (mean difference –0.10; 95% CI, –2.05-1.84). Two-thirds of studies compared reduction in body weight and found a statistically significant difference in favor of CInf (mean difference –1.08; 95% CI, –1.36 to –0.80). Total urine output was assessed in almost 90% of studies and was not found to be significantly different between CInf and BInj (mean difference –485.56; 95% CI, –1088.28-117.16). One-third of the studies reported reductions in BNP and found no difference between the groups (mean difference –220; 95% CI, –522.54-82.55). Lastly, 33% of studies compared the incidence of hypokalemia on Day 3 and at discharge between those who received CIinf and BInj and found that hypokalemia occurred less frequently in patients receiving the BIinj (17.52%) than in the CInf group (25.51%), but this difference was not statistically significant (RR 1.35; 95% CI, 0.55-3.27). Heterogeneity varied among the studies.

The authors concluded that CInf seemed to produce a greater reduction in body weight but not in 24-hour urine output, LOS, all-cause mortality, the incidence of hypokalemia, and BNP reduction; however, the investigators did not favor one regimen over the other, citing the small sample sizes of the study populations. The results were similar to a Cochrane Database Systematic Review from 2005 that found available data were insufficient to allow for definitive recommendations for clinical practice as to which administration method was superior. The systematic review had found greater diuresis and a better safety profile was associated with CInf administration compared with BInj.

As decompensated HF is one of the leading causes of hospitalizations in the United States, this paper provides acute care pharmacists with a comparative analysis of formulations that they frequently encounter in their routine practice.

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