Abstract
IV loop diuretics remain the cornerstone of treatment for acute decompensated heart failure (ADHF). Although previous meta-analyses have compared continuous infusion and intermittent bolus dosing of IV loop diuretics, their respective renal effects remain unclear. Given the prognostic significance of worsening renal function (WRF) or acute kidney injury in ADHF, evaluating the renal safety of different diuretic regimens is essential. We conducted a systematic search of the PubMed database and performed a meta-analysis of randomized controlled trials (RCTs) comparing both diuretic strategies. The primary outcome was WRF, while secondary outcomes included increases in serum creatinine (sCr), sCr levels at discharge, discharge blood urea nitrogen (BUN) levels, and length of hospitalization. A post hoc trial sequential analysis (TSA) was also conducted to assess the adequacy of the current pooled evidence. A total of 11 RCTs were included. There was no statistically significant difference in the incidence of WRF between continuous infusion and intermittent bolus dosing (RR 1.12; 95% CI, 0.86 to 1.48; I² = 0.00%). Similarly, no significant differences were found in secondary outcomes: increase in sCr (mean difference (MD) 0.24 mg/dL; 95% CI, -0.17 to 0.66 mg/dL; I² = 98.7%), sCr at discharge (MD 0.33 mg/dL; 95% CI, -0.13 to 0.80 mg/dL; I² = 69.6%), discharge BUN levels (MD 6.57 mg/dL; 95% CI, -7.93 to 21.80 mg/dL; I² = 78.7%), and length of hospitalization (MD -0.50 days; 95% CI, -2.75 to 1.76 days; I² = 93.0%). The post hoc TSA revealed that the current evidence base is underpowered and inconclusive. Limited heterogeneity (I² = 0%) was observed among studies reporting WRF, indicating consistency in this primary outcome. However, the high I² values and wide CIs in the secondary outcomes reflect imprecise effect estimates, thereby limiting the clinical certainty of these findings. The TSA calculated a required information size of 3,342 participants, whereas the accrued information size in this meta-analysis was only 693 participants. This discrepancy underscores the potential for a type II error and reinforces the conclusion that current evidence remains insufficient to draw definitive conclusions. Overall, continuous infusion of loop diuretics does not appear to provide a significant renal advantage over intermittent bolus administration. The substantial evidence gap highlights the need for larger, high-quality RCTs powered to detect clinically meaningful renal outcomes. This study represents the first meta-analysis to prioritize renal endpoints and incorporate TSA in comparing these two diuretic strategies.