Efficacy and Safety of Hypertonic Saline Solution With Loop Diuretics in Patients With Acute Heart Failure: A Protocol for Systematic Review and Meta-Analysis.

BACKGROUND: Intravenous loop diuretics are the cornerstone of acute heart failure treatment. Diuretic resistance limits the efficacy and reduces the effectiveness of decongestion, which is associated with increased mortality in AHF patients. We aim to investigate the effect of adding hypertonic saline solution (HSS) to intravenous loop diuretics in treating AHF.

METHOD: This protocol for a systematic review is conducted with guidance from the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We will systematically review randomised clinical trials (RCTs) comparing HSS with placebo or another control in patients hospitalised with AHF. The primary outcome is all-cause mortality. The secondary outcomes will be all-cause hospitalisation, change in body weight (kg), and volume of diuresis. Exploratory outcomes will be length of hospitalisation and serum creatinine. A comprehensive search will be performed across major databases, and Covidence will be used to screen all results from the combined search by two authors independently. The search is planned to begin in May 2025. Meta-analysis and trial sequential analysis will be conducted on eligible trials. Risk of bias will be evaluated using the cochrane risk of bias tool-version 2. The certainty of the evidence will be assessed using the grading of recommendations, assessment, development and evaluations (GRADE) and confidence in network meta-analysis (CINEMA) approach.