Document resource
Introduction Intravenous (IV) hypertonic saline alongside IV loop diuretics is sometimes used to enhance diuresis in people hospitalised with severe heart failure (HF) but is challenging to administer. Oral sodium chloride (NaCl) supplements might be a practical alternative, but little is known about their effects in patients with HF. We performed a rapid review of the relevant evidence.Methods A rapid systematic review was registered (PROSPERO: CRD420200618965) and reported following PRISMA guidelines. Medline and CENTRAL databases were searched for studies involving adults with HF administered oral NaCl supplements. Randomized and observational studies were included. Studies of oral sodium chloride restriction or IV hypertonic saline were excluded. Data on diuresis, symptoms, renal function, electrolytes, haemodynamic variables, neurohormonal markers, and clinical outcomes were extracted. Risk of bias was evaluated using ROB-2 and ROBINS-I tools.Results From an initial 335 records, 5 studies involving 139 patients met the inclusion criteria ( figure 1) (table 1). Oral NaCl supplements did not affect weight or urine volume but were associated with higher serum and urinary sodium concentrations. Some studies reported that NaCl supplementation was associated with smaller diuretic-induced increases in serum urea and creatinine; lower haematocrit; higher plasma volume; and less neurohormonal activation compared to normal NaCl intake (figure 2) (table 2). Clinical outcomes, including hospital length of stay and mortality, were unaffected. The quality of evidence was limited by small sample sizes and methodological heterogeneity.Conclusions For patients with HF treated with loop diuretics, higher NaCl intake may increase serum and urine sodium concentration, improve renal function, and reduce neurohormonal activation. There is insufficient evidence to support oral NaCl as an adjunct to diuretic treatment. More research is needed.Abstract 119 Figure 1Flow diagramAbstract 119 Table 1Study characteristicsStudy(year)Study design(N)Population & diuretic dosing(% or mean/median values)Form and dose of NaCl & Control groupDuration(days)Waldman (1953)Case series(N=4)Chronic congestive HF receiving IM mercurial diuretic – 2cc.4 g/d (~70 mmol) added to dietVs.Low salt diet (<2 g/d; ~34 mmol)1Dubiel (1972)Prospective, observational(N=23)Out-patients with HF. NYHA I-II; 79% women; 38 years; 53% CAD, 32% MV disease, 11% DCM; mean CI 2.4 L/min; mean RAP 2 mmHg.7 patients received 80 mg of furosemide. Unclear which patients or route given.~53 g (900 mmol) as tabletsVs.Healthy controls(N = 16)8Volpe (1997)Prospective observational(N=10)Out-patients with HF NYHA I; 20% women; 51 years; weight 67 kg; LVEF 30%; peak VO2 16.2 ml/kg/min; 90% on ACEI; 70% on oral nitrates)No HF treatment was permitted as per study protocol.150 mmol/d (~9 g) as tablets in divided doses added to low salt (100 mmol/d; ~6g/d)Vs.6 days on low salt diet (100 mmol/d; ~6 g/d) prior to initiation of NaCl supplements8Damgaard (2006)Randomised, crossover, open-label(N=12)Out-patients with HF (mean age 57 years; mean LVEF 26%)83% taking LD. Dose not reported.200 mmol (~15 g) Na+ day as part of a high sodium diet.Vs.70 mmol (4 g) NaCl / day as part of a low sodium diet7Damgaard (2007)†Randomised, crossover, open-label(N=12)Out-patients with HF. mean age 57 years; all male; mean LVEF 26%; 50% NYHA III; 83% taking loop diuretic. Dose not reported 200 mmol (~15 g) Na+ day as part of a high sodium diet.Vs.70 mmol (4 g) NaCl / day as part of a low salt diet7Montgomery (2023)Randomised, double-blind, placebo controlled(N=65)In-patients with HF. (age 70 years; 37% women; LVEF 45%; NT-proBNP 4040 ng/L)100% on LD(mean dose in 405-460 mg/d)6 g/d (102 mmol/d) as tablets added to low salt diet (34 mmol/d; 2 g/d).Vs.Low salt diet (34 mmol/d; 2 g/d)4Legend† - not explicitly stated in the publication but we suspect these data are the same as the Damgaard 2006 investigation. Abbreviations used: HF – heart failuire; NYHA – New York Heart Association; CAD – coronary artery disease; MV – mitral valve; DCM – dilated cardiomyopathy; CI – cardiac index; RAP – right atrial pressure; LVEF – left ventricular ejection fraction; ACEI – angiotensin converting enzyme inhibitor; NT-proBNP – N-terminal pro-B-type natriuretic peptide; DM – diabetes mellitus; IHD – ischaemic heart disease; AF – atrial fibrillation; RRT – renal replacement therapy; eGFR – estimated glomerular filtration rate; SBP – systolic blood pressure; IM – intra-muscular; LD – loop diuretic; ARB – angiotensin receptor blocker; ϐB – beta-blocker; MRA – mineralocorticoid receptor antagonist; ARNI – angiotensin receptor neprilysin inhibitor; SGLT2I – sodium glucose co-transporter 2 inhibitor; g – gram; d – day;Abstract 119 Table 2Effect of oral sodium chloride supplementation on measures of diuresis, natriuresis, serum electrolytes and renal functionInt.=Intervention, Con.=ControlAbstract 119 Figure 2Summary of effects of sodium chloride supplementation in patients with heart failure across 3 papers