Furosemide plus oral sodium chloride for syndrome of inappropriate antidiuresis after fluid restriction failure

Background: Syndrome of inappropriate antidiuresis (SIAD) is a common cause of hyponatraemia, with fluid restriction (FR) failing in nearly half of patients. Although furosemide combined with oral sodium chloride (NaCl) tablets is widely used as second-line therapy, evidence supporting its effectiveness after FR failure remains limited, and predictors of response have not been established. Methods: This prospective multicentre cohort study enrolled hospitalized adults with SIAD who failed FR at two tertiary centres in Thailand between October 2022 and September 2025. Patients received oral NaCl tablets (3.6 g daily) and furosemide (40 mg daily) while continuing FR. The primary outcome was the daily rate of serum sodium correction. Predictors of response were identified using multivariable linear mixed-effects models. Results: Among 88 patients (68% male; median age 65 years), the median baseline serum sodium was 124 mmol/l. Serum sodium increased by 1.51 mmol/l per day [95% confidence interval (CI) 1.37-1.66], reaching a median of 130 mmol/l by day 4 and 134 mmol/l by day 7. Three factors independently predicted faster correction: higher body weight (β 0.85 mmol/l per 10 kg; 95% CI 0.28-1.42), lower baseline sodium (β -0.58 per 1 mmol/l lower; 95% CI -0.77 to -0.39), and drug-induced aetiology (β 7.17 mmol/l; 95% CI 3.48-10.85). Adverse events included hypokalaemia (51%), hypomagnesaemia (29.5%), and acute kidney injury (18.2%). Overcorrection occurred in one (1.1%) patient. Conclusions: Furosemide combined with oral NaCl tablets is a practical second-line option for SIAD after FR failure, achieving sodium correction of 1.5 mmol/l per day. Higher body weight, lower baseline sodium, and drug-induced aetiology predict faster correction. Randomized controlled trials are needed to confirm efficacy.