Fluid Restriction Therapy for Chronic SIAD; Results of a Prospective Randomized Controlled Trial

Context: Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy. Design: A prospective nonblinded randomized controlled trial of FR versus no treatment in chronic SIAD. Interventions and Outcome: A total of 46 patients with chronic asymptomatic SIAD were randomized to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for 1 month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30. Results: Median baseline pNa was similar in the 2 groups [127 mmol/L (interquartile range [IQR] 126-129) FR and 128 mmol/L (IQR 126-129) NoTx, P= 0.361. PNa rose by 3 mmol/L (IQR 2-4) after 3 days FR, compared with 1 mmol/L (IQR 0-3) NoTx, P= 0.005.There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, P= 0.04. After 3 days, 17% of FR had a rise in pNa of >= 5 mmol/L, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), P= 0.35. After 3 days, 61% of FR corrected pNa to >= 130 mmol/L, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), P= 0.24. Conclusion: FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and it is well-tolerated. More than one-third of patients fail to reach a pNa >= 130 mmol/L after 3 days of FR, emphasizing the clinical need for additional therapies for SIAD in some patients.