Safety of Rapid Intermittent Bolus versus Slow Continuous Infusion of Hypertonic Saline for Managing Symptomatic Severe Hyponatremia: A Systematic Review and Meta-analysis

AIMS: Three percent hypertonic saline (3NS) is an established treatment for severe hyponatremia. The optimal regimen for administering 3NS for severe hyponatremia, with the aim to minimize side effects is not known. This systematic review and meta-analysis aimed to evaluate the safety profile of rapid intermittent bolus (RIB) versus slow continuous infusion (SCI) of 3NS for managing symptomatic severe hyponatremia. METHODS: Databases were searched for studies evaluating the use of RIB versus SCI/conventional therapy of 3NS for managing symptomatic severe hyponatremia. The primary outcome was to evaluate the occurrence of overcorrection of hyponatremia. Secondary outcomes were to evaluate the need for relowering therapy, duration of hospital stay, changes in sodium levels, osmotic demyelination syndrome (ODS), and mortality. RESULTS: Data from three studies (290 patients) with severe hyponatremia was analyzed. Patients receiving RIB had a similar occurrence of overcorrection (relative risk [RR]: 1.59 [0.40, 6.35]; I2 = 61%; P = 0.51), need for relowering treatment to bring down serum sodium back to the normal range (RR: 2.53 [0.32, 20.20]; I2 = 81%; P = 0.38), ODS (RR: 2.24 [0.09, 57.18]; P = 0.63) and mortality (RR: 0.51 [0.08, 3.30]; I2 = 31%; P = 0.48), as compared to those receiving SCI. Patients receiving RIB had a marginally higher duration of hospital stay, which approached statistical significance (mean difference: 3.71 days [-0.18, 7.59]; I2 = 0%; P = 0.06). CONCLUSION: Both RIB and SCI of hypertonic saline were safe and effective for managing severe symptomatic hyponatremia. The reduced duration of hospital stay with SCI of hypertonic saline may suggest this may be the optimal way of administering hypertonic saline.