Bolus administration of 3% saline (hypertonic saline) delivers faster elevation of plasma sodium levels with more effective neurologic changes within the first 6 hours of presentation of symptomatic severe hyponatremia from syndrome of inappropriate antidiuresis (SIADH), according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Guidelines for the management of hyponatremia have defined targets for safe elevation of plasma sodium concentration in patients with chronic hyponatremia. In a major policy change, recent guidelines have changed the recommendations for the management of acute symptomatic hyponatremia, specifying the use of bolus injection of hypertonic saline for a rapid early plasma sodium increase of 4 to 6 mmol/L over the initial 4 hours.

As there is limited evidence in literature regarding this recommendation, the researchers compared the biochemical and clinical outcomes following continuous vs bolus infusion of hypertonic saline for treating patients with symptomatic hyponatremia due to SIADH. They compared the rate of plasma sodium concentration increase using continuous infusion and bolus injection of 3% sodium chloride and also measured Glasgow Coma Scale and the need for rescue treatment for overcorrection of plasma sodium with dextrose or desmopressin.

The study enrolled patients admitted to Beaumont Hospital in Dublin, Ireland, between 2000 and 2013 with plasma sodium concentration <125 mmol/L, an underlying diagnosis of SIADH, and neurologic sequelae (diminished conscious level, confusion, coma, or seizures). Patients treated with bolus hypertonic saline had prospective data collection, while patients treated with continuous saline infusion were retrospectively identified.

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The study cohort included 50 patients treated for SIADH-induced hyponatremia with signs or symptoms of cerebral edema. Of these patients, 22 were treated with bolus hypertonic saline and 28 with continuous infusion.

Bolus injection was associated with a more rapid elevation of plasma sodium at 6 hours (median change of plasma sodium: 6 mmol/L vs 3 mmol/L; P <.0001) and at 12 hours (median change of plasma sodium: 8 mmol/L vs 5 mmol/L; P <.0001) compared with continuous infusion, but not at 24 hours. Median plasma sodium concentration was similar at 24 hours in both treatment groups. The more rapid increase in plasma sodium in the bolus group was associated with better improvement in Glasgow Coma Scale scores at 6 and 12 hours (P =.001).

Compared with continuous infusion, treatment with bolus injection of hypertonic saline was associated with an increased risk for requiring treatment to offset overcorrection of plasma sodium (0 of 28 patients vs 5 of 22 patients, respectively; P =.008).

During the study, 4 patients died; all were treated with continuous infusion of hypertonic saline. There were no cases of osmotic demyelination in either group.

The nonrandomized study design and the retrospective nature of the continuous infusion group were the major study limitations, according to the investigators.

“Bolus intravenous injection of 3% sodium chloride solution delivers faster elevation of [plasma sodium], with more effective restoration of [Glasgow Coma Scale score], within the first [6] hours of presentation of symptomatic severe hyponatremia due to [SIADH], than traditional continuous infusion of hypertonic saline,” concluded the researchers.

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Reference

Garrahy A, Dineen R, Hannon AM, et al. Continuous versus bolus infusion of hypertonic saline in the treatment of symptomatic hyponatremia due to SIAD [published online March 18, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00044