Proactive desmopressin for the prevention of serum sodium overcorrection in moderate-to-severe hyponatremia: a systematic review and meta-analysis.

BACKGROUND

Hyponatremia is the most common electrolyte disorder in hospitalized patients and is associated with increased morbidity and mortality. Correction is challenging because rapid increases in serum sodium may lead to osmotic demyelination. Desmopressin is used to stabilize free-water excretion, but the effectiveness of proactive administration has not been systematically evaluated.

METHODS

We searched PubMed-MEDLINE, Embase, and the Cochrane Library registries from inception through February 2026. We included studies enrolling adults with moderate-to-severe hyponatremia receiving standard therapy that compared proactive desmopressin with non-proactive usual-care strategies. Two reviewers independently extracted data and assessed risk of bias using ROBINS-I v2 and RoB 2. The primary outcome was serum sodium overcorrection using study-defined thresholds. Secondary outcomes included osmotic demyelination syndrome (ODS), mortality, hospital length of stay, worsening hyponatremia, and total hypertonic saline volume infused.

RESULTS

Six studies including 1,881 patients were included, of whom 168 received proactive desmopressin. Proactive desmopressin was associated with significantly lower odds of overcorrection compared with non-proactive usual-care strategies (OR, 0.29; 95% CI, 0.19-0.45; p < 0.001; prediction interval, 0.14-0.62). This association was consistent across thresholds of > 8, >10, and > 12 mEq/L at 24 h and > 18 mEq/L at 48 h. Cases of ODS were rare and did not differ significantly between groups. Mortality, hospital length of stay, total hypertonic saline volume infused, and worsening hyponatremia also did not differ significantly between groups.

CONCLUSIONS

In adults with moderate-to-severe hyponatremia receiving standard therapy, proactive desmopressin was associated with a lower risk of overcorrection. This reduction was not accompanied by clear differences in ODS, worsening hyponatremia, or mortality. Further prospective randomized studies are needed to better define the optimal timing, dosing, and patient selection for this strategy.

PROSPERO: CRD420251043907 CLINICAL TRIAL NUMBER: Not applicable.